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Spect ct -dan berman

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Spect ct -dan berman

  1. 1. SPECT/CT for Atherosclerosis Imaging: The Future is Clear Daniel S. Berman, MD Director, Cardiac Imaging Cedars-Sinai Medical Center Professor of Medicine David Geffen School of Medicine at UCLA
  2. 2. DISCLOSURE Daniel S. Berman, M.D. declares the following relationships: Grant Support: BMS Medical Imaging, Astellas, GE Amersham, Mallinckrodt-Tyco Speakers Bureau: Astellas Consultant: Mallinckrodt-Tyco Spectrum Dynamics Royalties: Cedars-Sinai Medical Center Stockholder: Spectrum Dynamics
  3. 3. MDCT Technical Parameters 2005 Four major manufacturers with 64 slice CT • ~.4-.5 mm3 isotropic voxels • Temporal resolution: 165-210 ms for 180° (330-420 ms rotation time) • Cardiac study in 5-10 beats
  4. 4. 76 M #3311-1526 Sx: ASYMPTOMATIC RISK FACTORS: ↑CHOLESTEROL RESTING ECG: NORMAL RESULTS OF EXERCISE: DURATION: 9:39 HR: 131 (91% MPHR) BP: 134/74 → 150/72 CLINICAL RESPONSE: NONISCHEMIC ECG RESPONSE: NONISCHEMIC
  5. 5. 73 M #3311-1526 EBT RESULTS Location # Calcified Lesions Calcified Plaque Volume (mm 3 ) Calcium Score LAD 3 97 126 * 32th percentile
  6. 6. 76 M #3311-1526 CTA
  7. 7. 76 M 11/3/05 #3311-1526 Stress MIBI Rest Tl Stress MIBI Rest Tl Stress MIBI Rest Tl Stress MIBI Rest Tl
  8. 8. 76 M #3311-1526
  9. 9. A B C D Calcification Soft Plaque D2 Lesion 76 M #3311-1526
  10. 10. Limitations of Anatomic Imaging Little information regarding disease activity • Two patients: with mild coronary calcium, score ~100 discovered on screening 1 yr ago and placed on statin, ASA, and ACE • Patient A: recently symptomatic • Patient B: still asymptomatic • Both undergo CT coronary angiography, and are found to have 75% mid LAD stenosis by CT angio AND extensive non-calcified plaque by IVUS • Should the treatment be the same?
  11. 11. It will be!
  12. 12. Why not catheterize all suspected CAD patients? Occulo-stenotic reflex*: unnecessary PCI• Immediate Risk – Death (rare) – Clinical MI (uncommon) – Subclinical MI (more frequent) – Branch occlusion (frequent) • Late risk – Possible higher mortality risk than medical therapy in patients without ischemia • Costs • Objective measurements of perfusion and function • Accurate for assessing risk of cardiac death (CD) • Relationship of degree of abnormality to risk • Identifies likely to benefit from revascularization • Proven as cost effective “gatekeeper” to the cath lab Limitations • Cannot detect early atherosclerosis • May underestimate extent of CAD *Topol
  13. 13. Cardiac CT Limitations • Densely calcified plaques: nondiagnostic • Dependence on low HR and regular rhythm • Radiation, iodinated contrast • Overestimation of stenosis • No information regarding plaque “activity”
  14. 14. • No Hx CAD • Known CAD • Post-PTCA • Post-CABG • Men and Women • Sx and Asx • DM • Elderly SPECT: Risk Increases as a Function of Stress Perfusion Abnormality Extent/Severity of Perfusion Defec Risk* *Adjusted or unadjusted Guidelines for Clinical Use of Cardiac Radionuclide Imaging 2003 Data from over 50,000 patients
  15. 15. logHazardRatio 0123456 % Myocardium Ischemic 0 12.5% 25% 32.5% 50% Medical Rx Revasc * * *p<0.001 Adjusted† Risk of Cardiac Death vs MPS ischemia Revascularization vs Medical Rx Hachamovitch, et al Circulation 2003 † Adjusted for predictors of revascularization as well as clinical, hx, stress SPECT data
  16. 16. VISUAL SSS STANDARD TPD stenosis ≥ 50% 1.00.75.50.250.00 1.00 .75 .50 .25 0.00 1 - Specificity Sensitivity Changes in Analytic Software Automatic Total Perfusion Deficit ** * P < 0.05 Slomka, et al J Nucl Cardiol 2005;12:66-77
  17. 17. When was the last fundamental change in the detector technology? Nuclear Cardiology: Single Photon Imaging
  18. 18. When was the last fundamental change in the detector technology? 1958: Hal Anger patented the current NaI (Tl) detector/photomultiplier array configuration (#3011057) Nuclear Cardiology: Single Photon Imaging
