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PET/CT in Cardiac Imaging

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PET/CT in Cardiac Imaging PET/CT in cardiac imaging Raffaele Giubbini Chair of Nuclear Medicine and Nuclear Medicine Unit University and Spedali Civili – Brescia, Italy [email protected] Hybrid Imaging: Providing• Any simple combination and accurate of structuralintegrated and measure functional of the effect of informationanatomic stenosis on coronary resistance and tissue perfusion. OptimizingCardiac selection Hybrid of patients Imaging: who may ultimately benefit from revascularization • The combination of two data sets in equally importance for the integration of one final image. • Referred to functional (PET/SPECT) and anatomical evaluation through Cardiac Computed Tomography Angiography (CCTA). Myocardial Endothelial Function Perfusion Correlation CCTA - PET Myocardial Viability Cardiac Inflammation of the Function atherosclerotic plaque Myocardial Molecular Imaging Blood Flow WHERE do we stand? • TheThe currentlimitations evidence forof anatomicmorphologic evaluation measures using for CCTAdelineating remarks its: the physiologic implications of– Highstenosis negative predictiveare well describedvalue i. e. The– Moderate vasomotor good capacitytone and to coronary collateral flow, bothpredict of which a >50% are coronary known to arteryaffect lesion myocardial • Makingperfusion it ,a verycannot reliable be estimated by measures of formstenosis to excludeseverity . significant CAD. WHERE do we stand? • It has been previously described that the majority of patients are referred to diagnostic invasive coronary angiography and consequently to PCI in the absence of any sort of functional evaluation. • Although professional guidelines call for objective documentation of ischemia prior to elective ICA and revascularization. WHERE do we stand? • PETIt is imaging very important with: to 1.denote82 Rubidium the diagnostic 2.accuracy15O Water of functional 3.techniques,13N ammonia that of the 4.case18F of-Flurpiridaz PET MPI with Opportunityan average tosensitivity evaluate: of 1.90%LV– 92myocardial% perfusion.and 2.specificityAbsolute quantificationof 85%–89 % of myocardial blood flow in▪ detectingml/gr/min flow- 3.limitingLVEF atCAD rest and. stress WHERE do we stand? K analogous, not linear PET imaging with: withlinear flow, with poor flow, quality no 1. 82 Rubidium Imaging possible, 20 min images,imaging, expensive, short half life - 2. 15O Water 122s,half time, injected on site directly 3. 13N ammonia fromcyclotron cyclotron, needed, no post QA 4. 18F-Flurpiridaz controls,injection researchQA, 2 only Opportunity to evaluate: bombardment for 2 1. LV myocardial perfusion. patients, no exercise 2. Absolute quantification of myocardial blood flow stress test ▪ ml/gr/min 3. LVEF at rest and stress Ideal PET MPI Imaging Agent • High cardiac uptake with minimal redistribution • Near linear myocardial uptake vs. flow up to 5 mL/min/g or more (high first pass extraction fraction) • High target to non-target ratio (vs. lung, liver, bowel) • Usable for both exercise and pharmacologic stress • Usable for quantitation of absolute myocardial flow • High quality imaging • adequate for gating • Available as unit dose (18F-labeled compound- 2h HT) Ver. 18Aug 09 Chemical Structure of BMS747158 Mitochondrial Complex 1 (MC-1) Inhibitor O C l N N O O 1 8 F 2-tert-Butyl-4-chloro-5-[4-(2- (18F)fluoro-ethoxymethyl)-benzyloxy]-2H-pyridazin-3-one Yu, et al., J Nucl Cardiol. 