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Tct mri 2001

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Tct mri 2001

  1. 1. Everybody Has Atherosclerosis The Question Is Who Has Vulnerable Plaque Paradigm Shift in Cardiology
  2. 2. Sudden Cardiac Death Acute MI Vulnerable Plaque(s) Stop Vulnerable Plaque, Prevent Heart Attack!
  3. 3.  On the basis of his studies of the triggers of MI, James E. Muller et al described “ coronary occlusive thrombi occurs when atherosclerotic 5 years later in 1994 he coined the term of Vulnerable Plaque. History of Atherosclerosis www.VP.org Who Brought the Name of “Vulnerable Plaque” to Medical Literature?
  4. 4. Vulnerable Plaque, the youngest creature in the land of cardiology has just turned in 8 y! VPiologists call him VP!!
  5. 5. Carl von Rokitansky (1804-1878) Rokitansky gaveearly detailed descriptionsof arterial disease. Heis alleged to haveperformed 30,000 autopsies. Rokitansky in 1841 championed theThrombogenic Theory. Heproposed that the depositsobserved in theinner layer of thearterial wall derived primarily from fibrin and other blood elementsrather than being theresult of apurulent process. Subsequently, theatheroma resulted from thedegeneration of thefibrin and other blood proteinsasaresult of apreexisting crasisof theblood, and finally thesedepositsweremodified toward apulpy masscontaining cholesterol crystalsand fatty globules. Thistheory cameunder attack by Virchow
  6. 6. First studies on inflammation of vessels, particularly phlebitis, Started at a time when Cruveilhier2had just stated: La phlebite domine toute la pathologie.3 First a great number of preparatory studies on fibrin, leukocytes, meta-morphosis of blood, published separately. … Rudolf Virchow 1821-1902 The Father of Cellular Pathology Virchow appreciates prior works. Virchow presented hisinflammatory theory. Heutilized thenameof "endarteritisdeformans." By thishe meant that theatheromawasaproduct of an inflammatory processwithin theintimawith thefibrous thickening evolved asaconsequenceof areactivefibrosisinduced by proliferating connectivetissuecells within theintima.
  7. 7. Olcott 1931 “plaque rupture” Leary 1934 “rupture of atheromatous abscess” Wartman 1938 “rupture-induced occlusion” Horn 1940 “plaque fissure” Helpern 1957 “plaque erosion” Crawford 1961 “plaque thrombosis” Gore 1963 “plaque ulceration” Friedman 1964 “macrophage accumulation” Byers 1964 “thrombogenic gruel” Chapman 1966 “plaque rupture” Plaque Fissure in Human Coronary Thrombosis (Abstract) Fed. Proc. 1964, 23, 443 Paris Constantinidis “Thedestruction of thehyalinized wall separating lumen from theatheromawas almost alwaysobserved to bepreceded by or associated with itsinvasion by lipid containing macrophages.” Friedman and van den Bovenkamp 1965 Unheralded Pioneers
  8. 8. Published in 1967
  9. 9. N Engl J Med 1999 “Atherosclerosis; an inflammatory disease” Ross R. Russell Ross Atherosclerosis; arterial “Response to Injury” N Engl J Med 1976 Aug 12;295(7):369-77 The pathogenesis of atherosclerosis (first of two parts). Ross R, Glomset JA.
  10. 10. Erling Falk Michael Davies Autopsy Series Thin Fibrous Cap + Large Lipid Core + Dense Macrophage A culprit ruptured plaque 1981-1990
  11. 11. Seymour Glagov Compensatory Enlargement of Human Atherosclerotic Coronary Arteries N Engl J Med 1987 May 28;316(22):1371-5 <50% stenosis Luminal area is not endangered until more than 40% of internal elastic lamina is destructed and occupied by plaque Coronary artery disease is a disease of arterial wall not lumen. Positive Remodeling <80% stenosis
  12. 12. Angiographic progression of coronary artery disease and the development of myocardial infarction. Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V. Department of Medicine, New York Cardiac Center, Mount Sinai Medical Center, New York 10029. Simultaneously, Little et al, Haft et al reported that majority of culprit lesions are found on previously non-critical stenosis plaques. Conclusion: “Myocardial infarction frequently develops from non-severe lesions.” J Am Coll Cardiol 1988 Jul;12(1):56-62 Ambrose, Fuster, and colleagues X-Ray Angiographically Invisible Plaques
  13. 13. Falk E., Shak P.K., Fuster V. Circulation 1995 Non-stenotic (<75%) plaques cause about 80% of deadly MI
  14. 14. Macrophage- driven MMPs soften plaquecap and prompt it to rupture P.K. Shah Peter Libby Thefateof atherosclerosisand itsthrombotic complication are governed by immunesystem. Goran Hansson Allard van der Wal and others
  15. 15. •Eroded Plaque Rupture-prone plaques are not the only type of vulnerable plaque •Calcium Nodule van der Wal - Netherlands Renu Virmani -USA Thiene - Italy Kolodgie F., Burk A.P., Farb A., and Virmani R.
