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Principles of nuclear cardiology History • Hermann blumgart-1927-injected radon to measure circulation time • Liljestrand-1939-normal blood volume • Myron prinzmetal-1948- radiolabelled albumin • Hal anger-1952-gamma camera-beginning of clinical nuclear cardiology • 1976-thallium201-two dimensional planar imaging • 1980s-SPECT using rotating anger camera • 1990-technetium99m based agents and gated SPECT • 90% of SPECT in U.S use technetium and 90% are gated SPECT SPECT single photon emission computed tomography Basic concept • Intravenously injected radiotracer distributes to myocardium proportional to blood flow • Gamma camera captures the photons, converts to digital data and displays it as a scintillation event • Parallel hole collimator-better localisation of source • Photomultiplier tubes-conversion of signals • Final result-multiple tomograms of radiotracer distribution SPECT image display • Short axis images-perpendicular to long axis of the heart,displayed from apex to base • Vertical long axis-parallel to long axis of heart and parallel to long axis of body • Horizontal long axis-parallel to long axis of heart,perpendicular to VLA slice SPECT SPECT perfusion tracers • Thallium 201 • Technetium–99m – Sestamibi (Cardiolyte) – Tetrafosmin (Myoview) – Teboroxime • Dual Isotope – Thallium injected for resting images – Tech -99m injected at peak stress Thallium-201 • Monovalent cation,property similar to potassium • Half life 73 hours,emits 80keV photons,t½ 73hrs,85% first pass extraction • Peak myocardial concentration in 5 min, rapid clearance from intravascular compartment • Redistribution of thallium-begins 10-15 min.after ,related to conc.gradient of thallium between myocyte and blood • Differential washout-clearance is more rapid from normal myocardium • Hyperinsulinemic states reduce blood conc.&slow redistribution.so fasting recommended • Thallium protocols– Stress protocols-injected at peak stress and images taken at peak stress and at 4 hrs,24hrs – Reversal of a thallium defect marker of reversible ischemia – Rest protocols-thallium defect reversibility from initial rest images to delayed redistribution images reflect viable myocardium with resting hypoperfusion – Initial defect persists-irreversible defect • Stress/redistribution/reinjection method commonly used • Reinjection if fixed defects seen at 4 hrs • Timing of stress image-early • Rest redistribution image for resting ischemia/viability Technetium-99m labelled tracers • Half life 6 hrs,140keV photons,60% extraction • Uptake by passive distribution by gradient • Minimal redistribution-require two separate injections-one at peak stress and one at rest • Single day study-first injected dose is low • Two day study-higher doses injected both rest and stress-optimise myocardial count ratelarger body habitus • Tc99m tracers bound by mitochondria.limiyed washout occurs.so imaging can commence later and can be repeated • 2 day image protocol better for image quality • Most common-same day low dose rest/high dose stress-disadvantage is reduction in stress defect contrast. • Viability assessment improved by NTG prior to rest study Dual isotope protocol • Anger camera can collect image in different energy windows • Thallium at rest followed by Tc 99m tracer at peak stress • If there is rest perfusion defect,redistribution imaging taken either 4 hrs prior or 24hrs after Tc99m injection Radionuclide Properties Property Thallous Chloride Tc-Sestamibi Chemistry +1 cation, hydrophilic +1 cation, lipophilic half life 73 hrs 6 hours Photon energy 68-80 keV 140 keV Uptake Active: Na-K ATPase pump Passive diffusion (if intact membrane potentials) Extraction fraction 85% 66% Heart uptake 4% 1.2% Redistribution Redistributes Fixed Stress protocols • Dipyridamole infusion for 4 min-isotope injection 3 min after infusion • Adenosine infusion for 6 min-isotope given 3 min into infusion Interpretation and reporting • Myocardium devided into 17 segments on the basis of 3 short axis and a long axis slice • Perfusion graded from 0(normal perfusion) to 4(no uptake) • SSS-summed stress score-stress perfusion abnormality • SRS –summed rest score-extent of infarction • SDS-summed difference score-stress induced ischemia Visual Analysis of Perfusion SPECT • • • • • 0-normal uptake, 1-mildly reduced uptake, 2-moderately reduced uptake, 3-severely reduced uptake, and 4-no uptake • bulls̒ eye polar plot-two dimensional compilation of all three dimensional short axis perfusion data Normal Ant Stress Apex Inf Rest Septum Lateral Stress Apex Lat Sep Rest Inferior Anterior Ant Stress Lat Sep Rest Inf Apex Base Ant Stress Apex Rest Inf Septum Lateral Stress Apex Lat Sep Rest Inferior Anterior Ant Stress Lat Sep Rest Inf Reversible Ischeamia, defect appears at stress and disappears during rest Apex Base Ant Stress Apex Rest Inf Septum Lateral Stress Apex Lat Sep Rest Inferior Anterior Ant Stress Lat Sep Rest Inf Apex Base Fixed Scar, defect is seen in both stress and rest Interpretation of the Findings-SPECT Stress • No defects • Defect Rest Interpretation No defects Normal No defect Ischemia • Defect Defect Scar/ hibernating (Stress-induced ischemia) • Defect location (anterior, posterior, lateral, or septal wall), size (small, medium, or big), severity (mild, moderate, absent), degree of reversibility at rest (completely reversible, partially reversible, irreversible) • Regional wall motion, EDV, ESV, EF Additional signs • Lung uptake of thallium • Transient ischemic dilatation of left ventricle Thallium-201 Lung Uptake • ↑ lung uptake of thallium following stress -marker of severe CAD,elevation