12. Nuclear Medicine

Authors: Dahnert, Wolfgang

Title: Radiology Review Manual, 6th Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > Nuclear Medicine

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Nuclear Medicine

Table of Dose, Energy, Half-Life, Radiation Dose

Organ	Pharmaceutical	Dose	keV	T1/2 phys	T1/2 bio
Brain	Tc-99m pertechnetate	10 30 mCi	140	6 h
	Tc-99m DTPA	10 mCi	140	6 h
	Tc-99m glucoheptonate	10 mCi	140	6 h
	Tc-99m Ceretec	20 mCi	140	6 h
	I-123 Spectamine	3 6 mCi	159	13.6 h
CSF	In-111 DTPA	500 Ci	173, 247	2.8 d
	Tc-99m DTPA	1 mCi	140	6 h
Cardiac	Tl-201	1 2 mCi	72, 135, 167	73 h
	Tc-99m pyrophosphate	15 mCi	140	6 h
	Tc-99m pertechnetate	15 25 mCi	140	6 h
	Tc-99m labeled RBCs	10 20 mCi	140	6 h
	Tc-99m sestamibi	25 mCi	140	6 h
	Tc-99m teboroxime	30 mCi	140	6 h
Liver	Tc-99m sulfur colloid	3 5 mCi	140	6 h
	Tc-99m DISIDA	4 5 mCi	140	6 h
Lung	Xe-127	5 10 mCi	172, 203, 375	36.4 d	13 s
	Xe-133	10 20 mCi	81, 161	5.3 d	20 s
	Kr-81m	20 mCi	176, 188, 190	13 s
	Tc-99m MAA aerosol	3 mCi	140	6 h	8 h
Kidney	Tc-99m DTPA	15 20 mCi	140	6 h
	Tc-99m DMSA	2 5 mCi	140	6 h
	Tc-99m glucoheptonate	15 20 mCi	140	6 h
	Tc-99m mercaptoacetyltriglycine	10 mCi	140	6 h
	I-131 Hippuran	250 Ci	365*	8 d	18 m
	I-123 Hippuran	1 mCi	159	13.2
Thyroid	Tc-99m pertechnetate	5 10 mCi	140	6 h
	I-123	50 200 Ci	159	13.2 h
	I-125	30 100 Ci	27, 35	60 d
	I-131	30 100 Ci	365*	8 d
Testes	Tc-99m pertechnetate	10 mCi	140	6 h
Gastric mucosa	Tc-99m pertechnetate	50 Ci / kg	140	6 h
Gallium	Ga-67 citrate	3 5 mCi	93, 184, 296, 388	3.3 d
WBC	In-111 oxine	550 Ci	173, 247	2.8 d
	Tc-99m Ceretec	10 20 mCi	140	6 h
mnemonic: * = as many days as in a year

P.1072

Radiation Dose

Radiopharmaceutical	Critical Organ	rad/mCi
I-131	Thyroid	1,000
I-125	Thyroid	900
In-111 oxine WBC	Spleen	26
I-123	Thyroid	15
In-111 DTPA	Spinal cord	12
Tl-201	Kidney	1.5
Ga-67 citrate	Colon	1.0
Tc-99m MAA	Lung	0.4
Tc-99m albumin microspheres	Lung	0.4
Tc-99m DISIDA	Large bowel	0.39
Tc-99m sulfur colloid	Liver	0.33
Tc-99m pertechnetate	Intestine	0.3
	Thyroid	0.15
Tc-99m glucoheptonate	Kidney	0.2
Tc-99m pertechnetate (+ perchlorate)	Colon	0.2
Tc-99m pyrophosphate	Bladder	0.13
Tc-99m phosphate	Bladder	0.13
Tc-99m DTPA	Bladder	0.12
Tc-99m tagged RBCs	Spleen	0.11
Tc-99m albumin	Blood	0.015
Xe-133	Trachea

Pediatric Dose

Actual doses for pediatric patients may vary in different institutions based on empirical data.As rough guidelines use:

1. Clark's rule (body weight):	DosePed = Body weight [in lbs] / 150 DoseAdult
2. Young's rule (child up to age 12):	DosePed = Age of child / (Age of child + 12) DoseAdult
3. Surface area:	DosePed = (weight [in kg] 0.7 / 11) / 1.73 DoseAdult

Lactating Patients

• Nursing mothers must be counseled about the need to interrupt / discontinue breast feeding

• Pumped milk may be refrigerated and used after the radioactivity has decayed

	Complete cessation of breast feeding:
Ga-67 citrate
I-131 sodium iodide therapy
	Interruption of breast feeding for 12 hours:
Tc-99m macroaggregated albumin
Tc-99m labeled RBCs (in vivo labeling)
In-111 labeled WBCs
	Interruption of breast feeding for 24 hours:
Tc-99m pertechnetate
I-123 metaiodobenzylguanidine
Tc-99m labeled WBCs
	Interruption of breast feeding for 168 hours:
Tl-210 chlorided

Quality control

P.1073

• Quality control logs should be kept for 3 years!

Radiopharmaceuticals

Production of Radionuclides

Reactor-produced Radionuclides

• Not carrier free = contamination with other forms

• Thermal neutrons captured by stable nuclides

• Used to produce standard generators

  • Mo-99/Tc-99m generator

    • (parent) (daughter)

    • ⁹⁹Mo ^99mTc ⁹⁹Tc ⁹⁹Ru

    • 67 hours 6 hours 2.1x10⁵ years stable

    • glass column filled with aluminum (Al₂O₃); parent and daughter isotopes are firmly absorbed onto aluminum at top of column; daughter isotope can be separated / eluted by passing isotonic oxidant-free NaCl through the column

  • Kr-81m generator

    • (parent) (daughter)

    • ⁸¹Rb ^81mKr ⁸¹Kr

    • 7 hours 13 seconds stable

Accelerator / Cyclotron-produced Radionuclides

• Generally carrier-free product

• collision of charged particles (protons, deuterons, helium, alpha particles) with target nuclide

• used to produce Ga-67, I-123, Tl-201

Fission-produced Radionuclides

• Carrier-free product

• splitting of a heavy nucleus into smaller nuclei

• used to produce I-131, Mo-99

Radionuclide Impurity

• = amount ( Ci) of radiocontaminant per amount ( Ci/mCi) of desired radionuclide

Mo-99 Breakthrough Test

Test frequency:

with every elution

• NRC allowable contamination of 1:1,000

  • = 1 Ci Mo-99 per 1 mCi of Tc-99m

• USP limit of 0.15 Ci Mo-99 per 1 mCi Tc-99m

• <5 Ci Mo-99 per administered dose (NRC dropped this requirement, but nonagreement states may still require this)

• chemical evaluation: Mo-99 contaminated eluate forms colored complexes with phenylhydrazine (for reactor product generators)

• measured in dose calibrator with lead shielding of vial (filters 140 keV but permits 740 and 780 keV of Mo-99 to pass through

Effect of impurity:

increased radiation dose, poor image quality

Radiochemical Impurity

Test frequency:

with every elution

Precise registration of different compounds of Tc-99m, eg,

• hydrolyzed reduced technetium (HR Tc)

  • a radiocolloid [TcO(OH)₂ H₂O]

  Limit:

  <2% (presently no legal limit)

  • free pertechnetate [TcO⁴]^-1

    • can be monitored by paper chromatography

    • Effect of impurity with hydrolyzed reduced Tc:

      • RES uptake, poor image quality, increased radiation dose

Chemical Impurity

Chemicals from elution process are restricted in their amount (NRC limit):

Tc-99m:

<10 g Al3+ per 1 mL eluate if radionuclide from fission generator; <20 g Al3+ per 1 mL eluate if radionuclide from thermal activation generator

Aluminum Ion Breakthrough Test

Test frequency:

with every elution

• one drop of generator eluate placed on one end of special test paper containing aluminum reagent

• equal-sized drop of a standard solution of Al³⁺ (10 ppm) is placed on other end of strip

• if color at center of drop eluate is lighter than that of standard solution, the eluate has passed the colorimetric test

Effect of impurity:

degradation of image quality

Radiopharmaceutical Sterility and Pyrogenicity

USP XX Test

Monitor rectal temperature of 3 suitable rabbits after injection of material through ear vein

Acceptable results:

no rabbit shows a rise of >0.6 C; total rise for all three rabbits <1.4 C

Limulus Amoebocyte Lysate Test (LAL)

• Highly specific for Gram-negative bacterial endotoxins, sensitivity 10 greater than USP XX test

Amoebocyte =	primitive blood cell of horseshoe crab (Limulus polyphebus); lysate formed by hydrolysis of amoebocyte
Positive result:	in the presence of minute amounts of endotoxin LAL forms an opaque gel; response to other pyrogens (particulate contaminations, chemicals) doubtful

Quality Control for Dose Calibrators

Test	When	Limit	Test Isotopes
Constancy	daily,*	< 5%	Cs-137
Channel check	daily,*	< 5%	Cs-137
Linearity	quarterly,*	< 5%	Tc-99m
Accuracy	annually,*	< 5%	Cs-137, Co-57, Ba-133
Geometry	*	< 1.6%	Tc-99m
* = after install / repair

P.1074

Calibrators

Dose Calibrator

• = gas ionization chamber that transforms photon flux into current with digital readout

Disadvantages:

• open top geometry

• nonlinearity between photon energy and measured current (corrected with a calibration factor)

Constancy = Precision

• = reproducibility over time

Test frequency:	daily
Method:	measurement of a long-lived source, usually a Cs-137 standard
Evaluation:	measurement must fall within 5% of the calculated activity

Linearity

• = accurate measurement over large range of activity levels

Test frequency:	4 per year
Method:	1 mCi source activity is measured every 4 hours for 10 / more measurements (down to 10 100 Ci)
Evaluation:	measurements must fall within 5% of the calculated physical decay curve

Accuracy

Test frequency:	annually
Method:	measurements of three different activity standards whose amount is certified by the National Bureau of Standards (NBS); standard values are decayed mathematically to calibrator date

Tc-99m:	140 keV, half-life of 6.01 hoursr
Co-57:	123 keV, half-life of 270 days
Ba-133:	356 keV, half-life of 10.5 years
Cs-137:	662 keV, half-life of 30.1 years

Evaluation:

measurements must fall within expected range

Geometry

• = to ensure that measurement is not dependent upon location of tracer within ionization chamber, usually done by manufacturer

Test frequency:	at installation / after factory repair / recalibration
Method:	0.5 mL of Tc-99m (activity 25 mCi) is measured in a 3-mL syringe; syringe contents are then diluted with water to 1.0 mL, 1.5 mL, and 2.0 mL and each level remeasured; test is repeated with a 10-mL glass vial

Scintillation camera

Peaking

• = ensures that window of pulse height selector is correctly set to desired photopeak

• for Tc-99m source: between 137 and 143 keV

• for Co-57 source: between 117 and 123 keV

Frequency of quality control:

daily

Field Uniformity

• = ability of camera to reproduce a uniform radioactive distribution = variability of observed count density with a homogeneous flux

(a) Integral uniformity =	maximum deviation
(b) Differential uniformity =	maximum rate of change over a specified distance (5 pixels)

Causes for nonuniformity:

• High kilovoltage drift of photomultiplier (PM) tubes

• Physical damage to collimator

• Improper photopeak setting

• Contamination

Frequency of quality control:

daily

Evaluation:

• Compare uncorrected with corrected images. Note acquisition time!

• Store correction flood

• Rerecord image with corrected flood + check for uniformity

• Variation in image should be <5% RMS

Intrinsic Field Uniformity Test

(without collimator)

• Remove collimator + replace with lead ring (to eliminate edge packing)

• Place a point source at a distance of at least 5 crystal diameters from detector (4 5 feet for small, 7 9 feet for large crystals)

• Point source contains 200 400 Ci of Tc-99m for minimal personnel exposure (avoid contamination of crystal)

• Set count rate below limit of instrument (<30,000 counts)

• Adjust the pulse height selector to normal window settings by centering at 140 keV with a window of 15% (for Tc-99m studies only)

• Use the same photographic device

• Acquire 1.25 million counts for a 10 field of view, 2.5 million counts for a 15 field of view

• Register counts, time, CRT intensity, analyzer settings, initials of controller

Extrinsic Field Uniformity Test

(with collimator on)

• Collimator is kept in place

  • Only 1 of 2,000 gamma rays that reach the collimator are transmitted to the sodium iodide crystal!

    Quality Control for Gamma Cameras

    Test	When	Test Result
    Peaking	daily	Tc-99m and Co-57
    Energy resolution	daily	<14% at FWHM
    Extrinsic field uniformity	daily	<5% RMS variation
    Bar phantom	weekly	visual assessment
    Field uniformity	monthly	visual assessment
    Center of rotation	monthly	visual assessment
    Jaczak phantom	quarterly	visual assessment

P.1075




• Sheet source / flood of 2 10 mCi activity is placed on collimator

  • fillable floods: mix thoroughly, avoid air bubbles, check for flat surface

  • nonfillable: commercially available Co-57 source

• Other steps as described above

Spatial Resolution / Linearity

• SPATIAL RESOLUTION

  • = parameter of scintillation camera that characterizes its ability to accurately determine the original location of a gamma ray on an X, Y plane; measured in both X and Y directions; expressed as full width at half maximum (FWHM) of the line spread function in mm

    • intrinsic spatial resolution

    • system spatial resolution

  • INTRINSIC SPATIAL LINEARITY

    • = parameter of a scintillation camera that characterizes the amount of positional distortion caused by the camera with respect to incident gamma events entering the detector

      • differential linearity = standard deviation of line spread function peak separation (in mm)

      • absolute linearity = maximum amount of spatial displacement (in mm)

Frequency of quality control:

every week

Method:

• Mask detector to collimated field of view (lead ring)

• Lead phantom is attached to front of crystal

  • Four-quadrant bar pattern (3 pictures each after 90 rotation to test entire crystal)

  • Parallel-line equal-spacing (PLES) bar pattern [2 pictures]

    • Change bar direction angles weekly

  • Smith orthogonal hole test pattern (OHP) [one picture only]

  • Hine-Duley phantom [2 pictures]

• Set symmetric analyzer window to width normally used

• Place a point source (1 3 mCi) at a fixed distance of at least 5 crystal diameters from detector on central axis (remove all sources from immediate area so that background count rate is low)

• Acquire 1.25 million counts for a small field, 2.5 million counts for a large field on the same media used for clinical studies

• Record counts, time, CRT intensity, analyzer setting, initials of controller

• (All new cameras are equipped with a spatial distortion correction circuit)

Evaluation:

visual assessment of

• Spatial resolution over entire field

• Linearity

Intrinsic Energy Resolution

= ability to distinguish between primary gamma events and scattered events; performed without collimator; expressed as ratio of photopeak FWHM to photopeak energy (in %)

Limit:	11% for SPECT, 14% for some planar cameras
Frequency of quality control:	daily (may be weekly for some cameras)

CRT-output / Photographic Device

• Check for dirt, scratches, burnt spots on CRT face plates

• Adjust gray scale + contrast settings to suit film

SPECT quality control

• = SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

• = gamma cameras rotating about a pallet supporting the patient obtain 60 120 views over 180 / 360 rotation with typically a field of view of 40 50 cm across the patient and 30 40 cm in axial direction

Spatial resolution:

~8 mm for high-count study

SPECT Uniformity

• 64 64 word matrix = 30 million count flood with collimator, orientation and magnification same as patient study

• Co-57 sheet source with <1% uniformity variance is necessary

• 128 128 word matrix = 120 million count flood with collimator, orientation, and magnification same as patient study

Frequency of quality control:

weekly

Center of Rotation (COR)

• Tc-99m filled line source (5 8 mCi) positioned 3 5 cm off the center of rotation while keeping scanning palette out of field of view

• Direction of rotation to be the same as patient study

• Number of steps (32, 64, or 128) to be the same as in patient study

• Time per step such that at least 100K counts are acquired

• COR must be done with same collimator, orientation, and magnification as patient study

Frequency of quality control:

weekly

Jaczak Phantom SPECT Study

tests multiple camera systems with a final image

• phantom contains multiple objects of various sizes (hot and cold rods and cold balls)

• final reconstructed image is visually assessed

SPECT Sources of Artifacts

• Scanning palette in field of view

• Collimator shifting + rotation on camera face

• Noncircular orbit of camera head

• PM tube failure

• PM tube uncoupling

• Cracked crystal

• Improper peaking of camera

Sources of artifacts

• Attenuator between source and detector

Materials:

cable, lead marker, solder dropped into collimator during repair, belt buckle / watch / key on patient, defective collimator

• (a) at time of correction flood procedure:

  • hot spot

P.1076




• (b) after correction flood procedure:

  • cold spot

• Cracked crystal

  • white band with hot edges

• PMT failure + loss of optical coupling between PMT and crystal

  • cold defect

• Problems during film exposure + processing

  • Double exposed film

  • Light leak in multiformat camera

  • Water lines from film processing

  • Frozen shutter:

    • part of film cut off

  • Variations in film processing

• Improper window setting

  • Photopeak window set too high:

    • hot tubes

  • Photopeak window set too low:

    • cold tubes

    • Administration of wrong isotope

      • atypically imaged organs

    • Excessive amounts of free Tc-99m pertechnetate

      • too much uptake in choroid plexus, salivary glands, thyroid, stomach

    • Faulty Injection Technique

      • eg, inadvertently labeled blood clot in syringe leading to iatrogenic pulmonary emboli

    • Contamination with radiotracer

      • on patient's skin, stretcher, collimator, crystal

    • CRT problems

      • Burnt spot on CRT phosphor

      • Dirty / scratched CRT face plates

P.1077

Positron emission tomography

• = PET = technique that permits noninvasive in vivo examination of metabolism, blood flow, electrical activity, neurochemistry

• Concept:

  • measurement of distribution of a biocompound as a function of time after radiolabeling and injection into patient

• Labeling:

  • PET compounds are radiolabeled with positron-emitting radionuclides

• Physics:

  • positron matter-antimatter annihilation reaction with an electron results in formation of annihilation photons, which are emitted in exactly opposite directions (511 keV each); detected by coincidence circuitry through simultaneous arrival at detectors (bismuth germanate-68) on opposite sides of the patient (= electronic collimation through coincidence circuit); lead collimators not necessary (= advantages in resolution + sensitivity over SPECT); spatial reconstruction similar to transmission CT

Radionuclide Production

• in nuclide generator / particle accelerator (positive / negative ion cyclotron; linear accelerator)

• Expected amount of radionuclide: 500 2,000 mCi

• Generator characteristics:

  • beam energy (radionuclide production rate increases monotonically with beam energy), beam current (production rate directly proportional to beam current), accelerated particle, shielding requirement, size, cost

Radiopharmaceutical production

• Initialize accelerator, setup

• Irradiation

• Synthesis

• Sterility test, compounding

PET Imaging Characteristics

Sensitivity

• = fraction of radioactive decays within the patient that are detected by the scanner as true events (measured in counts per second per microcurie per milliliter)

• 30 100 times more sensitive than SPECT (due to electronic collimation as opposed to lead collimation)!

Resolution

• = resolving power = smallest side-by-side objects that can be distinguished as separate objects in images with an infinite number of counts (measured in mm);

• determined by

  • distance a positron travels before annihilation occurs (usually 0.5 2 mm depending on energy)

  • angle variation from 180 ( 5 = 0.5 mm)

  • physical size of detector (1 3 mm)

• Typical spatial resolution: 4 7 mm

Measurement of Radioactivity Distribution

• Pixel values proportional to radioactivity per volume

• Unit: mg of glucose per minute per 100 g tissue

• Imaging time: 1 10 minutes

Organ-specific Concentration

• heart, brain: contain little glucose-6-phosphatase resulting in high concentrations of F-18 fluorodeoxyglucose

  • metabolic rate of glucose is proportional to phosphorylation rate of FDG

(b) liver:	abundance of glucose-6-phosphatase + low levels of hexokinase resulting in rapid clearing of FDG
(c) urine:	50% of injected activity excreted unmetabolized in urine
(c) neoplasm:	enhanced glycolysis with increased activity of hexokinase + other enzymes

FDG Distribution

• Intense accumulation in: brain, myocardium, intrarenal collecting system + ureter + bladder

• Moderate accumulation in: liver, spleen, bone marrow, renal cortex, mediastinal blood pool

Common Radiopharmaceuticals in Positron Emission Tomography

Isotope	Use	Half-life (min)	Average Positron Energy (keV)	Typical Reaction	Yield at 10 MeV (mCi/ A EOSB)
Rubidium Rb-82		1.23	1,409	Sr/Rb generator
Fluorine F-18	glucose metabolism	109	242	O-18(p, n)F-18	120
Oxygen O-15	O2, H2O, CO2, CO	2.1	735	N-15(p, n)O-15	70
Nitrogen N-13	perfusion of NH3	10	491	C-13(p, n)N-13	110
Carbon C-11	carbon metabolism	20.3	385	N-14(p, )C-11	85
p = proton injected; n = neutron ejected; = alpha particle; EOSB = end of saturated bombardment (infinitely long irradiation at which time the numbers of radionuclides produced equals the number of radionuclides that are decaying) per microampere of beam current (= number of particles per second emerging from accelerator and impinging on target material)

P.1078

Sites of variable physiologic Uptake

• @ Brown fat

  • = highly specialized heat producing tissue

  • Location:

    • suboccipital, supraclavicular, paraspinal region of neck and chest; retrocrural; mediastinum

    • Keep uptake room warm; use warm blankets

• @ Brain & spinal cord

  • intense uptake in cerebral > cerebellar cortex, basal ganglia, thalamus; moderate uptake in cervical + upper thoracic spine

  • Often used as a reference for semiquantification

• @ Bone marrow

  • usually mild uptake with homogeneous distribution; moderate to intense uptake after chemotherapy + treatment with GCsF (granulocyte colony-stimulating factor) + in anemic patients

• @ Nasopharynx

  • Waldeyer ring (negative correlation between age and uptake intensity); sublingual glands (mucous gland with inverted V-shaped uptake at floor of mouth)

• @ Thyroid gland

  • moderate / intense uptake in 1/3 of euthyroid patients; consistent with chronic thyroiditis, Graves disease

• @ Thymus

  • mild to moderate intensity; rebound hyperplasia + increased uptake for 3 months to 1 year

• @ Digestive tract

  • esophagus: more intense at GE junction

  • stomach:

    SUV usually <3.8, may be as high as 5.6

  • small bowel: isolated foci with SVU <4

  • colon

    • right colon may have an SVU as high as 10; moderate to intense uptake in rectum

    • Enemas do not reduce uptake

• @ Liver

  • hepatocytes have a higher concentration of phosphatase enzymes resulting in dephosphorylation of FDG-6-phosphate + a faster FDG washout

  • Delayed imaging for indeterminatre liver lesion

• @ Skeletal muscle

  • Major energy sources: fat and glucose (at rest 9:1, at low exercise 6:4, at high exercise 1:9);

    • Diabetics take medication, have morning meal within 4 hours prior to imaging

  • No muscle effort for 24 hours before PET imaging

  • No chewing gum / tobacco, reading, talking during uptake phase

  • Location:

    • extraocular muscles; paravertebral muscles in neck + thorax (stress-induced, patient anxiety); intrinsic laryngeal muscles (speech); diaphragm (hyperventilation, forced respiration)

• @ Myocardium

  • free fatty acids are predominant metabolic substrate; glucose utilization + insulin levels increase after carbohydrate intake

    • Fasting ( 4 hours since last meal) switches to predominantly fatty acid metabolism

• @ Genitourinary tract

  • pooling in upper pole calyx, dilated redundant ureter, bladder diverticulum, endometrial uptake, testes (young patients)