  16. 16. Dangerous forms of atherosclerotic plaques prone to thrombosis Vulnerable Plaque?
  17. 17. Ruptured Plaques (~70%) 1. Stenotic (~20%) 2. Non-stenotic (~50%) Non-ruptured Plaques (~ 30%) 1. Erosion (~20%) 2. Calcified Nodule (~5%) Plaque Pathology Responsible for Coronary Thrombotic Death In summary:
  18. 18.  Culprit Plaque; a retrospective terminology  Vulnerable Plaque; a prospective terminology  Vulnerable Plaque = Future Culprit Plaque Terminologies
  19. 19. Natural History of Vulnerable Plaques Illustrated:
  20. 20. ~70% Percent of stenosis Frequency of plaques “Risk” per each plaque Culprit Risk per each type of Vulnerable Plaque (Log) Culprit lesions found in autopsy series of acute MI Different Types of Plaque Vulnerable to Thrombosis All Male Female ~10% <5% ~20% 50% Angiography ~80% <5% ~20% ~55% ~20% <5% <5% ~20% Rupture Prone Eroded Calcified NoduleHemorrhage Positive Remodeling Fissured /Healed Natural History of Vulnerable Atherosclerotic Plaques
  21. 21. Rupture-Prone Plaque Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001 Macrophage Necrotic lipid core Thin fibrouscap
  22. 22. Eroded Plaque Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001 Endothelial denudation Proteoglycans
  23. 23. Fissured / Healed Plaque Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001 Mural thrombi Wounded plaque
  24. 24. Plaque with a Intimal Calcified Nodule Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001 Calcified nodule
  25. 25. Intra-Plaque Hemorrhage with Intact Cap Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001 Leaking angiogenesisor ruptureof vasa vaserum
  26. 26. Critically Stenotic but Asymptomatic Plaque Naghavi et al, Cur Ath Rep 2001Vulnerable Plaque >75% lumina narrowing
  27. 27. Different Types of Vulnerable Plaques Major Underlying Cause of Acute Coronary Events Normal Rupture-prone Fissured Eroded Critical Stenosis Hemorrhage Naghavi et al, Cur Ath Rep 2001
  28. 28. Emerging Techniques for Detection of Vulnerable Plaque
  29. 29. Emerging Diagnostic Techniques A. Invasive Techniques Angioscopy IntravascularUltrasound (IVUS) IntravascularThermography IntravascularOptical Coherence Tomography (OCT) IntravascularElastography Intravascularand Transesophageal MRI IntravascularNuclearImaging IntravascularElectrical Impedance Imaging IntravascularTissue Doppler IntravascularShearStress Imaging Intravascular(Photonic) Spectroscopy
  30. 30. - Raman Spectroscopy - Near-Infrared Diffuse Reflectance Spectroscopy -Fibrousis and lipid measurement -pH and lactate measurement - Fluorescence Emission Spectroscopy - Spectroscopy with contrast media … Invasive Techniques Intravascular (Photonic) Spectroscopy Intra-coronary assessment of endothelial function Intra-coronary measurement of MMPs and cytokines
  31. 31. Emerging Diagnostic Techniques B. Non-Invasive Techniques: A. MRI 1- MRI without contrast media 2- MRI with contrast media: Gadolinium-DPTA 2- MR Imaging of Inflammation: Super Paramagnetic Iron Oxide (SPIO and USPIO) 3- MR Imaging of Thrombosis using monoclonal Ab B. Electron Beam Tomography (EBT) C. Multi-Slice Fast Spiral / Helical Computed Tomography D. Nuclear Imaging (18-FDG, MCP-1, Annexin V, CD40)
  32. 32. Emerging Diagnostic Techniques C. Blood Tests / Serum Markers - CRP - ICAM-1, VCAM, p-Selectin, sCD40-L - Proinflamatory cytokines - Lp-PLA2 - Ox-LDL Ab - PAPP-A D. Endothelial Function Test -Intra coronary acethylcholine test -Noninvasive flow mediated dilatation of brachial artery - Anti-body against endothelial cells
