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Thermographya novel approach for the identification of vp

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Thermographya novel approach for the identification of vp

  1. 1. Thermography: a NovelThermography: a Novel Approach for Identification ofApproach for Identification of Vulnerable PlaquesVulnerable Plaques Mohammad Madjid, MD,Mohammad Madjid, MD, Ward Casscells, MD,Ward Casscells, MD, James T. Willerson, MD,James T. Willerson, MD, Morteza Naghavi, MDMorteza Naghavi, MD
  2. 2. Disclosure:Disclosure: Volcano Therapeutics, Inc.Volcano Therapeutics, Inc.
  3. 3. Holy Grail of Cardiology How can we identify vulnerable plaques?How can we identify vulnerable plaques?
  4. 4. Atherosclerosis:Atherosclerosis: An inflammatory diseaseAn inflammatory disease
  5. 5. Cardinal Signs of InflammationCardinal Signs of Inflammation PainPain RednessRedness HEATHEAT SwellingSwelling InflammationInflammation
  6. 6. HypothesisHypothesis Vascular inflammation and plaqueVascular inflammation and plaque vulnerability can be identified byvulnerability can be identified by the heat released from activatedthe heat released from activated macrophages in the plaque.macrophages in the plaque.
  7. 7. RationaleRationale  Macrophages are metabolically very active withMacrophages are metabolically very active with a high turn-over rate of total ATP content.a high turn-over rate of total ATP content. Newsholme P.Newsholme P. Biochem JBiochem J. 1989;261:211-8. 1989;261:211-8  This high metabolic rate can lead to increasedThis high metabolic rate can lead to increased heat production in areas of macrophageheat production in areas of macrophage accumulation while it cannot be observed inaccumulation while it cannot be observed in areas of smooth muscle cell accumulation in theareas of smooth muscle cell accumulation in the absence of inflammatory cell infiltration.absence of inflammatory cell infiltration. Bjornheden T.Bjornheden T. ArteriosclerosisArteriosclerosis. 1987;7:238-47. 1987;7:238-47
  8. 8. Temperature heterogeneity over the surfaceTemperature heterogeneity over the surface of an endartherectomized carotid plaqueof an endartherectomized carotid plaque Casscells W et al. Lancet. 1996;347:1447-51
  9. 9. While macrophage/monocytes (with high metabolic rate) density wasWhile macrophage/monocytes (with high metabolic rate) density was related to higher temperature, such a relation wasn’t seen with smoothrelated to higher temperature, such a relation wasn’t seen with smooth muscle cell density (with less metabolic activity)muscle cell density (with less metabolic activity)
  10. 10. Inverse relation between temperatureInverse relation between temperature difference and cap thicknessdifference and cap thickness
  11. 11. Infrared experiments showInfrared experiments show temperature heterogeneitytemperature heterogeneity Our dog model of atherosclerosis develops marked lesions in its coronary arteries (left panel). We observed significant temperature heterogeneity along the coronary arteries of these dogs using an infrared camera (right panel). An infrared camera image shows marked temperature heterogeneity over the surface of an atherosclerotic carotid plaque
  12. 12. Inverse correlation of pH and temperature (ºC) inInverse correlation of pH and temperature (ºC) in endartherectomized human carotid artery plaquesendartherectomized human carotid artery plaques Naghavi et al. Atherosclerosis, 2002, in press
  13. 13. In vivo StudiesIn vivo Studies
  14. 14. Thermosensor Basket CatheterThermosensor Basket Catheter
  15. 15. Basket CatheterBasket Catheter Thermal Resolution 0.01 C Thermal Accuracy 0.02 C Size (2-4 F expandable)  Spatial ResolutionSpatial Resolution 0.5 mm0.5 mm  Sampling RateSampling Rate 5-25 per sec5-25 per sec  Number of wall sensorsNumber of wall sensors 44  Blood sensorBlood sensor 11
  16. 16. Dog Model of AtherosclerosisDog Model of Atherosclerosis Femoral Artery Atherosclerotic With Temperature Heterogeneity Carotid Artery Non-Atherosclerotic Without Temperature Heterogeneity
  17. 17. Higher absolute temperature as well as temperature heterogeneity in femoral arteries of atherosclerotic dogs compared to their carotid arteries which are free of disease. P<0.05
  18. 18. Temperature heterogeneity inTemperature heterogeneity in atherosclerotic lesions of Watabae rabbitsatherosclerotic lesions of Watabae rabbits Temperature heterogeneity In aortae of atherosclerotic mice No temperature heterogeneity In aortae of normal mice
  19. 19. Infrared angio-thermographyInfrared angio-thermography cathetercatheter
  20. 20. Infrared angio-thermographyInfrared angio-thermography cathetercatheter  Thermal resolution of 0.01º CThermal resolution of 0.01º C  Spatial resolution of 100 microns.Spatial resolution of 100 microns.  Real-time image reconstruction softwareReal-time image reconstruction software  1mm window1mm window  Two-dimensional and virtual longitudinal color-Two-dimensional and virtual longitudinal color- coded thermographic imagescoded thermographic images  We have tested the catheter in our phantom modelWe have tested the catheter in our phantom model simulating “hot plaques” with continuous flow ofsimulating “hot plaques” with continuous flow of normal saline in a silicon tube with multiple hotnormal saline in a silicon tube with multiple hot spotsspots  In vivoIn vivo studies are under way to confirm our findingsstudies are under way to confirm our findings fromfrom ex vivoex vivo studies.studies.