    • Catheterization of bladder to reduce activity + filling with 200 mL of saline just before pelvic imaging

Sites of Benign Pathologic Uptake

• @ Healing bone

• @ Lymph nodes

  • active granulomatous disease (TB, sarcoidosis), infection, recent instrumentation

• @ Joints

  • degenerative / inflammatory joint disease (often in sternoclavicular + acromioclavicular + shoulder joints)

• @ Infection / inflammation

  • leukocytic infiltration in abscess, pneumonia, sinusitis, acute pancreatitis, healing by secondary intention, wound repair, resorption of necrotic debris, hematoma

FDG PET Imaging in Oncology

• FDG = glucose analogue tracer 2-[fluorine-18] fluoro-2-deoxy-D-glucose

• Indications:

  • Lung cancer

    • tumor uptake > mediastinal uptake of FDG (94 97% sensitive, 87 89% specific, 92% accurate)

    • FDG can differentiate adrenal incidentaloma from metastasis

  • Breast cancer

  • Colon cancer recurrence

  • Lymph node metastases from head and neck cancer (91% sensitive, 88% specific)

  • Brain tumor:

    • necrosis versus residual / recurrent tumor

      • decreased FDG uptake in necrosis

    • response to chemo- / radiation therapy

    • prediction of patient's average survival in pediatric primary brain tumors:

      6 months	if FDG uptake gray matter
      1 2 years	if FDG uptake > white matter
      2.5 years	if FDG uptake = white matter
      3 years	if FDG uptake < gray matter

  • Pancreatic cancer (96% sensitive + specific)

  • Lymphoma staging with whole-body scan

• Pathophysiology:

  • serum glucose competes with FDG for entry into tumor cells; trapped intracellularly as FDG-6-phosphate; malignant cells have a high rate of glycolysis

• Preparation:

  • fasting for 4 18 hours (FDG tumor uptake is diminished by an elevated serum glucose level)

• Dose: 10 mCi (370 MBq)

• Physical half-life: 110 minutes

• Imaging time:

  • 50 70 minutes after administration (trade-off between decreasing background activity and declining counting statistics)

P.1079




• Distortion correction in whole-body imaging:

  • attenuation correction can be achieved with a transmission scan before / after emission image acquisition at each corresponding bed position

Standardized Uptake Value (SUV)

• = normalized target-to-background measure to allow comparison within and between different patients and diseases

  • SUV = FDG_region / (FDG_dose/WT)

FDGregion	= decay-corrected regional radiotracer concentration
FDGdose	= injected radiotracer dose
WT	= body weight in kilograms (corrected for body fat as it elevates SUV spuriously)

Typical values:	soft tissue	0.8
	blood pool (at 1 hour)	1.5 2.0
	liver	2.5
	renal cortex	3.5
	malignant neoplasm	2 20
	non-small cell lung cancer	8.2
	breast cancer	3.2

P.1080

Immunoscintigraphy

• = imaging with monoclonal antibodies [= homogeneous antibody population directed against a single antigen (eg, cancer cell)], which are labeled with a radiotracer

• Hybridoma technique:

  • antibody-producing B lymphocytes are extracted from the spleen of mice that were immunized with a specific type of cancer cell; B lymphocytes are fused with immortal myeloma cells (= hybridoma)

• Agents:

  • Indium-111 satumomab pendetide = indium-111 CYT-103 (OncoScint CR/OV) = murine monoclonal antibody product derived by site-specific radiolabeling of the antibody B27.3-GYK-DTPA conjugate with indium-111

Use:	detection + staging of colorectal + ovarian cancers
Dose:	1 mg of antibody radiolabeled with 5 mCi of indium-111 injected IV
Biodistribution:	liver, spleen, bone marrow, salivary glands, male genitalia, blood pool, kidneys, bladder
Imaging:	2 sets of images 2 5 days post injection + 48 hours apart

P.1081

Lymphangioscintigraphy

Lymphangioscintigraphy Technique

Tc-99m albumin solution injected intradermally to raise a wheal in 1st interdigital web space of both feet / hands

Dose:	500 Ci (18.5 MBq); 92 98% of albumin are tightly bound to Tc-99m
Volume:	0.05 mL; >98% of albumin macromolecules (molecular weight of 60 kDa) enter lymphatic vessels
Imaging:	at 1 minutes, 10 40 minutes and 3 5 hours with parallel-hole collimator passing over patient

Transport Index Score (TIS)

• =semiquantitive measurement of objective + subjective criteria of peripheral lymphatic radiotracer transport

• TIS = K + D + 0.04T + N + V

• K = transport kinetics = degree of transport delay

• D = radionuclide distribution pattern = degree of dermal backflow

• T = timing of radionuclide appearance in regional lymph nodes (in minutes normalized for 200 minutes as maximal delay)

• N = demonstration + intensity of lymph nodes

• V = demonstration + intensity of lymphatic collectors

Lymph flow disorders

Primary Lymphatic Dysplasia

• uni- / bilateral swelling of lower / upper extremities

• resembles other angiodysplastic syndromes:

  • Klippel-Trenaunay-Servelle syndrome

    • =venous + lymphatic abnormalities

  • Klippel-Trenaunay-Weber syndrome

    • =venous + lymphatic + arterial disturbances

  • Milroy disease

    • =inherited autosomal disorder with high penetrance characterized by lymphedema of one / both lower /upper extremities, face, other body parts

Secondary Lymphatic Dysplasia

• =obstruction of lymph flow from an acquired cause

Cause:

• Treatment of cancer: obliteration of lymph nodes by excision or irradiation

  • Lymphedema may appear months to years after treatment due to gradual deterioration in intrinsic contractile force of lymphatic wall / valve incompetence

• Filariasis

  • =nematode (Wuchereria bancrofti, Brugia malayi) resides within peripheral lymphatic vessels + nodes + obstructs lymph flow

  • elephantine / pachydermatous extremities / genitalia

  • chyluria, hydrocele, chylous reflux (chylometrorrhagia, chylous vesicles), genital edema, massive breast engorgement

  • Long-standing venous disease / following venous stripping

  • Lymphatic obstruction by cancer, Kaposi sarcoma

  • Lymphatic inflammation: topical use of cantharone (for eradication of plantar warts); injection treatment of varicosities

  • Minor trauma to soft tissue / bone

  • Sedentary condition: eg, confinement to wheelchair

  • Morbid obesity

  • Lymphedema tarda

    • =congenital lymphedema with delayed manifestation secondary to superimposed secondary cause

Primary Lymphedema

• no history of cancer chemotherapy, nodal extirpation / irradiation, severe trauma

  Age:	birth to >25 years
  Cause:	primary / acquired lymphatic disorder

  • complete absence / delay of radiotracer transport

  • absence / paucity of lymphatic collectors (truncal flow)

  • intense dermal dispersion / backflow

    • chylous skin vesicles

    • external leakage of milky lymph

      • lymphatic dysplasia may involve viscera

Pitfall:

subcutaneous injection leads to factitious failure of radiotracer movement

Congenital Lymphedema

Age:	birth to 5 years

Lymphedema Precox

Age:	puberty to 25 years

• congenital

  • lack of lymph collectors, dermal diffusion, delayed transport

• acquired

  • intact collectors, rapid regional transport, delayed dermal diffusion

Secondary Lymphedema

• prominent lymphatic trunks:

• long-standing lymphatic obstruction leads to die-back (obliteration) of lymphatics due to intraluminal coagulum-gel deposition / reactive inflammation

• dermal diffusion (backflow) of variable intensity

• delayed radiotracer transport

• faintly visualized regional lymph nodes

P.1082

Non-Organ Specific Whole Body Scintigraphy

Indications for Non-organ specific Whole Body Imaging

• Tumor

  Agents:

  Ga-67 citrate, I-131 MIBG, In-111 pentetreotide (Octreoscan ), In-111 antiprostate antibody (ProstaScint ), In-111 Oncoscint, Tc-99m anti-CEA antibody (CEA-Scan ), F-18 deoxyglucose

• Inflammation / infection

  Agents:

  Ga-67 citrate, In-111 oxime labeled WBC, Tc-99m HMPAO labeled WBC

Agents for inflammation

Ga-67 citrate

• overall 58 100% sensitivity; 75 100% specificity (lower for abdominal inflammation because of problematic abdominal activity)

  Indication:

  Ga-67 mostly limited to

  • chest: interstitial pneumonia, opportunistic infection, sarcoidosis, drug toxicity

  • bone: osteomyelitis

    • Pathophysiology:

    • leakage of protein-bound Ga-67 into extracellular space secondary to hyperemia + increased capillary permeability; Ga-67 is preferentially bound to nonviable PMNs + macrophages

      • Leukocyte incorporation (rich in lactoferrin)

      • Bacterial uptake (iron-chelating siderophores)

      • Inflammatory tissue stimulates lactoferrin production

Gallium in Chronic Abdominal Inflammation

• 67% sensitivity, 64% specificity, 13% false-negative rate, 5% false-positive rate

Dose:	5 mCi
Imaging:	routine at 48 72 hours (after clearance of high background activity); optional at 6 24 hours (prior to renal + gastrointestinal excretion); delayed images as needed

• diffuse uptake in peritonitis

• localized uptake in acute pyogenic abscess, phlegmon, acute cholecystitis, acute pancreatitis, acute gastritis, diverticulitis, inflammatory bowel disease, surgical wound, pyelonephritis, perinephric abscess

Labeled Leukocyte Imaging

• =primary imaging method for inflammation / infection

• Indication:

• (1) Fever of unknown origin / bacteremia

• (2) Abdominal infection / abscess

• (3) Osteomyelitis

• (4) Inflammatory bowel disease

• (5) Vascular graft infection

• Preparation (3-hour time):

• 30 40 mL of whole blood drawn into syringe containing an anticoagulant

• syringe stands in upright position for 1 2 hours with addition of hydroxyethyl starch (for sedimentation of RBCs)

• under centrifugation leukocytes form a pellet at bottom of tube (allows separation of leukocytes from platelets)

• Requirements:

• 1. WBC count >2,000/mm3

• 2. Neutrophil-mediated inflammatory process

• Physiologic uptake:

• @ Granulation wounds = healing by secondary intention (eg, ostomies, skin graft)

  • Leukocytes do not accumulate in normally healing wounds

• @ Lung

  • physiologic diffuse lung uptake up to 4 hours

    • Lung uptake >24 hours due to pneumonia / ARDS

  • physiologic diffuse lung uptake in severely septic patient (due to cytokine release at site of infection + subsequent activation of pulmonary vascular endothelium)

In-111 labeled WBC

• = In-111-oxime labeled autologous leukocytes with 80% sensitivity; 97% specificity, 91% accuracy (superior to Ga-67 citrate); no activity in intestinal contents / urine

• Indications:

  • occult sepsis (postoperative fever), acute pyogenic infection, abdominal + renal abscess, inflammatory bowel disease, nonpulmonary infection with HIV positivity, prosthetic graft infection (bone / cardiovascular graft), acute + chronic + complicated bone / joint infection

  • Technique:

  • chelating agents (oxime = 8-hydroxyquinoline / tropolone) used for labeling of leukocytes; lipophilic oxime-indium complex penetrates cell membrane of white cells; intracellular proteins scavenge the indium from oxime; oxime diffuses out from cell; requires 2 hours of preparation time

    Recovery rate:	30% at 1 4 hours after injection
    Limitations:	19 gauge IV access, leukopenia, impaired chemotaxis, abnormal WBCs, children
    Dose:	0.5 mCi
    Half-life:	67 hours
    Useful photopeaks:	173 keV (89%), 247 keV (94%)

    • Radiation dose:

    • 13 18 rad/mCi for spleen; 3.8 rad/mCi for liver; 0.65 rad/mCi for red marrow; 0.45 rad/mCi for whole body; 0.29 rad/mCi for testes; 0.14 rad/mCi for ovaries (compared with Ga-67 higher dose to spleen, but lower dose to all other organs)

      Biodistribution:

      spleen, liver, bone marrow; blood clearance halftime of 6 7 hours; NO bowel activity

      P.1083

      
      

      • Imaging:

      • best at 18 24 hours following injection of cell preparation; optional at 2 6 hours (eg, in inflammatory bowel disease); delayed images as needed; bone marrow uptake provides useful landmarks

        • SPECT imaging >> standard planar imaging

      • focal activity greater than in spleen is typical for abscess (comparison based on liver, spleen, bone marrow activity)

      • activity equal to liver (significant inflammatory focus)

      • abdominal activity is always abnormal (eg, pseudomembranous / ischemic colitis, inflammatory bowel disease, GI bleeding)

      • False positives:

      • @ Chest: CHF, RDS, embolized cells, cystic fibrosis, vascular access lines, dialysis catheter

      • @ Abdomen: accessory spleen, colonic accumulation, renal transplant rejection, active GI hemorrhage, vasculitis, ischemic bowel disease, following CPR, uremia, postradiation therapy, Wegener granulomatosis, ALL, lumbar puncture

      • @ Miscellaneous: IM injection, histiocytic lymphoma, cerebral infarction, arthritis, skeletal metastases, thrombophlebitis, hematoma, hip prosthesis, cecal carcinoma, postsurgical pseudoaneurysm, necrotic tumors that harvest WBCs

      • False negatives:

      • chronic infection, aortofemoral graft, LUQ abscess, infected pelvic hematoma, splenic abscess, hepatic abscess (occasionally)

      • Disadvantages:

      • 2-day procedure, low-quality images especially of extremities

    • Advantages:

      • no activity in normal GI / GU tract (preferred in postoperative patient + vascular grafts); simultaneous WBC + sulfur colloid bone marrow scan possible

Tc-99m HMPAO Labeled WBC

Optimal use:	osteomyelitis in extremities
Biodistribution:	bone marrow, little soft tissue, spleen > liver, renal + bladder activity
Excretion:	in bile + urine

• Advantages over In-111 WBC imaging:

  • improved photon flux with lower dose

  • earlier imaging (same day)

  • Disadvantages:

  • (1)Biliary excretion leads to bowel activity, which may obscure abdominal / graft abscess if not imaged early

  • (2)Heart and blood pool activity

  • (3)Nonspecific accumulation in lung may obscure lung disease

  • Technique:

    • chelating agents (exametazine oxime) used for labeling of leukocytes; Tc-99m Ceretec binds with autologous WBCs and is reinjected

    Dose:

    up to 10 mCi

    • Imaging:

    • 30 minutes (optimum for use in abdomen), 60 minutes, 3 4 hours, 4 8 hours (optimum outside abdomen); 24 hours (optional)

    • False positives:

    • may be due to unusual marrow distribution, correlation with bone marrow (sulfur colloid) scan may be necessary

Gallium-67 Citrate

Ga-67 acts as an analogue of ferric ion; used as gallium citrate (water-soluble form)

Production:	bombardment of zinc targets (Zn-67, Zn-68) with protons (cyclotron); virtually carrier-free after separation process
Decay:	by electron capture to ground state of Zn-67

Energy levels:

(a) used:

93 keV (38%), 184 keV (24%), 296 keV (16%), 388 keV (8%)

(b) unused:

91 keV (2%), 206 keV (2%)

Physical half-life:	3.3 days (= 78 hours)
Biologic half-life:	2 3 weeks
Adult dose:	3 6 mCi or 50 Ci/kg
Radiation dose:

• 0.3 rads/mCi for whole body; 0.9 rads/mCi for distal colon (= critical organ); 0.58 rads/mCi for red marrow; 0.56 rads/mCi for proximal colon; 0.46 rads/mCi for liver; 0.41 rads/mCi for kidney; 0.24 rads/mCi for gonads

Binding Sites of Gallium-67 Citrate

Physiology:

• Ga-67 is bound to iron-binding sites of various proteins (strongest bond with transferrin in plasma, lactoferrin in tissue); multiexponential + slow plasma disappearance; competitive iron administration (Fe-citrate) enhances target-to-background ratio by increasing Ga-67 excretion

  • fluid spaces

    • Transferrin, haptoglobin, albumin, globulins in blood serum (90%)

    • Interstitial fluid space (increased capillary permeability and hyperemia in inflammation + tumor)

    • Lactoferrin in tissue

    • cellular binding

      • Viable PMNs incorporate 10% of Ga-67 (bound to lactoferrin in intracytoplasmic granules)

      • Nonviable PMNs + their protein exudate (iron-binding proteins are deposited at sites of inflammation; these remove iron from the extracellular space; iron is no longer available for bacterial growth)

      • Lymphocytes have lactoferrin-binding surface receptors

      • Phagocytic macrophages engulf protein-iron complexes

      • Bacteria + fungi (siderophores = lysosomes = low-molecular weight chelates produced by bacteria) have iron-transporting protein mechanism

      • Tumor cell-associated transferrin receptor + transportation into cells (lymphocytes bind Ga-67 less avidly than PMNs; RBCs do not bind Ga-67)

        mnemonic:

        LFT'S

  • Lactoferrin (WBCs)

  • Ferritin

  • Transferrin

  • Siderophores (bacteria)

P.1084

Uptake of Gallium-67 Citrate

at 24 hours:	most intense in RES, liver, spleen (4%), bone marrow (lumbar spine, sacroiliac joints), bowel wall (chiefly colonic activity on delayed images), renal cortex, nasal mucosa, lacrimal + salivary glands, blood pool (20%), lung (<3% = equivalent to background activity), breasts
at 72 hours:	75% of dose remains in body its activity equally distributed among soft tissue (orbit, nasal mucosa, large bowel), liver, bone or bone marrow (occiput); kidney activity no longer detectable; lacrimal + salivary glands may still be prominent

Excretion of Gallium-67 Citrate

• via urinary tract (10 25% within 24 hours)

  • no activity in kidneys + urinary bladder after 24 hours

• via GI tract (10 20%)

  • hepatobiliary pathway + colonic mucosal excretion

  • Enemas + laxatives promote clearing of bowel activity!

  • Bowel cleansing not optimal as gallium lies also within colonic wall

• via various body fluids

  • eg, human milk (mandates to stop nursing for 2 weeks)

Imaging of Gallium-67 Citrate

• usually [6, 24], 48 72 hours (up to 7 days)

• Best target-to-background ratio generally at 72 hours

• Optimal target-to-background ratio at 6 24 hours for abscess

• Optimal target-to-background ratio at 24 48 hours for tumor

  • 500,000 count spot views / whole body

  • SPECT useful

Degrading Factors of Gallium-67 Imaging

• lesions <2 cm are not detectable

• photon scatter within overlying tissues

• physiologic high activity of liver, spleen, bones, kidney, GI tract may obscure lesion

Normal Variants of Gallium-67 Uptake

• Breasts:

  • increased uptake under stimulus of menarche, estrogens, pregnancy, lactation, phenothiazine medication, renal failure, hypothalamic lesion

• Liver:

  • suppressed uptake by chemotherapeutic agents / high levels of circulating iron / irradiation / severe acute liver disease

• Lung:

  • prominent uptake after lymphangiography

• Spleen:

  • increased uptake in splenomegaly

• Thymus:

  • uptake in children

• Salivary glands:

  • uptake within first 6 months after radiation therapy to neck (may persist for years)

• Epiphyseal plates in children

• Previous steroid therapy, chemotherapy, and radiation therapy may decrease Ga uptake

• Healing surgical incision

No Gallium-67 Uptake

• most benign neoplasms; hemangioma; cirrhosis; cystic disease of the breast, liver, thyroid; reactive lymphadenopathy; inactive granulomatous disease

Indications for Gallium-67 Imaging

• Infection

  • Gallium has been largely replaced with WBC imaging but can be used in chronic infection

    • Inflamed / infarcted bowel (eg, Crohn disease)

  DDx:	normal bowel excretions (must be cleared by enema; bowel pathology shows persistent activity)

• Diffuse lung uptakesarcoidosis, diffuse infections (TB, CMV, PCP), lymphangitic metastases, pneumoconioses (asbestosis, silicosis), diffuse interstitial fibrosis (UIP), drug-induced pneumonitis (bleomycin, cyclophosphamide, busulfan), acute radiation pneumonitis, recent lymphangiographic contrast

• Lymph node involvement

  • sarcoidosis, TB, MAI, Hodgkin disease

    DDx:	NOT seen in Kaposi sarcoma, a useful distinction in AIDS patients with hilar nodes

• Tumor

  • Neoplastic uptake is variable; prominent uptake is usually seen in:

  • Non-Hodgkin lymphoma (especially Burkitt)

  • Hodgkin disease

  • Hepatoma

  • Melanoma

  • Useful in:

    • detection of tumor recurrence

    • DDx of focal cold liver lesions on Tc-99m sulfur colloid scan

Gallium in Bone Imaging

• Increased activity in:

  • Active osteomyelitis (90% sensitivity is higher than for Tc-99m MDP)

  • Sarcoma

  • Cellulitis (bone scan followed by gallium scan)

  • Septic arthritis, rheumatoid arthritis

  • Paget disease

  • Metastases (65% sensitivity, less than for bone agents)

Gallium in Tumor Imaging

Particularly useful in evaluating extent of known tumor disease + in detection of tumor recurrence

• A. USEFUL CATEGORY

  • Lymphoma

    • Hodgkin disease: 74 88% sensitivity

    • NHL: sensitivity varies

      histiocytic form: 85 90% sensitivity

      lymphocytic well-diff.: 55 70% sensitivity

      • 95% sensitivity for mediastinal disease,

      • 80% sensitivity for cervical + superficial lesions;

      • poor sensitivity below diaphragm

  P.1085

  
  

  • Burkitt lymphoma: almost 100% sensitivity

  • Rhabdomyosarcoma: >95% sensitivity

  • Hepatoma: 85 95% sensitivity

  • Melanoma: 69 79% sensitivity

• B. PPOSSIBLY USEFUL

  • NHL: good for large + mediastinal lesions

  • Nodal metastases from seminoma + embryonal cell carcinoma: 87% sensitivity

  • Non-small cell lung cancer: 85% sensitivity for primary of any histologic type, 90% probability for uptake in mediastinal nodes, 67% probability for uptake in normal mediastinal nodes, 90% probability for uptake in extrathoracic metastases

• C. NOT USEFUL

  • head & neck tumors, GI tumors (especially adenocarcinomas; 35 40% sensitivity), breast tumor (52 65% sensitivity), gynecologic tumors (<26% sensitivity), pediatric tumors

Gallium in Lung Imaging

• Scans obtained at 48 hours, because 50% of normals show activity at 24 hours

• FOCAL UPTAKE

  • Primary pulmonary malignancy (>90% sensitivity)

  • Benign disorders: granuloma, abscess, pneumonia, silicosis

• MULTIFOCAL / DIFFUSE UPTAKE

  • Infection

    • Tuberculosis

      • intense uptake in active lesions (97%) = parameter of activity

      • diffuse uptake in miliary TB + rapidly progressive TB pneumonia

    • Pneumocystis carinii

      • increased uptake at time when physical signs, symptoms, and roentgenographic changes are unimpressive

    • Cytomegalovirus

  • Inflammation

    • Sarcoidosis

      • 70% sensitivity for active parenchymal disease,

      • 94% sensitivity for hilar adenopathy

      • = indicator of therapeutic response to steroids

    • Interstitial lung disease

      • pneumoconiosis, idiopathic pulmonary fibrosis, lymphangitic carcinomatosis

    • Exudative stage of radiation pneumonitis

  • Drugs

    • Bleomycin toxicity

    • Amiodarone

  • Contrast lymphangiography (in 50%)

• GALLIUM UPTAKE + NORMAL CHEST FILM

  • Pulmonary drug toxicity

  • Tumor infiltration

  • Sarcoidosis

  • Pneumocystis carinii

Panda Sign

= facial uptake of Ga-67 in both parotid glands + both lacrimal glands + nose

• Sarcoidosis

  • 100% specific for sarcoidosis if lung infiltrates are present!