  33. 33. Angioscopy Advantages: Intuitive (anatomic) Simple (easy to understand) Disadvantages: Visualizes only the surface of the plaque Requires a proximal occluding balloon The spatial resolution is limited Glistening yellow plaque Uchida et al, Japan
  34. 34. Intravascular Ultrasound (IVUS): Advantage: Reveals the morphology of the plaque Differs between soft (hypo-echoic) and Hard (hyper-echoic) plaques Disadvantages: Doesn’t give information about plaque inflammation Low spatial resolution (~ 200 µm) Nissen, Yock, and Fitzgerald
  35. 35. Optical Coherence Tomography (OCT) Advantage: Very high-resolution Disadvantages: Needs continuous saline wash / proximal occlusion Limited penetration Does not give information about plaque inflammation Light Lab Inc.Mark Brezinski, James Fujimoto, Eric Swanson
  36. 36. Intravascular Thermography Advantages: Simplicity in theory; hot plaque Gives information about plaque inflammation Disadvantages: Plaque temperature is affected by blood flow Volcano Therapeutics Inc.
  37. 37. Casscells W, et al. Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis. Lancet. 1996 May 25;347(9013):1447-51. Vulnerable plaques are hot and acidic! Ward Casscells and James Willerson showed ex-vivo that human carotid atherosclerotic plaques have temperature heterogeneity and plaques with thinner cap and higher macrophage infiltration give off more heat. Two years later Morteza Naghavi invented Thermosensor Basket catheter and showed invivo temperature heterogeneity in Hypercholestrolemic Dogs and Watanabe Rabbits. Coincidentally Stefanadis et al in 1999 confirmed significant temperature heterogeneity invivo in patients with unstable angina and acute MI. Stefanadis C, et al. Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: A new method of detection by application of a special thermography catheter. Circulation. 1999 Apr 20;99(15):1965-71.
  38. 38. Photonic Spectroscopy Advantage:  Chemical compounds Disadvantage: Based on statistical analysis and calibration is always an issue S/N is a serious problem Still not proven to be able to distinguish vulnerable plaques from stable ones Near Infrared Reflectance Spectroscopy InfraReDx Inc. NIR Spectroscopy Robert Lodder, James Muller, and Pedro Moreno
  39. 39. Intravascular Elastography Advantages: Provides novel information, showing stiffness Small added cost to IVUS Disadvantage: Does not give any chemical – compositional data, nor shows inflammation de Korte et al. Thorax Center, Erasmus University Rotterdam
  40. 40. Intravascular Nuclear Imaging Immuno-scintigraphy Advantage: One may use radio-labeled antibodies to detect specific antigens in plaque like MCP-1 Disadvantages: Radiation and safety problems Poor resolution and flow artifacts Lack of specificity ImetrX Inc.William Strauss and Vartan Ghazarossian
  41. 41. Magnetic Resonance Imaging Plaque Characterization and Angiography Advantages: Lack of ionizing radiation Non-invasive Provides enormous information about flow as well as plaque Enhancement by contrast agents and NMR spectroscopy Disadvantages: Ineligibility of patients with metal prostheses High cost Longer time for adoption by cardiologists
  42. 42. Human Carotid Plaque Courtesy of Dr. Chun Yuan University of Washington
  43. 43. Fuster and Fayad and colleagues reinforced earlier MRI investigation of plaque for invivo non-invasive detection of vulnerable plaque with large lipid pool and thin fibrous caps.
