The Most Attractive Hyderabad Call Girls Kothapet 𖠋 6297143586 𖠋 Will You Mis...
Krucoff infra redx_aha_2002_x2
1. VP.Org
November 16, 2002
Mitchell W. Krucoff, MD, FACC
Associate Professor Medicine/Cardiology
Duke University Medical Center
Director, Interventional Devices Clincal Trials
Duke Clinical Research Institute
2. Discrimination of Ex Vivo Lipid-Discrimination of Ex Vivo Lipid-
Rich Plaques in Human AortaRich Plaques in Human Aorta
Specimens with NIR SpectroscopySpecimens with NIR Spectroscopy
through Whole Bloodthrough Whole Blood
B.Marshik, H.Tan, J.Tang, A. Zuluaga,B.Marshik, H.Tan, J.Tang, A. Zuluaga,
A. Lindquist, P.R.Moreno, K.R.Purushothaman,A. Lindquist, P.R.Moreno, K.R.Purushothaman,
W.O’Connor, G.TearneyW.O’Connor, G.Tearney
3. First results on freshFirst results on fresh
human tissue sampleshuman tissue samples
through variable depthsthrough variable depths
of bloodof blood
(updated from TCT 2002 poster)(updated from TCT 2002 poster)
4. Tissue Evaluation by NIR SpectroscopyTissue Evaluation by NIR Spectroscopy
Absorbance of NIR light varies by wavelengthAbsorbance of NIR light varies by wavelength
Absorbance patterns (spectra) unique for different chemicalsAbsorbance patterns (spectra) unique for different chemicals
Reflection patterns (spectra) unique for different chemicalsReflection patterns (spectra) unique for different chemicals
5. NIR Spectra of Human Aorta SamplesNIR Spectra of Human Aorta Samples
Source: Infraredx, 2002
Normal 1
Normal 2
Plaque 1
Plaque2
Cholesterol
Collagen
Wavelength
(Intensity)
6. NIR Spectra of Human Aorta SamplesNIR Spectra of Human Aorta Samples
Source: Infraredx, 2002
Normal 1
Normal 2
Plaque 1
Plaque2
Cholesterol
Collagen
7. ChemometricsChemometrics
Set of methods to predict chemical properties of unknownSet of methods to predict chemical properties of unknown
samples using spectroscopy and linear algebrasamples using spectroscopy and linear algebra
Commonly used in pharmaceutical, chemical and foodCommonly used in pharmaceutical, chemical and food
processing; also being applied to glucose monitoringprocessing; also being applied to glucose monitoring
8. Advantages of NIR Spectroscopy +Advantages of NIR Spectroscopy +
Chemometrics for Coronary TCFA DetectionChemometrics for Coronary TCFA Detection
Identifies chemical composition ofIdentifies chemical composition of
vessel wallvessel wall
specificity and sensitivity > 85%specificity and sensitivity > 85%
potential to guide therapiespotential to guide therapies
3.2Fr coronary catheter compatible3.2Fr coronary catheter compatible
Works fast – insensitive to motionWorks fast – insensitive to motion
Chemometrics discriminatesChemometrics discriminates
chemical composition independentchemical composition independent
of blood depthof blood depth
no flushing neededno flushing needed
no tissue contactno tissue contact
9. Near Infrared (NIR) SpectroscopyNear Infrared (NIR) Spectroscopy
Previous ReportsPrevious Reports
1.1. Cassis, Lodder (1993)Cassis, Lodder (1993)
Discrimination of lipid-filled and normal rat aorta tissue specimensDiscrimination of lipid-filled and normal rat aorta tissue specimens
2.2. Jaross (1999)Jaross (1999)
Determined cholesterol content in human aorta tissue specimensDetermined cholesterol content in human aorta tissue specimens
3.3. Moreno (2002)Moreno (2002)
Identified lipid pool, thin cap, and inflammatory cells in human aortaIdentified lipid pool, thin cap, and inflammatory cells in human aorta
tissue specimenstissue specimens
4.4. Wang (2002)Wang (2002)
Analyzed lipid and protein content in carotid endarterectomy specimensAnalyzed lipid and protein content in carotid endarterectomy specimens
5.5. Neumeister, Jaross (2002)Neumeister, Jaross (2002)
Determined cholesterol and collagen content in human aorta tissue withDetermined cholesterol and collagen content in human aorta tissue with
NIR spectroscopyNIR spectroscopy
LimitationsLimitations: Not through blood, room temperature, fixed probe-target: Not through blood, room temperature, fixed probe-target
distance, tissue fixed or frozen/thawed (except Wang)distance, tissue fixed or frozen/thawed (except Wang)
10. Study PurposeStudy Purpose
NIR spectroscopy and chemometrics:NIR spectroscopy and chemometrics:
discriminate large lipid pool specimensdiscriminate large lipid pool specimens
from other tissue typesfrom other tissue types
using fresh human arterial tissueusing fresh human arterial tissue
through variable amounts of bloodthrough variable amounts of blood
11. InstrumentationInstrumentation
FOSS NIRSystems Model 6500FOSS NIRSystems Model 6500
½” diameter fiber optic SmartProbe™½” diameter fiber optic SmartProbe™
Central fiber delivery bundleCentral fiber delivery bundle
Outer fiber collection bundleOuter fiber collection bundle
Broad spectral range: 400 to 2500 nm.Broad spectral range: 400 to 2500 nm.