• Treated lymphoma

• Systemic lupus erythematosus

• Sj gren syndrome

Gallium in Renal Imaging

Abnormal uptake on delayed images at 48 72 hours

• A. Renal tumor

  • Primary renal tumor (variable uptake)

  • Lymphoma / leukemia

  • Metastases (eg, melanoma)

• B. Renal inflammation

  • Acute pyelonephritis (88% sensitivity)

    • diffuse / focal uptake

  • Lobar nephronia

  • Renal abscess

• Others

  • Collagen-vascular disease, vasculitis, Wegener granulomatosis

  • Amyloidosis, hemochromatosis

  • Hepatic failure

  • Administration of antineoplastic drugs

• Transplant

  • Acute / chronic rejection

  • Acute tubular necrosis

• Urinary bladder

  • Cystitis

  • Tumor

mnemonic:

CHANT An OLD PSALM

• Chemotherapy

• Hemochromatosis, Hepatorenal failure

• Acute tubular necrosis, Acute lobar nephronia

• Neoplasm

• Transfusion, Tuberous sclerosis

• Abscess

• Obstruction

• Lymphoma

• Drugs (Fe, drugs causing ATN)

• Pyelonephritis, Polyarteritis nodosa

• Sarcoidosis

• Amyloidosis, Allograft

• Leukemia

• Metastasis, Myeloma

Gallium Imaging in Lymphoma

= chief use of gallium in tumor imaging before + after chemo- / radiation therapy:

• persisting Ga-67 uptake indicates residual tumor

• reversion to normal of a previously Ga-67 avid mass indicates fibrosis

• new Ga-67 uptake during therapy indicates tumor progression

• A. Hodgkin disease

  • 50 70% average sensitivity dependent on size, location, technique

• B. Non-Hodgkin lymphoma

  • 30% sensitivity for lymphocytic subtype,

  • 70% sensitivity for histiocytic subtype

P.1086

Sensitivity:

• 90% for mediastinal nodes80% for neck nodes48% for periaortic nodes47% for iliac nodes36% for axillary nodes

Gallium Imaging in Malignant Melanoma

Types:

• Lentigo maligna: low invasiveness, low metastatic potential

• Superficial spreading melanoma: intermediate prognosis

• Nodular melanoma: most lethal

• Prognosis (level of invasion versus 5-year survival):

Level	I	(in situ)	100%
Level	II	(within papillary dermis)	100%
Level	III	(extending to reticular dermis)	88%
Level	IV	(invading reticular dermis)	66%
Level	V	(subcutaneous infiltration)	15%

Ga-67:

• >50% sensitivity for primary + metastatic sites

• Detectability versus tumor size:

  • 73% sensitivity >2 cm; 17% sensitivity <2 cm

• Bone, brain, liver scintigraphy:

  • show very low yield in detecting metastases at time of preoperative assessment and are not indicated

P.1087

Bone Scintigraphy

Bone agents

• polyphosphates = LINEAR PHOSPHATES = CONDENSED PHOSPHATES

  • First agents described; contain up to 46 phosphate residues; simplest form contains 2 phosphates = pyrophosphate (PYP)

• DIPHOSPHONATES

  • Organic analogs of pyrophosphate characterized by P-C-P bond; chemically more stable; not susceptible to hydrolysis in vivo; most widely used agents:

    • ethylene hydroxydiphosphonate (EHDP)

  • = ethane-1-hydroxy-1,1-diphosphonate

• methylene diphosphonate (MDP)

• imidodiphosphonates (IDP)

  • Characterized by P-N-P bond

Biodistribution of Bone Agents

Physiologic Uptake of Bone Agents

• rapid distribution into ECF (78% of injected dose with biologic half-life of 2.4 minutes) directly related to blood flow + vascularity; blood clearance rate determines ECF (= background) activity (at 4 hours 1% for diphosphonates, 5% for pyrophosphate / polyphosphate secondary to greater degree of protein binding)

• chemisorbs on hydroxyapatite crystals in bone + in calcium crystals in mitochondria; MDP concentration at 3 hours is directly proportional to calcium contents of tissues (14 24% calcium in bone, 0.005% calcium in muscle); 50 60% (58% for MDP, 48% for EHDP, 47% for PYP) are localized in bone by approx. 3 hours depending on blood flow + osteoblastic activity; 2 10% of the dose are present within soft tissues; myocardial uptake depends on at least some revascularization of infarcted muscle

Excretion of Bone Agents

• via urinary tract by 6 hours in 68% of MDP / EHDP, in 50% of PYP, in 46% of polyphosphates

• Forcing fluids + frequent voiding reduces radiation dose to bladder!

Indications for Bone Imaging

• Imaging of bone, myocardial / cerebral infarct, ectopic calcifications, some tumors (neuroblastoma)

• Rx for Paget disease, myositis ossificans progressiva, calcinosis universalis (inhibits formation + dissolution of hydroxyapatite crystals)

Pediatric Indications for Bone Scan

• Back pain

  • Diskitis

  • Pars interarticularis defect: SPECT imaging adds sensitivity

  • Osteoid osteoma: can be used intraoperatively to ensure removal of nidus

  • Sacroiliac infection

• Nonaccidental trauma

Imaging with Bone Agents

• @ Bone: 2 3 hours post injection

  • Fractures may not show positive uptake until 3 10 days depending on age of patient

• @ Myocardium: 90 120 minutes post injection

  • Ideal imaging time is 1 3 days post infarction

    Usual dose:	20 mCi (740 MBq)
    Radiation dose:	0.13 rad/mCi for bladder (critical organ), 0.04 rad/mCi for bone, 0.01 rad/mCi for whole body
    Labeling:	Tc (VII) is eluted as a pertechnetate ion; chemical reduction with Sn (II) chloride; chelated into a complex of Tc-99m (IV)-tin-phosphate

Quality Control:

• <10% Tc-99m tin colloid / free Tc-99m pertechnetate (a good preparation is 95% bound)

• Agent should not be used prior to 30 minutes after preparation

• Avoid injection of air in preparation of multidose vials (oxidation results in poor Tc bond)

• Kit life is 4 5 hours after preparation

Three-Phase Bone Scanning

• over area of interest

  • Rapid sequence flow study (2 5 seconds/frame) = early arterial flow = 1st phase

  • Immediate postflow images (1 million counts for central body + 0.5 million counts for extremities) = blood pool = 2nd phase

  • Delayed images (0.5 1.0 million counts) between 3 4 hours following injection = 3rd phase

Bone marrow agents

for assessment of hematopoiesis / phagocytosis by RES

• 1. Tc-99m sulfur colloid (10% uptake in bone marrow)

• In-111 chloride

• Tc-99m MMAA

  • = mini-microaggregated albumin colloid for liver, spleen, hematopoietic marrow

  Particle size: 30 100 m
  Dose:	10 mCi
  Marrow dose:	0.55 rad

• Marrow accumulation at 1 hour:

  6	x higher than for sulfur colloid
  3	x higher than for antimony-sulfur colloid

Indications for Bone Marrow Imaging

• expansion of hematopoietically active bone marrow

  • Hematologic disorders to reveal presence of peripheral expansion of functional marrow

• focal defect from displacement by infiltrating disease

  • Marrow replacement disorders: eg, Gaucher disease

  • Bone infarction: eg, sickle cell anemia (DDx from osteomyelitis)

  • Avascular necrosis in children

P.1088

Superscan

Cause:

• Metabolic

  • Renal osteodystrophy

  • Osteomalacia

    • randomly distributed focal sites of intense activity = Looser zones = pseudofractures = Milkman fractures (most characteristic)

  • Hyperparathyroidism

    • focal intense uptake corresponds to site of brown tumors

  • Hyperthyroidism

    • rate of bone resorption more increased than rate of formation (= decrease in bone mass)

    • hypercalcemia (occasionally)

    • elevated alkaline phosphatase

    • NOT visible on radiographs

    • susceptible to fracture

• Widespread bone lesions

  • Diffuse skeletal metastases (most frequent) from prostate, breast, multiple myeloma, lymphoma, lung, bladder, colon, stomach

  • Myelofibrosis / myelosclerosis

  • Aplastic anemia, leukemia

  • Waldenstr m macroglobulinemia

  • Systemic mastocytosis

  • Widespread Paget disease

  • diffusely increased activity in bones: particularly prominent in axial skeleton, calvarium, mandible, costochondral junctions (= rosary beading ), sternum (= tie sternum ), long bones

  • increased metaphyseal + periarticular activity

  • increased bone-to-soft-tissue ratio

  • absent kidney sign = little / no activity in kidneys but good visualization of urinary bladder

  • femoral cortices become visible

CAVE:

scan may be interpreted as normal, particularly in patients with poor renal function!

Hot Bone Lesions

mnemonic:

NATI MAN

• Neoplasm

• Arthropathy

• Trauma

• Infection

• Metastasis

• Aseptic Necrosis

Long Segmental Diaphyseal Uptake

• BILATERALLY SYMMETRIC

  • Hypertrophic pulmonary osteoarthropathy

  • Thigh / shin splints = mechanical enthesopathy

  • Ribbing disease

  • Engelmann disease = progressive diaphyseal dysplasia

• UNILATERAL

  • Inadvertent arterial injection

  • Melorheostosis

  • Chronic venous stasis

  • Osteogenesis imperfecta

  • Vitamin A toxicity

  • Osteomyelitis

  • Paget disease

  • Fibrous dysplasia

Photon-deficient Bone Lesion

• = decreased radiotracer uptake

  • Interruption in local bone blood flow

    • = vessel trauma or vascular obstruction by thrombus / tumor

      • Early osteomyelitis

      • Radiation therapy

      • Posttraumatic aseptic necrosis

      • Sickle cell crisis

    • Replacement of bone by destructive process

      • Metastases (most common cause): central axis skeleton > extremity, most commonly in carcinoma of kidney + lung + breast + multiple myeloma

      • Primary bone tumor (exceptional)

mnemonic:

HM RANT

• Histiocytosis X

• Multiple myeloma

• Renal cell carcinoma

• Anaplastic tumors (reticulum cell sarcoma)

• Neuroblastoma

• Thyroid carcinoma

Benign Bone Lesions

• NO TRACER UPTAKE

  • Bone island

  • Osteopoikilosis

  • Osteopathia striata

  • Fibrous cortical defect

  • Nonossifying fibroma

• INCREASED TRACER UPTAKE

  • Fibrous dysplasia

  • Paget disease

  • Eosinophilic granuloma

  • Melorheostosis

  • Osteoid osteoma

  • Enchondroma

  • Exostosis

Soft-tissue Uptake

• Physiologic

  • Breast

  • Kidney: accentuated uptake with dehydration, antineoplastic drugs, gentamicin

  • Bowel: surgical diversion of urinary tract

• Faulty preparation with radiochemical impurity

  • free pertechnetate (TcO4-)

    Cause:

    introduction of air into the reaction vial

• activity in mouth (saliva), salivary glands, thyroid, stomach (mucus-producing cells), GI tract (direct secretion + intestinal transport from gastric juices), choroid plexus

P.1089




• Tc-99m MDP colloid

  Cause:

  excess aluminum ions in generator eluate / patient ingestion of antacids; hydrolysis of stannous chloride to stannous hydroxide, excess hydrolyzed technetium

• diffuse activity in liver + spleen

• Neoplastic conditions

  • Benign tumor

    • Tumoral calcinosis

    • Myositis ossificans

  • Primary malignant neoplasm

    • Extraskeletal osteosarcoma / soft-tissue sarcoma: bone forming

    • Neuroblastoma (35 74%): calcifying tumor

    • Breast carcinoma

    • Meningioma

    • Bronchogenic carcinoma (rare)

    • Pericardial tumor

  • Metastases with extraosseous activity

    • to liver: mucinous carcinoma of colon, breast carcinoma, lung cancer, osteosarcoma

      mnemonic:

      LE COMBO

  • Lung cancer

  • Esophageal carcinoma

  • Colon carcinoma

  • Oat cell carcinoma

  • Melanoma

  • Breast carcinoma

  • Osteogenic sarcoma

  • to lung: 20 40% of osteosarcomas metastatic to lung demonstrate Tc-99m MDP uptake

  • Malignant pleural effusion, ascites, pericardial effusion

• Inflammation

  • Inflammatory process (abscess, pyogenic / fungal infection):

    • adsorption onto calcium deposits

    • binding to denatured proteins, iron deposits, immature collagen

    • hyperemia

  • Crystalline arthropathy (eg, gout)

  • Dermatomyositis, scleroderma

  • Radiation: eg, radiation pneumonitis

  • Necrotizing enterocolitis

  • Diffuse pericarditis

  • Bursitis

  • Pneumonia

• Trauma

  • Healing soft-tissue wounds

  • Rhabdomyolysis:

    • crush injury, surgical trauma, electrical burns, frostbite, severe exercise, alcohol abuse

  • Intramuscular injection sites:

    • especially Imferon (= iron dextran) injections with resultant chemisorption; meperidine

  • Ischemic bowel infarction (late uptake)

  • Hematoma: soft tissue, subdural

  • Heterotopic ossification

  • Myocardial contusion, defibrillation, unstable angina pectoris

  • Lymphedema

• Metabolic

  • Hypercalcemia (eg, hyperparathyroidism):

    • uptake enhanced by alkaline environment in stomach (gastric mucosa), lung (alveolar walls), kidneys (renal tubules)

    • uptake with severe disease in myocardium, spleen, diaphragm, thyroid, skeletal muscle

  • Diffuse interstitial pulmonary calcifications: hyperparathyroidism, mitral stenosis

  • Amyloid deposits

• Ischemia with dystrophic soft-tissue calcifications

  • = necrosis with dystrophic calcification

    • @ Spleen: infarct (sickle cell anemia in 50%), microcalcification secondary to lymphoma, thalassemia major, hemosiderosis, glucose-6-phosphate-dehydrogenase deficiency

    • @ Liver: massive hepatic necrosis

    • @ Heart: transmural myocardial infarction, valvular calcification, amyloid deposition

    • @ Muscle: traumatic / ischemic skeletal muscle injury

    • @ Brain: cerebral infarction (damage of blood-brain barrier)

    • @ Kidney: nephrocalcinosis

    • @ Vessels: calcified wall, calcified thrombus

Abnormal Uptake within Kidneys

• Effect of chemotherapeutic drugs:

  • bleomycin, cyclophosphamide, doxorubicin, mitomycin C, 6-mercaptopurine

• S/P radiation therapy

• Metastatic calcification

• Pyelonephritis

• Acute tubular necrosis

• Iron overload

• Multiple myeloma

• Renal vein thrombosis

• Ureteral obstruction

Abnormal Uptake within Breast

• Breast carcinoma

• Prosthesis

• Drug-induced

Abnormal Uptake in Ascitic, Pleural, Pericardial Effusion

• Uremic renal disease

• Infection

• Malignant effusion

Incidental Urinary Tract Abnormalities

• >50% of injected dose of Tc-99m MDP is excreted by 3 hours

  • Bilateral diffuse increased uptake

    • = uptake greater than that of lumbar spine

      • excess tissue calcium

        • Hyperparathyroidism

        • Hypercalcemia

        • Osteosarcoma metastatic to kidney

      • tissue damage

        • Drug-induced nephrotoxicity

          P.1090

          
          

          • chemotherapy (eg, cyclophosphamide, vincristine, doxorubicin, bleomycin, mitomycin-C, S-6-mercaptopurine, mitoxantrone)

          • aminoglycosides

          • amphotericin B

        • Radiation therapy

        • Necrotic renal cell carcinoma (rare)

        • Renal metastasis (rare)

        • Acute pyelonephritis

        • Acute tubular necrosis

        • Multiple myeloma

      • iron overload

        • Sickle cell anemia

        • Thalassemia major

          mnemonic:

          rich con

      • Radiation therapy to kidney

      • Iron overload

      • Chemotherapy (cytoxan, vincristine, doxorubicin)

      • Hyperparathyroidism

      • Calcification (metastatic), Carcinoma

      • Obstruction (urinary)

      • Nephritis, Normal variant

    • Bilateral decreased renal uptake

      • loss of renal function

        • End-stage renal disease

      • increased osteoblastic activity (= superscan)

    • Focally decreased renal uptake

      • space-occupying lesion replacing normal renal parenchyma

        • Abscess

        • Cyst

        • Primary / metastatic renal neoplasm

      • scar

        • Infarct

        • Chronic pyelonephritis

        • Partial nephrectomy

      • Uni- / bilateral focally increased GU uptake due to urine accumulation

        • normal upper pole calices (supine position)

        • Urinary tract diversion / ileal conduit

        • Urinoma

      • Change in location of kidney

        • Congenital anomaly (eg, pelvic kidney)

P.1091

Brain Scintigraphy

Radionuclide angiography

Increased perfusion in:

1.	Primary / metastatic brain tumor
2.	AVM, large aneurysm, tumor shunting
3.	Luxury perfusion after infarction
4.	Infections (eg, herpes simplex encephalitis)
5.	Extracranial lesions: bone metastasis, fibrous dysplasia, Paget disease, eosinophilic granuloma, fractures, burr holes, craniotomy defects

Blood-Brain Barrier Agents

= old-style agents requiring a disruption of blood-brain barrier to diffuse into brain

• Tc-99m glucoheptonate

  • 15 20 mCi bolus injection in <2 mL saline; 30 flow images of 2 seconds' duration; static image of 1 million counts after 4 hours; delayed image after 24 hours (higher target-to-background ratio than DTPA)

• Tc-99m DTPA

• Thallium-201: best predictor for tumor burden

Brain Perfusion Agents

= lipophilic agents rapidly crossing blood-brain barrier with accumulation in brain

Applications:

• any disease in- / decreasing regional perfusion

  • Brain death (most common)

  • Refractory seizure disorder

  • Dementia

potential:

stroke, receptor imaging, activation studies, tumor recurrence

Tc-99m HMPAO

= hexamethylpropylene amine oxime = exametazine

Product:

Ceretec

Projections of Vascular Territories in brain scintigraphy

Dose:	10 30 mCi
Imaging:	as early as 15 minutes post injection
Pharmacokinetics:
lipophilic radiopharmaceutical distributing across a functioning blood-brain barrier proportional to cerebral blood flow; no redistribution
Indication:
acute cerebral infarct imaging before evidence of CT / MRI pathology; positive findings within 1 hour of event

Tc-99m ECD

= ethyl cysteinate dimer = bicisate

Product:	Neurolite
Dose:	10 30 mCi
Imaging:	30 60 minutes post injection

I-123 Iofetamine

= N-isopropyl-p[123I]iodoamphetamine iodine = I-123-IMP

Product:

Spectamine

• Pharmacokinetics:

  • initially distributes proportional to regional cerebral blood flow with increased flow to basal ganglia and cerebellum; homogeneous uptake in gray matter; decreased activity in white matter; redistribution over time

  • activity in an area of initial deficit on reimaging (after 4 hours) implies improved prognosis

Indications for Radionuclide Angiography

Seizures

• Abnormal cerebral radionuclide angiography within 1 week of seizure activity even without underlying organic lesion

• Etiology:

  • 35% cerebral tumors (meningioma in 34%, metastases in 17%)

  • Cerebrovascular disease (more common in age >50 years)

  • Trauma, inflammation, CNS effects of systemic disease

• transient hyperperfusion of involved hemisphere

Seizure Focus Imaging

for localizing intractable seizures

• focal hypoperfusion during interictal injection of tracer (less sensitive)

• focal hyperperfusion during ictal injection of tracer (better detection)

Alzheimer Disease

• bilateral temporoparietal hypoperfusion

Brain Tumor

Etiology:

• good correlation between hyperperfusion and enlarged supplying vessels:

  • Meningioma (increased activity in 60 80%);

  P.1092

  
  

  • Metastases (increased activity in 11 23%);

  • Vascular metastases: thyroid, renal cell, melanoma, anaplastic tumors from lung / breast

• asymmetric decreased perfusion in mass lesions:

  • Tumor

  • Hemorrhage

  • Subdural hematoma

Cerebral Death

• Pathophysiology:

  • increased intracranial pressure results in markedly decreased cerebral perfusion, thrombosis, total cerebral infarction

• Path:

  severe brain edema, diffuse liquefactive necrosis

• carotid arteries visualized (= confirmation of good bolus)

• activity stops abruptly at the skull base

• sagittal sinus not visualized

• activity in arteries of face + scalp with hot nose sign

• DDx by EEG:

  • severe barbiturate intoxication may produce a flat EEG response in the absence of brain death

Arterial Stenosis

• Radionuclide angiography of limited value!

