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Phil graham new

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SHAPE Society

Publicada em: Saúde e medicina
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Phil graham new

  1. 1. 1 MR Contrast Agents for Vulnerable Plaque Imaging Philip Graham, PhD EPIX Medical, Inc. Cambridge, MA 02142
  2. 2. 2 MS-325: Vascular Contrast Agent • Albumin binding •Extends plasma t1/2 •4-10X increase in signal •Slows ECS uptake • Phase III angiography trials ongoing • Hypothesis: MS- 325, an albumin- targeted Gd contrast agent, highlights inflamed vessel wall and facilitates plaque Equilibrium Phase MS-325Arterial Phase
  3. 3. 3 Vessel Wall Enhancement with MS-325 Courtesy of: T. Grist (University of Wisconsin, Madison, WI)
  4. 4. 4 Vessel Wall Enhancement with MS-325 • Atherosclerosis = inflammation • Leaky capillaries supplying vessel wall – Increased albumin conc. in wall • Consistent enhancement of wall in patients with MS-325 • Implications for stenosis identification and quantitation (and plaque burden) • Enhancement may correlate with risk of rupture Aorta Right Iliac Artery Vessel Wall Vessel Wall Courtesy of: Dr. J Maki (UW/Puget S VA)
  5. 5. 5 Arterial Phase Equilibrium Phase MS-325 Source Images - Left External Iliac Artery Artery Vein
  6. 6. 6 0 0.5 1 1.5 2 2.5 3 Adj to Plaque No Plaque Wall Thickness (mm) Related to Plaque Results Adj to Plaque No Plaque P < 0.01
  7. 7. 7 Pharmacological trigger histamine = vasoconstrictor -> increases mechanical force on fibrous cap -> plaque disruption Russells viper venom -> triggers blood clotting cascade fresh thrombus lipid core? thin fibrous cap? fresh thrombus vasoconstriction pre-trigger post-trigger disrupted plaque T2w Visualization of Plaque Rupture in Rabbit Model Johnstone MT, Botnar RM, Perez AS, Stewart R, Quist W, Hamilton J, Manning WJ. In Vivo Magnetic Resonance Imaging of Experimental Thrombosis in a Rabbit Model. Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1556-60. Courtesy: Johnstone, Botnar, Manning: BIDMC
  8. 8. 8 baseline MS-325 MS-325 improves Plaque Visualization plaque contrast uptake no uptake wall plaque thrombus MS-325 Post-trigger Courtesy: Johnstone, Botnar, Manning: BIDMC
  9. 9. 9 Direct Clot Detection with Fibrin- Targeted Contrast Agent • Fibrin targeting lead discovered in a collaboration with Dyax • MR contrast agents EP-1242 and EP-1873 resulted from extensive modifications by EPIX of the original leads • Elimination profile similar to Magnevist® EP-1242 Enhanced Carotid Clot in Guinea Pig In collaboration with Z. Fayad, Ph.D., Mt. Sinai, New York
  10. 10. 10 To be annotated, final copy will be printed high definition Post Gd-BSA (angiography) Pre contrast 1 minute post EP-1873 36 minute post EP-1873 Jugular thrombus Rabbit Carotid thrombus Jugular thrombus Carotid thrombus In collaboration with E. Kent Yucel, Li Zhou Brigham & Women’s, Boston
  11. 11. 11 Pre contrast 10min 1.5h 1h Post EP-1873 (fibrin agent) aorta thrombus thrombus thrombus Botnar RM, Perez AP, Johnstone MT, Manning WJ EP-1873 injected 75 mins after triggering
  12. 12. 12 15minbaseline 5:45h Post EP-1873 35min post histamine 3D Inversion Sequence fibrin
  13. 13. 13 3D Inversion Sequence 5:45h after EP-1873 QuickTime™ and a decompressor are needed to see this picture.
  14. 14. 14 Summary • Fibrin-binding agent makes thrombotic consequences of plaque rupture directly visible on standard MR scans – Potential for assessing thromboembolic risk in a variety of vascular beds – Follow clot resolution after treatment administration? • Vascular Agent MS-325 shows strong wall enhancement because of increased capillary volume and binding to extravasated albumin – Low signal between wall and lumen represents atherosclerotic plaque – Prolonged enhancement of wall and lumen allows high resolution measurement of plaque burden – Potentially straightforward method of plaque visualization and quantification • ? Follow statin therapy progress