  44. 44. Noninvasive Coronary Vessel Wall and Plaque Imaging With Magnetic Resonance Imaging René M. Botnar; Matthias Stuber; Kraig V. Kissinger; Won Y. Kim; Elmar Spuentrup; Warren J. Manning. Circulation. 2000;102:2582
  45. 45. Intravascular MRI Advantages: Lack of ionizing radiation High resolution Potential for NMR spectroscopy Disadvantages: Invasive and slower than fluoroscopy Needs open/short bore high field magnet Longer time for adoption by cardiologists Surgi-Vision Inc.Ergin Atalar IVUS
  46. 46. Coronary Calcium Imaging EBT and MSCT Advantages: Quick and easy Provide information about total burden of atherosclerosis Disadvantages: Cannot distinguish vulnerable from stable plaque (poor plaque characterization) Inadequate specificity, may not accurately predict near future event May not be suitable for monitoring treatment Calcium Score Imatron Inc.Rumberger, Aard, Raggi, and others
  47. 47. Race for Non-Invasive Coronary Angiography • Multi-Slice Fast Computed Tomography (MSCT) • Magnetic Resonance Angiography (MRA) • Electron Beam Tomography (EBT)
  48. 48. Two Major Players in Massive Clinical VP Screening •MRI •CT •A new competitor is warming up in our lab!
  49. 49. Plaque Morphology vs. Plaque Activity Why do we need both?
  50. 50. Morphology vs. Activity Imaging Inactive and non-inflamed plaque Active and inflamed plaque May Appear Similar in IVUS OCT MRI w/o CM Morphology Show Different Activity Thermography, Spectroscopy, immunoscientigraphy, MRI with targeted contrast media…
  51. 51. Which one is vulnerable plaque?
  52. 52. High Level of Sensitivity and Specificity Needed • Knowing the extensive prevalence of atherosclerosis, in order to accurately detect vulnerable plaques and vulnerable patients, it is imperative to obtain information about both structure and activity of plaque assuring minimum false positive and false negative results. NO MORE TREADMILL TEST!
  53. 53. Major Criteria of Vulnerable Plaque • Cap Thickness • Lipid Core • Macrophage Density If you were to have only ONE choice, which one would you pick for clinical screening to identify vulnerable plaques?
  54. 54. Good News! •MRI can give us more than one choice, indeed it can provides the three. •CT can do too, but there is more homework for CT fans.
  55. 55. Plaque Activity = Plaque Inflammation Plaque Inflammation = Plaque Macrophage Density = Plaque Monocyte Recruitment Rate Note: leaking angiogenesis follows inflammation but is not specific enough.
  56. 56. Vulnerable plaque targeted contrast media needed to identify the following: 1- Inflammation (macrophage infiltration), 2- Fissured/Permeable Cap, 3- Leaking Angiogenesis and 4- Intra-Plaque Hemorrhage 5- Denuded Endothelium
  57. 57. SSuperuper PParamagneticaramagnetic IIronron OOxide andxide and Ultra-small Super Paramagnetic IronUltra-small Super Paramagnetic Iron OxideOxide ((SPIOSPIO – USPIO)– USPIO) Blood 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
  58. 58. 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 Available SPIOs
  59. 59. Reported Applications of SPIO in MR Imaging: -Detection of Hepatic Lesions (primary and metastatic cancers) -Experimental nephritic syndrome in laboratory animals -Monitoring rejection of transplanted heart or kidney in the animal model of allograft transplantation. -Experimental detection of CNS lesions in laboratory animals. MR Imaging of Inflammation is not New
  60. 60. HypothesisHypothesis Active macrophages residing inside the plaque and recruitment of monocytes into an inflamed vulnerable plaques can be visualized by MRI after SPIO injection. A significant decrease in MR signal intensity (negative enhancement) is correlated with the density of active macrophages residing inside plaque.
  61. 61. Our proposed solution: SPIO MR Imaging MR contrast media for imaging inflammation and other characteristics of vulnerable plaque
  62. 62. USPIOs Enter the AtheroscleroticUSPIOs Enter the Atherosclerotic Plaque ThroughPlaque Through Monocyte containing engulfed SPIO particles Fissured or thin cap  Extensive angiogenesis l and leaking vasa vasorum  Intra plaque hemorrhage
  63. 63. 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).
