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Will PET Replace Single Photon Emission Computed Tomography? T.H. Schindler, MD Deputy Head Physician, Division of Cardiology, University Hospitals of Geneva, Geneva, Switzerland Disclosures • None CASE 1: N-13 Ammonia PET in a 58 Old Asymptomatic Diabetic Patient (Schindler TH et al, JACC Cardiovasc Imaging 2010) Quantification of Myocardial Blood Flow (MBF) by PET Imaging: Technical and Methodological Aspects Compartment Models for Tracers of MBF Estimates in ml/g/min Serially Acquired Images of a Bolus Transit of N-13 Ammonia 2-Compartment Model for N-13 Ammonia (Schelbert HR et al., Circulation 1981) Arterial Radiotracer Input Function and Myocardial Tissue Response Through fitting of the time activity curves with the operational equation formulated by the 2-compartment tracer kinetic model, estimates of MBF in ml/g/min are obtained Added Value of MFR in the Identification of Flow-Limiting Lesions Coronary Angiography Three vessel disease LAD: 100% stenosis LCX: 85% stenosis RCA: 50% stenosis (Schindler TH . JACC Cardiovasc Imaging 2010) Coronary Angiography Unmasking Multivessel Disease LCx: >80% 50% rMFR: 1.41 50% LAD:100% rMFR: 1.20 rMFR: 1.35 50% Left Coronary Tree Right Coronary Tree Coronary Revascularization 1) Re-opening of the chronic LAD occlusion with stent deployment? 2) PCI of LAD and LCx with stenting? 3) CABG of all three main territories ? Stress-Induce Myocardial Ischemia, invasivelydetermined Coronary Flow Reserve (CVR) and Fractional Flow Reserve (FFR) (Kern MJ . Circulation 2000) Added Diagnostic Value of MFR Stress-induced myocardial perfusion defect commonly signifies the « culprit lesion » in multivessel CAD disease. Adding regional MFR may also unmask flow-limiting downstream effects of lesions with intermediate severity (>70% diameter stenosis). Keep in mind: Reductions of MFR are related to increases in epicardial and microcirculatory resistance and, thus, non-specific! In this case, however, adding regional MFR translated a functional 1-vessel to a three vessel disease and the patient was referred to CABG. Coronary Vasodilator Capacity related to Stenosis (Uren MG et al. N Engl J Med 1994 ) (DiCarli MF et al. Circulation 1995) Integration of PET Perfusion Imaging and MFR (Schindler TH et al. JACC Cardiovasc Imaging 2010) CASE 2 62 year old type 2 diabetic patient. The patient was refered for N-13 ammonia PET/CT stress-rest perfusion imaging as pre-operative risk stratification (bioprothese for abdominal aneurysm). N-13 ammonia PET/CT perfusion imaging was performed with dipyridamole-induced hyperemic flow increases. N-13 ammonia PET/CT Perfusion Images Left Coronary Angiography and regional MFR - LAD: 60-70% stenosis - Marginal branch of the LCx: 100% -RCA: lesion <50% (not shown) PET-determined MBF (ml/g/min) rest stress MFR LAD: 1.00 1.77 1.77 LCX: 1.07 1.32 1.23 RCA: 0.91 1.95 2.14 Clinical decision: PTCA and stent employment of the proximal LAD stenosis in view of abnormally reduced MFR. Interpretation Stress-induced regional perfusion defect identifies « culprit lesion » in multivessel CAD disease. Abnormally-reduced MFR in the LAD territory gave an argument for PTCA and stent employment of the proximal LAD stenosis of intermediate range. Conceptually, preventive medical care with statine and/or ACEInhibitors could have improved coronary microcirculatory dysfunction leading to a normalization the MFR! This again could have avoided the coronary intervention. Reductions of MFR are related to increases in epicardial and microcirculatory resistance and, thus, non-specific! Abnormal Epicardial Vasomotion During CPT in a Smoker Baseline Cold Pressor Test (Schindler TH, J Nucl Med 2004) Diameter of LAD PET Flow Measurements: 0.51 ml/min/g 0.61 ml/min/g (Schindler TH, J Nucl Med 2004) Prognostic Value of MFR to Sympathetic Stimulation with Cold Pressor Testing in Cardiovascular Risk Individuals 1.0 Normal Endothelial Function: MBF40%, Event Free Survival 0.9 0.8 Mild to Moderate Endothelial Dysfunction: >0 MBF<40% 0.7 + 0.6 ++++ + ++ Severe Endothelial Dysfunction: MBF 0% Log rank 7.42 p = 0.024 0.5 0.4 0 20 40 60 80 Follow-up (months) (Schindler TH. J Am Coll Cardiol 2005) Hyperemic MBF Increases to Adenosine Stimulation (4 mg L-NAME / kg BW