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Plaque petct

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Plaque petct

  1. 1. Plaque Characterization with PET-CT Ahmed Tawakol, M.D. Cardiology Division Massachusetts General Hospital & Harvard Medical School
  2. 2. Vascular inflammation is an attractive target for the detection of high-risk plaques.
  3. 3. Inflammatory Markers Predict Coronary Events Ridker PM et al. N Engl J Med 2000;342:836 4 3 2 1 1 RelativeRiskofFuture CoronaryEvents Quartile of Inflammatory Marker hs-CRP 2 3 4 SAA IL-6 sICAM-1
  4. 4. Inflammation is an Important Participant in All Phases of Atherothrombotic Disease • Lesion initiation • Lesion progression • Plaque Rupture • Thrombosis
  5. 5. Imaging technologies that characterize plaque inflammation may prove useful for assessment of risk of an ischemic event.
  6. 6. Nuclear Methods to Image Inflammation • Nuclear probes long been used to non-invasively localize inflammation in humans. • Examples: – 67 Ga citrate, – 111 In- or 99m Tc-labeled leukocytes, – 111 In-labeled IgG. • Perhaps the best clinically available method is FDG- PET
  7. 7. FDG Uptake Reflects Glycolysis Adapted from: Hughes: Thorax, Volume 51(2S) 16S-22S K1 18 FDG 18 FDG 18 FDG K2 18 FDG-6-phosphate Glycogen Glycolysis Hexokinase K3 Vessel Cell transporter protein x x
  8. 8. Metabolic Basis for Using FDG-PET for Macrophage Imaging • Macrophages: – Have high basal metabolic rates, – Rely on external glucose source as fuel (macrophages do not store glycogen) – Increase glucose consumption further when activated. • FDG uptake by inflamed tissues is 10-20 times that of most other tissues. • FDG uptake is often higher in inflammatory tissue than in tumor cells.
  9. 9. Increased FDG Uptake has been Observed in Human Atherosclerotic Plaques
  10. 10. Increased FDG Uptake in Vascular Inflammatory Diseases Increased FDG uptake has been reported in: -Takayasu's arteritis, -Giant cell arteritis, -Polymyalgia rheumatica and -Nonspecific aortitis -Patients with atherosclerosis
  11. 11. Increased FDG Uptake Observed in Symptomatic Carotid Disease Symptomatic CarotidStenosis Asymptomatic CarotidStenosis PET CT Co-Registered Image J.H.F. Rudd et al,. Circulation 2002
  12. 12. Can FDG uptake, (PET), be used to measure vascular inflammation? -Animal study
  13. 13. PET-FDG Methods Histology3 hr PET ImagingFDG administered (IV) to balloon- injured, cholesterol-fed atherosclerotic rabbits +/- 16s CT Angiography
  14. 14. Rabbit Model: Histopathology H&E Trichrome RAM-11 InflamedFibrous Tawakol, JNC 2005
  15. 15. Co-Registered Control Rabbit Aorta ImagesPETCT AxialSagittal
  16. 16. Co-Registered Atherosclerotic Rabbit Aorta Images Axial PETCT Axial
  17. 17. P<0.001, r=0.79 FDG Uptake vs. Inflammation in Atherosclerotic Rabbits Vessel Inflammation (% RAM-11 Staining) FDGUptake (%ID/gm*103 ) 0 20 40 60 80 100 120 140 0 >0-5 >5-15 >15Blood Activity
  18. 18. P<0.0001, r =0.93 PET - SUV vs. Inflammation in Atherosclerotic Rabbits Inflammation (% RAM-11 Staining) 0 10 20 30 FDGUptake (SUV) 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6
  19. 19. Plaque inflammation can be characterized with FDG-PET
  20. 20. Can FDG-PET be used to measure vascular inflammation in humans?
  21. 21. Carotid PET Study Histologic correlationCEA 17 patients w carotid stenosis scheduled for CEA FDG- PET Merged with MRI or CT
  22. 22. Patient 1: Low FDG Uptake
  23. 23. Trichrome Collagen-rich plaque Thick Fibrous Cap Low lipid content CD68 <1% plaque area composed of inflammatory cells Patient 1 Histology
  24. 24. Patient 2: High FDG Uptake
  25. 25. CD68 Stain 20-30% plaque area composed of inflammatory cells Trichrome Thin Fibrous Cap (50 microns) Large necrotic core Patient 2 Histology
  26. 26. Carotid FDG Uptake
  27. 27. FDGUptake(T/B) Macrophage Staining (% plaque area) Inflammation vs. FDG Uptake (PET) N=10 P<0.0001 r=0.82 J J J JJJ JJJJJJJ JJJ JJ JJJ J JJJ JJJ J J J JJ JJ J JJJ JJ JJ J J J J JJJ J J JJ J JJ JJ J J J J J J J J J J J J J J 0.5 1 2 3 0 5 10 15 20 25
  28. 28. FDGUptake(T/B) Collagen Staining (% plaque area) Collagen vs. FDG Uptake (PET) J J J J J J J J JJ J J 0.5 1 2 3 50 60 70 80 90 100 P<0.01 r=-0.76
  29. 29. Smooth Muscle Cell Staining (%) 0 10 20 30 40 50 FDGUptake(T/B) 0.5 1.0 1.5 2.0 2.5 3.0 3.5 P=NS Smooth Muscle Cells vs. FDG Uptake
  30. 30. Carotid FDG uptake correlates with histological evidence of inflammation.