• asymmetric decreased perfusion in acute / chronic cerebrovascular disease:

  • Complete occlusion / >80% stenosis of ICA:

    • 53 80% sensitivity

  • 50 80% stenosis of ICA: 50% sensitivity

  • <50% stenosis of ICA: 10% sensitivity

• Problematic lesions:

  • Bilaterally similar degree of stenosis

  • Occlusion of MCA + unilateral ACA

  • Vertebrobasilar occlusive disease (20% sensitivity)

Stroke

• flip-flop phenomenon (= decreased perfusion in arterial phase, equalization of activity in capillary phase, increased activity in venous phase) secondary to late arrival of blood via collaterals + slow washout

Positron emission tomography

• REGIONAL CEREBRAL BLOOD FLOW

  • breathing of carbon monoxide (C-11 and O-15), which concentrates in RBCs

  • Xe-133 inhalation / injection into ICA / IV injection after dissolution in saline: volume distribution is in the water space of the brain; no correction for recirculation necessary because all Xe is exhaled during lung passage, but correction for scalp + calvarial activity is required (for inhalation method)

    • washout rate of gray matter:white matter = 4 5:1

• GLUCOSE METABOLISM

  • for measurements of metabolic rate + mapping of functional activity

    • C-11 glucose: rapid uptake, metabolization, and excretion by brain

    • F-18 fluorodeoxyglucose (FDG): diffuses across blood-brain barrier + competes with glucose for phosphorylation by hexokinase, which traps FDG-6-phosphate within mitochondria; FDG-6-phosphate cannot enter most metabolic pathways (eg, glycolysis, storage as glycogen) and accumulates proportional to intracellular glycolytic activity; FDG-6-phosphate is dephosphorylated slowly by glucose-6-phosphatase and then escapes cell

Indications:

• Focal epilepsy prior to seizure surgery

  • interictal decreased uptake of FDG of >20% at seizure focus (70% sensitivity, 90% for temporal lobe hypometabolism)

  • hypermetabolism within 30 minutes of seizure

  • measurement of opiate receptor density with C-11-labeled carfentanil (= high-affinity opium agonist) uptake by receptors (found in thalamus, striatum, periaqueductal gray matter, amygdala), which mediate analgesia and respiratory depression

• Alzheimer disease

  • clinical diagnosis false positive in 35%

  • bilateral temporoparietal hypoperfusion + hypometabolism resulting in decreased FDG uptake (92 100% sensitive)

  • sparing of sensory and motor cortex + basal ganglia + thalamus

• DDx:	frontal lobe dementia, primary progressive aphasia without dementia, normal-pressure hydrocephalus, multi-infarct dementia

• Parkinson disease

  • = deficient presynaptic terminals with normal postsynaptic dopaminergic receptors

  • clinical diagnosis in 50 70% accurate

  • DDx:	drug-induced chorea, Huntington disease, tardive dyskinesia, progressive supranuclear palsy, Shy-Drager syndrome, striatonigral degeneration, alcohol-related cerebellar dysfunction, olivopontocerebellar atrophy

• Huntington disease, senile chorea

  • hypometabolism of basal ganglia

• Schizophrenia

  • abnormally reduced glucose activity in frontal lobes

  • dopamine receptors in caudate / putamen elevated to 3 that of normal levels

• Stroke, cerebral vasospasm

  • disassociated oxygen metabolism + brain blood flow

Radionuclide cisternography

• Indications:

  • Suspected normal pressure hydrocephalus

  • Occult CSF rhinorrhea / otorrhea

  • Ventricular shunt

  • Porencephalic cyst, leptomeningeal cyst, posterior fossa cyst

• Technique:

  • Measurement of spinal subarachnoid pressure

  • Sample of CSF for analysis

  • Subarachnoid injection of radiotracer

• Normal study (completed within 48 hours):

  • symmetric activity sequentially from basal cisterns, up the sylvian fissures + anterior commissure, eventual ascent over cortices with parasagittal concentration

  P.1093

  
  

  • image lumbar region immediately after injection to ensure subarachnoid injection

  • activity in basal cistern by 2 4 hours

  • activity at vertex by 24 48 hours

  • no / minimal lateral ventricular activity (may be transient in older patients)

• Agents:

  • Indium-111 DTPA

  • Physical half-life:	2.8 days
    Gamma photons:	173 keV (90%), 247 keV (94%) detected with dual pulse height analyzer

    Dose:

    250 500 Ci

    Radiation dose:

    9 rads/500 Ci for brain + spinal cord (in normal patients)

    Imaging:

    at 10-minute intervals / 500,000 counts up to 4 6 hours; repeat scans at 24, 48, 72 hours

  • Technetium-99m DTPA

    • Not entirely suitable for imaging up to 48 72 hours; DTPA tends to have faster flow rate than CSF; used for shunt evaluation + CSF leak study since leak increases CSF flow

    Dose:	4 10 mCi
    Radiation dose:	4 rads for brain + spinal cord

  • Iodine-131 serum albumin (RISA)

    • prototype agent; beta emitter

  • Physical half-life:

    8 days; high radiation dose of 7.1 rads/100 Ci; no longer used secondary to pyrogenic reactions

  • Ytterbium-169 DTPA

  • Physical half-life:	32 days
    Gamma decay:	63 keV; 177 keV (17%); 198 keV (25%); 308 keV; dual pulse height analyzer set for 177 + 198 keV
    Dose:	500 Ci
    Radiation dose:	9 rads/500 mCi for brain + spinal cord (in normal patients)

CSF Leak Study

Purpose:	localization of origin of CSF leak in patient with CSF rhinorrhea / otorrhea
Causes of dural fistula:
(a) traumatic:	in 30% of basilar skull fractures
(b) nontraumatic:	brain, pituitary and skull tumors; skull infections; congenital defects

• Location of dural fistula:

  • cribriform plate > ethmoid cells > frontal sinus

• Method:

  • Weigh cotton pledgets

  • Pledgets placed by ENT surgeon in the anterior and posterior turbinates bilaterally

  • Radiopharmaceutical injected intrathecally via lumbar puncture; immediate postinjection view of lumbar region to ensure intrathecal placement

  • Pledgets removed and weighed 4 6 hours after lumbar injection

  • Pledget activity counted + indexed to weight

  • Results compared with 0.5-mL serum specimens drawn at the time of pledget removal

  • Pledget to serum count ratio of >1.5 is evidence of CSF leak

  • With active leak patient should be placed in various positions with various maneuvers to accentuate leak

Hydrocephalus

• Normal-pressure hydrocephalus

  • reversal of normal CSF flow dynamic = tracer moves from basal cisterns into 4th, 3rd, and lateral ventricles

  • loss of w sign

• Obstructive hydrocephalus

  • delay (up to 48 hours) for tracer to surround convexities + reach arachnoid villi

  • positive w sign

P.1094

Thyroid and Parathyroid Scintigraphy

Thyroid scintigraphy

Indications:

• Evaluation of solitary / dominant nodule

• Evaluation of upper mediastinal mass

• Classification of hyperthyroidism

• Detection and staging of postoperative thyroid cancer

• Evaluation of neonatal hypothyroidism

• Evaluation of developmental anomalies

• SUPPRESSION SCAN

  • = to define autonomy of a nodule

  • suppression of a hot nodule following T₃/ T₄ administration is proof that autonomy does not exist

• STIMULATION SCAN

  • = to demonstrate thyroid tissue suppressed by hyperfunctioning nodule

  • administration of TSH documents functioning thyroid tissue (rarely done)

• PERCHLORATE WASHOUT TEST

  • = to demonstrate organification defect

  • repeat measurement of radioiodine uptake following oral potassium perchlorate shows lower values if organification defect present

Tc-99m Pertechnetate

Physical decay:	10 mCi Tc-99m decays to 2.7 10-7 mCi Tc-99m
Physical half-life:	2 105 years
Biologic half-life:	6 hours
Decay:	by photon emission of 140 keV

• Quality control:

  • <0.1% Mo-99 (= 1 Ci/mCi), maximum of Mo-99 at 5 Ci

  • <0.5 mg aluminum/10 mCi Tc-99m

  • <0.01% radionuclide impurities

• Administration:	oral / IV
  Dose:	3 5 mCi administered IV 20 minutes prior to imaging (100 300 mrad/mCi)

• Pharmacokinetics:

• Uptake:	in thyroid, salivary glands, gastric mucosa, choroid plexus
  Excretion:	mostly in feces, some in urine

  Thyroid Agents

  	I-131	I-123	Tc-99m
  Physical half-life	8 days	13 hours	6 hours
  Main photopeak	364 keV	159 keV	140 keV
  Usual dose	50 100 Ci	100 300 Ci	2 10 mCi
  Absorbed dose	50 100 rad	2 5 rad	0.2 1.8 rad
  Administration	PO	PO	IV
  Interval to image	24 hours	6 hours	20 minutes

• Uptake in thyroid:

  • 0.5 3.7% at 20 minutes (time of maximum uptake) assessment of trapping function only; NO organification; may be almost completely discharged by perchlorate

• Imaging:

  • Collimator: usually with pinhole collimator for image magnification (5-mm hole)

  • Distance: selected so that organ makes up 2/3 of field of view; significant distortion of organ periphery occurs if detector too close

  • Counts: 200,000 300,000 counts are usually acquired within 5 minutes after a dose of 5 10 mCi of Tc-99m pertechnetate

  • Image must include markers for scale + anatomic landmarks + palpatory findings

• Advantages:

  • low cost

  • reduced radiation exposure

  • greater photon flux than iodine = detectability of small thyroid lesions (>8 mm) is improved

  • excellent physical characteristics

• Disadvantages:

  • high neck background (target-to-background ratio less favorable than with iodine)

  • lesions with pertechnetate-iodine discordance

    • (= hot on Tc-99m pertechnetate + cold on radio-iodine) are very rare + due to Tc-99m avid cancer

  • Poor for substernal evaluation

Iodine-123

• Agent of choice for thyroid imaging!

• Production:

  • in accelerator; contamination with I-124 dependent on source (Te-122 in ~ 5%, Xe-123 in ~ 0.5%); contamination with I-125 increases with time elapsed after production

• Physical half-life:	13.3 hours
  Decay:	by electron capture with photon emission at 159 keV (83% abundance) + x-ray of 28 keV (87% abundance)
  Dose:	200 400 Ci orally 24 hours prior to imaging (radiation dose of 7.5 mrad/ Ci)
  Uptake:	iodine readily absorbed from GI tract (10 30% by 24 hours), distributed primarily in extracellular fluid spaces; trapped + organified by thyroid gland; trapped by stomach + salivary glands
  Excretion:	via kidneys in 35 75% during first 24 hours + GI tract

• Advantages:

  • Low-radiation exposure

  • Excellent physical characteristics

  • Uptake + scan with one agent (organified)

• Disadvantages compared with Tc-99m pertechnetate:

  • More expensive

  • Less available with short shelf-life

  • More time-consuming

  • Radionuclide impurities

  • Higher dose to thyroid (but less to whole body)

P.1095

Iodine-131

Indication:	thyroid uptake study, thyroid imaging, treatment of hyperthyroidism, treatment of functioning thyroid cancer, imaging of functioning metastases
Production:	by fission decay
Physical half-life:	8.05 days (allows storing for long periods)
Decay:	principal gamma energy of 364 keV (82% abundance) + significant beta decay fraction of a mean energy of 192 keV (92% abundance)
Dose:	30 50 Ci (1.2 rad/ Ci = 50 rad for thyroid)
Radiation dose:
(90% from beta decay, 10% from gamma radiation) 0.6 mrad/mCi for whole body; 1.2 mrad/ Ci for thyroid (critical organ)
Pharmacokinetics:	identical to I-123

• Advantages:

  • Low cost

  • Ectopic tissue search

  • Uptake and scan at same time

• Disadvantages:

  • Too energetic for gamma camera, well suited for rectilinear scanner with limited resolution

  • High radiation exposure (due to beta decay) prohibits use for diagnostic purposes

  • Ectopic thyroid tissue just as well detectable with I-123 or Tc-99m pertechnetate

Iodine Fluorescence Imaging

• Technique:

  • collimated beam of 60 keV gamma photons from an Am-241 source is directed at thyroid, which results in production of K-characteristic x-rays of 28.5 keV; x-rays are detected by semiconductor detector

• Advantages:

  • No interference with flooded iodine pool / thyroid medication

  • Measures total iodine content

  • Low radiation exposure (15 mrad) acceptable for children + pregnant women

• Disadvantage:

  dedicated equipment necessary

Thyroid Uptake Measurements

Agents:

I-123 / I-131 (easier to use), Tc-99m pertechnetate (requires calibration)

• Method:

  • orally administered isotope of iodine is absorbed from upper GI tract

  • tracer mixes with intravascular iodine pool

  • iodine is cleared by thyroid in competition with kidneys

  • uptake parallels thyroidal clearance of plasma inorganic iodide

  • all measurements are taken for 3 minutes at 4 and 24 hours (measurements at both 4 and 24 hours prevent missing the occasional rapid-turnover hyperthyroid patient returning to normal by 24 hours)

• Radioactive Iodine Uptake (RAIU):

  • RAIU = Thyroid Counts* / Capsule Counts[g with caron above]

  • * = background corrected (thigh) + decay corrected

  • [g with caron above] = decay corrected

• Interpretation:

• (a) normal:	<25% at 4 hours, <35% at 24 hours
  (b) increased:	in Graves disease
  (c) decreased:	in subacute thyroiditis
  N.B.:	Uptake values do not diagnose hyperthyroidism, which is done with laboratory values (T4, T3, TSH) and clinical history

Parathyroid scintigraphy

for the evaluation of primary hyperparathyroidism after other causes for hypercalcemia have been excluded

[Technetium-thallium Subtraction Imaging]

• superceded by Tc-99m MIBI at most centers

• = DUAL ISOTOPE SCINTIGRAPHY

• Sensitivity:	72 92% (depending on size, smallest adenoma was 60 mg)
  Specificity:	43% (benign thyroid adenomas, focal goitrous changes, Hashimoto thyroiditis, parathyroid carcinoma, cancer metastatic to neck, lymphoma, sarcoidosis, lymph nodes also concentrate thallium)

• Method:

  • IV injection of 1 3.5 mCi Tl-201 chloride; images recorded for 15 minutes with 2-mm pinhole collimator

    • concentrates in normal thyroid + enlarged parathyroid glands (extraction proportional to regional blood flow + tissue cellularity)

  • IV injection of 1 10 mCi Tc-99m pertechnetate; images recorded at 1-minute intervals for 20 minutes

    • pertechnetate concentrates only in thyroid

  • Computerized subtraction

    • focal / multifocal excess Tl-201

• Limitations:

  • unfavorable dosimetry + poor quality images of Tl-201 (up to 3.5 mCi, 80 keV photons)

  • prolonged patient immobilization (motion artifact)

  • processing artifacts (eg, over- / undersubtraction)

  • poor Tc-99m thyroid uptake from interfering medications / recent iodinated contrast media

  • parathyroid pathology may be mimicked by coexisting thyroid disease (eg, nonfunctioning adenoma, multinodular goiter)

• Indication:

  • localization of one / more parathyroid adenoma (hyperplasia not visualized), may be more sensitive than CT / MRI in detection of ectopic mediastinal parathyroid tissue and in postoperative context

Technetium-99m Sestamibi

• = Tc-99m MIBI

• Indication:	recurrent hypercalcemia following previous parathyroid surgery
  Sensitivity:	88 100% (smallest adenoma weighed 150 mg); 91% for early SPECT imaging For unknown reasons even large tumors (2 g) may not accumulate sufficient MIBI for detection!

P.1096




• Pharmacokinetics:

  • MIBI localizes in myocardium + mitochondria-rich tumors proportional to regional blood flow + cellular metabolic activity; MIBI washes out of thyroid quickly, but is retained in abnormal parathyroids (= need for dual-phase study)

• Method:

  • IV injection of 20 25 mCi Tc-99m MIBI

  • 10 15 30 minutes after injection anterior cervicothoracic images (5 minutes/view) with large-field-of-view camera equipped with low-energy high-resolution parallel-hole collimator

  • Repeat set of images at 2 4 hours post injection (10 minutes/view)

  • Adjunctive dual phase imaging with thyroid-selective agent for computer-aided subtractions is optional (I-123, Tc-99m)

  • combined CT-gamma camera imaging with coregistration most effective

• Advantages (over thallium):

  • Physical properties:

    • optimal gamma emission (140 keV)

    • abundant photons (high dose of 20 mCi)

    • favorable dosimetry

    • high parathyroid-to-thyroid ratio

    • unaffected by medications / iodinated contrast

  • Technical features:

    • Single readily available radiopharmaceutical

    • Simple protocol of early + delayed images

    • No prolonged patient immobilization

    • No subtraction study / computer processing

    • SPECT / multiple projections possible

  • Scan interpretation

    • sharp images

    • clear visualization of abnormal parathyroid glands

    • ectopic sites surveyed

P.1097

Lung Scintigraphy

Perfusion agents

Tc-99m Macroaggregated Albumin (MAA)

• Preparation:

  • human serum albumin (HSA) is heat-denatured + pH adjusted; added stannous chloride precipitates albumin into tin-containing macroaggregates; lyophilization prolongs stability; added Tc-99m pertechnetate is reduced by SnCl₂ and tagged onto the MAA particles

• Quality control (USP guidelines):

  • 90% of particles should have a diameter between 10 and 90 m

  • No particle should exceed 150 m

  • Should be at least 90% pure (by ascending chromatography)

  • A batch of Tc-99m MAA should not be used >8 hours after preparation

  • Preparation should not be backflushed with blood into syringe, causes hot spots on lungs

• Physical half-life: 6 hours

• Biologic half-life: 6 hours

• Dose:

  • approximately 2 4 6 mCi + 0.14 g/kg albumin, which corresponds to >60,000 particles (recommended number of particles is 200,000 700,000 particles for even spatial distribution + good image quality)

  • N.B.: reduce number of particles to 50,000 80,000 in

    • critically ill patients with severe COPD, on mechanical ventilator support, documented pulmonary arterial hypertension, significant left-to-right cardiac shunts need reduction in number of particles but not tagged activity!

    • children up to age 5 need reduction in number of particles + tagged activity!

• IV injection in supine position to give an even distribution between base + apex of lung (ventral to posterior gradient persists)

• imaging in upright position to allow maximum expansion of lung, especially at lung bases

• Radiation dose (rads/mCi):

  • 0.013 for whole body, 0.25 for lung (critical organ), 0.01 for gonads

• Physiology:

  90% of MAA particles act as microemboli and will be trapped in lung capillaries on first pass; there are an estimated 600 million pulmonary arterioles small enough to trap the particles; the effect is insignificant physiologically as only 500,000 particles are injected per study; 0.22% of capillaries become occluded (= 2 of 1,000); protein is lysed within 6 8 hours and taken up by RES; particles <1 m are phagocytized by RES in liver + spleen

• Imaging:

  • Large-field-of-view scintillation camera + parallel-hole low-energy collimator with identical recording times for corresponding views

• Views:

  • anterior, posterior

  • posterior oblique (LPO, RPO): additional information in 50% due to segmental delineation of basal segments and separation of both lungs

  • anterior oblique (LAO, RAO): additional information in 15%

  • lateral: shine through from contralateral lung

  • Oblique views reduce equivocal findings from 30% to 15%

• Counts: 750,000 1,000,000 counts for each image

Tc-99m Human Albumin Microspheres

Particle size:	20 30 m
Biologic half-life:	8 hours

Ventilation agents

Xe-133, Xe-127, Xe-125, Kr-81m, N-13, O₂-15, CO₂-11, CO-11, radioactive aerosol (Tc-99m DTPA, Tc-99m-PYP, Tc-99m labeled ultrafine dry dispersion of carbon soot )

Xenon-133

• Fission product of U-235

• Decay:	to stable Cs-133 under emission of beta particle (374 keV), gamma ray (81 keV), x-ray (31 keV); beta-component responsible for high radiation dose of 1 rad to lung)
  Physical half-life:	5.24 days
  Biologic half-life:	2 3 minutes
  Physical properties:	highly soluble in oil + grease, absorbed by plastic syringe
  Administration:	injection into mouth piece of a disposable breathing unit at the beginning of a maximal inspiration
  Dose:	15 20 mCi

• Technique:

  • Ventilation study preferably done before perfusion scan to avoid interference with higher-energy Tc-99m (Compton scatter from Tc-99m into lower Xe-133 photopeak); [may be feasible after perfusion scan if dose of Tc-99m MAA is kept below 2 mCi + concentration of Xe-133 is above 10 mCi/L of air and if Xe-133 acquisition times for washing, equilibrium, washout images are kept to about 30 seconds]

  • Posterior imaging routine, ideally in upright position

  • Phase 1 = single-breath image:

    • = inhalation of 10 20 mCi Xe-133 to vital capacity with breath-holding over 10 30 seconds (65% sensitivity for abnormalities)

    • cold spot is abnormal

  • Phase 2 = equilibrium phase:

    • = tidal breathing = closed-loop rebreathing of Xe-133 + oxygen for 3 5 minutes for tracer to enter poorly ventilated areas; also functions as internal control for air leaks; posterior oblique images + posterior images are obtained to improve correlation with perfusion scan.

    • activity distribution corresponds to aerated lung

  P.1098

  
  

  • Phase 3 = washout phase:

    • = clearance phase after readjusting intake valves of spirometer permitting patient to inhale ambient air and to exhale Xe-133 into shielded charcoal trap; washout phase should last >5 minutes

    • images taken at 30 60-sec intervals for >5 minutes

    • rapid clearance within 90 seconds with slight retention in upper zones is normal

    • tracer retention (hot spot) at 3 minutes reveals areas of air-trapping

  • poor image quality secondary to significant scatter

  • abnormal scan:

    • COPD / acute obstructive disease:

      • delayed wash-in (during initial 30 seconds of tidal breathing)

      • tracer accumulation on equilibrium views (partial obstruction with collateral air drift + diffusion into affected area via bloodstream)

      • delayed washout = retention >3 minutes due to air trapping

      • tracer retention in regions not seen on initial single-breath view (from collateral airdrift into abnormal lung zones)

    • consolidated lung disease

      • no tracer uptake throughout imaging sequence

Xenon-127

• cyclotron-produced with high cost

• Physical half-life: 36.4 days

• Photon energies: 172 keV (22%), 203 keV (65%)

• Advantages:

  • High photon energy allows ventilation study following perfusion study

  • Decreased radiation dose (0.3 rad)

  • Storage capability because of long physical half-life

Krypton-81m

• insoluble inert gas; eluted from Rb-81 generator (half-life of 4.7 hours); decays to Kr-81 by isomeric transition

• Physical half-life: 13 seconds

• Biologic half-life: <1 minute

• Principal photon energy: 190 keV (65% abundance)

• Advantages:

  • Higher photon energy than Tc-99m so that ventilation scan can be performed following perfusion study

  • Each ventilation scan can be matched to perfusion scan without moving patient

  • Can be used in patients on respirator (no contamination due to short half-life)

  • Low radiation dose (during continuous inhalation for 6 8 views 100 mrad are delivered)

• Disadvantages:

  • High cost

  • Limited availability (generator good only for one day, so weekend availability may not be possible

  • No washout images possible due to short half-life

  • Decreased resolution due to septal penetration with low-energy collimators

• lack of activity = abnormal area (tracer activity is proportional to regional distribution of tidal volume because of short biologic half-life, washout phase not available)

Tc-99m DTPA Aerosol

• = Tc-99m diethylenetriaminepentaacetic radioaerosol

• = UltraVent

• Biological half-life: 55 minutes

• Administration: delivery through a nebulizer during inspiration

• Dose: 30 50 mCi in 2 3 mL of saline added to nebulizer unit and connected to wall oxygen at a flow rate of 8 10 L/min

• Physiology:

  • radioaerosols are small particles that become impacted in central airways, sediment in more distal airways, experience random contact with alveolar walls during diffusion in alveoli; cross respiratory epithelium with rapid removal by bloodstream

    • Less physiologic indicator of ventilation + subject to nebulization technique

    • Erect position preferable for basilar perfusion defects (dependent lung region receives more ventilation + radiotracer)

• Technique:

  • Aerosol applied ideally before perfusion; postperfusion aerosol imaging possible to assess for fill-in of aerosol in region of perfusion defect

  • breathe from nebulizer for 3 5 minutes

  • images recorded in multiple projections, each for 100,000 counts

• abnormal scan:

  • COPD

    • decreased activity in peripheral lung (slow and turbulent airflow prevents a normal amount of aerosol to reach the involved lung)

    • central airway deposition (aerosol sticks to trachea + bronchial walls)

  • consolidated lung disease

    • absent tracer

Carbon Dioxide Tracer

• O-15 labeled carbon dioxide

• Physical half-life: 2 minutes (requires on-site cyclotron)

• Physiology:

  • inhalation of carbon dioxide; rapid diffusion across alveolar-capillary membrane; clearance from lung within seconds

• cold spot due to failure of tracer entry into airway= airway disease

• hot spot due to delayed / absent tracer clearance= perfusion defect (87% sensitivity, 92% specificity)

• Indications:

  • Emboli can be detected in preexisting cardiopulmonary disease

  • Equivocal / indeterminate V/Q studies

P.1099

Tumor imaging

Positron Emission Tomography

• Dose: 10 mCi FDG

• Technique:

  • patient fasts for 4 hours

    • Elevated serum glucose may cause a decrease in FDG uptake!

  • imaging 30 60 minutes after IV injection in 30 45 image planes (15 cm axial field of view; resolution of 5 mm)

  • calculation of standardized uptake ratio (SUR) in region of interest (ROI) = mean activity in ROI [mCi/mL] divided by injected dose [mCi]

  • SUR >2.5 indicates malignant disease

• Indications:

  • Focal pulmonary abnormality

    accurate differentiation of benign and malignant lesions as small as 1 cm

    • low FDG uptake = benign

    • increased FDG uptake = cancer, active TB, histoplasmosis, rheumatoid nodule

  • Staging lung cancer

    • Occult metastases detected in up to 40% of cases!