  21. 21. Human StudiesHuman Studies Our findings have been confirmedOur findings have been confirmed in clinical settings by the Hellenicin clinical settings by the Hellenic group of Stefandis andgroup of Stefandis and colleagues, and also in Belgiumcolleagues, and also in Belgium and the Netherlands.and the Netherlands.
  22. 22. In vivoIn vivo thermal heterogeneity within humanthermal heterogeneity within human atherosclerotic coronary arteriesatherosclerotic coronary arteries Stefanadis et al. Circulation. 1999;99:1965-71
  23. 23. The risk of an adverse cardiac event in patients with highThe risk of an adverse cardiac event in patients with high temperature difference is significantly higher than that intemperature difference is significantly higher than that in ACS patients with low temperature differenceACS patients with low temperature difference Stefanadis et al. J Am Coll Cardiol. 2001;37:1277-83Stefanadis et al. J Am Coll Cardiol. 2001;37:1277-83
  24. 24. Stefanadis et al. J Mol Cell Cardiol. 2000;32:43-52 Strong correlation between C-reactive protein (CRP) (and serum amyloid A (SAA) ) and the temperature differences
  25. 25. Administration of atorvastatin in patients with coronary arteryAdministration of atorvastatin in patients with coronary artery disease results in less heat production from the culprit lesion anddisease results in less heat production from the culprit lesion and less temperature difference.less temperature difference. Stefanadis et al. Eur Heart J (in press) StatinsNo statin Temperaturedifference 2.5 2.0 1.5 1.0 .5 0.0 -.5 P<0,001
  26. 26.  Toutozas et al reported correlation betweenToutozas et al reported correlation between temperature and expansive remodeling andtemperature and expansive remodeling and MMP-9 concentrationMMP-9 concentration  Verheye et al showed that temperatureVerheye et al showed that temperature heterogeneity was reduced after change fromheterogeneity was reduced after change from high to low-cholesterol diet in rabbits.high to low-cholesterol diet in rabbits. Toutouzas et al. Circulation. 2000;102:II-707; Toutouzas et al. J Am Coll Cardiol. 2001;37:356A Verheye et al. Circulation Supple Oct. 2001;
  27. 27. FutureFuture CombinationCombination with anatomical imaging methodswith anatomical imaging methods to yield additional functional information aboutto yield additional functional information about the lesionthe lesion
  28. 28. FutureFuture A combination ofA combination of ultrasound andultrasound and thermography couldthermography could provide thermal, andprovide thermal, and structural datastructural data valuable for detectingvaluable for detecting and determination ofand determination of functional status offunctional status of plaques.plaques.
  29. 29. IVUS or OCT + ThermographyIVUS or OCT + Thermography ActivityActivity ThermographyThermography Anatomy (shape)Anatomy (shape) IVUS - OCTIVUS - OCT ElasticityElasticity ElastographyElastography Chemical compositionChemical composition Integrated RFIntegrated RF BackscatteringBackscattering SpectroscopySpectroscopy
  30. 30. Conclusion:Conclusion:  As cardiology enters into the arena of vulnerable plaqueAs cardiology enters into the arena of vulnerable plaque and vulnerable patient, along with the other emergingand vulnerable patient, along with the other emerging diagnostic techniques such as OCT, elastography, anddiagnostic techniques such as OCT, elastography, and near infrared spectroscopy,near infrared spectroscopy, thermographythermography catheter iscatheter is ready to enter into cat labs.ready to enter into cat labs.  Clinical studies in 2002 and 2003 will shed light on howClinical studies in 2002 and 2003 will shed light on how we can utilize these emerging technologies to improvewe can utilize these emerging technologies to improve our ability for identifying patients at extreme risk ofour ability for identifying patients at extreme risk of coronary event, namely vulnerable patients.coronary event, namely vulnerable patients.  The ultimate solution must be sought in non-invasiveThe ultimate solution must be sought in non-invasive techniques where by developing a proper combination oftechniques where by developing a proper combination of novel serum markers and non-invasive imaging tools thenovel serum markers and non-invasive imaging tools the world of cardiology would be ready toworld of cardiology would be ready to attack the long-attack the long- standing dilemma of out-of-hospital sudden heart attackstanding dilemma of out-of-hospital sudden heart attack and coronary death.and coronary death.
  31. 31. ThermaStar Catheter Not cleared by the FDA and not available for commercial sale.
  32. 32. Center for Vulnerable Plaque ResearchCenter for Vulnerable Plaque Research Houston, TexasHouston, Texas Khawar Gul, MDKhawar Gul, MD Said Siadaty, MDSaid Siadaty, MD Sameh Naguib, MDSameh Naguib, MD Bujin Gu, PhDBujin Gu, PhD Reji John, MDReji John, MD Basit Malik, MDBasit Malik, MD KC Courian, MDKC Courian, MD Roxana Grausu, MDRoxana Grausu, MD Mohammad Madjid, MD, Ward Casscells, MD, James T. Willerson, MD, Morteza Naghavi, MDMohammad Madjid, MD, Ward Casscells, MD, James T. Willerson, MD, Morteza Naghavi, MD

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