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Detection of vp with spectroscopy

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Detection of vp with spectroscopy

  1. 1. Identifying Vulnerable Plaque with Spectroscopy Strategic Plan: Determine pH and Lactate by Fiber Optic Catheter and Near Infrared (NIR) Spectroscopy By Tania Khan UMass Medical, THI, UTH, WPI, LMNOP….ubiquitous!
  2. 2. Spectroscopy Basics In general, spectroscopy is the use of the electromagnetic spectrum to perform physical or chemical analysis
  3. 3. Spectroscopy Basics 1) Non-ionizing radiation (light) is used to interrogate sample E=hc/λ. Example wavelengths: ♦ Visible 0.4 – 0.7 microns ♦ Near-Infrared 0.7 – 2.5 microns ♦ Infrared 2.5 – 10 microns 2) Wavelengths are separated for detection 3) Detector converts intensity to voltage signal as a function of wavelength Energy is either absorbed, transmitted, or reflected by molecules present in sample
  4. 4. Other Investigators of Vulnerable Plaque Focus on lipid accumulation to predict vulnerability ♦ Feld et.al. (MIT) – Raman spectroscopy: currently working on building Raman fiber optical catheter; TC, logistic regression – FTIR spectroscopy: only for ex-vivo pathological identification (microscopy) ♦ Lodder et.al. (Univ. of Kentucky) – NIR Catheter to study in-vivo rabbits cholesterol contents; source-detector separation not identified or optimized – Lasers and super computers calculations does not take into account inflammatory responses; not full
  5. 5. Fig. 1. (a) NIR spectra of several pure compounds of an arterial intima; (b) NIR spectra of the model mixtures without water; (c) NIR spectra of the model mixtures with water; (d) NIR spectra of aortic specimens (1 Micron=Wavelength 1000 nm). ♦Jaross et.al. (Germany) – FT-NIR spectroscopy and Partial Least Squares for total cholesterol Atherosclerosis 147 (1999): 327- 337.
  6. 6. Dr. Soller’s Lab ♦ Optical measurement of tissue pH: Patent #5,813,403 ♦ Uses Partial Least Squares to calibrate the spectrometer to pH (multivariate; several wavelengths contribute to pH determination) ♦ Based on full spectrum analysis of pH-induced change of proteins ♦ Lessons Learned: volume of optical measurement >> volume of electrode measurement ♦ Tissue pH heterogeneity can be solved with smaller optical probe (my research) ♦ Optimize source-detector separations with knowledge of optical properties as a function of wavelength (Monte Carlo Modeling)
  7. 7. Hypotheses Focuses of inflammatory response that leads to vulnerability. Activated macrophages make environment acidic. Lactate predominates due to anaerobic metabolism. ♦ Smaller source-detector separations may improve multivariate calibration to reference pH or lactate measurements. ♦ Lactate concentration and/or tissue pH may be better predictors of plaque vulnerability. ♦ Near infrared spectroscopy, combined with multivariate calibration, will assess the lactate concentration and pH; distinguish between different stages of atherosclerotic plaques.
  8. 8. NIR Spectrum 0.15 0.2 0.25 0.3 0.35 0.4 0.45 1700 1800 1900 2000 2100 2200 2300 2400 2500 wavelength (nm) arbitraryunits(absorbance) Near infrared absorbance of lactic acid
  9. 9. Diffuse Reflectance NIR Spectroscopy ♦ Absorption is due to combinations and overtones of fundamental vibrations ♦ Reflectance Mode: path length varies for different tissues and wavelengths ♦ Catheter geometry and optical coupling important ♦ Small source-detector separations: light penetrates tissue while restricting volume interrogated plaque interface to spectrometer ~3 mm
  10. 10. Tissue Penetration Study ♦ NIR reflectance off mirror 100% signal ♦ Tissue stacks placed on probe end ♦ Incremental increase in signal with mirror ~50 um slices Aortic tissue Mirror-Enhanced Reflectance Tissue Absorption & Scattering Mirror Fiber Probe
  11. 11. Plaque Measurements ♦ Full spectrum absorbance data (400-2500 nm, FOSS NIRSystems) ♦ 24 gauge needle thermistors (Cole-Parmer model 8402-20) ♦ 750 µm diameter pH electrodes (Microelectrodes, MA) ♦ Punch needle biopsy 1 – 5 mg pieces for lactate assay ♦ Measurements on plaque in 37° incubator ♦ Histology on the rest of the plaque °C pH spectrometer 10-20 m m ~2 mm
  12. 12. Small Diameter Probe ♦ Preliminary visible/NIR spectra (UMass Worcester) Visible Spectra 0.1 0.15 0.2 0.25 0.3 0.35 0.4 400 500 600 700 800 900 1000 1100 Wavelengt h Fibrofatty Ulcerated FTNIR Plaque 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1000 1100 1200 1300 1400 1500 1600 1700 1800 1900 w avelength A.U. fibrofatty ulcerated area
  13. 13. Large Diameter Probe: Full Spectrum of Rabbit Aortic Arch Aortic Arch -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 400 550 700 850 1000 1150 1300 1450 1600 1750 1900 2050 2200 2350 2500 wavelength absorbance aortic arch WHHL 0.9 mm NZ aortic arch WHHL New Zealand
  14. 14. Long-Term Goals ♦ Determine a mathematical model to train the spectrometer to determine pH and lactate ♦ Correlate spectroscopically measured pH and lactate to histology ♦ Determine optimal penetration depth and the minimum number of wavelengths needed for accurate, repeatable plaque measurements ♦ Incorporate linear scanning or detector arrays for a “spectral image” of vessel wall ♦ Locate and identify vulnerable plaque with Near Infrared Spectroscopy
  15. 15. Plan for Next 4 Weeks: ♦ Identify and assess lactate assay (Dr. Dasgupta’s lab) ♦ Identify appropriate culture medium and environment (DMEM, pO2, pCO2, other parameters) ♦ Calibrate pH electrodes, temperature probes, etc. ♦ Test on normal and atherosclerotic rabbit aorta in culture ♦ Conduct depth penetration study with current probe (~1 cm) ♦ Receive parts for small dimension probe (~3 mm) ♦ Plan pH, lactate, fresh human specimens and spectroscopic analysis study ♦ Get THI lab up and running!! NIR Spectroscopy: the right key to open the lock!

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