    • (a) intrathoracic lymph nodes

      • lymph node with short-axis diameter > 1 cm by CT + not FDG avid = 100% NPV

      • small lymph node by CT + intense FDG uptake = 100% PPV

    • adrenal metastasis: 100% sensitive, 80% specific

  • Recurrent disease

    • increased FDG uptake at sites of residual radiographic abnormality >8 weeks after completion of therapy

Quantitative lung perfusion imaging

• Indication:

  • determination of postresection pulmonary function when combined with pulmonary function testing (FEV₁)

• Technique:

  • Acquire posterior and anterior perfusion (MAA) image and calculate geometric mean

  • Separate into right + left and into 2 equal lung zones from top to bottom, which yields 4 segments (upper left, bottom right, etc)

• Result:

  • activity in each segment is compared with total activity, which yields % perfusion to each lung field

Unilateral Lung Perfusion

Incidence: 2%

• PULMONARY EMBOLISM (23%)

• AIRWAY DISEASE

  • Unilateral pleural / parenchymal disease (23%)

  • Bronchial obstruction

    • Bronchogenic carcinoma (23%)

    • Bronchial adenoma

    • Aspirated endobronchial foreign body

• CONGENITAL HEART DISEASE (15%)

• ARTERIAL DISEASE

  • Swyer-James syndrome (8%)

  • Congenital pulmonary artery hypoplasia / stenosis

  • Shunt procedure to pulmonary artery (eg, Blalock-Taussig)

• ABSENT LUNG

  • Pneumonectomy (8%)

  • Unilateral pulmonary agenesis

• mnemonic: SAFE POEM

  • Swyer-James syndrome

  • Agenesis (pulmonary)

  • Fibrosis (mediastinal)

  • Effusion (pleural)

  • Pneumonectomy, Pneumothorax

  • Obstruction by tumor

  • Embolus (pulmonary)

  • Mucous plug

Perfusion Defects

• VASCULAR DISEASE

  • Acute / previous pulmonary embolus

    • Pulmonary thromboembolic disease

    • Fat embolism

      • nonsegmental perfusion defect

    • Air embolism

      • characteristic decortication appearance in uppermost portion on perfusion scintigraphy

    • Embolus of tumor / cotton wool / balloon for occlusion of AVM / obstruction by Swan-Ganz catheter, other foreign body

    • Dirofilaria immitis (dog heartworm): clumps of heartworms break off cardiac wall + embolize pulmonary arterial tree

    • Sickle cell disease

  • Vasculitis

    • Collagen vascular disease: sarcoidosis

    • IV drug abuse

    • Previous radiation therapy:

      • defect localized to radiation port

    • Tuberculosis

  • Vascular compression

    • Bronchogenic carcinoma:

      • perfusion defect depending on tumor size + location

    • Lymphoma / lymph node enlargement

    • Pulmonary artery sarcoma

    • Fibrosing mediastinitis due to histoplasmosis

    • Idiopathic pulmonary fibrosis:

      • small subsegmental defects in both lungs

    • Aortic aneurysm (large saccular / dissecting)

    • Intrathoracic stomach

  • Altered pulmonary circulation

    • Absence / hypoplasia of pulmonary artery

    • Peripheral pulmonary artery stenosis

    • Bronchopulmonary sequestration

    • Primary pulmonary hypertension

      • upward redistribution + large hilar defects

      • multiple small peripheral perfusion defects

    • Pulmonary venoocclusive disease

    • Mitral valve disease

P.1100

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P.1101

• predilection for right middle lobe + superior segments of lower lobes

• Congestive heart failure

  • diffuse nonsegmental V/Q mismatch

  • enlargement of cardiac silhouette + perihilar regions

  • reversed distribution: more activity anteriorly than posteriorly

  • accentuation of fissures

  • flattening of posterior margins of lung (lateral view)

  • pleural effusion

• AIRWAY DISEASE

  • Nearly all pulmonary disease produces decreased pulmonary blood flow to affected lung zones!

    • Asthma, chronic bronchitis, bronchospasm, mucus plugging

    • Bronchiectasis (bronchiolar destruction)

    • Emphysema (bulla / cyst)

    • Pneumonia / lung abscess

    • Lymphangitic carcinomatosis

    • perfusion defects in area of hypoxia (autoregulatory reflex vasoconstriction)

    • abnormal ventilation to a similar / more severe degree

    • mostly nonanatomic multiple defects (in 20%)

Pulmonary thromboembolism

• Rationale for ventilation-perfusion scan:

  • A pulmonary embolus presents as segmentally hypoperfused but normally ventilated lung (V/Q mismatch).

  • A normal perfusion scan excludes an embolus for practical purposes.

  • A perfusion defect requires further evaluation with a ventilation scan and CXR to determine the most likely etiology.

  • If ventilation scan and CXR are normal an embolus must be suspected.

  • A ventilation scan detects obstructive lung disease because a CXR is insensitive for this entity.

• Terminology:

  Nonsegmental	=	does not conform to a lung segment (eg, enlarged hilar structures / aorta, small pleural effusion, elevated hemidiaphragm, cardiomegaly);
  Subsegmental	=	involves 25 75% of a known bronchopulmonary segment;
  Segmental	=	involves >75% of a known bronchopulmonary segment;
  V/Q match	=	area of abnormal ventilation identical to perfusion defect in size, shape, and location;
  Triple match	=	matched ventilation-perfusion defect with an associated matching area of increased opacity on CXR;
  V/Q mismatch	=	normal ventilation / normal CXR in region of perfusion defect or perfusion defect larger than ventilation defect / CXR abnormality

• Probabilities:

  high	=	>85%
  intermediate	=	perfusion abnormality falling short of diagnostic confidence for PE (eg, single segmental mismatch);
  indeterminate	=	lungs cannot be adequately evaluated because of underlying consolidation / obstructive disease
  low	=	<15%

• Perfusion images will detect:

  • 90% of emboli that completely occlude a vessel >1 mm in diameter

  • 90% of surface perfusion defects that are larger than 2 2 cm

  • 26% of emboli that partially occlude a vessel

  • A history of prior PE decreases probability of acute embolism because small V/Q mismatches never resolve!

• Therapeutic implications:

  (a) high probability scan	:	treat for PE
  (b) indeterminate scan	:	pulmonary angiogram
  (c) low probability scan	:	consider other diagnosis, unless clinical suspicion very high

  Combined Interpretation of V/Q Scans and Chest X-Ray

  P.1102

  
  

  Interpretation Criteria for V/Q Lung Scans

  Probability of PE	Modified Biello Criteria	Modified PIOPED Criteria
  Normal	normal perfusion	normal perfusion
  Low(0 19%)	small (<25% segment) V/Q mismatches	small perfusion defects regardless of number / ventilation scan finding / CXR finding
  	focal V/Q matches without corresponding CXR consolidation	perfusion defect substantially smaller than CXR abnormality; ventilation findings irrelevant
  	perfusion defects substantially smaller than CXR abnormality	V/Q match in 50% of one lung / 75% of upper / mid / lower lung zone; CXR normal / nearly normal
  		single moderate perfusion defect with normal CXR; ventilation findings irrelevant
  		nonsegmental perfusion defects
  IndeterminateIntermediate(25 50%)	severe COPD with perfusion defects	1 large (segmental) 1 moderate (subsegmental) V/Q mismatch
  	perfusion defect with corresponding CXR consolidation	1 3 moderate (subsegmental) V/Q mismatches
  	single moderate / large V/Q mismatch without corresponding CXR abnormality	1 matched V/Q with normal CXR
  High (>85%)	perfusion defects substantially larger than CXR abnormalities	2 large (segmental) perfusion defects without match
  	2 moderate (25 90% segment) / 2 large (>90% segment) V/Q mismatches; no corresponding CXR abnormality	>2 large (segmental) perfusion defects substantially larger than matching ventilation / CXR abnormality
  		2 moderate (subsegmental) + 1 large (segmental) perfusion defect without match
  		4 moderate (subsegmental) perfusion defects; ventilation + CXR findings normal

• Interpretative algorithm:

  • no perfusion defect

    Diagnosis:	normal
    Interpretation:	no PE

  • perfusion defect without lung disease (= normal ventilation + normal CXR = V/Q mismatch)

    Diagnosis:	PE
    Interpretation:	high probability for PE, >1 perfusion defect needed to increase certainty

  • perfusion defect with lung disease

    • ventilation abnormality + clear CXR:

      Diagnosis:	COPD
      Interpretation:	low probability for PE

    • absent ventilation + consolidation on CXR:

      Diagnosis:	lung infarction / pneumonia /atelectasis
      Interpretation:	indeterminate

• Effect of a priori suspicion for pulmonary embolus:

  • increased in patients with risk factors (immobilization, recent surgery, known hypercoagulable state, malignancy, previous pulmonary embolus, DVT, estrogen therapy)

  • incidence of PE for a low probability scan increases from 15% to 40% in patients with a high clinical risk!

• Overall accuracy:

  • 68% for perfusion scan only,

  • 84% for ventilation-perfusion scan

  • 100% sensitivity in detection of PE is due to the occurrence of multiple emboli (usually >6 8), at least one of which causes a perfusion defect!

  • A normal perfusion scan virtually excludes PE!

  • In an individual <45 years of age a subsegmental perfusion defect + pleuritic chest pain in the same region is indicative of pulmonary embolism in 77%! (DDx: idiopathic / viral pleurisy)

  • 73 82% of patients have equivocal perfusion scans (ie, low and intermediate probability)!

    Study Results of Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)

    Probability of PE	in	Angiogram Positive in
    High	13%	88%
    Intermediate	39%	33%
    Low	34%	16%
    Normal	14%	9%

  P.1103

  
  

  • Interobserver variability for intermediate- and low-probability scans is 30%!

    False-positive scans:	nonthrombotic emboli, IV drug abuse, vasculitis, redistribution of flow, acute asthma (due to mucus plugging)
    False-negative scans:	saddle embolus

• stripe sign = rim of preserved peripheral activity to a perfusion defect usually indicates

  • nonembolic cause

  • old / resolving pulmonary embolism

• Indications for pulmonary angiography:

  • Embolectomy is a therapeutic option

  • Indeterminate V/Q scan with high clinical suspicion + risky anticoagulation therapy

  • Specific diagnosis necessary for proper management (vasculitis, drug induced, lung cancer with predominant vascular involvement)

• TEMPORAL RESOLUTION

  • abnormality resolves within weeks / months (in most)

  • abnormality may last permanently

  • Baseline study necessary to detect new emboli!

  • focal lung opacity + not ventilated + not perfused = indeterminate scan

    Cause:

    pneumonia, pulmonary embolism with infarction, segmental atelectasis

    • perfusion defect larger than CXR opacity = high probability for PE

    • perfusion defect substantially smaller than CXR opacity = low probability for PE

    • perfusion defect of comparable size = intermediate probability

  • focal lung opacity (not changed >1 week) + not ventilated + not perfused = low probability for PE

  • When there is lung opacity, evaluate well-aerated areas for perfusion defects!

  • COPD does not diminish usefulness of V/Q scan, but does increase likelihood of an indeterminate result!

  • 75% of patients with pulmonary edema + without pulmonary embolism have a normal perfusion scan!

Indeterminate V/Q Lung Scans

Criterion	PPV
Q defect << CXR consolidation	14%
Q defect equal to CXR	26%
Q defect >> CXR consolidation	89%

Criteria for Very Low Probability Interpretation of V/Q Lung Scans (<10% PPV for thromboembolism)

Criterion	PPV
nonsegmental perfusion abnormality	8%
perfusion defect smaller than corresponding radiographic defect	8%
stripe sign	7%
triple matched defect in upper / middle lung zone	4%
matched ventilation-perfusion defects in 2 / 3 zones of a single lung + normal CXR	3%
1 to 3 small segmental perfusion defects	1%

Correlation between V/Q Scan and Chest X-Ray (CXR should be taken within 6 12 hours of scan)

CXR Category	Nondiagnostic V/Q Scan
No acute abnormality	12%
Linear atelectasis	12%
Pulmonary edema	12%
Pleural effusion	36%
Parenchymal consolidation	82%

Effect of Clinical Probability and V/Q Scan on Presence of PE

V/Q scan	Clinical Probability	PE Present
High-probability	>80%	96%
Low-probability	<20%	4%
Indeterminate	DVT present	93%

Influence of Cardiopulmonary Disease (CPD) and V/Q Scan on Presence of PE

V/Q Probability	Normal CXR	No prior CPD	Any prior CPD	COPD
High	67%	93%	83%	100%
Intermediate	24%	39%	26%	22%
Low	17%	15%	14%	6%
Near normal	3%	4%	4%	0%

P.1104

Heart Scintigraphy

Cardiac imaging choices

• PLANAR imaging

  • tracer defect may be visible on only one image projection

  • 15 20% regional tracer intensity variation is normal

• SPECT imaging

  • improves object contrast by removing overlying tissues;

  • cinematic display of wall motion; EF calculation

  • tracer defect should be visible on more than one image set

  • up to 30% regional tracer intensity reduction compared with peak activity is normal

  • Standard

    • 180 acquisition extending from 45 RAO to 45 LPO for single-head camera

  • Gated SPECT

    • tomographic data acquired gated to ECG (8 frames per cardiac cycle)

    • viable although hypoperfused myocardium may demonstrate systolic contraction + wall thickening

    • geometric EF calculation based on ROIs drawn on end-systolic + end-diastolic frames (different from blood pool scans)

• QUANTITATIVE analysis

  • = circumferential profiles

  • = plotting of average counts along equally spaced radii emanating from center of LV makes interpretation more objective + reproducible

Myocardial ischemia & viability

Imaging of Coronary Artery Disease

• (1) DIRECTLY with myocardial perfusion imaging providing a pictorial representation of the relative perfusion of viable myocardial tissue using exercise + rest physiology images

  • Tl-201 chloride SPECT imaging (92% sensitive, 68% specific)

  • Tc-99m sestamibi / tetrofosmin SPECT imaging (89% sensitive, 90% specific)

  • PET

• (2) INDIRECTLY with imaging of ventricular function,

  • i.e., evaluation of wall motion + ejection fraction

    • multigated acquisition studies (MUGA)

      • Tc-99m labeled RBCs

      • Tc-99m human serum albumin

    • first-pass radionuclide angiography

      • sodium pertechnetate

      • diethylenetriamine pentaacetic acid (DTPA)

      • sulfur colloid

      • gold-195m

      • iridium-191m

    • (3) SIMULTANEOUS assessment of myocardial perfusion + ventricular function

      • = first-pass radionuclide angiography + gated SPECT perfusion imaging

    • Interpretation:

      • Normal myocardium:

        • homogeneous perfusion

        • similar appearance at rest + with exercise

      • Ischemic viable myocardium:

        • normal perfusion at rest

        • relative hypoperfusion with exercise (= reversible defect)

      • DDx:

        • Reversible septal defect in left bundle branch block

        • Differing soft-tissue attenuation artifact

      • Myocardial infarction:

        • reduced muscle mass

        • absent / reduced uptake at rest + with exercise (= fixed defect)

      • DDx:

        • Hibernating myocardium = chronic myocardial hypoperfusion producing abnormal regional ventricular function

        • Soft-tissue attenuation artifacts

          • marked variability in LV tracer uptake of inferior wall (diaphragmatic attenuation) + anterior wall (breast attenuation)

        • Infiltrative disorders

• DDx of a mild fixed defect:

  • Scar

  • Hibernating myocardium

  • Attenuation artifact

Myocardial Viability Assessment

• Perfusion

  • Tl-201 rest injection with redistribution images preferable to sestamibi

  • uptake >50% of maximum

• Metabolic activity

  • FDG may provide best assessment (normal myocardium uses fatty acids as chief metabolic substrate, but can switch to glucose metabolism)

  • enhanced glucose uptake by ischemic but viable myocardium

Planar Imaging

Left ventricular anatomy and projections

• AP

  • displays anterolateral wall, apex, inferior wall

  • decreased activity at apex of LV due to thinning in 50%

• LEFT LATERAL

  • displays inferior + anterior wall

• LAO 40 / LAO 70

  • Most often used projection; for all exercise studies

  • displays interventricular septum, posterior wall, inferior wall

  • best projection to separate right + left ventricles

  • best projection to evaluate septal + posterior LV wall motion

• RAO 45

  • displays anterior + inferior ventricular wall

  • useful during 1st-pass studies with temporal separation of ventricles

P.1105




• LPO 45 (rarely used)

  • 10 caudal tilt minimizes LA contamination of LV region

  • displays anterior + inferior ventricular wall

  • preferred over RAO 45 because LV is closer to camera

• Angled LAO (slant-hole collimator/caudal tilt)

  • separates ventricular from atrial activity

  • highlights apical dyskinesis

Planar Reconstruction Planes

LAD supplies:	upper 2/3 of interventricular septum, anterior wall + part of lateral wall, apex of left ventricle (in most patients)
LCX supplies:	posterior portion of left ventricle (in 10%)lateral portion of left ventricle
RCA supplies:	lower 1/3 of interventricular septum, inferior wall of LV + entire RV
PDA supplies:	(through RCA) posterior wall (in 90%)

Location of Perfusion Defects on Planar Images

• Right coronary artery (RCA)

  • best seen on left LAT/AP projections

  • inferior + posteroseptal segments

• Circumflex branch of left coronary artery (LCX)

  • best seen on LAO projection

  • posterolateral segment

• Anterior descending branch of left coronary artery (LAD)

  • anteroseptal, anterior, anterolateral segments

    N.B.: decreased activity in apical + posterior segments is not reliably correlated with disease of any vessel!

Spect Myocardial Perfusion Imaging (MPI)

Display of SPECT Images

• stress study = top row

• resting study = second row

• short-axis views (SA)

  • apex base

• horizontal long axis (HLA)

  • inferior superior (anterior)

• vertical long axis (VLA)

  • septum lateral

Rotating (Cine) Planar Images

• = cine loop of stress + rest planar images for a review of unprocessed raw data to recognize

• Patient Motion

  • superior inferior

  • laterally

  • upward creep due to increase of respiratory excursion after strenuous exercise

  • motion 2 pixels requires repeating the image acquisition

  • hurricane sign / apical flame

• Cardiac size

• Lung activity

  • increased in severe left ventricular dysfunction

• RV uptake

  • usually RV intensity 50% of peak LV intensity; increased in

  • RV hypertrophy (2 to pulmonary HTN)

  • globally reduced LV uptake

• Extracardiac activity

  • skin/clothing contamination

  • intense subdiaphragmatic activity from liver/GI tract

    • ramp artifact

    • repeat image acquisition after delay + drinking water

  • neoplastic lesions

    • lung, breast, sarcoma, lymphoma, thymoma, parathyroid tumor, thyroid abnormality, kidney tumor, liver tumor

• Attenuation (in up to 40% of all studies)

  • overlapping breast tissue (women)

  • diaphragm (men)

  • attenuation correction method prone imaging

P.1106

SPECT Reconstruction Planes

Analysis of Tomographic Slices

• Check for adequate count statistics (poor, fair, good, excellent)

  • peak pixel activity in LV myocardium should exceed 100 counts for Tl-201 and 200 counts for Tc-99m

• CAVITY SIZE

  • cavity-to-wall thickness ratio

  • poststress images with larger cavity than rest images = transient ischemic dilatation (TID) as a marker of multivessel disease

  • dilatation on rest + stress images indicates LV dysfunction/volume overload

• SEVERITY OF PERFUSION DEFECT

  • qualitative

    • mild = 10% reduction of peak tracer activity, of unknown clinical significance

    • moderate

    • severe

  • semiquantitative

    • summed stress score (SSS)

    • summed rest score (SRS)

    • summed difference score = SRS - SSS = measure of reversibility ( 2-grade improvement represents substantial ischemia)

    • 0 = normal perfusion

    • 1=

    • 2 =

    • 3 =

    • 4 = absent activity

      Polar Map for SPECT Myocardial Perfusion Imaging (17-segment model)

• EXTENT OF PERFUSION DEFECT

  • small = 5 10% of LV

  • medium = 15 20% of LV

  • large = 20% of LV

• TYPE OF PERFUSION ABNORMALITY

  • fixed defect

    • = myocardial scar/severe myocardial ischemia

  • reversible defect

    • = perfusion abnormality on poststress images which normalizes on resting images

  • partially reversible defect

    • = 20 30% improvement in regional activity

• LOCATION OF PERFUSION ABNORMALITY

  • apical, anterior, inferior, lateral

  • Avoid the term posterior as it has been variably assigned to the lateral wall (LCX) or basal inferior wall (RCA)

• QUANTITATIVE ANALYSIS

  • using a reference profile (gender specific, radiopharmaceutical specific, population specific) displayed as a polar map/bull's-eye projection/circumferential profile serves as a second observer

  • blacked-out segment = area of activity below threshold deemed as normal (>2.5 SD below mean)

ECG-Gated SPECT

• displayed as individual slices/3-D cine loop (8 frames per cardiac cycle); spatial + temporal changes in tracer activity reflect regional myocardial wall motion + thickening;

• evaluation for

  • global function

    • LV ejection fraction normal/ 60%

    • end-diastolic + end-systolic LV volumes

  • endocardial surface

  • motion of endocardial + epicardial surfaces

  • myocardial thickening (brightening)

  • regional LV wall motion abnormalities

    • graphically depicted as 3-D plot

    • 0= normal

    • 1 = mildly hypokinetic

    • 2 = moderately hypokinetic

    • 3 = severely hypokinetic

    • 4 = akinetic

    • 5 = dyskinetic

  • RV size + wall motion

P.1107

Ejection fraction

• Ejection fraction (EF) = stroke volume (SV) divided by end-diastolic volume (EDV)

  stroke volume =	end-diastolic volume (EDV) minus end-systolic volume (ESV)
  	EF = [EDV - ESV]/[EDV]
  	= [EDcounts - EScounts]/[EDcounts - BKGcounts]
  sensitive indicator of left ventricular function

  • @ Left ventricle

    • calculated on shallow LAO view

      Normal value:	50 65% (5% variation)
      Definitely abnormal	<50%
      Hypertrophic myocardium	>65%

    • Peak exercise LVEF is an independent predictor of coronary artery disease

  • @ Right ventricle

    • mean normal value >45%

    • (RV ejection fraction is smaller than for LV because RV has greater EDV than LV but the same stroke volume)

• Variability of EF:

  • LVEF is not a fixed number for any patient but varies with:

    • heart rate, blood pressure, level of circulating cathecholamines, patient position, medication

• Accuracy in detection of coronary artery disease:

  • Exercise EF: 87% sensitivity; 92% specificity

  • Exercise ECG: 60% sensitivity; 81% specificity

• Interpretation:

  • Ventricular function at rest is insensitive to CAD!

  • at rest

    • EF may be decreased in CAD

      DDx:	cardiomyopathy, valvular disease

    • correlates well with clinical severity + regional distribution of myocardial infarction

  • during exercise

    • reduced (hypokinetic)/absent (akinetic)/paradoxical (dyskinetic) wall motion indicate varying degrees of CAD/myocardial infarction

  • focal akinetic/dyskinetic area = aneurysm

  • paradoxical septal motion (= septal movement to right in systole) may reflect septal infarction, left bundle branch block, S/P bypass surgery

• Shortcoming:

  • poor study in patients with atrial fibrillation because of inability to achieve adequate cardiac gating (exercise MUGA can yield more sensitive assessment of coronary artery disease)

    False-positive with	(a) inadequate exercise
    	(b) recent ingestion of meal

Blood Pool Agents

Tc-99m DTPA/Tc-99m Sulfur Colloid

• preferred for cardiac first-pass studies as they allow multiple studies with little residual from any preceding study

Tc-99m labeled Autologous RBCs

• = agent of choice because of good heart-to-lung ratio

• Technique:

  • IN VIVO LABELING

    • > IV injection of reducing agent stannous pyrophosphate (1 vial PYP diluted with 2 mL sterile saline = 15 mg sodium pyrophosphate containing 3.4 mg anhydrous stannous chloride)

    • > 15 20 30 minutes later injection of Tc-99m pertechnetate (+7), which binds to pretinned RBCs (reduction to Tc-99m [+4])

    • Least time-consuming + easiest method!

    • Worst labeling efficiency (30% not tagged to RBCs + excreted in urine)!

  • IN vivtro LABELING

    • = MODIFIED IN VIVO METHOD

    • Preferred over in vivo because of high labeling efficiency within syringe, which reduces exposure to plasma constituents + creates little free pertechnetate!