i.v.) p < 0.001 3 Baseline 2.5 -21% 2 MBF 1.5 (ml/min/g) L-NAME endotheliumrelated NS smooth muscle cell relaxation to adenosine 1 0.5 0 Rest MBF Adenosine MBF Measure of Integrated Coronary Circulatory Function (Buus et al, Circulation 2001) Epicardial Flow-Mediated Vasomotor Function Baseline Papaverin-induced Hyperemic Flow (Drexler H et al. Prog Cardiovasc Dis 1997) Myocardial Perfusion, Flow Reserve and Prognosis (Herzog B et al, J Am Coll Cardiol 2009) Myocardial Perfusion, Flow Reserve and Prognosis (Herzog B et al, J Am Coll Cardiol 2009) Myocardial Flow Reserve by PET and Outcomes in Ischemia (Ziadi C. et al. J Am Coll Cardiol 2011) Vasomotor Function, Medical Intervention and Outcome (Kitta J et al, J Am Coll Cardiol 2009) Clinical Utility of Quantification of Myocardial Blood Flow with PET 1. Identification of subclinical CAD. 2. Improved characterization of CAD burden. 3. Identification of “balanced” reduction of MBF in all vascular territories. 4. MFR as index of coronary vascular health with prognostic implications 5. Image-guided and individualized cardiovascular therapy may be attained in the near future. (Schindler TH et al. JACC Img 2010) Cardiac SPECT and PET Perfusion Imaging in a 43 yrs Old Obese Women (BMI: 43kg/m2) Non Attenuation Correction (AC) 99mTc-SPECT 99mTc- SPECT with AC 82Rubidium-PET (Flotats A et al. Eur J Nucl Med Mol Imaging 2012) Quality Distribution of SPECT and PET Studies (Flotats A et al. Eur J Nucl Med Mol Imaging 2012) Interpretive Confidence of SPECT and PET Studies (Flotats A et al. Eur J Nucl Med Mol Imaging 2012) Methodological Considerations Spatial Resolution: Contrast Resolution: (First Pass extraction fraction) Energy Levels: PET SPECT 4-7mm 10-12mm N-13 ammonia 80% 82-Rubidium 70% 511 keV 99mTc-labelled tracers 60% 140 keV robust and precise vague and inhomogen Attenuation Correction: (« photon attenuation free ») Hot Spot Artifacts: (liver or bowel uptake) rare frequent High spatial and contrast resolution in concert with photon-attenuation free images of PET versus SPECT leads to: Higher image quality associated with higher sensitivity and specifity for PET. Higher interpretative confidence and interreader agreement. (Valenta et al. Eur J Nucl Med Mol Imaging 2012: editorial) Dipyridamole stress and rest 82Rb PET/CT images in a 56 year old obese (BMI33kg/m2) patient In obese individuals and women: Sensitivity: 95% Specifity: 90% Optimal attenuation correction with CT ! (Di Carli MF Circulation 2007) Gated Rest-Stress 82-Rb Myocardial Perfusion PET Multivessel CAD with stenoses > 70 % Unmasked with gated PET Gated PET at “ Peak Stress“ ! (Dorbala S. J Nucl Med 2007) Attenuation Correction with CT for SPECT 99mTc-SPECT/CT Attenuation Correction (AC) Without AC With AC Stress Rest Stress Rest Stress Rest (University Hospitals of Geneva) SPECT, CMR, and PET for Detecting CAD: Diagnostic Accuracy (Meta-Analysis) ? ? SPECT/CT PET SPECT/CT ??? (attenuation correction by CT and expert reading) (Jaarsma C et al. JACC 2012) SPECT/CT: Resolution Recovery Algorithm allows HalfTime Acquisition or Half-Dose Radiotracer Injection 1. SPECT/CT-Geneva : -Sensitivity: 88% -Specifity: 75% 2. Low Radiation Exposure: 4-6 mSv ! -Environmental exposure 3-4 mSv -Heavy smokers /year 3 mSv -Cath-Lab USA 8-12 mSv Ultra-Fast SPECT Camera Designs Schematic Detector Array Cadmium Zinc Telluride (CZT) Detector 5- to 10-fold increase in count sensitivity at no loss or even a gain in resolution: acquiring a stress myocardial perfusion scan injected with a standard dose in 2 minutes or less ! (Garcia EV J Nucl Cardiol 2012) CZT Detector SPECT CT in the Assessment of Flow-Limiting CAD Lesions Stress Rest MPI polar plots demonstrating inferior ischemia corresponding to angiographic stenosis in the RCA. (Fiechter M et al. Eur J Nucl Med Mol Imaging 2011 ) Will PET Replace Single Photon Emission Computed Tomography? Decision relevant aspects: 1. Availability of PET/CT scanners for cardiac studies. 2. Patient volume. 3. Preference for bicycle stress test? 4. Reembursement for PET? 5. Clinical role of MFR quantification with PET? 6. Will flow quantification with SPECT/CT be feasible in the near future? The future will tell! University Hospitals of Geneva, Division of Cardiology Thank You for your Attention !