  64. 64. Fluorescent-labeled SPIO incubated with macrophages 24 hr Macrophages avidly take up SPIO nano-particles
  65. 65. SPIO and T2 Effect In-vitro relaxation study shows the effect of SPIO dose and incubation time on intra-macrophage SPIO negative enhancement
  66. 66. 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
  67. 67. In-vivo distribution of SPIO in ApoE deficient and wild type mice: •For the initial study, we use the mouse model of atherosclerosis. • •ApoE deficient mouse has similar atherosclerotic lesions to human and the lesions are more common in the aortic arch and thoracic aorta. • We used ApoE deficient mice and normal variant (C57BL mice) as control. •The SPIO that we used was Feridex (Berlex) injectable solution. •Animals were sacrificed on day 3 and 5 after injection.
  68. 68. Pre and Post-SPIO Enhanced Magnetic Resonance Imaging of ApoE K/O and Wild Type Mice: We used 4.7 tesla MRI unit (University of Texas, Galveston MRI Unit, Galveston, TX) in our study. After baseline MR imaging with respiratory gating, we injected 1mMolFe/kg super paramagnetic iron oxide to six ApoE deficient and two C57bl mice through the tail vein. Post-contrast MR imaging were performed in day 5 with the same parameters (TR=2.5 sec, TE=0.012 sec, FOV=6.6 cm, slice thickness=2.0mm, flip angle (orient)=trans, and matrices=256x256). We selected the aorta at the level of kidney for comparison of the baseline and post-contrast images.
  69. 69. Apo E deficient mice MRI SPIO experiment
  70. 70. SPIO Accumulation in Atherosclerotic Plaque Atherosclerotic plaque in aortic root Normal aortic segment Iron staining of Apo E K/O Aorta, 24 hour after SPIO injection Iron particles
  71. 71. Histopathologic study of the Mouse injected With SPIO (Thoracic Aorta) ApoE KO mouse, Movat staining, proximal aorta Coronary Cross section Atherosclerosis plaque
  72. 72. Histopathologic study of ApoE KO Mouse injected With SPIO (Thoracic Aorta) CD68 staining (aortic plaque) Iron Staining (aortic plaque) Iron Staining (coronary section) Iron particles Iron particles
  73. 73. Histopathologic study of ApoE KO Mouse injected With SPIO (Abdominal Aorta) H&E staining Iron Staining CD 68 staining Iron particles
  74. 74. Histopathologic study of wild type Mouse injected With SPIO (Thoracic Aorta) H&E staining CD68 stainingIron staining
  75. 75. MR Image of Abdominal Aorta After SPIO Injection in Mouse Apo E deficient mouse C57B1 (control) mouse Before Injection After Injection (5 Days ) Dark (negatively enhanced) aortic wall, full of iron particles Bright aortic lumen and wall without negative enhancement and no significant number of iron particles
  76. 76. Rabbit Aorta, x10 magnification Iron
  77. 77. Rabbit Aorta, x40 magnified, Iron
  78. 78. Watanabe hereditary hypercholesterolemic rabbits (WHHR) and New Zealand white rabbits (NZW) were studied. We injected them with SPIO 1 mMol Fe/kg and obtained baseline as well as 5-day post-SPIO injection MR images of the aorta (1.5 Tesla MRI system). Then we compared the images in hypercholesterolemic rabbits with the normal,wild type NZW rabbits. Rabbit ex-vivo MRI studies: After the in-vivo MR images, we sacrificed the animals and excised the aorta. Then we put the isolated aorta in a gel medium, clamped both ends and any side branches and injected gadolinium inside the lumen. We did the same procedure for all rabbits. We also used 2 more rabbits, one WHHR and one NZW that were not injected with SPIO, as control, in the ex-vivo MR study. SPIO-Enhanced MRI study in rabbits
  79. 79. Histopathologic studies of Thoracic aorta in Watanabe Hereditary Hypercholesterolemic rabbit after SPIO injection H&E staining Iron staining Iron staining
  80. 80. Histopathologic studies of Thoracic aorta in Watanabe Hereditary Hypercholesterolemic rabbit after SPIO injection H&E staining Iron staining Iron staining Iron particles
  81. 81. Plaque Cell Density vs SPIO 0 10 20 30 40 50 60 0 10 20 30 40 50 60 70 Cell Denity in H&E staining SPIOpositivecell-Iron staining Series1 R=0.956 Correlation between Iron positive cells in Iron staining and cell density in H&E staining in rabbit atherosclerotic aorta.
