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Challenges and Opportunities for SPECT & PET in 2013: Implementing Latest Acquisition and Processing Protocols Timothy M. Bateman M.D. Co-Director, Cardiovascular Radiologic Imaging Mid America Heart Institute Professor of Medicine University of Missouri-Kansas City Kansas City, Missouri Conflict of Interest Disclosure Dr. Bateman declares that the following relationships constitute a potential conflict of interest with respect to this presentation: Research Grants: Astellas, GE, Lantheus, Philips, SpectrumDynamics Advisory Boards: Astellas, GE, Lantheus, SpectrumDynamics Royalties: ExSPECT II TM, ImagenPro/MD/Q TM Stock Ownership: Cardiovascular Imaging Technologies

Challenges and Opportunities for SPECT and PET in 2013 The challenges are the opportunities - Necessity to reduce dosimetry - Necessity to reduce costs - Necessity to improve image quality/information - Necessity to prove judicious utilization - Necessity to show patient centricity - Necessity to prove value (referral to cors/pci/cabg) Radiation Dosimetry Growing public concern in U.S. Ave. annual exposure 6.2 msv* (3.2 msv in 1980) 25% of annual exposure is from medical imaging ~22% of medical imaging exposure is from nuclear cardiology!** Teaching Point: Need to consider dosimetry in imaging test selection * NCRP 160 ** Fazel et al, N Engl J Med 2009; 361: 849-857

Recommendations for Reducing Radiation Exposure in Myocardial Perfusion Imaging Limit SPECT/PET to appropriate indications Eliminate Tl-201 whenever possible (~30 mci) Adopt new hardware/software to permit micro or at least low doses of Tc-99m tracers Perform stress-first/stress-only imaging for ~ 50% of referrals Use PET in favor of SPECT when rest/stress studies needed Adapted from Cerqueira et al, ASNC Information Statement, J Nucl Cardiol 17: 709-718, 2010 Dosimetry Estimates for Radionuclide Myocardial Perfusion Imaging Tracer Stress Dose Rest Dose msv Tc-99m MIBI 30 mci 10 mci 12 msv Tc-99m MIBI SO 30 mci 9 msv Tc-99m MIBI SD 4 mci 12 mci ~ 5 msv Tc-99m MIBI SO 9 mci 2.7 msv Tc-99m MIBI SO-SD 4 mci ~ 1 msv Rb-82 40 mci 40 mci 3.6 msv NH 3 -Ammonia 20 mci 20 mci 3 msv 3.5 mci Tc-99m ~ 1 msv 25 mci Rb-82 ~ 1 msv 15 mci NH 3 -Ammonia ~ 1 msv

Prevalence of LV Ischemia by Exercise Capacity (974 SPECT pts achieving > 85% MPHR) 31% of pts: >85% MPHR, > 10 METS, non-ischemic ECG 19/473 (4%) = any ischemia 2/473 (0.4%) = sig ischemia Bourque et al. J Am Coll Cardiol 2009;54:538-545 Relationship of Ischemic ST-Segment Depression on the Exercise ECG and Workload Achieved to the Percentage of LV Ischemia Bourque et al. J Am Coll Cardiol 2009;54:538-545

Reducing Radiation While Maintaining Quality Using Novel Technologies Stress-Only Imaging for Lower-Likelihood Patients Value of attenuation correction Value of solid-state detectors Low-Dose Stress-First Imaging Challenges and Strategies Cardiac Mortality Following Normal Stress-Only vs Normal Rest/Stress SPECT Duvall et al, J Nucl Cardiol 2010: 17: 370-377

Survival According to SPECT Protocol in Patients With Normal Attenuation-Corrected Scans (by either line-source or CT): Entire Pt Cohort Chang et al. J Am Coll Cardiol 2010;55:221-230 Survival According to SPECT Protocol in Patients With Normal Attenuation-Corrected Scans (by either line-source or CT): Subgroup Analyses Chang et al. J Am Coll Cardiol 2010;55:221-230

Lower Likelihood Patients Who Are Good Candidates For Stress-Only Imaging Targetting Pts Who Most Likely Will Not need Rest Imaging Selected Asymptomatic Patients High Framingham risk High CACS New onset atrial fibrillation Elevated troponin w/o other evidence for ACS More than 2 years after PCI Selected Symptomatic Patients Anginal equivalents Normal/near normal ECG s Arrhythmias, syncope/near-syncope Intermediate risk Duke Treadmill Score Stress-Only Imaging For Appropriate Patients Conclusions From the Published Literature 1. Most of the scans are normal 2. It seems that simple algorithms are useful for identifying a fairly low-risk group of patients for stress-only imaging 3. Most of the data is derived from attenuation-corrected SPECT 4. If normal, risk of MACE is extremely low Could We Lower the Risk of Testing for this Select Group of Patients?