2007;14(6):789-98 11 Ver. 18Aug 09 First Pass Uptake in Isolated Rabbit Hearts * Indicates p<0.05 3 BMS747158 (n=4) 201Tl (n=3) 99mTc-sestamibi (n=3) 2 * * Uptake 1 0 0 1 2 3 4 5 Coronary perfusion flow (ml/min/g) Yu, et al., J Nucl Cardiol. 2007;14(6):789-98 Proprietary and Confidential. For internal use only. Do not disseminate. 12 Ver. 18Aug 09 Pre-Clinical Cardiac PET Imaging with BMS747158 Normal Rat your and Coronary ligation in Rat Normal primate Yu, M et al. J Nucl Cardiol 2007, 14(6):789-98 Ver. 18Aug 09 First Human Study of BMS747158 Time activity curve (subject JAL) SUV Myocardium Liver Blood Lung Minutes Maddahi J, et al. JNM 2008 14 Ver. 18Aug 09 BMS747158 Preliminary Stress Dosimetry Comparison 0.18 0.16 Mean of Adenosine Stress, Full (n=5) Mean of Exercise Stress, Full (n=5) 0.14 18F-FDG from ICRP 80 0.12 Radiation Dose Comparison 0.10 0.08 0.06 Radiation Dose(mGy/MBq) Radiation 0.04 0.02 Stress and FDG 0.00 ED Brain Liver Skin Lungs Spleen Testes Uterus Breasts ULI WallLLI Wall Kidneys MuscleOvaries ThymusThyroid Adrenals Pancreas Heart Wall Total Body Red Marrow StomachSmall Wall Intestine Salivary Glands Gallbladder Wall Osteogenic Cells Urinary Bladder Wall Maddahi J, et al. JACC 2009; abstract in press – Ver. 18Aug 09 Rest and Stress Myocardial SUVs SUV 2 10 19 38 56 149 MINUTES Maddahi J, et al. JACC 2009; Adenosine 21 min. 35 min. 165 min. 202 min. BMS747158 Exercise Maddahi J, et al. JNM press 2008; J, abstract in JNM et al. Maddahi 21 min. 35 min. 165 min. 202 min. Ver. 18Aug Ver. 18Aug 09 Study 201, Patient 006-003 Stress Rest SA Stress BMS747158 Rest J. Maddahi, UCLA Maddahi, J. Stress HLA Rest BMS747158 Stress VLA Rest BMS747158 18 Ver.18Aug 09 WHEN? There is not current agreement in the appropriate indications for Hybrid Cardiac Imaging methods Although there is clear evidence about the incremental value of those techniques in certain groups at risk and also in those with previous history of MI and revascularization. Myocardial Endothelial Function Perfusion Correlation CCTA - PET Myocardial Viability Cardiac Inflammation of the Function atherosclerotic plaque Myocardial Molecular Imaging Blood Flow MPI+CCTA • Compared to CCTA alone the combination of MPI and CCTA results in a significant increase in: – Specificity (from 80 to 92%) and PPV (from 69 to 85%) • Without any change in: – Sensitivity (95%) and NPV (97%). • This effect was preserved across all vascular territories and on a patient-based analysis. Sato A et al. Incremental value of combining 64-slice computed tomography angiography with stress nuclear myocardial perfusion imaging to improve noninvasive detection of coronary artery disease. J Nucl Cardiol 2010;17:19–26 MPI+CCTA • After adjustment for clinical risk factors, obstructive plaque visualized by CCTA and abnormal MPI were independent predictors of late events. • An annual event rate of 1% was found in those with concordantly normal CCTA and MPI, and conversely those with concordantly abnormal CCTA and MPI had an event rate of 9%. With significant incremental improved prediction of risk by the combination of the two modalities. Van Werkhoven JM et