  19. 19. Resolution & Contrast - a Comparison Total counts: 2,500K Total counts: 2,500K Spectrum-Dynamics Coronal Sagittal Transverse Net acquisition time: 9 minutes Frame angle: 3°, positions:60, 9sec per position Net acquisition time: 1 minute positions:40, 1.5sec per position Millennium VG a Spectrum Dynamics Measured Contrast Target A: 1.6 Target B: 2.2 Millenium Measured Contrast Target A: unseen 3:1 2:1
  20. 20. Cardiac Phantom Conventional • No AC • Acquisition time 12.5 m Spectrum Dynamics • No AC • Acquisition time 1.25 m •Tc99m •Heart : .5mCi •Background : 2mCi (.19mCi/l) •Liver : .23mCi (.19mCi/liter)
  21. 21. Cardiac SPECT Improvements Implications for CHD and Atherosclerosis Testing • Increased sensitivity: reduced acquisition time – Dynamic cardiac SPECT: • time-activity curves for blood and myocardium • Compartment modeling results in: – Absolute blood flow (voxel) – Coronary Flow Reserve: a region compared to itself – Coronary endothelial function (CPT) • Increased resolution: – Potential to directly image plaque • quantify “activity” of atherosclerosis
  22. 22. SPECT/CT Philips Precedence Siemens Simbia
  23. 23. Dynamic SPECT for Molecular Imaging • Noninvasive biopsy • Specific diagnosis CT for Structure DynaQ™ hybrid scanner
  24. 24. Who needs PET/CT or SPECT/CT • Equivocal nuclear • Follow-up studies after initial CT (or nuclear) • Why simultaneous: molecular imaging
  25. 25. Comparative Spatial Resolution and Tracer Concentration SPECT PET ECHO MRI CT Resolution (mm) 7-15 3-10 < 1 < 1 < 1 Tracer Concentration pM-nM* pM-nM* 10-100 μM 10-100 μM 10-100 μM *picomolar-nanomolar concentrations employed are key advantage of the radionuclide methods
  26. 26. translocase death domains mediated signaling activation of the executioner of apoptosis scramblase floppase ? binding followed by 2D-crystallization Annexin V Detection of the apoptotic cell TNF or Fas Ligand TNFR or CD95 + +- Courtesy Chris Reutlingsperger, Maastricht University Tc-99m Annexin V: Probe for Vulnerable Plaque
  27. 27. Old TIA Recent TIA A B C D Transverse Coronal ANT L Annexin IHC in Endarterectomy Keitselaar, Hofstra, Narula; NEJM 2004 Annexin-V Imaging For ApoptosisAnnexin-V Imaging For Apoptosis
  28. 28. Annexin V-Tc99m autoradiograph Digital photograph dissected apoE-/- aorta H & E Histological AHA classification Stage IVa (vulnerable plaque) Tc-99m Annexin dissected aorta apoE -/- mouse C. Mori Stanford, 2005
  29. 29. 99m Tc-Annexin V SPECT for In Vivo Detection of Atherosclerotic Lesions in Porcine Coronary Arteries Johnson et al. J Nucl Med 2005;46:1186-93 Scan positive Scan negative
  30. 30. Imaging of Atherosclerotic Plaques Using a Human Antibody Against the Extra-Domain B of Fibronectin Matter et al. Circ Res 2004;95:1225-33 125 I-labeled L19 to atherosclerotic plaques in ApoE-/- mice.
  31. 31. OxLDL AB uptake reflects plaque burden R=0.95 P<0.001 0.00 0.05 0.10 0.15 0.20 0.25 0 500 1000 1500 2000 Aortic weight (mg) (%ID) MDA2 125 I-MDA2 Uptake in Mouse and Rabbit Atherosclerotic Plaques Tsimikas J Nucl Cardiol 1999, ATVB 2001
  32. 32. IL2 SPECT in 2 pts with bi-lateral carotid plaques A Annovazzi e A Signore ACC 2005
  33. 33. IL2 SPECT: Carotid T/B ratios in patients from LS before and after 3 month treatment 1 1,5 2 2,5 3 3,5 Before therapy After therapy 99mTc-IL2uptake(C/Bratios) Atorvastatin 1 1,5 2 2,5 3 3,5 Before diet After diet Hypocholesterolemic diet
  34. 34. SPECT for imaging vulnerable plaque Potential to Image Multiple Molecular Processes Simulaneously • Apoptosis • IK-17 • Oxidized LDL • Interleukin 2 • Thrombus • Activated platelets • Neovascularization
  35. 35. Molecular Imaging Needed Developments • Discovery in molecular biology • New probes (with FDA approval) • Multimodality technology – Structure/function Post-processing software • Reimbursement
  36. 36. SPECT/CT for Atherosclerosis Imaging • CT: quantify plaque volume • SPECT or PET: – quantify plaque activity – Potential to quantify rest/stress blood flow Advantage of SPECT • Multiple tracers simlutaneously • Possible wider availability of tracers and cameras • Potential of SPECT • Increased sensitivity and resolution need to be realized

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