    • > IV injection of 1 mg stannous pyrophosphate

    • > 10 minutes later 2 5 10 mL of blood are drawn into a heparinized syringe

    • > 10 20-minute incubation period with Tc-99m pertechnetate

    • > reinjection of preparation in 3-way stopcock technique

    • N.B.: poor tagging in

      • heparinized patient

      • injection through IV line (adherence to wall)

      • syringe flushed with dextrose instead of saline

  • IN VITRO LABELING

    • Most reliable labeling method!

    • > 50 mL drawn blood incubated with Tc-99m reduced by stannous ion; RBCs washed and reinjected

    • N.B.: Labeling kit (with chelating + oxidizing substances) allows excellent in vitro labeling with only 3 mL of blood and 15-minute incubation period!

• Dose: 15 20 30 mCi (larger dose required for stress MUGA + obese patients); for children: 200 Ci/kg (minimum dose of 2 3 mCi)

• Radiation dose: 1.5 rad for heart, 1.0 rad for blood, 0.4 rad for whole body

Tc-99m HSA

• HSA = human serum albumin

• Indication: drug interference with RBC labeling (eg, heparinized patient)

• Physiology: (a) albumin slowly equilibrates throughout extracellular space (b) poorer heart-to-lung ratio than with labeled RBCs

Ventricular Function

First-pass Ventriculography

• = FIRST-PASS RADIONUCLIDE ANGIOGRAPHY = FIRST TRANSIT

• = recording of initial transit time of an intravenously administered tight Tc-99m bolus through heart + lungs; limited number of cardiac cycles available for interpretation; additional projections/serial studies require additional bolus injection

P.1108




• Accuracy: good correlation with contrast ventriculography

• Agents: pertechnetate, pyrophosphate, albumin, DTPA, sulfur colloid (almost any Tc-99m labeled compound except lung scanning particles), Tc-99m labeled autologous RBCs

• Indications:

  • Only 15 seconds of patient cooperation required

  • Calculation of cardiac output + ejection fraction (RBCs)

  • Subsequent first-pass studies within 15 20 minutes of initial study possible (DTPA)

  • Separate assessment of individual cardiac chambers in RAO projection (temporal separation without overlying atria, pulmonary artery, aortic outflow tract), eg, for right ventricular EF and intracardiac shunts

• Minimal dose: 10 mCi

• Technique:

  • > cannulation of antecubital/external jugular vein with 20 ga needle attached to 3-way stopcock and two syringes:

    • > syringe 1 contains 1 mL of radiotracer

    • > syringe 2 contains a saline flush (10 20 mL)

  • > injection of radiotracer is followed by a strong flush of saline

• Gating:

  • improved images obtained by selection of time interval corresponding only to RV passage of bolus averaged over several (3 5) individual beats; gating may be done intrinsically or with ECG guidance

• Imaging:

  • region of interest (ROI) over RV silhouette in RAO projection; background activity taken over horseshoe-shaped ventricular wall; counts in ROI displayed as function of time; 25 frames/second for 20 30 seconds

• Quality Control:

  • Bolus Adequacy:

    • good = FWHM of time activity curve <1 second

    • adequate = FWHM of 1 1.5 seconds

    • delayed = FWHM of >1,5 seconds

    • split = more than one discrete peak

      Problem:

      delayed bolus may cause oversubtraction of background resulting in spurious increase in LVEF, decrease in LV volume, overestimation of regional wall motion

  • Count Statistics

    • >4000 5000 cps of LV end-diastolic counts in the representative cycle

  • Tracer Transit Time

    • visual examination of bolus transiting the central circulation

  • Beat Selection

    • only beats with end-diastolic counts of 70% of peak end-diastolic counts

  • Background Selection

    • a frame close to the beginning of the LV phase

      Normal passage of bolus:	SVC, RA, RV, lungs, LA, LV, aorta
      R-to-L shunt:	tracer appears in left side of heart before passage through lungs

• Evaluation of:

  • Obstruction in SVC region

  • Reflux from RA into IVC/jugular vein

  • Stenosis in pulmonary outflow tract

  • R-L shunt

  • Contractility of RV

  • Sequential beating of RA and RV

  • Ejection fraction of RV and LV

• Cardiac Rhythm & Conduction:

  • Regional wall motion + LVEF may be effected by:

    • frequent premature ventricular contractions (PVCs)

    • ventricular bigeminy

    • very irregular atrial fibrillation

    • pacemaker rhythm: starting at apex proceeding to base

    • left bundle branch block (LBBB)

      • inferoapical/anteroapical wall motion abnormalities

      • N.B.: paradoxical septal motion not detectable in RAO projection

Equilibrium Images

• = blood pool radionuclide angiography

• Agents: Tc-99m labeled autologous RBCs (most commonly)/human serum albumin

• Imaging: after thorough mixing of radiotracer throughout vascular space

• > acquisition of images during selected portions of cardiac cycle triggered by R-wave; each image is composed of >200,000 counts (2 10 minutes) obtained over 500 1,000 beats after equilibrium has been reached; high-quality images can be obtained in different projections

• > gated acquisition from 16 32 equal subdivisions of the R-R cycle (electronic bins) allows display of synchronized cinematic images (assembled to composite single-image sequence) of an average cardiac cycle

  • may be displayed as time activity curves reflecting changes in ventricular counts throughout R-R interval

  • measured functional indices: preejection period (PEP), left ventricular ejection time (LVET), left ventricular fast filling time (LVFT1), left ventricular slow filling time (LVFT2), PEP/LVET ratio, rate of ejection + filling of LV

• > at rest: count density 200 250 counts/pixel requires generally 7 10 minutes acquisition time for 200,000 250,000 counts/frame

• > during exercise: 100,000 150,000 counts/frame requires an acquisition time of 2 minutes

• Evaluation of:

  • LV ejection fraction

  • Regional wall motion

  • Valvular regurgitation

• Interpretation:

  • Heart failure: decreased EF, prolongation of PEP, shortening of LVET, decreased rate of ejection

  • Hypertensive heart: normal systolic indices, normal EF, prolonged LVFT1

  P.1109

  
  

  • Hypothyroidism: prolonged PEP, normal EF

  • Aortic stenosis: mild reduction of EF, prolonged LV emptying time, decreased rate of ejection, normal rate of filling

  • area of decreased periventricular uptake secondary to

    • pleural effusion >100 mL

    • ventricular hypertrophy

Gated Blood Pool Imaging

• = MULTIPLE GATED ACQUISITION (MUGA)

• = gated equilibrium images depict average cardiac contraction by summation over several minutes

• Recording of:

  • Ejection fraction (EF) of left ventricle before + after exercise (>6 million counts, 32 frames)

  • Regional wall motion of ventricular chambers (>4.5 million counts, 24 frames)

    • at rest: myocardial infarction, aneurysm, contusion

    • during exercise: ischemic dyskinesia (detectable in 63%)

  • Regurgitant index

    • Projection:

      • best septal view (usually LAO 45 ) for EF; often requires some cephalad tilting of detector head

      • two additional views for evaluation of wall motion (usually anterior + left lateral views)

• Imaging:

  • physiologic trigger provided by R-R interval of ECG ( bad beat rejection program desirable); R-R interval divided into typically about 20 frames; several hundred cardiac contractions are summed (depending on count density) for each planar projection

    • gated images obtained for 5 minutes

    • 2-minute image acquisition time for each stage of exercise

• PROs: (1) Higher information density than 1st-pass method

• (2) Assessment of pharmacologic effect possible

• (3) Bad beat rejection possible

• CONs: (1) Significant background activity

• (2)Inability to monitor individual chambers in other than LAO 45 projection

• (3) Plane of AV valve difficult to identify

• Radiation dose: 1.5 rad for heart; 1.0 rad for blood; 0.4 rad for whole body

• Qualitative evaluation:

  • chamber size

  • wall thickness

  • regional wall motion

Myocardial perfusion imaging agents

Potassium-43

• Not suitable for clinical use because of its high energy

Thallium-201 Chloride

• = cation produced in cyclotron from stable Tl-203

• = image agent of choice to assess myocardial viability

• Cyclotron: by (p,3n) reaction to radioactive Pb-201 (half-life of 9.4 hours), which decays by electron capture to Tl-201

• Decay: by electron capture to Hg-201

• Energy spectrum: 69 83 keV of Hg-K x-rays (98% abundance); 135 keV (2%) + 167 keV (8% abundance) gamma photons

• Physical half-life: 74 hours

• Biologic half-life: 10 2.5 days

• Dose: low dose of 3 4 mCi (the larger dose for SPECT) because of long half-life and slow body clearance

• Radiation dose:

  • 3 rad for kidneys (critical organ) (1.2 rad/mCi); 1.2 rad for gonads (0.6 rad/mCi); 0.7 rad for heart + marrow (0.34 rad/mCi); 0.5 rad for whole body (0.24 rad/mCi)

• Quality control: should contain <0.25% Pb-203, <0.5% Tl-202 (439 keV)

• Indications:

  • Acute myocardial infarction

  • Coronary artery disease

  • particularly useful over ECG in:

    • conduction disturbances (eg, bundle branch block, preexitation syndrome)

    • previous infarction

    • under drug influence (eg, digitalis)

    • left ventricular hypertrophy

    • hyperventilation

    • ST depression without symptoms

    • if stress ECG impossible to obtain

• Thallium uptake & distribution:

  • intracellular uptake via Na/K-ATPase (analogue to ionic potassium), but less readily released from cells than potassium

  • distribution is proportional to regional blood flow

  • uptake depends on

    • quality of regional perfusion

    • viable cells with integrity of Na/K pump

  • @ Blood pool

    • <5% remain in blood pool 15 minutes post injection

  • @ Myocardium

    • uptake depends on

      • myocardial perfusion

      • myocardial mass

      • myocardial cellular integrity

    • First-pass extraction efficiency is 88%!

      • REMEMBER: 90% in 90 seconds!

    • 4% of total dose localizes in myocardium at rest (myocardial blood flow = 4% of cardiac output)

    • peak myocardial activity occurs at 5 15 minutes after injection

    • uptake can be increased to 8 10% with dipyridamole stress

      Interpretation of Stress Thallium Images

      Immediate Image	Delayed Image	Diagnosis
      Normal	normal	normal
      Defect	fill-in	exertional ischemia
      Defect	persistent	myocardial scar
      Defect	partial fill-in	scar + ischemia / persistent ischemia

    P.1110

    
    

    • clearance from myocardium is proportional to regional perfusion + begins within a few minutes after injection ( wash out ); zones of initially higher uptake wash out more rapidly than areas of low uptake (= redistribution )

  • @ Skeletal muscle + splanchnicus:

    • first-pass extraction efficiency is 65%

    • accumulate 40% of injected dose

    • 4 6 hours fast + exercise decreases flow to splanchnicus and increases cardiac uptake

  • @ Lung:

    • 10% of total dose localizes in lung

    • augmented pulmonary extraction with left ventricular dysfunction, bronchogenic carcinoma, lymphoma of lung

    • <5% activity over lung is normal

    • heart-to-lung ratio decreased with triple-vessel disease

  • @ Kidney:

    • accumulates 4% of injected dose

    • excretion of 4 8% within 24 hours

  • @ Thyroid:

    • increased uptake >1% in Graves disease + thyroid carcinoma

  • @ Brain:

    • uptake only if blood-brain barrier disrupted

• Technique:

  • Single dose method

    • > 3 mCi injected at peak exercise for exercise image immediately + rest image 3 hours later

  • Split dose method

    • > 2 mCi injected for exercise image

    • > 1 mCi reinjected at rest after 3 hours with rest image taken 30 minutes later

  • Booster reinjection technique

    • > reinjection of thallium followed by imaging after 18 24 72 hours augments blood concentration of isotope

    • = late reversibility provides evidence of regional myocardial ischemia + viability not appreciated even on very delayed (24 72 hours) redistribution images; predicts scintigraphic improvement post intervention

    • Reasoning: 50% of irreversible persistent defects improve significantly after booster reinjection

• Imaging:

  • EXERCISE IMAGE = DISTRIBUTION IMAGE

    • = stress thallium image

    • = map of regional perfusion obtained within minutes after injection at peak exercise; initial distribution proportional to myocardial blood flow, arterial concentration of radioisotope, and muscle mass; 300,000 400,000 counts/view (approximately 5 8 minutes sampling time), should be completed by 30 minutes

  • REDISTRIBUTION IMAGE

    • = equilibrium between tracer uptake and efflux dependent on blood flow + mass of viable tissue + concentration gradients

    • = map of hypoperfused ischemic but viable myocardium obtained at rest after 2 3 4 6 hours; washout half-life from normal myocardium is 54 minutes

  • DELAYED IMAGE (optional)

    • = viability study at 24 hours

• Interpretation:

  • apical thinning = less myocardial mass of cardiac apex as a normal finding

  • normally diminished tracer uptake at basal portions of ventricle (near plane of mitral valve) due to more fibrous tissue + less muscle mass

  • variation in tracer intensity by 15 20% between regions on planar images may be normal (due to soft-tissue attenuation artifacts from subdiaphragmatic abdominal contents or breast tissue)

  • Initial phase = first-pass extraction

    • temporary defect accentuated by exercise

    • defect >15% of ventricular surface suggests >50% stenosis of coronary artery

    • right heart well seen during stress test, tachycardia, volume/pressure overload

    • dilated heart cavity on stress images (but not on rest images) due to exercise-induced LV dysfunction

  • Redistribution phase (on 2 4-hour images)

    • washout in normal areas

    • slow continued accumulation of tracer for areas of greatly reduced perfusion

    • increased uptake in viable ischemic zones ( redistribution )

    • permanent defect = nonviable myocardium as in myocardial infarction/fibrosis

    • increased lung activity (ie, >50% of myocardial count) indicative of

      • left ventricular failure due to severe LCA disease/myocardial infarction

      • pulmonary venous hypertension due to cardiomyopathy/mitral valve disease

    • right heart faintly visualized during rest (15% of perfusion to right side); increased activity in RV due to

      • increase in ventricular systolic pressure

      • increase in mean pulmonary artery pressure

      • increase in total pulmonary vascular resistance

  • Sensitivity: overall 82 84% for stress Tl-201 (60 62% for exercise ECG)

    • increased with:

      • severity of stenosis (86% + 67% sensitive with stenosis >75% + <75%)

      • greater number of involved arteries

      • stenosis of left main > LAD > RCA > LCX

      • prior infarction

      • high work load during exercise testing in patients with single-vessel disease

    • decreased with:

      • presence of collateral

      • beta blockers

      • time delay for poststress images

  • Specificity: overall 91 94% for stress Tl-201 (81 83% for exercise ECG)

  P.1111

  
  

  False-positive thallium test (37 58%):

  • Infiltrating myocardial disease

    • Sarcoidosis

    • Amyloidosis

  • Cardiac dysfunction

    • Cardiomyopathy

    • IHSS

    • Valvular aortic stenosis

    • Mitral valve prolapse (rare)

  • Decreased cardiac perfusion other than myocardial infarction

    • Cardiac contusion

    • Myocardial fibrosis

    • Coronary artery spasm

      • (severe unstable angina may cause defect after stress + on redistribution images, but will be normal at rest!)

  • Normal variant

    • Apical myocardial thinning

    • Attenuation due to diaphragm, breast, implant, pacemaker

  mnemonic:

  I'M SIC

  • Idiopathic hypertrophic subaortic stenosis

  • Myocardial infarct without coronary artery disease

  • Scarring, Spasm, Sarcoidosis

  • Infiltrative / metastatic lesion

  • Cardiomyopathy

  False-negative thallium test:

  • Under influence of beta-blocker (eg, propranolol)

  • Balanced ischemia = symmetric 3-vessel disease

  • Insignificant obstruction

  • Inadequate stress

  • Failure to perform delayed imaging

  • Poor technique

  mnemonic:

  3NMRS COR

  • 3-vessel disease (rare)

  • Noncritical stenosis

  • Medications interfering

  • Right coronary lesion (isolated)

  • Submaximal exercise

  • Collateral (coronary) blood vessels

  • Overestimation of stenosis on angiography

  • Redistribution (early / delayed)

  Advantages compared with Tc-99m compounds:

  • Higher total accumulation in myocardium

  • Provides redistribution information

  Disadvantages:

  • Low energy x-rays result in poor resolution (improved with SPECT)

  • Dose is limited by its long half-life

  • Half-value thickness of 3 cm results in less avid appearing myocardium: inferior wall (deeper part of myocardium) / anterolateral wall (overlain by breast)

  • Imaging must be completed by 45 minutes post injection or redistribution occurs

Tc-99m MIBI (Sestamibi)

• = cationic lipophilic isonitrile complex, which associates with myocyte mitochondria

Pharmacokinetics:

• relatively rapid clearance from circulation (40% first-pass extraction) due to passive diffusion across cell membranes

• high myocardial accumulation (4%) with nonlinear uptake proportional to regional perfusion (fall-off in extraction at higher rates of flow)

• slow washout with long retention time in myocardium and little recirculation

• significant hepatic + gallbladder activity

Excretion:	through biliary tree (give milk after injection and before imaging to decrease GB activity)
Dose:	25 30 mCi (Cardiolite )
Imaging:	optimum images 1 hour after injection (may be imaged up until 3 hours)
Technique:	separate injections for stress and rest studies because of slow washout

• 1-day protocol (rest-stress protocol)

  • Improved detection of reversibility compared with stress-rest protocol

  • inject of 5 8 mCi Tc-99m sestamibi

  • rest images 60 90 minutes after injection

  • wait 0 4 hours

  • stress patient followed by injection of 15 25 mCi Tc-99m sestamibi at peak stress (increased myocardial blood flow means increased myocardial uptake)

  • image 30 60 minutes later (optimum imaging time of stress-induced defects)

• 2-day protocol (impractical stress-rest protocol):

  • stress images on 1st day: Tc-99m sestamibi given at peak stress; imaging after 30 60 minutes' delay to allow some clearing of liver activity

  • repeat on 2nd day if stress views abnormal

• DUAL TRACER STRATEGY

• Tl-201 for initial injection

• Tc-99m sestamibi as 2nd injection immediately afterwards (as its higher energy photons are unaffected by residual Tl-201

Advantages over thallium:

• Low radiation dose related to shorter half-life allowing larger doses with less patient radiation

• Excellent imaging characteristics due to

  • improved photon flux, which means faster imaging + ability for cardiac gating

  • higher photon energy means less attenuation artifact from breast tissue / diaphragm + less scatter

• NO redistribution

• Temporal separation of injection and imaging allows injection during acute myocardial infarct when patient may not be stable for imaging; after stabilization + intervention (angioplasty / urokinase) imaging can demonstrate the pre-intervention defect

• Low cost

• Easy availability

• Flexible scheduling

• Increased patient throughput

Disadvantage:

less well suited to assess viability

P.1112

Tc-99m Teboroxime

• = neutral boronic acid oxime complex

• Pharmacokinetics:

  • very rapid clearance time from circulation (rapid uptake by myocardium with high extraction efficiency)

  • distribution proportional to cardiac blood flow EVEN at high blood flow levels (sestamibi + thallium plateau at high levels of flow)

  • biexponential washout from myocardium

  • high background from lung + liver

Dose:	25 30 mCi (Cardiotec )
Imaging:	must begin immediately post injection due to rapid washout; rest image can immediately follow stress image

Tc-99m Tetrofosmin

= diphosphine complex (Myoview )

Related compounds:

Q12 (furifosmin), Q3

Pharmacokinetics:

• lower first-pass extraction and accumulation than thallium

• slow myocardial washout

• rapid background clearance

• quicker liver excretion than sestamibi

Positron Emission Tomography

Perfusion agents:	N-13 ammonia, O-15 water, Rb-82 (available from a strontium generator)
Metabolic agents:	Fluorine-18-deoxyglucose = FDG (glycolysis), carbon-11-palmitate (beta-oxidation), carbon-11-acetate (tricarboxylic acid cycle)
Pathophysiology: in myocardial ischemia glycolysis (utilization of glucose) increases while mitochondrial -oxidation of fatty acids decreases!
Sensitivity:	>95%
Technique:

• give oral glucose load

• inject 10 mCi FDG

• image after 30 minutes

  Variation:

  simultaneously injection of perfusion tracer

  Interpretation:

  • mismatched defect (= decreased perfusion but enhanced metabolism indicated by FDG uptake) indicates viable myocardium (= dysfunctional myocardium salvageable by revascularization procedure)

  • matched defect (= flow + FDG accumulation both decreased) indicate nonviable myocardium

    • 80 90% of matching defects do not improve after bypass

  • C-11-acetate superior to FDG (accurately reflects overall oxidation metabolism, not influenced by myocardial substrate utilization)

Comparison with thallium:

• accuracy for fixed lesions similar; higher for reversible ischemia

Stress test

Rationale:

• Rest-injected images can separate viable from nonviable myocardium + detect very severe ischemia (with stenosis of >90 95%), but cannot detect most coronary artery disease (CAD)!

• Exercise increases myocardial work and oxygen requirement; at peak exercise blood flow may rise 5-fold from baseline through coronary artery dilatation + increase in heart rate; exercise will unveil CAD-related regional hypoperfusion relative to normal regions, if coronary artery stenosis >50%

Physical Stress Test

• Exercise in erect position (peak heart rate lower if supine) on treadmill or bicycle; isometric handgrip exercise raises blood pressure less (but adequate for evaluation)

• Starting point of workload selected according to preliminary exercise results (at an average of 200 kilowatt pounds)

• Bruce treadmill protocol:

• grade of exercise incrementally increased by inclination + belt speed (200 kilowatt pounds)

• graded exercise in 3-minute stages of increasing workload

• endpoints for discontinuing exercise:

• attainment of 85% of predicted maximal heart rate = 220 age in years

• Inability to continue due to fatigue, dyspnea, leg cramps, dizziness, chest pain

• Severe angina / hypotension

• Severe ECG ischemic changes / arrhythmia

• Fall in BP >10 mm Hg below previous stage

• Ventricular tachycardia

• Run of 3 successive premature ventricular beats

• Cardiologist with crash cart should be available!

Problems with exercise imaging:

• Sensitivity to detect ischemic lesions decreases with suboptimal exercise (in particular for older population)

• Higher false-positive tests in women (artifacts from overlying breast tissue)

• Propranolol (beta blocker) interferes with stress test, should be discontinued 24 48 hours prior to testing

Pharmacologic Stress Test

Advantages:

• Reproducibility

• Independent from patient motivation

• Freedom from patient infirmities, eg, severe peripheral vascular disease, arthritis, pain

Vasoactive drugs:

• Vasodilators

Action:	binding to A2 receptors affects the intracellular cyclic AMP, GMP, and calcium levels resulting in coronary hyperemia
N.B.:	Discontinue use of caffeine, tea, chocolate, cola drinks for 24 hours prior to test

• Cannot be used in patients on theophylline!

