PET MYOCARDIAL PERFUSION AND QUANTIFICATION OF FLOW Robert Bober, MD, FACC Director of Nuclear Cardiology and Molecular Imaging John Ochsner Heart and Vascular Institute The Ochsner Clinical School University of Queensland Ochsner Medical Center, New Orleans, LA Disclosures • Bracco – research support, consultant • Off-label discussions - None Learning Objectives 1. Discuss the basics of positron emission tomography (PET) imaging and how PET differs from standard single-photon emission computed tomography (SPECT) 2. Discuss evaluation of coronary flow reserve, myocardial perfusion, and absolute myocardial flow by PET imaging and their value in the assessment and management of coronary artery disease (CAD) 3. Introduce the concept of coronary flow capacity and its potential impact on patient care 4. Use cardiac PET imaging to help identify patients for whom revascularization procedures may reduce coronary events Program Agenda • PET Instrumentation and how it differs from SPECT • Using PET and Flow to Guide Revascularization • Measurements of Myocardial Flow Kinetic Models • Cases • Self Assessment Module PET Instrumentation Conventional SPECT • Limited count sensitivity • Limited energy resolution • Limited spatial and contrast resolution • Limited accuracy of measuring uptake without AC Garcia EV, et al. Cardiol Clin. 2009;27(2):227-236. PET Instrumentation Line of Response P N N B+ N P P P P N 0-5 mm Annihilation γ 511 KeV 511 KeV γ B+ Coincidence Event Detected in Ring PET Scanner Cardiac PET. In: Heller GV, Hendel RC. Handbook of Turkington TG. J Nucl Med Technol. 2001;29(1):4-11. Nuclear Cardiology. 1st ed. London, UK: Springer; 2013. 2D vs 3D Acquisition 2D 3D Multi-ring PET Acquisition Modes Turkington TG. J Nucl Med Technol. 2001;29(1):4-11. Camera Specifications PET SPECT • 511 KeV photons • Photon energies <140KeV • LIST mode (most) • Binned mode (most) • >3 million counts/sec • 500-3000 counts/sec • ~35 M counts/study • 7-10 M counts/study • Sensitivity (detection of emitted photons) 2%-15% • Sensitivity 2-3x’s less than PETàlonger acquisition • Spatial resolution < 2-3 mm • Spatial resolution 6.0-10.1 mm • Wackers, JACC. 2010;55(18) • GB Saha, Basics of Pet Imaging • Gould, State of the Art PET 2013, supplement • Salerno, Circ Imaging. 2009;2:412-424 Attenuation Correction • Photon attenuation results from emitted radiation interacting with tissue. • For PET, the path length represents the LOR, along which the dually emitted photons travel. – Therefore, attenuation is independent of the point of origin along the LOR. • For SPECT, due to its single-photon emission nature, attenuation changes depending on the point of emission. LOR, line of response. Courtesy K. Lance Gould, MD. Courtesy K. Lance Gould, MD. How PET Differs From SPECT Higher Accuracy • Current literature supports a high diagnostic accuracy for cardiac PET perfusion imaging, due to: – Robust attenuation correction – High count densities (improved image quality and interpretation) – Tracers that follow MBF in a more linear fashion than current SPECT tracers MBF, myocardial blood flow SROC Curves for Diagnostic Accuracy of Rb-82 PET and Tc-99m SPECT With ECG-Gating and Attenuation Correction Sensi*vity 85% Sensi*vity 90% Specificity 85% Specificity 88% N = 1755 N = 1344 AUC, area under the curve; Q, Cochran Q statistic; SROC, summary receiver-operating characteristic. Mc Ardle BA, et al. J Am Coll Cardiol. 2012;60(18):1828-1837. Summary ROC Curves for SPECT and PET MPI N = 11,862 patients MPI, myocardial perfusion imaging; ROC, receiver operating characteristic Parker MW, et al. Circ Cardiovasc Imaging. 2012;5(6):700-707. Overall Diagnostic Accuracy for PET and SPECT: 70% Stenosis Threshold 100 93 87 89 90 82 79 80 73 70 P = 0.02 P = 0.03 60 50 SPECT PET 40 30 20 10 0 Sensi1vity Specificity Accuracy Bateman TM, et al. J Nucl Cardiol. 2006;13(1):24-33. Diagnostic Accuracy for Localizing Disease to Individual Coronary Arteries: 70% Threshold 100 P = 0.007 90 P = 0.0001 80 P = 0.003 70 60 50 40 30 20 10 0 Sensi1vity Specificity Accuracy SPECT PET Bateman TM, et al. J Nucl Cardiol.2006;13:24-33. Body Habitus and Gender Results from studies by Bateman and colleagues demonstrate superior accuracy of PET, independent of both body habitus and gender Bateman TM, et al. J Nucl Cardiol. 2006;13(1):24-33. Diagnostic Accuracy 69% *P=0.05 Men 84% 67% Women 88% *P=0.01 70% *P=0.05 BMI<30 87% 67% *P=0.02 BMI>30 85% 48% *P=0.03 MVD Sensi1vity 71% 0 25 50 75 100 SPECT PET MVD, multivessel disease. Based on data from Bateman TM, et al. J Nucl Cardiol. 2006;13(1):24-33. Risk Stratification • SPECT has a wealth of data on risk stratification. • More data are emerging for cardiac PET risk stratification. • For PET, risk stratification is based on: – Size and severity of perfusion abnormalities – Decreased ejection fraction at stress – Overall ventricular function – Coronary flow reserve (CFR) Unadjusted Hazard of Events by % Myocardium Abnormal on Vasodilator Stress Rb-82 PET All-cause Death Cardiac Death Dorbala S, et al. J Am Coll Cardiol. 