1. Advances in Nuclear Cardiology Matthew Schumaecker, MD, FACC, FASNC Medical Director, Nuclear Cardiology Carilion Clinic Cardiology Assistant Professor of Medicine Virginia Tech Carilion School of Medicine

2. Educational Objectives Review advances in nuclear cardiology in: Novel radiopharmaceuticals Advances in camera software and hardware Molecular imaging

3. Very Brief History of Nuclear Cardiology 1958 Scintillation Camera: Hal Anger 1972 Thallium 201 1976 SPECT camera: Keys, Jaszczak 1984 Cardiac PET Rb-82 1996 Cardiolite® (sestamibi) approved

4. Current State Most nuclear cameras in use are the same technology from 1970’s Sestamibi has been on the market for over 17 years Thallium mostly gone MRI has replaced MUGA as gold standard for LVEF assessment PET imaging only in large academic centers

5. PET Advantages of PET over SPECT Higher energy resolution Mandatory attenuation correction Quantification of coronary blood flow Disadvantages of PET over SPECT Camera is MUCH more expensive Radioisotopes are very short-lived

6. SPECT vs PET Tc 99m 140 keV ɣ ray F 18 E=mc 2 511keV photon 511keV photon e-e- β+β+

7. 18 F-Flurpiridaz PET Half life of currently utilized cardiac PET perfusion agents: AgentT 1/2 N-13132 seconds O-15148 seconds Rb-8275 seconds

8. 18 F-Flurpiridaz PET 18 F Fludeoxyglucose has t 1/2 of 110 minutes BUT This is a viability agent, not a perfusion agent

9. 18 F-Flurpiridaz PET Jamshid Maddahi, M.D., FACC, FASNC, and René R. S. Packard, M.D.

10. 123 I-BMIPP 99m Tc can be used to evalulate chest pain at rest but only if patient is having pain at the time.

11. Cardiac Memory Myocytes preferentially metabolize FFA In ischemia millieu, switch to glycolysis

12. Cardiac Memory Substrate switch can last up to 24 hours If injected with 123 I-BMIPP, SPECT images will show defect if patient has been ischemic within 24 hours Dilsizian et al, Circ 2005;112:2169-2174

13. BMIPP Trial J Am Coll Cardiol. 2010 Jul 20;56(4):290-9

14. 123 I-MIBG MIBG is a sympathetic neurotransmitter radionuclide analog Cardiac uptake of MIBG is assessed by heart/mediastinal ratio. Correlates to heart failure severity, pre- disposition to cardiac arrhythmias, and poor prognosis

15. 123 I-MIBG As CHF progresses, there is a reduction in the number of presynaptic neurons and the function of the norepinephrine terminal resulting in decreased uptake of mIBG. Therefore, lower H/M ratios confer a more negative prognosis

16. 123 I-MIBG Yazaki et al. Cardiomyopathies Chap 11

17. 123 I-MIBG ADMIRE-HF Trial Jacobson et al J Am Coll Cardiol. 2010;55(20):2212-2221 ”Two-year event rate was 15% for H/M ≥1.60 and 37% for H/M <1.60”

18. 123 I-MIBG ADMIRE-HF Trial Jacobson et al J Am Coll Cardiol. 2010;55(20):2212-2221

19. 123 I-MIBG  > $1000 per dose  No reimbursement in US

20. SPECT/CT Gaemperli et al, Journal Nuc Med May 2007; 5:696

21. FBP vs OSEM Filtered backprojection suppresses high- frequency image data thereby decreasing noise. This causes image blurring and subjects the image to ramp filter artifact Iterative reconstruction provides an estimated reconstruction volume and compares it to image. This occurs until images converge

22. Depth Dependent Resolution Loss

23. Depth Dependent Resolution Recovery Wide beam reconstruction suppresses noise and enhances signal-to-noise ratio by modeling the statistical characteristics the collimator detector response. Statistical filters using Gaussian and Poisson Fourier transforms allow the deeper voxels to appear as they were closer, thereby eliminating DDRL

24. Depth Dependent Resolution Recovery

26. Hardware: Optimized Detector Geometry

28. Solid State Detectors

29. Attenutation Correction Two ways to do AC:

30. Attenutation Correction

31. Prone Imaging Shifts the heart off the diaphragm and places breasts in different position. Not as valuable as attenuation correction BUT – added counts in prone imaging are always real

32. Molecular Imaging Two major targets: Vulnerable Plaque Cardiac remodeling

33. Potential Targets IL-6 VCAM – 1 LT B4 Matrix metalloproteases Cathepsins Anti-myosin antibodies Beta receptors ACE receptors

34. Apoptosis Nahrendorf M et al. Circ Cardiovasc Imaging 2009;2:56-70 Copyright © American Heart Association

35. Atherosclerosis imaging Nahrendorf M et al. Circ Cardiovasc Imaging 2009;2:56-70 Copyright © American Heart Association