• IV infusion of 140 g/kg/min dipyridamole (= Persantine ) causes 3 5-fold increase in coronary artery blood flow

  P.1113

  
  

  Total dose:	0.84 mg/kg
  Drug action:	30 minutes
  Side effects:	flushing, nausea, bronchospasm (reversible with aminophylline)

  • dipyridamole injection over 4 minutes

  • wait 10 minutes for maximum effect

  • inject radiotracer

  • Prolonged supervision after test necessary

• IV infusion of 140 g/kg/min adenosine(= Adenocard , Adenoscan )

  Drug action:	2 3 minutes (half life of 15 sec)
  Side effects:	flushing, nausea, transient AV block, bronchospasm
  Drug reversal:	theophylline

• continuous IV infusion for 3 minutes

• radiotracer injection

• continue infusion for additional 3 minutes

• Supervision after test not needed

• Contraindication:

  significant pulmonary disease requiring use of inhalers

• Inotropes

  Drug action:	beta-1 agonist increasing myocardial contractility + work thus oxygen demand
  Candidates:	patients with COPD, asthma, allergy to vasodilators, patients on theophylline preparations

• IV infusion of 5 g/kg/min dobutamine for 5 minutes, increased in steps of 5 g/kg every 5 minutes to a maximum infusion rate of 30 40 g/kg/min titrated to patient's response

  • radiotracer injected at onset of significant symptoms / ECG changes / achievement of maximal rate of infusion or heart rate

  • infusion maintained for an additional 2 minutes with dose adjusted to patient's condition

• IV infusion of arbutamine with its own computerized delivery system titrating dose rate automatically

Contraindication:

severe hypertension, atrial flutter / fibrillation

• Applied to:

• THALLIUM IMAGING (redistribution images after stress test):

• injection of 1.5 2 mCi of Tl-201 during peak exercise, continuation of exercise for additional 60 seconds before imaging commences

• Clues for stress images:

  • RV myocardium well visualized

  • little pulmonary background activity

  • little activity in liver, stomach, spleen

  • distribution more uniform after stress than during rest

  • Degree of liver uptake useful as direct measure of level of exercise!

  • Sources of technical errors:

    mnemonic:

    ABCDE PS

  • Attenuation from overlying breast / diaphragm

  • Background oversubtraction

  • Camera field nonuniformity

  • Drugs, Delayed (excessively) imaging, Dose infiltration

  • Eating / Exercising between stress + delayed images

  • Positioning variation between stress + delayed images

  • Submaximal exercise

• GATED BLOOD POOL IMAGING (response of EF)

• increase in ejection fraction from 63 93% in normals

• increase in ventricular wall motion (anterolateral > posterolateral > septal)

Infarct-avid imaging

• = hot spot imaging

Agent:

Tc-99m pyrophosphate (standard), Hg-203 chlormerodrin, Tc-99m tetracycline, Tc-99m glucoheptonate, F-18 sodium fluoride, Indium-111 antimyosin (murine monoclonal antibodies to myosin), Tc-99m antimyosin Fab fragment

Tc-99m Pyrophosphate

• Pathophysiology in MYOCARDIAL INFARCTION:

• pyrophosphate is taken up by myocardial necrosis through complexation with calcium deposits >10 12 hours post infarction

• requires presence of residual collateral blood flow

• 30 40% maximum accumulation in hypoxic cells with a 60 70% reduction in blood flow (greater levels of occlusion reduce uptake)

• Uptake post infarction:

• earliest uptake by 6 12 24 hours;

• peak uptake by 48 72 hours;

• persistent uptake seen up to 5 7 days with return to normal by 10 14 days

Sensitivity:	90% for transmural infarction, 40 50% for subendocardial (nontransmural) infarction
Specificity:	as low as 64%
Dose:	15 20 mCi IV (minimal count requirement of 500,000/view)
Imaging:	at 3 6 hours (60% absorbed by skeleton within 3 hours)

• Indications:

  • Lost enzyme pattern = patient admitted 24 48 hours after infarction

  • Equivocal ECG + atypical angina:

    • left ventricular bundle branch block

    • left ventricular hypertrophy

    • impossibility to perform stress test

    • patient on digitalis

  • ST depression without symptoms

  • Equivocal enzyme pattern + equivocal symptoms

  • S/P cardiac surgery (perioperative infarction in 10%, enzymes routinely elevated, ECG always abnormal), requires preoperative baseline study as 40% are preoperatively abnormal

  • For detection of right ventricular infarction

• NOT HELPFUL:

  • In differentiating multiple- from single-vessel disease

  • Typical angina

  • Normal ECG stress test + NO symptoms

P.1114

• Scan interpretation:

• [Grade 2+ and above are positive]

Grade 0	no activity
Grade 1+	faint uptake
Grade 2+	slightly less than sternum, equal to ribs
Grade 3+	equal to sternum
Grade 4+	greater than sternum

• doughnut pattern = central cold defect (necrosis in large infarct) usually in cases of large anterior + anterolateral wall infarctions

• uptake in inferior wall extending behind sternum (anterior projection) suggests RV infarction

• SPECT imaging improves sensitivity (eliminates rib overlap)

• diffuse uptake can be seen in angina, cardiomyopathy, subendocardial infarct, pericarditis and normal blood pool (normal blood pool can be eliminated with delayed imaging)

FALSE POSITIVES (10%):

• Cardiac causes

  • Recent injury: myocardial contusion, resuscitation, cardioversion, radiation injury, Adriamycin cardiotoxicity, myocarditis, acute pericarditis

  • Previous injury: left ventricular aneurysm, mural thrombus, unstable angina, previous infarct with persistent uptake

  • Calcified heart valves / calcified coronary arteries (rare) / chronic pericarditis

  • Cardiomyopathy: eg, amyloidosis

• Extracardiac causes:

  • Soft-tissue uptake: breast tumor / inflammation, chest wall injury, paddle burns from cardioversion, surgical drain, lung tumor

  • Osseous: calcified costal cartilage (most common), lesions in rib / sternum

  • Increased blood pool activity secondary to renal dysfunction / poor labeling technique (improvement on delayed images)

    mnemonic:

    SCUBA

  • Subendocardial infarction (extensive)

  • Cardiomyopathy / myocarditis

  • Unstable angina

  • Blood pool activity

  • Amyloidosis

  FALSE NEGATIVES (5%)

  • Myocardial metastasis

  PERSISTENTLY POSITIVE SCAN (>2 weeks)

  • = ongoing myocardial necrosis indicating poor prognosis, may continue on to cardiac aneurysm, repeat infarction, cardiac death

  • in 77% of persistent / unstable angina pectoris

  • in 41% of compensated congestive heart failure

  • in 51% of ECG evidence of ventricular dyssynergy

    Prognosis:

    the larger the area, the worse the mortality + morbidity

Tc-99m Antimyosin Fab Fragments

• = specific marker for myocyte damage

• = Fab fragments of an antibody raised against water-insoluble heavy chains of cardiac myosin that are exposed due to necrosis

  Sensitivity:

  95%

• uptake ONLY in acute infarct with decreasing intensity as the infarct heals

Nonavid infarct imaging

• = COLD SPOT IMAGING

• = myocardial perfusion study for acute myocardial infarct

Agent:

Tl-201 (at rest)

• Sensitivity after onset of symptoms:

• 96% within 6 12 hours, 79% after 48 hours, 59% in remote infarction; sensitivity for SPECT (seven pinhole tomography) 94% > planar scintigraphy 75%

• fixed permanent defect in acute infarction

• fixed permanent defect at rest + on stress thallium + redistribution images in old infarction

• cold defect at rest may represent transient ischemia in unstable angina

• N.B.: Tl-201 cannot distinguish between recent + remote infarction!

Intracardiac shunts

• Blood-pool agents administered by peripheral IV injection:

• Tc-99m pertechnetate, DTPA, sulfur colloid, macroaggregated albumin, labeled RBCs

• Method:

• C2/C1-method measures hemodynamic significance of a shunt; raw data obtained from pulmonary activity curve (gamma variate method, Q_p:Q_s ratio = two-area ratio method, count method); accuracy depends on the shape of the input bolus (single peak of <2 seconds' duration); measuring C1, C2, T1, T2

• Normal

  • C2/C1 is <32%

• L-R shunt

  Indication:

  ASD, VSD, AV canal, aortopulmonic window, rupture of sinus of Valsalva aneurysm

• C2/C1 >35% (area A = primary pulmonary circulation; area B = L-R shunt; area (A - B) = systemic circulation; Q_P / Q_S = area A / area (A - B) >1.2

• R-L shunt

  Indication:

  Tetralogy of Fallot, transposition, truncus, Ebstein anomaly

• early arrival of tracer in left side of heart + aorta (first-pass method) prior to arrival of activity from lungs to LV

• quantification possible only by registration of sum of activity of trapped macroaggregate / microspheres in brain + kidneys

• Causes of abnormal nonshunt-related activity:

  • Radiopharmaceutical breakdown

    • free pertechnetate activity in salivary glands, gastric mucosa, thyroid, kidney

• Hepatic cirrhosis

  • abnormal pulmonary vascular channels bypassing the lung (in 10 70%)

• Pulmonary AVM

P.1115

Normal N-R Shunt

Pulmonary Activity Curves

P.1116

Liver and Gastrointestinal Tract Scintigraphy

Biliary scintigraphy

• Application:

  • Acute cholecystitis

  • Congenital biliary atresia

  • Evaluation of bile leak

  • Choledochal cyst

  • Biliary-enteric fistula

  • Chronic GB dysfunction

Tc-99m IDA analogs = HIDA agents

• = Tc-99m acetanilide iminodiacetic acid analogs (IDA)

• Dependent on the substance's lipophility, there is a trade-off between renal excretion + hepatic uptake (BIDA is the most lipophilic, HIDA the least lipophilic)

• 1. HIDA (2,6-dimethyl derivative): [H = hepatic] bilirubin threshold of <18 mg/dL; 15% renal excretion

• 2. BIDA (parabutyl derivative): bilirubin threshold of <20 mg/dL

• 3. PIPIDA (paraisopropyl derivative): 2% renal excretion

• 4. DIDA (diethyl derivative)

• 5. DISIDA (diisopropyl derivative) = Disida , Disofenin , Hepatolite : bilirubin threshold of <30 mg/dL

• 6. TMB-IDA (m-bromotrimethyl IDA) = Mebrofenin , Choletec : T_1/2 uptake is 6 minutes, T_1/2 excretion is 14 minutes in normals; bilirubin levels may be as high as 30 mg/dL

  Quality control:

  the final compound should contain

• 90 100% Tc-99m IDA

• <10% Tc-99m tin colloid

• <10% Tc-99m sodium pertechnetate

• Pharmacokinetics:

• @ Bloodstream

  • tracer binds predominantly to albumin, which decreases renal excretion (renal excretion seen in most normals); dissociation of albumin + Tc-99m-IDA takes place at space of Disse

• @ Liver

  • peak liver activity 5 15 minutes post injection

  • = hepatic phase; 85% extracted by hepatocytes; tracer enters anion pathway of bilirubin

  • Delayed liver uptake implies hepatocyte dysfunction / CHF (less likely)

  • Look for liver lesions on early images

• @ Bile

  • secretion by hepatocytes without conjugation; CBD + cystic duct visualized within 10 30 minutes (not always visualized in normals); GB visualized by 20 60 minutes

  • Activity in right paracolic gutter / intraperitoneal space implies postoperative bile leak

• @ Bowel

  • excretion into duodenum by 30 minutes; bowel visualized within 1 hour; no enterohepatic recirculation

• Dose:	2 8 mCi for adults
  Radiation dose:	2 rad for upper large bowel; 0.55 rad for gallbladder; 3 rad/mCi for small bowel; 0.01 rad/mCi for whole body

• Patient preparation:

  • Fasting for at least (2 )4 hours to avoid a contracted gallbladder (because endogenous cholecystokinin contracts gallbladder)

  • Injection of 0.02 g/kg Kinevac over >3 minutes to empty gallbladder about 30 minutes before tracer injection in patients on prolonged fasting (fasting >24 hours causes an overdistended GB)

  • Narcotics (opiates) + sedatives increase tone of sphincter of Oddi and have to be stopped 6 12 hours before exam

• Equipment:

  • Large field-of-view scintillation camera fitted with LEAP collimator; spectrometer set at 140 keV with 20% window

  • Computer software for deconvolutional analysis allows determination of percent of hepatic arterial and percent of portal venous blood flow to liver (helpful in assessment of liver transplants)

• Imaging:

  • at 5 10-minute intervals for 60 minutes; if gallbladder not visualized for at least up to 4 hours; RLAT, RAO, LAO projections to confirm gallbladder position

  • Look for enterogastric reflux as a cause of biliary gastritis!

• IV morphine sulfate (0.04 mg/kg or up to 3 mg):

  • contracts sphincter of Oddi + raises intrabiliary pressure with retrograde filling of gallbladder; maximal effect 5 minutes post injection; shortens study time in cases of nonvisualization of gallbladder; increases accuracy from 88% to 98% and specificity from 83% to 100%

  • redose patient with a small amount of radiotracer

  • inject morphine at 45 60 minutes if tracer in bowel

  • image for 45 minutes after injection

• Normals:

  • gallbladder appearance within 60 minutes (90% within 30 minutes)

    • excludes diagnosis of acute cholecystitis

    • gallbladder visualization within 30 minutes after administration of morphine

    • small bowel activity within 90 minutes (80% within 60 minutes)

False-positive DISIDA Scan

mnemonic:

F2C2 PAL

• Food (meal within last 4 hours = GB empty)

• Fasting / total parenteral nutrition (GB full)

• Cystic duct cholangiocarcinoma

• Chronic cholecystitis

• Pancreatitis, acute

• Alcoholism (= alcohol-toxic hepatitis)

• Liver dysfunction (hepatitis)

False-negative DISIDA Scan

mnemonic:

ADA

• Acalculous cholecystitis

• Duodenal diverticulum simulating GB

• Accessory cystic duct

P.1117

Rim Sign

• = curvilinear pericholecystic rim of increased hepatic tracer activity adjacent to a photopenic gallbladder fossa

  Cause:

  local hyperemia with increased perfusion + injury of hepatocytes with impaired excretion of radiotracer

• Acute cholecystitis (34 61% sensitive)

• Complicated acute cholecystitis (nonvisualization of GB @ 1 hour: 94 100% PPV, 95 100% specific)

• Chronic cholecystitis

Gallbladder Ejection Fraction (GBEF)

• GBEF = [GB_initial GB_post] GB_initial

  • Indications:

    • to increase sensitivity of study for acute (acalculous) cholecystitis

    • in patients with atypical GB pain and no cholelithiasis

  • Technique:

    • Select ROI about GB

    • Administer Sincalide 1 hour post HIDA in a dose of 0.02 g/kg body weight IV over 30 minutes (with infusion pump)

    • Image acquisition for 30 more minutes

      Normal result:

      >30% GBEF

Liver scintigraphy

Technetium-99m Sulfur Colloid

• = LIVER-SPLEEN SCAN

• Indications:	liver, spleen, bone marrow, acute rejection in renal transplant, lower GI bleeding, gastric emptying
  Physiology:	small colloid particles are phagocytized by reticuloendothelial system (RES); 90% of RES function lies within liver + spleen, 10% primarily within bone marrow

• Preparation:

  • Tc-99m pertechnetate and sodium trisulfate are heated in a water bath (95 5 C) for 10 2 minutes; sulfur atoms aggregate to form a colloid (average particle size 0.1 1 m with a range of 0.001 1 m; true colloid has a particle size of 0.001 0.5 m); gelatin is added to prevent further growth of particles

• Quality control:

  • (a) >92% remain at origin of ascending chromatography

  • (b) upper limit for particle size is 1 m

  • Usual cause for poor preparation is excessive / prolonged heating or a pH >7

  • Preparation should not be used >6 hours (agglomeration of particles with aging)

• Dose:	usually 3 6 mCi (8 mCi for SPECT)
  Radiation dose:	0.3 rad/mCi for liver (critical organ);0.02 rad/mCi for whole body;0.025 rad/mCi for bone marrow
  Imaging:	15 30 minutes post IV injection

• Pharmacokinetics:

  • accumulation in liver (85%), spleen (10%), bone marrow (5%); lung localization is rare (presumably secondary to circulating endotoxins + macrophage infiltration)

• A. RETICULOENDOTHELIAL LOCALIZATION

  • colloid shift away from liver in diffu7 hepatic dysfunction / decreased hepatic perfusion

  • increased bone marrow activity in hemolytic anemia

  • increased splenic activity in hypersplenism of splenomegaly / cancer / systemic illness

• B. BONE MARROW LOCALIZATION

  • Hematopoietic system extends into long bones in children; recedes to axial skeleton, femora, and humeri with age

  • Bone marrow distribution cannot be used to determine sites of erythropoiesis!

• C. ABSCESS LOCALIZATION

  • Sulfur colloid phagocytized by PMNs + monocytes

  • Labeling:

    (a) in vivo:	small labeling yield
    (b) in vitro:	40% labeling efficiency, but difficult + time-consuming preparation

Colloid Shift

• =increased uptake of injected colloid by bone marrow

• A. Hepatic dysfunction

  • Cirrhosis

  • Hepatitis

  • Chronic passive congestion

• B. Augmented perfusion of spleen + bone marrow

  • Hematopoietic disorders

  • Long-term corticosteroid therapy

Focal Hot Liver Lesion

• IVC / SVC obstruction

  • increased perfusion of quadrate lobe located at posterior aspect of medial segment left hepatic lobe (collateral pathway via umbilical vein)

• Budd-Chiari syndrome

  • increased perfusion of caudate lobe (actually decrease of activity elsewhere in liver)

• FNH (varying amount of Kupffer cells)

  • hot (DIAGNOSTIC) / cold / isoactive with surrounding parenchyma

• Regenerating nodules of cirrhosis

Defects in Porta Hepatis

• Normal variant (thinning of hepatic tissue overlying portal veins + gallbladder)

• Biliary causes: dilatation of bile ducts, gallbladder hydrops

• Enlarged portal lymph nodes

• Metastases

• Hepatic cyst

• Hepatic parenchymal disease (pseudotumor)

• Hepatic compression by adjacent extrinsic mass

• Postsurgical changes following cholecystectomy

Focal Liver Defects

• Neoplastic

  • primary liver tumor: hepatoma, hemangioma, hepatic adenoma, FNH

  • metastases: 85% sensitivity, 75 80% specificity (for lesion >1 2 cm)

P.1118




• INFECTIOUS DISEASE / ABSCESS

• BENIGN CYST

• TRAUMA

• PSEUDOTUMOR = normal variant

  • mnemonic:

    L-CHAIM

    • Lymphoma

    • Cyst

    • Hematoma

    • Abscess

    • Infarct

    • Metastasis

Mottled Hepatic Uptake

• Cirrhosis

• Acute hepatitis

• Lymphoma

• Amyloidosis

• Granulomatous disease (sarcoid, fungal, viral, parasitic)

• Chemo- / radiation therapy

Splenic scintigraphy

• Tc-99m sulfur colloid: 3 5 mCi

• Tc-99m heat-denatured erythrocytes

  • Indication:

    • Splenic trauma

    • Accessory + ectopic spleen

  • Technique:

    • 20 30 minutes after injection of pyrophosphate IV 15 20 mL of blood are drawn + incubated with 2 mCi of pertechnetate; blood is heated to 49.5 C for 35 minutes and reinjected

    • Fragmentation of RBCs from overheating increases hepatic uptake!

  • Imaging:

    20 minutes post injection

Hyposplenism

• = no uptake of Tc-99m sulfur colloid

• A. ANATOMIC ABSENCE OF SPLEEN

  • Congenital asplenia = Ivemark syndrome

  • Splenectomy

• B. FUNCTIONAL ASPLENIA

  • = marked decrease in splenic phagocytic function despite presence of splenic tissue within the body

  • 1. Circulatory disturbances:

    • occlusion of splenic artery / vein, hemoglobino-pathies (sickle cell disease, hemoglobin-SC disease, thalassemia), polycythemia vera, idiopathic thrombocytopenic purpura

• 2. Altered RES activity:

  • thorotrast, irradiation, combined splenic irradiation + chemotherapy, replacement of RES by tumor / infiltrate, splenic anoxia (cyanotic congenital heart disease), sprue

• 3. Autoimmune disease

  Cx:	children at risk for pneumococcal pneumonia (liver partially takes over immune response later in life)

• C. FUNCTIONAL ASPLENIA + SPLENIC ATROPHY

  • Ulcerative colitis, Crohn disease, celiac disease, tropical sprue, dermatitis herpetiformis, thyrotoxicosis, idiopathic thrombocytopenic purpura, thorotrast

• D. FUNCTIONAL ASPLENIA + NORMAL / LARGE SPLEEN

  • Sarcoidosis, amyloidosis, sickle cell anemia (if not infarcted), after bone marrow transplantation

  • RBC (acanthocytes, siderocytes)

  • lymphocytosis, monocytosis

  • Howell-Jolly bodies (intraerythrocytic inclusions)

  • thrombocytosis

  • spleen not visualized on Tc-99m sulfur colloid

  • Tc-99m heat-damaged RBCs / In-111 labeled platelets may demonstrate splenic tissue if Tc-99m sulfur colloid does not

  • Cx:	increased risk of infection (pneumococcus, meningococcus, influenza)

Gastrointestinal scintigraphy

Radionuclide Esophagogram

Preparation:	4 12 hours fasting; imaging in supine / erect position
Dose:	250 500 Ci Tc-99m sulfur colloid in 10 mL of water taken through straw
Imaging:	when swallowing begins

• normal transit time: 15 seconds with 3 distinct sequential peaks progressing aborally

• prolonged transit time: achalasia, progressive systemic sclerosis, diffuse esophageal spasm, nonspecific motor disorders, nutcracker esophagus, Zenker diverticulum, esophageal stricture + obstruction

• Difficult interpretation in:

  hiatal hernia, GE reflux, Nissen fundoplication

Gastroesophageal Reflux

• 89% correlation with acid reflux test

• Cause:

  • Decreased pressure of lower esophageal sphincter

    • transient-complete relaxation of LES

    • low resting pressure of LES

  • Transient increase in intraabdominal pressure

  • Short intraabdominal esophageal segment

• Age of population:

  usually 6 9 months, up to 2 years

• poor weight gain

• vomiting, aspiration, choking

• asthmatic episodes, stridor, apnea

• Detection:	upper GI examination with barium, distal esophageal sphincter pressure measurements, 24-hour pH probe measurement in distal esophagus (gold standard), radionuclide examination
  Preparation:	4 hours / overnight fasting; abdominal sphygmomanometer (for adults)
  Dose:	0.5 1.0 mCi Tc-99m sulfur colloid in 300 mL of acidified orange juice (150 mL juice + 150 mL 0.1 N hydrochloric acid) followed by cold acidified orange juice
  Imaging:	at 30 60-second intervals for 30 60 minutes, images taken in supine position from anterior; sphygmomanometer inflated at 20, 40, 60, 80, 100 mm Hg

P.1119




• Interpretation:

  • Reflux (in %) = ([esophageal counts background] / gastric counts) 100

  • up to 3% magnitude reflux is normal

  • evidence of pulmonary aspiration (valuable in pediatric age group)

• Cx:	reflux esophagitis secondary to

  • delayed clearance time of esophageal acid load: tertiary / repetitive esophageal contractions, supine position of refluxor, aspiration of saliva, stimulation of salivary flow, stretched phrenoesophageal membrane in hiatal hernia

  • delayed gastric emptying: increased intragastric pressure (gastric outlet obstruction), viral gastropathy, diabetes

• Prognosis:

  • Self-limiting process with spontaneous resolution by end of infancy (in majority of patients)

  • Persistent symptoms until age 4 (1/3 of patients)

  • Death from inanition / recurrent pneumonia (5%)

  • Cause of recurrent respiratory infections, asthma, failure to thrive, esophagitis, esophageal stricture, chronic blood loss, sudden infant death syndrome (SIDS)

• Rx:

  • Conservative therapy:

    • avoidance of food + drugs that decrease pressure in LES, elevation of head during sleep, acid neutralization, cimetidine / ranitidine (reduction of acid production), metoclopramide / domperidone (increase sphincter pressure + promote gastric emptying)

  • Antireflux surgery

Gastric Emptying

• Rates of gastric emptying vary widely between subjects and even in the same subject at different times

• Dose:

  0.5 1 mCi

  • Tc-99m sulfur colloid cooked with egg white / liver p t as solid food

  • In-111 DTPA in milk, water, formula, juice for simultaneous measurement of liquid phase

• Imaging:

  1-minute anterior abdominal images obtained at 0, 10, 30, 60, 90 minutes in erect position if dual-head camera available; anterior and posterior imaging performed with geometric mean activity calculated

• Pharmacokinetics:

  • 79% tracer activity in stomach for solid phase at 10 minutes; 65% at 30 minutes; 33% at 60 minutes; 10% at 90 minutes

• Normal result:

  50% of activity in stomach at time zero; should empty by 60 30 minutes

• acutely delayed emptying in stress (pain, cold), drugs (morphine, anticholinergics, levo-dopa, nicotine, -adrenergic antagonists), postoperative ileus, acute viral gastroenteritis, hyperglycemia, hypokalemia

• chronically delayed gastric emptying in gastric outlet obstruction, postvagotomy, gastric ulcer, chronic idiopathic intestinal pseudoobstruction, GE reflux, progressive systemic sclerosis, dermatomyositis, spinal cord injury, myotonia dystrophica, familial dysautonomia, anorexia nervosa, hypothyroidism, diabetes mellitus, amyloidosis, uremia

• abnormally rapid gastric emptying in gastric surgery, Z-E syndrome, duodenal ulcer disease, malabsorption (pancreatic exocrine insufficiency / celiac sprue)

Gastrointestinal Bleeding

• Detection depends on:

  • Rate of hemorrhage

    • If bleeding not detectable by RBC scintigraphy, it will not be detectable by angiography!

