Radiology Review Manual (Dahnert, Radiology Review Manual)

Authors: Dahnert, Wolfgang

Title: Radiology Review Manual, 6th Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > Nuclear Medicine

Nuclear Medicine

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

P.1072

Radiation Dose

Pediatric Dose

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

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

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

• 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

Radiochemical Impurity

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):

Aluminum Ion Breakthrough Test

• 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

Radiopharmaceutical Sterility and Pyrogenicity

USP XX Test

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

Limulus Amoebocyte Lysate Test (LAL)

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

Quality Control for Dose Calibrators

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

Linearity

• = accurate measurement over large range of activity levels

Accuracy

Geometry

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

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

Field Uniformity

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

Causes for nonuniformity:

• High kilovoltage drift of photomultiplier (PM) tubes

• Physical damage to collimator

• Improper photopeak setting

• Contamination

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)

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 %)

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

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

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

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

• (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

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

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)

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

P.1081

Lymphangioscintigraphy

Lymphangioscintigraphy Technique

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

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

Congenital Lymphedema

Lymphedema Precox

• 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

• 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

• 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)

Energy levels:

• 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

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

• 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):

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

Hot Bone Lesions

• 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)

• 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:

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

Tc-99m HMPAO

= hexamethylpropylene amine oxime = exametazine

Tc-99m ECD

= ethyl cysteinate dimer = bicisate

I-123 Iofetamine

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

• 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

• 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

• 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

• 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

• 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

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

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

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

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

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

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

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

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

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