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Visualization of atherosclerotic vulnerable plaque

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Visualization of atherosclerotic vulnerable plaque

  1. 1. Visualization of Atherosclerotic Vulnerable Plaque Super Paramagnetic Iron Oxide As a Contrast Media for MRI Mitra Rajabi, MD Mohammed Asif, MD
  2. 2. 2 Atherosclerosis • Coronary artery disease is the leading cause of death in the USA and the developed countries. • The majority of myocardial infarctions are not caused by atherosclerotic plaques that cause a hemodynamically significant stenosis, but rather by smaller plaques, which called ”vulnerable “plaque.
  3. 3. 3 Vulnerable Plaque • Large lipid core • Thin fibrous cap • Inflammation
  4. 4. 4
  5. 5. 5 Ruptured Vulnerable Plaque
  6. 6. 6 Available/Suggested Techniques for Detection of Vulnerable Plaques   Invasive  Angiography  IVUS  MRI  OCT  Angioscopy  Spectroscopy  Thermography  Elastography Non-Invasive  MRA&MRI  EBCT  Radioisotope Imaging
  7. 7. 7 Intra Vascular Ultra Sound
  8. 8. 8 Angioscopy A B C
  9. 9. 9 Optical Coherence Tomography
  10. 10. 10 Spectroscopy
  11. 11. 11 Thermography
  12. 12. 12 Electron Beam Computed Tomography
  13. 13. 13 Magnetic Resonance Angiography(MRA)
  14. 14. 14 Magnetic Resonance Imaging
  15. 15. 15 Intravascular MRI
  16. 16. 16 Elastography Femoral artery
  17. 17. 17 Nuclear Cardiology • Instrumentations and techniques Planar SPECT PET • Radiopharmaceuticals Thallium201 Technetium99
  18. 18. 18 Radiotracers for imaging Atherosclerosis • Platelets • Low density Lipoproteins (LDL) • Lipoprotein(a) • Modified LDL • Monocytes • Fibrinogen • Fibronectin
  19. 19. 19 ….Continue • Porphyrins • Human IgG • Peptides • Monoclonal antibodies
  20. 20. 20 A patient with 80% stenosis of the right 1 hour after injection of 99 Te-ox-LDL. R L Transaxial section of neck obtained by SPET Anteroposterior gamma camera image
  21. 21. 21 Gamma images of an experimental atherosclerotic rabbit injected with negative charge–modified 111 In-labeled chimeric Z2D3- 73.30 F(ab')2 Immediately 24 hours 48 hours
  22. 22. 22
  23. 23. 23 SPECT Images: Focal uptake of the right carotid artery absent uptake on the left side. Carotid angiogram showing the stenotic region corresponding to the plaque.
  24. 24. 24 Endarterectomy specimen With Intense Radioactivity to the Z2D3 Antibody Uptake
  25. 25. 25 Immunoperoxidase staining of the endarterectomy specimen demonstrates antibody uptake in the region that contains smooth muscle cells. The uptake is represented by the brown peroxide stain. The lipid- and foam cell-rich areas are negative for color reaction
  26. 26. 26
  27. 27. 27 Cerebral angiography(A), US (B), and platelet imaging (C ,D) in a patient with T.I.A. obvious ulcerated lesions in the right internal carotid artery(Rt) (Large arrows in A and B ) (57% stenosis with a unilateral plaque score of 6.0); carotid bifurcation (small arrows in B&C), pathological, positive platelet accumulation in the right carotid artery. Images in C and D were obtained by means of a dual-tracer method that used (C) In 111-labeled platelets and (D) Tc 99m-labeled human serum albumin
  28. 28. 28 Other Targeted studies Lipid-conjugated Gd-DTPA was incorporated into the surfactant layer of biotinylated perfluorocarbon emulsions (Biotinylated antifibrin monoclonal antiobodies and avidin were used to couple the emulsion nanoparticles to fibrin clots. (Flacke et al, ISMRM 2000)
  29. 29. 29 The need for assessment of functional properties of plaques in particular its macrophage activity is beyond doubt, as these inflammatory cells are considered the major culprit agents promoting plaque rupture Presence of inflammation has led to find new diagnostic ways based on thermal and or PH detection of vulnerable plaques, and the idea of finding active macrohages by using new contrast media for MR imaging of plaques. MR spectroscopy
  30. 30. MRI Study of Macrophages Activity and Functional Property of Atherosclerotic Plaques (SPIO,USPIO)
  31. 31. 31 SPIO, USPIO • Magnetic resonance imaging contrast medium with a central core of iron oxide generally coated by a polysaccharide layer • Shortening MR relaxation time • Phagocyted by and accumulated in cells with phagocytic activity
  32. 32. 32 SPIO in Macrophages
  33. 33. 33 SPIO Injection A 4-cm metastasis in segment 4
  34. 34. 34 SPIO /USPIO • MR contrast for detection of cancer and liver diseases • MR contrast for MR angiographies • MR contrast for detection of apoptosis(ISMRM)
  35. 35. 35 Our Previous Study Shows the Iron Particles in The Plaques No plaque, No Iron
  36. 36. 36 Comparison of the Number of Iron Particles in ApoE &Normal Mice 0 5 10 15 Atherosclerotic Aorta Average number of iron particles per sample P <0.001 Normal
  37. 37. 37 Extra Magnification withSPIO
  38. 38. 38 Normal artery Stable Plaque
  39. 39. 39 Vulnerable Plaque
  40. 40. 40
  41. 41. 41 Stable Plaque
  42. 42. 42 Inflammation Imaging
  43. 43. 43 USPIOs Enter the Atherosclerotic Plaque Through • Macrophages that engulfed them • Fissured or thin cap • Extensive angiogenesis • vasa vasorum leakage • Intra plaque hemorrhage
  44. 44. 44 Hypotheses • Active macrophages in the inflamed vulnerable plaques can be visualized following injection of USPIO into the systemic circulation by virtue of a significant change in T1 and T2 relaxation time of the plaque after injection. Also other characteristics of vulnerability such as thin/disrupted cap shoulders, extensive angiogenesis associated with loose vasa vaserum which causes extravasation and leaking of macromolecules… and intra plaque hemorrhage all of them representing vulnerable plaque may contribute to retaining of USPIO inside the plaque. • These MR imaging findings correlate with vulnerability of the plaque
  45. 45. 45 Study Design P a t h o lo g y e v a lu a t io n H & E , P e a r l's , I m m u n o s t a in in g S a c r if ic e & in v it r o M R I M R I w it h a n d w it h o u t in t r a v a s c u la r c o il in 3 t h , 5 t h , 7 t h d a y U S P I O in je c t io n M R I w it h & w it h o u t in t r a v a s c u la r M R c o il 1 0 R a b b it s
  46. 46. 46 Under Study • Magnetic resonance imaging of carotid atherosclerotic plaques with MRI using a dedicated phase array coil (special superficial coil)
  47. 47. 47 Preliminary studies in Imaging the Aorta in Apo-E mice • MRI of the thoracic and abdominal aorta of Apo-E mouse with Respiratory gating • Intravenous injection of 40µmol Fe/Kg Feridex to Apo-E mice • MRI in Days 1,2 ,5 and 10 after injection
  48. 48. 48 Pre injection MRI
  49. 49. 49 MRI 5 Days After Injection
  50. 50. 50 • We have seen Feridex particles are trapped by RES mostly in liver and spleen, some pulmonary macrophages, and also lymphatic nodes. • 5- We plan to redo the study with other soon to be available contrast media names Combidex, Clariscan, MION, LCIO, AND our own plaque specific USPIO in collaboration with Dr Daniel Chan.
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