    • RBC scan detects bleeding as low as 0.1 mL/min

    • Catheter angiography requires bleeding rates of 0.5 mL/min:

      • 63% sensitive for upper GI bleed

      • 39% sensitive for lower GI bleed

      • Only 50% of angiograms will be positive after a positive scintigram!

      • A positive scintigram increases likelihood of a positive angiogram from 22% to 53%!

      • Hemodynamically unstable patients with systolic pressures <100 mm Hg should go to angiography!

  • Continuous versus intermittent bleeding (most GI hemorrhages are intermittent)

  • Site of hemorrhage

  • Characteristics of radionuclide agent

Tc-99m labeled RBCs (In Vivtro Labeling Preferred)

• Generally preferred and accepted most sensitive imaging method for lower GI bleeding

• Serves to triage patients for angiography as a negative exam predicts a negative arteriogram

Indications:

acute / intermittent bleeding (0.35 mL/min); NOT useful in occult bleeding

• Pharmacokinetics:

  • remains in vascular system for prolonged period

  • liver + spleen activity are low allowing detection of upper GI tract hemorrhage

  • low target-to-background ratio (high activity in great vessels, liver, spleen, kidneys, stomach, colon; probably related to free pertechnetate fraction)

• Dose:

  10 25 mCi

• Imaging:

  • (a) every 2 seconds for 64 seconds

  • (b) static images for 500,000 1,000,000 counts at 2, 5, and every consecutive 5 minutes up to 30 minutes + every 10 minutes until 90 minutes; cine clips requiring 1-minute frame acquisition

  • (c) delayed images at 2, 4, 6, 12 hours up to 24/36 hours, each time coupled with cine loop

  • Patient can be reimaged within 24 hours without relabeling RBCs when initial scintigram negative!

• Localization of bleeding site:

  • may be difficult secondary to rapid transit time (bowel motility reduced with 1 mg glucagon IV) or too widely spaced time intervals; overall 83% positive correlation with angiography

  • progressive tracer accumulation over time in abnormal location

  P.1120

  
  

  • bleeding site conforms to bowel anatomy (localizing information may be misleading due to forward / backward peristalsis)

  • change in appearance over time consistent with bowel peristalsis

• Sensitivity:

  • in 83 93% correctly identified bleeding site (50 85% within 1st hour, may become positive in 33% only after 12 24 hours); collection as small as 5 mL may be detected; superior to sulfur colloid

  • 50% sensitivity for blood loss <500 mL/24 hours

  • >90% sensitivity for blood loss >500 mL/24 hours

• False positives (5%):

  • free pertechnetate fraction: physiologic uptake in stomach + intestine, renal pelvis + bladder uptake

    • Spot view of thyroid shows contamination!

  • hepatic hemangioma, varices, inflammation, isolated vascular process (AVM, venous / arterial graft)

• False negatives:

  • 9% for bleeding of <500 mL/24 hours

Tc-99m Sulfur Colloid

• Indication:

  bleeding must be active at time of tracer administration; length of active imaging can be increased by fractionating dose

  • Disappearance half-life of 2.5 3.5 minutes (rapidly cleared from blood by RES + low background activity)

  • Active bleeding sites detected with rates as low as 0.05 0.1 mL/min

  • Not useful for upper GI bleeding (interference from high activity in liver + spleen) or bleeding near hepatic / splenic flexure

• Dose:

  10 mCi (370 MBq)

• Imaging:

  • every image should be for 500,000 1,000,000 counts with oblique + lateral images as necessary

  • (a) every 5 seconds for 1 minute ( flow study

  • = radionuclide angiogram)

  • (b) 60-second images at 2, 5, 10, 15, 20, 30, 40, 60 minutes; study terminated if no abnormality up to 30 minutes

  • (c) delayed images at 2, 4, 6, 12 hours

• extravasation of tracer seen in active bleeding

• Specificity:

  almost 100% (rare false-positives due to ectopic RES tissue)

• False positives:

  transplanted kidney, ectopic splenic tissue, modified marrow uptake, male genitalia, arterial graft, aortic aneurysm

Tc-99m Pertechnetate

• Indication:	bleeding from functioning heterotopic gastric mucosa in Meckel diverticulum / intestinal duplication; consider in adults up to age 25; independent of bleeding rate
  Pathophysiology:	tracer accumulation in mucus-secreting cells

• Avoid barium GI studies + endoscopy + irritating bowel preparation prior to study!

• Dose:

  5 10 mCi (185 370 MBq)

• Imaging:

  • radionuclide angiogram 2 3 seconds/frame for 1st minute

  • sequential 5-minute images up to 20 minutes with 500,000 1,000,000 counts per image

• Sensitivity:

  >80% enhanced by

  • fasting for 3 6 hours to reduce gastric secretions passing through bowel

  • nasogastric tube suction to remove gastric secretions

  • premedication with pentagastrin (6 g/kg SC 15 minutes before study) to stimulate gastric secretion of pertechnetate

  • premedication with cimetidine (300 mg qid 48 hours) to reduce release of pertechnetate from mucosa

  • voiding just prior to injection

• False positives:

  • bowel inflammation (Barrett esophagus, duodenal ulcer, ulcerative colitis, Crohn disease), enteric duplication, hemangioma, AV malformation, aneurysm, volvulus, intussusception, urinary obstruction, uterine blush

• False negatives:

  • ulcerated epithelium

Levine / Denver Shunt Patency

• Technique:

  • sterile injection of 0.5 1 mCi Tc-99m MAA / sulfur colloid via paracentesis

• Imaging:

  • over abdomen (or chest) to detect uptake in liver (or lung), which confirms patency

P.1121

Renal and Adrenal Scintigraphy

Renal agents

• Agents for renal function: Tc-99m DTPA, I-131 Hippuran

• Renal cortical agent: Tc-99m DMSA

• Renal combination agent: Tc-99m glucoheptonate

Tc-99m DTPA

• = Tc-99m diethylenetriamine pentaacetic acid

• = agent of choice for assessment of

• Perfusion

• Glomerular filtration = relative GFR

• Obstructive uropathy

• Vesicoureteral reflux

• Pharmacokinetics:

  • chelating agent; 5 10% bound to plasma protein; extracted with 20% efficiency on each pass through kidney (= filtration fraction); excreted exclusively by glomerular filtration (similar to inulin) without reabsorption / tubular excretion / metabolism

  • Time-activity behavior:

    • abdominal aorta (15 20 seconds)

    • kidneys + spleen (17 24 seconds); liver appears later because of portal venous supply

    • renal cortical activity (2 4 minutes): mean transit time of 3.0 0.5 minutes; static images of cortex taken at 3 5 minutes

    • renal pelvic activity (3 5 minutes): peak at 10 minutes; asymmetric clearance of renal pelvis in 50%; accelerated by furosemide

• Biologic half-life: 20 minutes

• Dose: 10 20 mCi

• Radiation dose: 0.85 rad/mCi for renal cortex; 0.6 rad/mCi for kidney; 0.5 rad/mCi for bladder; 0.15 rad/mCi for gonads; 0.15 rad/mCi for whole body

• Adjunct:

• Lasix administration (20 40 mg IV) 20 minutes into exam allows assessment of renal pelvic clearance with accuracy equal to Whitaker test (DDx of obstructed from dilated but nonobstructed pelvicaliceal system)

[Tc-99m Glucoheptonate]

• largely replaced by Tc-99m MAG3

• Pharmacokinetics:

  • rapid plasma clearance + urinary excretion with excellent definition of pelvicaliceal system during 1st hour; extracted by (a) glomerular filtration and (b) tubular excretion (30 45% within 1st hour);

  • 5 15% of dose accumulates in tubular cells by 1 hour,

  • 15 25% by 3 hours; cortical accumulation remains for 24 hours

• Imaging:

  • collecting system within first 30 minutes

  • renal parenchyma after 1 2 hours (interfering activity in collecting system)

• Biologic half-life: 2 hours

• Dose: 15 (range 10 20) mCi

• Radiation dose: 0.17 rad/mCi for kidney; 0.008 rad/mCi for whole body; 0.015 rad/mCi for gonads

Tc-99m DMSA

• = Tc-99m dimercaptosuccinic acid

• = suitable for imaging of functioning cortical mass: pseudotumor versus lesion

  Renal Scintigraphic Agents

  Agent	Dose	Pharmacokinetics	Imaging Characteristics
  MORPHOLOGIC AGENTS
  Tc-99m GHA	5 mCi	proximal tubular uptake + glomerular filtration	collecting system visualized on delayed images
  Tc-99m DMSA	2 5 mCi	proximal + distal tubular uptake	limited availability, relatively high radiation dose, collecting system not visualized on delayed images
  FUNCTIONAL AGENTS
  I-131 OIH	200 400 Ci	80% secreted, 20% filtered	routinely used for ERPF measurement, analog of PAH, highest renal extraction fraction, poor image detail, high radiation dose, requires high-energy collimator
  Tc-99m DTPA	10 15 mCi	nearly 100% filtered	GFR calculation, delayed time-to-peak with slow clearance
  Tc-99m MAG3	2 10 mCi	99% secreted	ERPF estimate, good cortical detail, high target-to background ratio

P.1122




• Pharmacokinetics:

  • high protein-binding + slow plasma clearance; 4% extracted per renal passage; 4 8% glomerular filtration within 1 hour and 30% by 14 hours; 50% of dose accumulates in proximal + distal renal tubular cells by 3 hours (= cortical agent)

• Imaging: after 1 3 24 hours (optimal at 34 hours); improved sensitivity to structural defects with SPECT

• Biologic half-life: >30 hours

• Dose: 5 10 mCi

• Radiation dose: 0.014 rad/mCi for gonads; 0.015 rad/mCi for whole body

[I-131 OIH]

• largely replaced by Tc-99m MAG3

• = I-131 orthoiodohippurate (Hippuran )

• = good for evaluation of renal tubular function / effective renal plasma flow; agent with highest extraction ratio without binding to renal parenchyma; visualizes kidney even in severe renal failure

• Pharmacokinetics:

  • 80% secreted by proximal tubules; 20% filtered by glomeruli; maximal renal concentration within 5 minutes; normal transit time of 2 3 minutes; approximately 2% free iodine

  • Lugol's solution is administered to protect thyroid

• Imaging:

  • in 15 60-second intervals for 20 minutes; renal uptake determined from images obtained by 1 2 minutes (patient in supine position for equidistance of kidneys to camera)

• Biologic half-life: 10 minutes (with normal renal function)

• Dose: 200 (range 150 300) Ci

• Radiation dose: 0.06 rad/200 Ci for bladder; 0.02 rad/200 Ci for kidney; 0.02 rad/200 Ci for whole body; 0.02 rad/200 Ci for gonads

Tc-99m Mercaptoacetyltriglycine (MAG3)

• = renal plasma flow agent similar to OIH but with imaging benefits of Tc-99m label (improved dosimetry)

• Pharmacokinetics:

  • correlates with renal plasma flow; clearance is less than Hippuran

• Dose: 10 mCi

• Evaluation:

  • true renal plasma flow = MAG₃ flow (obtained off renogram curve) multiplied by a constant (varies between 1.4 and 1.8)

ACE Inhibitor Scintigraphy

• = screening test for renovascular hypertension (not renal artery stenosis) with angiotensin-converting enzyme inhibitor (ACEI) challenge

• ACE inhibition may impair overall renal function due to disruption of autoregulatory mechanism of GFR (with renal artery stenosis in both kidneys / solitary kidney)

• Pharmacology:

  • the affected kidney responds to decreased arteriolar flow by releasing renin + angiotensin II (= extremely potent vasoconstrictor acting on the efferent renal arteriole to increase filtration pressure) in juxtaglomerular apparatus; ACE inhibitors (eg, captopril, enalapril) block the angiotensin-converting enzyme which reduces GFR (51 96% sensitive, 80 93% specific)

• unilateral parenchymal retention after ACEI (reduced GFR results in reduced urinary output and increased radiotracer retention)

  • = >90% probability of renovascular hypertension

• change from baseline grade 0 / 1 by >1 grade

  • = high probability for renal artery stenosis

• abnormal baseline curve without change

  • = indeterminate for renovascular hypertension

• functional improvement following ACEI challenge

  • = low probability for renovascular hypertension

• Semiquantitative interpretation of time-activity renograms:

  • normal ACE inhibitor scintigram (<10% probability for renovascular hypertension)

  • criteria for high probability (>90%):

    • worsening of scintigraphic curve

    • reduction in relative uptake with >10% change after ACE inhibition

    • prolongation of parenchymal transit time with >2 minutes delay of excretion into renal pelvis

    • increase in 20-min/peak uptake ratio >0.15 from baseline

    • prolongation of T_max of >2 minutes / 40%

  • asymmetry of renal uptake <40% of total renal uptake

• bilateral symmetrical changes are usually due to:

  • hypotension

  • salt depletion

  • use of calcium channel blockers

  • low urine flow rate

    Time-Activity Renograms

P.1123




• Decreased accuracy with:

  • bilateral renal artery stenosis

  • impaired renal function

  • urinary obstruction

  • chronic ACE inhibitor therapy

• Sources of error:

  • Failure to administer ACEIs properly:

    • ingestion of food within 4 h of taking captopril

    • paravenous infiltration

  • Causes of abnormal whole-kidney renograms:

    • renal pelvic retention

    • dehydration

    • hypotension

    • full bladder impairing drainage

Enalaprilat (Vasotec )-enhanced Renography

• Technique:

  • Blood pressure check (to prevent testing excessively hypertensive patients)

  • Discontinue captopril / lisinopril 3 d before study

  • Discontinue enalaprilat

  • Stop any other antihypertensive medications overnight (except for -blockers)

  • Fasting (liquids acceptable)

  • Bladder catheterization to monitor urinary output

  • 1/2 normal saline IV drip at 75 mL/hr at a dose of 10 mL fluid/kg body weight (to ensure adequate hydration)

  • Furosemide (= Lasix ) IV

    • 20 mg if serum creatinine <1.5 mg/dL,

    • 40 mg if serum creatinine >1.5 mg/dL,

    • 60 mg if serum creatinine >3.0 mg/dL

    • (not to exceed 1.0 mg/kg)

  • 2.5 5 mCi Tc-99m MAG3 IV for baseline study

    • flow phase with 1 sec/frame for 60 frames

    • tracer kinetic (dynamic) phase with 15 sec/frame for 120 frames

  • Rehydration with 1/2 normal saline keeping a 250 300 mL negative fluid balance

  • Postvoid image (or Foley catheter with PVR)

  • 0.04 mg/kg enalaprilat IV (up to a maximum of 2.5 mg) infused over 5 minutes + blood pressure and heart rate checks q 5 minutes

  • Repeat furosemide (= Lasix ) IV

  • 5 7.5 mCi Tc-99m MAG₃ IV [or 10 mCi Tc-99m MAG₃ IV single post-enalaprilat study for patients already on ACEI therapy]

  • Image acquisition:

    • 1 3 s / frame for first 60 s

    • 10 30 s / frame thereafter

    • image display at 1 3 minute intervals

    • total acquisition time of 20 30 minutes

  • whole-kidney ROI (better count statistics) / cortical ROI (for unusual retention in renal pelvis)

• 2-day protocol:

  • ACEI renography on day 1

  • if test abnormal patient has to return on day 2 for a baseline study to maximize specificity

Captopril (Capoten )-enhanced Renography

• Dose: 1 mg/kg PO for pediatric patient,

  • 25 or 50 mg PO for adult patient (crush tablets + dissolve in 200 mL of water)

• Technique:

  • no solids for 4 h prior to study

  • moderate hydration with 7 mL water / kg BW ingested 30 60 minutes before study

  • radiopharmaceutical injected 60 minutes after ingestion of captopril

  • at the same time 20 mg furosemide IV (to wash out radiopharmaceutical from distal nephron + calices + pelvis thereby improving detection of cortical retention)

Cold Defect on Renal Scan

• mnemonic: CHAT SIN

  • Cyst

  • Hematoma

  • Abscess

  • Tumor

  • Scar

  • Infarct

  • Neoplasm

Differential Renal Function

• Agents:

  • Tc-99m DTPA:

    • measurements prior to excretion within first 1 3 minutes; images taken at 1.5-second intervals for 30 seconds followed by serial images for next 30 minutes

  • I-131 Hippuran:

    • measurements prior to excretion within first 1 2 minutes

• Evaluation: generation of time-activity curves

  • upslope (= accretion phase)

  • peak activity (maximal uptake phase)

  • downslope (excretion phase)

• increased hepatic + soft-tissue uptake with impaired renal function

  Grading of Differential Renal Function

P.1124




• measurements usually not significantly affected with differences in renal depth

• measurements are accurate in renal obstruction if obtained within 1 3 minutes

• prediction about functional recovery not possible following surgical relief of obstruction

Radionuclide cystogram

• Use: evaluation of bladder volume at reflux, volume of refluxed urine, residual urine volume, ureteral reflux drainage time

• Technique:

  • indirect: IV injection of Tc-99m DTPA

  • direct: instillation of 0.5 1 mCi Tc-99m pertechnetate-saline mixture into bladder (more sensitive for reflux during filling phase, which occurs in 20%)

• Imaging:

  • posterior upright views throughout filling and voiding phases; review on cinematic loop helpful; residual bladder volume can be calculated

• Advantage:

  • lower radiation dose to gonads than fluoroscopic contrast cystography (5 mrad)!

Adrenal Scintigraphy

• ADRENOCORTICAL IMAGING AGENTS

  • NP-59

  • Selenium-75 6- -selenomethylnorcholesterol (Scintadrin )

• SYMPATHOADRENAL IMAGING AGENTS

  • I-131 / I-123 metaiodobenzylguanidine (MIBG)

I-131 Metaiodobenzylguanidine (MIBG)

• Indications:

  • APUDomas = tumors of neural crest origin (C cells of thyroid, melanocytes of skin, chromaffin cells of adrenal medulla, pancreatic cells, Kulchitsky cells), which share the presence of neurosecretory granules capable of accumulating I-131 MIBG

  • (1) Pheochromocytoma (80 90% sensitivity, >90% specificity); tumors as small as 0.2 g have been detected

  • (2) Neuroblastoma, carcinoid, medullary thyroid carcinoma, nonfunctioning retroperitoneal neuroendocrine tumor, middle mediastinal paraganglioma, adrenal metastasis of choriocarcinoma, Merkel (skin) tumor

• Pharmacokinetics:

  • chemically similar to norepinephrine, which is synthesized by adrenergic neurons + cells of the adrenal medulla; localizes in storage granules of adrenergic tissue by means of energy- and sodium-dependent uptake mechanism; not metabolized to any appreciable extent;

  • Normal activity is seen in liver, spleen, bladder, salivary glands, myocardium, lungs; 85% of injected dose is excreted unchanged by kidneys

• Method:

  • Lugol solution administered orally (50 mg of iodine per day) for 4 5 days starting the day before injection (to block thyroid uptake of free iodine)

• Dose: 0.4 0.5 mCi/1.73 square meters of body surface MIBG, up to 500 Ci

• Radiation dose: 35 rad/mCi for adrenal medulla, 1.0 rad/mCi for ovaries, 0.4 rad/mCi for liver, 0.22 rad/mCi for whole body

• Imaging: 24 48 (72) hours after injection with 100,000 counts / 20 minutes per image

• False-negative scan:

  • uptake blocked by reserpine, imipramine, other tricyclic depressants, amphetamine-like drugs

I-123 Metaiodobenzylguanidine

• agent of choice, also allows SPECT imaging

• Dose: 10 mCi

• Radiation dose: 2.76 rad/mCi for adrenals, 0.07 rad/mCi for ovaries, 0.05 rad/mCi for liver, 0.02 rad/mCi for whole body

• Imaging: at 6 and 24 hours

Indium-111 Pentetreotide

• = Octreotide = somatostatin analogue

• Indication: pituitary tumor, gastrinoma, paraganglioma, carcinoid, neuroblastoma, small cell lung cancer, pheochromocytoma

• Dose: 3 6 mCi

• Imaging: 4 24 (48) hours

• Distribution: kidneys, spleen, liver, bladder, intestines, thyroid, pituitary gland

• Advantage: superior to MIBG

Iodocholesterol

• Agent: I-131 6- -iodomethyl-19-norcholesterol (NP-59); no FDA approval (available as investigational new drug)

• Indications: adrenocortical imaging

  • ACTH-independent Cushing syndrome (adenoma, cortical nodular hyperplasia)

  • Adrenocortical carcinoma

    • spectrum from nonfunctioning to functioning

  • Primary aldosteronism (adenoma, bilateral adrenal hyperplasia) improved scintigraphic discrimination requires dexamethasone suppression before + during imaging

  • Hyperandrogenism (adrenal adenoma, zona reticularis hyperplasia, polycystic ovary disease, ovarian stromal hyperplasia, androgen-secreting ovarian neoplasm)

  • Incidentaloma (= adrenal mass)

    • localization to side of CT-depicted adrenal mass (= concordant uptake) suggests hyperfunctioning adenoma

    • markedly diminished / absent uptake (= discordant uptake) or symmetric uptake (= nonlateralization) suggests space-occupying mass (eg, cyst) / malignant adrenal mass

• Pharmacokinetics:

  • NP-59 is incorporated into low-density lipoproteins (LDL), circulates to adrenal cortex, absorbed from LDL complex by low-density lipoprotein receptors, esterified in adrenal cortex; adrenocortical uptake affected by adrenocortical secretagogues (corticotropin, angiotensin II); enterohepatic excretion may obscure adrenals (prior laxative administration beneficial)

P.1125




• Dose: 1 mCi (37 MBq) with slow IV injection

• Radiation dose: 26 rad/mCi for adrenals, 8.0 rad/mCi for ovaries, 2.4 rad/mCi for liver, 2.3 rad/mCi for testes, 1.2 rad/mCi for whole body

• Method: Lugol solution administered orally (50 mg of iodine per day) for 4 5 days starting the day before injection (to block thyroid uptake of free iodine); mild laxative administered to decrease bowel activity

• Imaging:

  • 5 7-day interval between injection + imaging;

  • 3 5-day interval between injection + imaging in case of dexamethasone suppression (1 mg four times daily for 7 days prior to and throughout 4 5 days of postinjection imaging interval)