  31. 31. Implications • FDG-PET may be useful for non-invasive characterization of vascular inflammation • Technique has promise: – for targeting therapies to patients at potentially higher risk for stroke – as an end-point for drug testing – to identify event-causing carotid plaques • Findings warrant further verification in a larger patient population.
  32. 32. Structural imaging (CT or MR) is needed for PET measurements
  33. 33. CT is useful for detection and characterization of coronary plaques
  34. 34. MPR of LAD in Cross SectionThin MIP Detection of Plaque Compared w IVUS: Sensitivity 82%, Specificity 88% Achenbach et al. Circulation 2004
  35. 35. r = 0.64, p < 0.001 Moselewski et al. AJC 2004 Plaque Area Potential to detect and quantify coronary plaque
  36. 36. Plaque CompositionPlaque Composition Leber et al JACC
  37. 37. MDCT Plaque Remodeling: 0.34 cm² 0.43 cm² Achenbach et al. JACC 2004
  38. 38. Coronary CT is here now…
  39. 39. Coronary CT is here now… Are we ready for Coronary PET-CT ?
  40. 40. PET-CT Characterization of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion •Myocardial uptake of FDG •Smaller volume of coronary plaques.
  41. 41. •Cardiac and respiratory motion Gating PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  42. 42. •Cardiac and respiratory motion Gating •Myocardial uptake of FDG PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  43. 43. •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Suppression of myocardial FDG uptake PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  44. 44. Suppression of Myocardial FDG Uptake • Relatively simple • Healthy myocardium prefers lipids to glucose • High fat, low glucose diet results in suppression of myocardial FDG uptake
  45. 45. Suppression of Myocardial FDG Uptake after Atkins-Type Diet for 24 Hrs
  46. 46. •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  47. 47. •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Are we limited by PET’s spatial resolution? PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  48. 48. •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Not necessarily- With PET, it’s about target-to-background ratio PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  49. 49. •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Not necessarily- With PET, it’s about target-to-background ratio Lighthouse effect PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  50. 50. •Cardiac and respiratory motion Gating Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Higher target to background •More specific tracers PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  51. 51. Novel Tracers Potential Targets: – Inflammation • Scavenger receptor • P2 purine receptors • others – Apoptosis – Thrombus – Neovascularization – Others
  52. 52. Purine Receptor Imaging 18 F-Meth-Ap4A Sagittal Aorta Transverse Aorta Coronal Spine Aorta Micro-PET
  53. 53. P<0.001 r=0.87 AP4AUptake (%ID/cc) 0.00 0.02 0.04 0.06 0.08 0.10 0-7 8-16 >16 Plaque Inflammation (% Ram-11 Staining) Ap4A uptake vs. Inflammation
  54. 54. Annexin V Kietselaer BL, NEJM 2004
  55. 55. ConjugatedF FreeF ConjugatedF FreeF 0 10 20 30(molce6equivalent/gmtissuex10-10 ) FlurochromeConcentration Inflamed Ao Control Ao Targeting Scavenger Receptor-A: Increased Uptake By Inflamed Plaques P<0.001
  56. 56. •Cardiac and respiratory motion Gating Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Higher target to background More specific tracers •Improved instrumentation PET-CT Characterization of Coronary Plaques: Additional Technical Challenges
  57. 57. Improved Instrumentation • Intravascular positron detectors • Improved PET and PET-CT • PET-MRI
  58. 58. Volume CT System Canine heart 150 micron isotropic resolution VCT Lab in Bldg 149 Detector Tube
  59. 59. Crossflex 3 x 18 mm Stent VCT MDCT 150 x 150 x 150µ 650 x 650 x 1250µ
  60. 60. Case: Middle Aged Woman w CP
  61. 61. Could we have intervened and prevented the MI? What if… we also detected a high degree of plaque inflammation?
  62. 62. Acknowledgements Cardiology • Kusai Aziz, MD • Gregory Bashian, MD • Henry Gewirtz, MD • Alex Morss, MD • James Muller, MD • Raymond Migrino, MD • Jane Sherwood, RN • Jeffrey Swanson, BS Neurology • Karen Furie, MD Radiology • Suhny Abbara, M.D. • Nathaniel Alpert, PhD • Ali Bonab, PhD • Thomas Brady, MD • Ricardo Curry, MD • Maros Ferencik, MD • Alan Fischman, MD, PhD • Denise Hinton, PhD • Udo Hoffmann, MD • Koen Nieman, MD Pathology • Shahinaz Bedri, MD • Stuart Houser, MD • James Stone, MD

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