al, Prognostic value of multislice computed tomography and gated single-photon emission computed tomography in patients with suspected coronary artery disease. J Am Coll Cardiol 2009;53:623–32 N=9 (normals) Stress Flow Rest Flow CFR (LAD/LCX/RCA) (LAD/LCX/RCA) (LAD/LCX/RCA) A(QPET) 2.25/2.25/2.27 0.57/0.60/0.59 4.02/3.88/3.99 B (SyngoMBF) 3.21/3.22/3.34 0.86/0.83/0.88 3.89/3.98/3.97 C (PMOD) 3.20/3.41/3.33 0.80/0.75/0.80 4.1/4.83/4.38 N =18 (all) Stress Flow Rest Flow CFR r/Slope/Intercept r/Slope/Intercept r/Slope/Intercept A vs. B 0.92/0.71/0 0.84/0.66/0 0.86/0.96/0 A vs. C 0.85/0.60/0.3 0.88/0.59/0.1 0.89/0.77/0.6 C vs. B 0.9/0.98/0.0 0.76/0.89/0.1 0.78/1.00/0.1 P. J. Slomka, L. Le Meunier, E. Alexanderson, R. Jácome, M. Jiménez, E. Romero, A. Meave, M. Dahlbom, D. S. Berman, G. Germano, H. Schelbert Presented on the ASNC2010 in Philadelphia, EU. Eur J Nucl Med Mol Imaging 2010; 38 (1); 201-212. CTA: Positive and negative predictive value for ischemia Min JK et l, J. Am. Coll. Cardiol. Img. 2010;3;305-315 Risk of cardiac death Relation to inducible ischemia on SPECT 6 *p<0.001 5 * 4 Medical Rx 3 * 2 Revasc 1 log Hazard Hazard Ratio log 0 0 12.5% 25% 32.5% 50% % Total Myocardium Ischemic Hachamovicth et al. Circulation, Jun 2003; 107: 2900 - 2907 Evaluation of Ischemic Burden Remains the Main Stay for Management of a Patient With Stable CAD Evaluation of CAD symptoms Low-Int Lk High Int Lk High Lk (.15- 0.5) (0.5-0.85) (>0.85) CTA CTA, MPI Imaging High NPV High Diagnostic Value Guide Management Courtesy MF Di Carli PET/CTA: A Sequential Approach CT Scan Normal Mild/moderately Severely abnormal abnormal Suspect microvascular dysfunction Ischemia evaluation Invasive Angiogram ± Medical Therapy revascularization Atherosclerosis Chronic Myocardial Asymptomatic Atherosclerosis Damage ACS Endothelial HF Damage Atherosclerosis Atherotrombosis Endothelial Dysfunction Methodology REST CPT STRESS ENDEVI >1.5 CFR >2.5 Endothelial-dependent vasodilation index (MBF after CPT) Myocardial flow reserve Endothelial Dysfunction Diabetes Dyslipidemia Hypertension Mellitus 2 Metabolic Tobacco Others Syndrome MBF (mean±SE) after adjustment for mean group differences in MBF at rest, age, gender, and BMI by ANCOVA. A, In response to adenosine or dipyridamole and compared with IS control group, MBF was decreased significantly in DM (−17%) and HTN (−35%) g... (1) IS group without coronary risk factors and normal insulin sensitivity; (2) IR group without coronary risk factors and normal carbohydrate tolerance; (3) IGT group, impaired glucose tolerance (4) DM group without hypertension (5) HTN; hypertensive group of diabetic individuals Prior J O et al. Circulation 2005;111:2291-2298 Effect of ezetimibe–simvastatine over endothelial dysfunction in dyslipidemic patients: Assessment by 13N-ammonia positron emission tomography Pre-TX Post-TX MFR Post-TX MFR Pre-TX 2.79 3.14 ENDEVI ENDEVI 1.28 1.65 Endothelial-dependent vasodilation index (MBF after CPT) Myocardial flow reserve Alexanderson E et al. J Nucl Cardiol. 2010 Dec;17(6):1015-22 Endothelial Dysfunction in Hypertension 3.5 3.27 3 2.5 2.06 2 1.55 SanosHealthy n= 17 1.5 1.32 HASHAS 1 n= 19 0.5 0 CFRRFC ENDEVIIVED E Alexánderson, Hypertension Endothelial Function in SLE P = 0.2 P = 0.03 N = 32 Alexanderson E.
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