Reducing Radiation While Maintaining Quality Using Novel Technologies Stress-Only Imaging for Lower-Likelihood Patients Value of attenuation correction Value of solid-state detectors Low-Dose Stress-First Imaging Challenges and Strategies Why consider a solid-state camera for SO imaging? High count sensitivity High spatial resolution High contrast resolution Permits use of much lower doses Much lower radiation exposure 4 mci Tc-99m ~ 10 min acquisition 10 6 myocardial cts Dosimetry ~ 1 msv Reduced Tc-99m cost

Supine Sitting Supine Sitting

Results Total n = 500 Anger n = 250 D-SPECT n = 250 p-value Need for a Rest Image to Improve Diagnostic Certainty 19 (3.8%) 2 (0.8%) 17 (6.8%) 0.0005 Need for Additional Downstream Testing < 30 Days 2 (0.4%) 0% 2 (0.8%) 0.157 Unnecessary Cor Angiography (UCA): No Stenosis > 50% 3 (0.6%) 1 (0.4%) 2 (0.8%) 0.563 Unexpected Adverse Cardiac Event < 90 days 3 (0.6%) 1 (0.4%) 2 (0.8%) 0.563 Bateman et al, J Am Coll Cardiol 2012;59;E1316 Conclusions Lower-likelihood patients who are candidates for stress-only SPECT MPI may ideally be imaged using new CZT systems vs current standard Anger cameras because: 1. The effective dosimetry is ~ 10% of the standard approach 2. These patients usually have normal scans 3. The 2 approaches provide comparably accurate information 4. Although ~7% (vs ~1%) require rest images, the inconvenience is minimal as this can be performed on same day Bateman et al, J Am Coll Cardiol 2012;59;E1316

Current Clinical Paradigm for Solid-State Cameras Stress-first imaging at 4 mci for all pts except: - BMI > 40 - Prior MI - Known COM If normal, study is finished If rest image needed & > 4 hrs: 3X stress dose If rest image needed & < 4 hrs, 4X stress dose ~60% of pts do not have a rest study Variation on Same Theme Small FOV Anger cameras with AC 9 mci at stress If normal, finished If abnl, 4X stress dose if < 4 hrs, 3X if > 4 hrs

Implications 1. MUCH lower radiation exposure 2. Rapid through-put 3. Shorter days 4. Excellent image quality 5. Substantial overhead reduction - Staff reductions - Lower radionuclide costs 6. Volume growth - Better poised for competition with alternatives - Marketing Reducing Radiation While Maintaining Quality Using Novel Technologies Stress-Only Imaging for Lower-Likelihood Patients Value of attenuation correction Value of solid-state detectors Low-Dose Stress-First Imaging Challenges and Strategies

Some Challenges: 1. Interpreter availability 2. Patient handling post-stress imaging (stay around; return) 3. Effective injected dose of Tc-99m (plastic syringes) 4. Low dose stress/high dose rest in large patients 5. Patient selection (who should be done with rest first) Opportunity to Markedly Improve SPECT Image Quality Solid-state detectors New processing algorithms

SPECT AC Images Acquired Into 128 X 128 Matrix Lexiscan stress Same-day Tc/Tc study 10 mci rest; 28 mci stress 40 secs/stop rest 30 secs/stop stress 261 lb man BMI 35 Ischemia in Distribution of Obtuse Marginal Branch 64 X 64 128 X 128

Acquiring Rb-82 PET in 3D 2D-Septa In 3D-No Septa Advantages of 3D Higher sensitivity (4-6 X higher than 2D) Lower radiotracer dose Lower radiation exposure Potential cost savings Challenges with 3D Higher scatter (30%-40% vs 10-15% for 2D) Effective sensitivity is lower (randoms, scatter, camera dead time) More processing time & disc space Prompt-gamma problem Importance of prompt-gamma compensation ~ 13% of Rb-82 nuclear decays are associated with a 776 kev emission in addition to the positron Because of their wider acceptance angle, images acquired on 3D systems (eg LSO) can be affected Esteves et al, J Nucl Cardiol; 17: 247 53, 2010

Stress-Only PET Imaging? Not so much benefit (dosimetry; efficiency) Longer wait-time vs SPECT No validation studies Lose stress/rest MBF information Routine Flow Quantitation Overcomes issues with spatial-relativity Knowledge of stress adequacy Complete depiction of myocardial blood flow A physiologic measure resembling invasive FFR Numerous commercially-available packages