  82. 82. MR Angiography 3D with Gadolinium-DTPA in Watanabe Rabbit Before SPIO injection After SPIO injection
  83. 83. Ex-vivo MR study of the thoracic aorta in Watanabe and Wild type rabbit after SPIO injection compared to control. 3D MR Angiography with Gadolinium-DTPA Watanabe rabbit post-SPIO Watanabe rabbit control NZW rabbit control NZW rabbit post-SPIO
  84. 84. Ex-vivo MR study of the thoracic aorta in Watanabe and Wild type rabbit after SPIO injection compared to control. (Gradient Echo) Watanabe rabbit Post-SPIO Watanabe rabbit control NZW rabbit Post-SPIO NZW rabbit control
  85. 85. No cytokines C1Cx10 Apo E SPIO Injected Iron Staining H&E Staining
  86. 86. No cytokines C1Cx10 Apo E SPIO Injected Iron Staining H&E Staining
  87. 87. No cytokines SPIO Injected Apo E Only plaque with SPIO C3Ex40
  88. 88. No Cytokines SPIO Injected Apo E C3E SPIO Found in Circulating Monocytes Iron Staining H&E Staining
  89. 89. T2Fx10 TNFα/IL-1ß SPIO Injected Apo E Iron Staining H&E Staining
  90. 90. TNFα/IL-1ß SPIO Injected Apo E H&E StainingH&E Staining Increased Superficial Macrophage Density
  91. 91. TNFα/IL-1ß
  92. 92. TNFα/IL-1ß
  93. 93. TNFα/IL-1ß
  94. 94. TNFα/IL-1ß T4Bx10
  95. 95. TNFα/IL-1ß T4Bx40
  96. 96. TNFα/IL-1ß T4B
  97. 97. TNFα/IL-1ß T4F
  98. 98. TNFα/IL-1ß T4Cx10
  99. 99. TNFα/IL-1ß T4Cx40
  100. 100. TNFα/IL-1ß T4Fx10
  101. 101. TNFα/IL-1ß T4Fx10bc
  102. 102. Infarct and coronary involvement T4F
  103. 103. TNFα/IL-1ß T4Fx40bcd
  104. 104. TNFα/IL-1ß T3Ex10
  105. 105. TNFα/IL-1ß T3Efex40
  106. 106. TNFα/IL-1ß T3Bx10
  107. 107. TNFα/IL-1ß T3Bx40ab
  108. 108. New SPIO Development Towards Plaque Targeted SPIO Six mice were injected IP with mineral oil, and 24 hours later same amount of above SPIOs were injected IP, 24 hours later, macrophages were isolated from the mice, 24 hours later, the following pictures were taken .
  109. 109. New SPIO Development Towards Plaque Targeted SPIO Bare SPIO
  110. 110. New SPIO Development Towards Plaque Targeted SPIO Dextran Coated
  111. 111. New SPIO Development Towards Plaque Targeted SPIO Lipid Coated
  112. 112. New SPIO Development Towards Plaque Targeted SPIO Receptor Targeted SPIO
  113. 113. Imaging of inflammation in rabbit model of atherosclerosis using USPIO Ruehm et al. Circulation 2001
  114. 114. Imaging of inflammation in rabbit model of atherosclerosis using USPIO Ruehm et al. Circulation 2001
  115. 115. SPIO Clinical Trial: • The first human clinical trial on detection of carotid vulnerable plaque using SPIO in patients undergoing carotid endartherectomy Baseline Scan SPIO Injection 1hr post- injection 5days Scan Surgery days 5-7
  116. 116. No more iron deficiency and hair loss! 0.05 mg/kg
  117. 117. The Beat Goes On…
  118. 118. SPIO Clinical Trial: • The first human clinical trial on detection of carotid vulnerable plaque using SPIO in patients undergoing carotid endartherectomy Baseline Scan SPIO Injection 1hr post- injection 5days Scan Surgery days 5-7
  119. 119. … the question is not only vulnerable plaque Stay Tuned!
  120. 120. HotPlaque.com 2000!
  121. 121. Texas Heart Institute University of Texas-Houston Center for Vulnerable Plaque Research Denton A. Cooley Building (floor 10th ) www.CVPR.org 2002
  122. 122. Association for Eradication of Heart Attack www.VP.org