Sixty seconds for spectral acquisitionSixty seconds for spectral acquisition
12. TissueTissue
Human Aorta TissueHuman Aorta Tissue
Aorta from 72 human subjects (avg age 69.6 ±12.8)Aorta from 72 human subjects (avg age 69.6 ±12.8)
751 tissue specimens cut to 2x2 cm from diseased and751 tissue specimens cut to 2x2 cm from diseased and
non-diseased sitesnon-diseased sites
Stored in phosphate buffered saline solutionStored in phosphate buffered saline solution
Shipped on wet ice less then 24 hours after autopsyShipped on wet ice less then 24 hours after autopsy
13. NIR MethodNIR Method
Tissue placed on rubberTissue placed on rubber
mat in glass dishmat in glass dish
Blood and tissue at 38°CBlood and tissue at 38°C
NIR spectra acquired atNIR spectra acquired at
probe-to-tissue separationsprobe-to-tissue separations
0.0, 0.25, 0.5, 1.0, 1.5, 2.0, 2.50.0, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5
and 3.0 mmand 3.0 mm
Probe on z-stage micrometerProbe on z-stage micrometer
FOSS
Probe
Plaque Tissue
SampleRubber Mat
Blood Depth
Bovine Blood
Tissue Pins
Broadband
Light SourceDetector
Data
Acquisition
Computer
18. Example Spectra – 0 and 3 mmExample Spectra – 0 and 3 mm
.5
1
1.5
2
2.5
3
400 600 800 1000 1200 1400 1600 1800 2000 2200 2400
0.0 mm Normal
3.0 mm
0.0 mm Fibrotic
3.0 mm
0.0 mm Lipid Pool
3.0 mm
0.0 mm Calcific
3.0 mm
Wavelength (nm)
ABS.
21. Summary Prediction ResultsSummary Prediction Results
NIR (+) NIR (-) Results (a)
Lipid Pool (+)Lipid Pool (+) 164164 1616
Sensitivity:Sensitivity:
91%91%
No Lipid Pool (-)No Lipid Pool (-) 6666 484484
Specificity:Specificity:
88%88%
22. 0 mm 0.25 mm 0.5 mm 1.0 mm 1.5 mm 2.0 mm 3.0 mm
SENSSENS 86%86% 92%92% 92%92% 94%94% 92%92% 83%83% 86%86%
SPECSPEC 88%88% 87%87% 87%87% 90%90% 87%87% 85%85% 72%72%
Sample-to-Probe Depth PredictionsSample-to-Probe Depth Predictions
0.0 mm 0.25 mm 0.5 mm 1.0 mm 1.5 mm
2.0 mm 3.0 mm
SENSSENS SPECSPEC
23. ConclusionsConclusions
NIR can discriminate atherosclerotic plaqueNIR can discriminate atherosclerotic plaque
lipid poolslipid pools
through variable blood depthsthrough variable blood depths
with high sensitivity and high specificitywith high sensitivity and high specificity
Study illustrates the potential clinicalStudy illustrates the potential clinical
feasibility of near-infrared spectroscopy tofeasibility of near-infrared spectroscopy to
detect vulnerable plaque in perfused coronarydetect vulnerable plaque in perfused coronary
arteries.arteries.
24. Ongoing workOngoing work
Reproduce results with ex vivo coronaryReproduce results with ex vivo coronary
tissue through bloodtissue through blood
Complete prototype console with 5 msecComplete prototype console with 5 msec
spectral acquisitionspectral acquisition
Overcomes motionOvercomes motion
Complete prototype human use catheterComplete prototype human use catheter
with 2.5 mm optical penetration depthwith 2.5 mm optical penetration depth
Begin human studies – To discriminateBegin human studies – To discriminate
disrupted plaques from normal tissuesdisrupted plaques from normal tissues
through bloodthrough blood
25. VP.OrgVP.Org
November 16, 2002November 16, 2002
Mitchell W. Krucoff, MD, FACCMitchell W. Krucoff, MD, FACC
Associate Professor Medicine/CardiologyAssociate Professor Medicine/Cardiology
Duke University Medical CenterDuke University Medical Center
Director, Interventional Devices Clincal TrialsDirector, Interventional Devices Clincal Trials
Duke Clinical Research InstituteDuke Clinical Research Institute
Hinweis der Redaktion
Near Infrared Spectroscopy is performed by shining light on tissue, collecting the returned light, and measuring the absorbance as a function of wavelength.
Chemicals each have their own absorbance characteristics.
Mixtures of chemicals provide spectra that are convolutions of chemical spectra.
Similar tissue types have similar spectral signatures.
One tissue sample was measured at two spots – normal and diseased - with no blood. The normal spot was measured twice and the diseased spot was measured twice.
Differences between normal and plaque spectra can be seen visually.
Spectra of cholesterol and collagen are also shown, and account for some of the differences.
One tissue sample was measured at two spots – normal and diseased - with no blood. The normal spot was measured twice and the diseased spot was measured twice.
Differences between normal and plaque spectra can be seen visually.
Spectra of cholesterol and collagen are also shown, and account for some of the differences.
Chemometrics is a powerful tool for detecting subtle differences between spectra and is needed to distinguish TCFA’s from all other plaques and normal tissues through blood.
First, a calibration is performed. A database of spectra and histology is created. A correlation is determined and a model is built.
Second, the model is applied to new spectra, and histology is predicted.
NIR spectroscopy is most appropriate solution to challenge of TCFA detection. NIR spectroscopy can discriminate morphologically similar but chemically distinct tissue types.
Chemometrics works because differences in spectra taken at multiple sites are caused by changes in the chemical composition of the target. Chemometric algorithms are developed by correlating changes in spectra with changes in known targets. Chemometric algorithms can be defined to work independently of blood depth, by incorporating spectra with many blood types in the calibration process.