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Spio mri studies by dr naghavi - amersham oct 2003 - part 1


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Spio mri studies by dr naghavi - amersham oct 2003 - part 1

  1. 1. Non-Invasive Macrophage Imaging for Detection of Vulnerable Plaque Applications and Limitations Amersham Oct 2003 Morteza Naghavi, MD
  2. 2. A B
  3. 3. Which one is vulnerable, A or B? The one with inflammation (macrophage infiltration)
  4. 4. Morphology vs. Activity Imaging Inactive and non-inflamed plaque Active and inflamed plaque Similar in IVUS OCT MRI w/o CM Morphology Different Activity Thermography, Spectroscopy, immunoscintigraphy, MRI with targeted contrast media…
  5. 5. Plaque Morphology vs. Plaque Activity We Need Both
  6. 6. Imaging Inflammation - by MRI - by CT Both are available today!
  7. 7. Imaging Inflammation - by MRI Pioneered in 1980s Rummeny E, Weissleder R, Stark DD, Elizondo G, Ferrucci JT. Radiologe. 1988 Aug;28(8):380-6.
  8. 8. SuperparamagneticSuperparamagnetic andand Ultra-superparamagneticUltra-superparamagnetic Iron OxideIron Oxide lBlood pool Magnetic resonance (MR) imaging contrast media with a central core of iron oxide generally coated by a polysaccharide layer Shortening MR relaxation time Engulfed by and accumulated in cells with phagocytic activity
  9. 9. Particle Core Size Particle Size Blood (nm) (nm) Half-life Combidex 5-6 20-30 8h Feridex 4-6 35-50 2.4±0.2h DDM 43/34/102 6.4 20-30 6h Clariscan MION 4-6 17 varies Feruglose --- --- --- --- Examples of commercially available SPIOs
  10. 10. USPIOs Enter the AtheroscleroticUSPIOs Enter the Atherosclerotic Plaque ThroughPlaque Through lMacrophages that engulfed them lFissured or thin cap l Extensive angiogenesis l vasa vasorum leakage l Intra plaque hemorrhage
  11. 11. In-vitro Study of Macrophage SPIO Uptake  In a series of in-vitro studies we have tested the rate of SPIO uptake by human activated monocytes in different conditions regarding incubation time and concentration of SPIO. All SPIO were labeled by a fluorescent dye (DCFA).
  12. 12. FL-labeled SPIO Incubated Macrophages 24hr
  13. 13. Double DAPI Staining with Fluorescence-labeled SPIO Macrophages after 24hr Incubation
  14. 14. Hypothesis
  15. 15. vasa vasorum Over magnification is a major advantage of SPIO Darkening property of SPIO in the white background of fat and water of plaque is another advantage
  16. 16. SPIO and T2 Effect In-vitro study to show the effect of macrophage SPIO uptake on their T2 relaxation time
  17. 17. 0 10 20 30 40 50 60 70 80 90 50 250 control 20 min 60 min 6 hours 24 hours Macrophage Uptake of Feridex with Time and Concentration Shown by T2 Reduction Concentration µmol/ml
  18. 18. Histopathologic Studies of ApoE KO Mice Injected with SPIO (Abdominal Aorta) H&E staining Iron Staining CD 68 staining Iron particles