2013;61(2):176-184. Downstream Testing • Because of improved image quality, reader confidence is increased. • The downstream effect is referral to catheterization for consideration for potential revascularization, NOT to confirm diagnosis. • Studies have demonstrated fewer catheterizations following PET compared with SPECT studies. CAD Intervention Utilization Rates vs CAD Management Costs Utilization Rates of Diagnostic Coronary Arteriography, PTCI, and CABG in Pts Studied with SPECT vs PET MPI CAD Management Costs in Pts Studied with SPECT vs PET MPI 50% ↓ 67% ↓ 50% ↓ CABG, coronary artery bypass graft; CAD, coronary artery disease; PTCI, percutaneous transluminal coronary intervention Merhige ME, et al. J Nucl Med. 2007;48(7):1069-1076. Radiation Exposure • Radiation exposure reduction has become an import consideration when selecting a test. • ASNC recommended target dose <9 mSv for a routine study (recommended to be implemented by 2014). • PET flow tracers have been examined, and it has been demonstrated that patient exposure is below that recommended by ASNC. ASNC, American Society of Nuclear Cardiology Cerqueira MD, et al. J Nucl Cardiol. 2010; 17(4):709-718. Typical Effective Doses From Cardiac Imaging Procedures Einstein AJ. J Am Coll Cardiol. 2012;59(6):553-565. Protocol – Patient Convenience Rest/stress Rb-82 protocols can be accomplished in 30-45 minutes. Rb-82 Rb-82 20-60 mCi 20-60 mCi Pharmacologic stress* Gated Gated CT transmission rest stress CT transmission 70-90 sec 70-90 sec Approx 1 min Approx 7 min Approx 6 min Approx 7 min Approx 1 min *Dipyridamole, adenosine, or dobutamine USING PET AND FLOW TO GUIDE REVASCULARIZATION Current Revascularization Practice • LHC (angiogram) – “gold standard” • “See and fix” approach based on % stenosis • Current guidelines: 50% LM and 70% for revascularization • FFR/stress “intermediate lesions”1 • FFR used in 6% of patients2 LHC, left heart catheterization; LM, left main; FFR, fractional flow reserve 1. Levine GN, et al. J Am Coll Cardiol. 2011;58(24):e44-e122. 2. Dattilo PB, et al. J Am Coll Cardiol. 2012;60(22):2337-2339. Revascularization guided by % stenosis will lead to better outcomes DATA??? COURAGE and STICH • Revascularization based on % stenosis • Stress testing NOT mandatory • Decisions to guide revascularization based on judgment of angiographer • FFR not utilized Boden WE, et al. N Engl J Med. 2007;356(15):1503-1516. Velazquez EJ, et al. N Engl J Med. 2011;364(17):1607-1616. COURAGE, Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; STICH, Surgical Treatment for Ischemic Heart Failure. Rates of SurvivalRates of Survival and and Freedom Freedom from Major From Cardiovascular Events Major Cardiovascular Events The BARI 2D Study Group. N Engl J Med. 2009;360(24):2503-2515. The BARI 2D Study Group. N Engl J Med 2009;360:2503-2515 Revascularization Guided by % Stenosis Will Lead to Better Outcomes DATA Revascularizaon guided by % stenosis will lead to beTer outcomes “Repe11on of Error Does Not Cons1tute EXperience” – Edmund Tramont, MD 1999ish FAME I and II • FFR-guided revascularization • I - FFR vs angiography • II - FFR vs optimal medical therapy Pijls N, et al. J Am Coll Cardiol. 2010;56(3):177-184. De Bruyne B, et al. N Engl J Med. 2012;367(11):991-1001. FAME, Fractional Flow Reserve versus Angiography for Multivessel Evaluation; MACE, major adverse cardiac events; PCI, percutaneous coronary intervention Herzog BA, et al. J Am Coll Cardiol. 2009;54(2):150-156. Ziadi MC, et al. J Am Coll Cardiol. 2011;58(7):740-748. MFR, myocardial flow reserve; SSS, Murthy VL, et al. Circulation. 2011;124(20):2215-2224. summed stress score. Introduction to Coronary Blood Flow • Ischemia – myocardial O2 supply vs demand • Adequate supply is maintained with ability to increase CBF • 2 major resistances to flow – Epicardial arteries (>350 µm) – Arterioles and capillaries (microvasculature) § Resting microvascular (R2) >>> epicardial (R1) § Normally regulation occurs at level of microvasculature • CBF increases automatically to increase O2 demands – Exercise – Pharmacologic stress – Neurohormonal CBF, coronary blood flow Epicardial Vessels and the Microvasculature Pathologic Conditions • R1 > R2 – Coronary stenosis and diffuse disease à Flow impaired at level of epicardial artery • R2 > R1 – Autoregulation impaired à Flow impaired within microvasculature Coronary Flow Reserve 3.2 = 2.9 1.1 • Baseline flow remains stable up to ~83% stenosis. • Hyperemic flow starts diminishing ~40% stenosis. Gould KL, et al. Am J Cardiol. 1974;33(1):87-94. A Brief Word on FFR • FFR = fractional flow reserve • Pressure-derived flow surrogate • “Stress test” of an artery in the cath lab Distal coronary pressure FFR = ---------------------------------- Proximal coronary pressure During Maximal Hyperemia Relationships of CFR, FFR, and Absolute Flow Danad I, et al. J Am Coll Cardiol. Johnson NP, et al.