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  • 1. Raman Spectroscopy in Medicine Werner Gellermann, Ph.D. Professor, Department of Physics University of Utah Salt Lake City, Utah 84112
  • 2. Center for Biomedical Optics Laser Institute Igor Ermakov, Ph.D. Robert McClane Maia Ermakova Steven Wintch Lihong Jin Mohsen Sharifzadeh Moran Eye Center Paul Bernstein, Ph.D, M.D. Nikita Katz, Ph.D Da-You Zhao, M.D. Prakash Bohsale, M.D. Department of Dermatology Tissa Hata, M.D. Lynn Pershing, Ph.D. Theresa Scholz, M.D. Funding: National Institute of Health National Eye Institute Research to Prevent Blindness, Inc. Spectrotek, L.C. Projects Raman Detection of Carotenoid Pigments Coherence Domain Optical Imaging Photodynamic Therapy Solid State Laser Development
  • 3. Age-related Macular Degeneration (AMD) Healthy retina Dry AMD Wet AMD
  • 4. AMD Risk versus Age 0% 5% 10% 15% 20% 25% 30% 20 50 70
  • 5. Carotenoids in Human Retina • Macula: retinal area of highest visual acuity • High concentrations of xanthophyll carotenoids lutein and zeaxanthin (yellow coloration) • Role of carotenoids: optical filtering; antioxidants (protection of macula from light-induced damage) • Individuals with high dietary intakes and blood levels of lutein and zeaxanthin have a lower rate of visual loss from age-related macular degeneration (AMD), the leading cause of blindness in the elderly. Macula
  • 6. Raman Scattering Sir Chandrasekhar Raman, Nobel Prize in Physics 1930 Vibronic Energy Levels Laser light Raman scattered light Carotenoid molecules shift blue laser light color to green
  • 7. Raman Spectroscopy of Carotenoids Carotenoids have a characteristic Raman spectral “fingerprint” generated from vibrations of their long carbon backbone. Any other molecule would produce a different fingerprint (peaks with different locations and intensities) 8 0 0 1 2 0 0 1 6 0 0 Raman Shift / cm - 1 15 28 5 cm -1 1 158 9 cm -1 C- C O H O H C- C C= C C-CH3 f ilt er paper
  • 8. Portable Clinical Raman Instrument CCD Camera Fiber Bundle Ar+ laser V H G Eye Eyepiece Shutter L E D Synchronizing electronics L3 BS M NF F L2 L1 Fiber L4 TB
  • 9. Loss of Macular Pigment with Increasing Age
  • 10. Comparison of Health Screening Tests Cholesterol Test Heart Disease PSA Test Prostate Cancer PAP Smear Cervical Cancer Mammography Breast Cancer Bone Density Test Osteoporosis
  • 11. Carotenoids in other Tissues Largest Organ of the Human Body ? ! Skin !
  • 12. Sunlight - induced Singlet Oxygen / Reactive Oxygen Species 1Sens 3Sens* 1 Sens*hν 3 O2 Epidermal Lipids Epidermal Protein Damage Epidermal DNA Damage Skin Photosensitizers Porphyrins, Flavins, Melanins, etc. Lipid Peroxyl Radical Chain Reaction 1O2 carotenoids
  • 13. • Most potent singlet oxygen quenchers found in the human body • Predominant carotenoids found in skin • Lipophilic molecules making them especially well suited to act as chain-breaking antioxidants in the lipid-rich epidermis • Resonant Raman spectroscopy for non-invasive detection ? Wavelength, nm 300 400 500 600Opticaldensity 0.00 0.04 0.08 0.12 β,β-carotene lycopene Absorption Lycopene and β -Carotene
  • 14. Typical Raman spectra for human ventral forearm skin, measured in vivo. Illumination conditions: 488 nm laser wavelength, 10 mW laser power, 20 sec exposure time, 2 mm spot size. Spectrum shown at top is spectrum obtained directly after exposure, and reveals broad, featureless, and strong fluorescence background of skin with superimposed sharp Raman peaks characteristic for carotenoid molecules. Spectrum at bottom is difference spectrum obtained after fitting fluorescence background with fifth-order polynomial and subtracting it from top spectrum. The main characteristic carotenoid peaks are clearly resolved with good signal-to-noise ratio, at 1159 and 1524 cm-1 . Raman Spectra of Human Skin Measured in Vivo Wavenumber, cm-1 800 1200 1600 RamanIntensity,10 3 Counts 0 5 10 200 300 1124 cm-1 1524 cm-1
  • 15. Non-Invasive Laser Raman Detection of Carotenoids in Human Skin • Feasible to assess carotenoid content in large numbers of subjects • Permits study of correlation between disease and tissue antioxidant levels • Also: Nutrition (bioavailability studies, uptakes, correlation with blood levels, etc.)
  • 16. • Measured carotenoid antioxidants in living human tissues in vivo using novel non- invasive optical method • Sensitive, specific and precise optical technique • Future use: Improve the health of the world with simple high-tech screening test Summary
  • 17. Patents