of PCWP,↓EF • ↑PCWP-slow pulmonary transit-more extraction • Minimal splanchnic uptake,early image after stress-lung uptake more apparent in thallium • More liver uptake,delayed imaging-lung uptake missed with Tc99m TID: transit Ischemic Dilation (Stress induced LV Cavity Dilation) • Severe, extensive CAD (usually with classic ischemic defect) Left Main Prox LAD MVD diffuse subendocardial ischemia Variations • • • • Dropout of the upper septum Apical thinning Lateral wall may appear brighter than septum Minimised by review of series of normal volunteers Technical artifacts • Breast attenuation– Minimised by Tc99m agents,ecg gated SPECT – Presence of preserved wall motion and thickening • Inferior wall attenuation – Diaphragm overlapping inferior wall – Minimised by gated SPECT,prone position • Extracardiac tracer uptake – Repeat imaging,drink cold water to clear tracer from visceral organs • LBBB– isolated reversible perfusion defects of septum – Heterogeneity of flow b/w LAD &LCx due to delayed septal relaxation – Reduced O2 demand due to late septal contraction,when wall stress is less • HCM– due to ASH,appearance of lateral perfusion defect • Combined SPECT/CT or PET/CT scannerscomplementary anatomical and functional information Gated SPECT • Simultaneous assessment of LV function and perfusion • Each R-R interval is devided into prespecified number of frames • Frame one represent end diastole,middle frames end systole • An average of several hundred beats of a particular cycle length acquired over 8-15 min. • Normal regional systolic function-brightening of wall during systole • Quantitative analysis of LV function-three dimensional display representing global LV function created by information from all tomographic slices-EF and LV volumes calculated Radionuclide ventriculography • MUGA scanning-multiple gated acquisition – Tc 99m labelled r.b.c or albumin – Image constructed over an average cardiac cycle by e.c.g gating,16-32 frames /cycle – Image acquired in antr.,LAO, left lateral projections – Size of chambers,RWMA,LV function – Time activity curve-LV volumes • First pass RVG-i.v injected radioactive tracer passes through rt.chambers-lungs-lt.chambers • Tc99m DTPA preferred • RAO projection • 2-5 cycles summed for RV phase,5-7 for LV phase • Time activity curves generated-quantitative analysis PET • Radiotracers labelled with positron emitting isotopes • Perfusion tracers-Rb82 and n13 ammonia • Metabolic tracer-F18 FDG • Beta decay-positron emission • Annihilation-collide with electron-give two gamma rays of 511keV-travel in opp.direction • PET scanner detects opposing photons in coincidence-spatial and temporal resolution Perfusion tracers • Diffusible tracers-O-15-accumulate and wash out. • Non diffusible-Rb82,N13ammonia • Rb82-generator produced,t½76s. Advantage of PET • Higher spatial resolution • Improved attenuation correction • Quantification regional blood flow – SPECT may fail to detect balanced ischemia in multivessel CAD – ↓blood flow reserve by PET –early identification of CAD • Higher sensitivity and specificity(95%)for detection of CAD Limitations • High cost • Requirement of cyclotron • Short half life-pharmacological stress only Metabolic tracers • C-11 palmitate • I-123 BMIPP-Ischemic memory-fatty acid metabolism suppressed for longer time after an ischemic event • F18 FDG-imaging myocardial glucose utilisation with PET – Phosphorylated and trapped in myocardium – Uptake may be increased in hibernating but viable myocardium • FDG uptake in regions with reduced blood flow at rest –marker of hibernation • FDG studies performed after 50 to 75 gm glucose loading 1-2 hrs prior to injection – ↑glucose metabolism,FDG uptake and improves image quality • Enhanced FDG uptake relative to blood flow referred to as PET mismatch pattern indicative of viable myocardium Viability PET Study • Traditionally the gold standard • Two sets of resting images to detect viable and hibernating myocardium: – Perfusion image (usually with N-13 ammonia or rubidium-82) – Glucose metabolic image (with F-18 fluorodeoxyglucose = FDG) * PET Viability Scan Patterns Normal Stunning Hibernation Scar Contractility N Perfusion N -N Metabolism N N- Guidelines • Acute syndromes – Assessment of patients presenting to ED with chest pain – Diagnosis of AMI when other measures non diagnostic-Tc99m – Risk assessment,prognosis in AMI – Risk assessment,prognosis in NSTEMI/UA Chronic syndromesrecommendations Class1• Exercise SPECT for identifying location ,severity of ischemia in pts without baseline ECG abnormalities that interfere with ST seg.analysis • Adenosine SPECT for LBBB,paced rhythem,unable to exercise • To assess functional significance of an intermediate coronary lesion(25-75%) • Intermediate duke TMT score • Rpt.MPI for recent change of symptoms • Class 2a– 3-5 yrs after revascularisation in asymptomatic patients – As initial test in high risk patients(>20% 10yr risk) • Class 2 b– Pts with cor.calcium score more than 75 percentile – Asymptomatic pts.high risk occupation Indications for PET for risk stratification of patients with intermediate likelihood of CAD CLASS1– SPECT study equivocal • Class 2a– As initial test in patients unable to exercise – As initial test in pts. With baseline ECG abnormalities Risk Stratification • Normal perfusion imaging after adequate stress: very low cardiac event rate < 1% • Small fixed defect with normal global LV function: good prognosis • High risk: (reversible defects) more than one territory, LAD (most important coronary artery), post-stress LV (left ventricular) dysfunction (LV dilatation, abnormal wall motion, decreased LVEF, lung uptake)