Medical Applications of Lasers

My research is in the field of biophotonics and biomedical optics. We use optical and photonic technologies to address fundamental and applied biomedical problems such as early diagnosis and effective treatment of disease. Three specific research areas are outlined below.

(1) Optical coherence tomography: OCT is an emerging biomedical imaging technique with very high spatial resolution. It relies on the wave nature of the light, and on the coherence properties of lasers, to generate micron-scale cross sectional subsurface images of tissue. OCT is similar to ultrasound, except reflections of near-infrared light, and not sound echoes, are used to produce a 2D or a 3D images of tissue microstructure. It is also possible to detect motion within the imaged object by measuring the frequency / phase shift of the OCT interference fringes, thus generating flow-sensitive (Doppler) maps of micro-circulatory blood perfusion; these can then be superposed upon the structural OCT images. Clinically, several uses of this imaging method appear attractive; for example, a high-resolution, high-speed fiber-optic based OCT probe may assist a physician in early detection and classification of cancers during gastro-intestinal endoscopy. We are currently pursuing this application with clinical colleagues at St. Michael’s hospital in Toronto. OCT’s ability to quantify blood flow dynamics in-vivo also opens up several exciting possibilities to study diseases and treatments with significant involvement of microcirculation; for example, we are quantifying the measured changes in blood flow during and following radiation and photodynamic therapies, in an effort to understand tissue responses, derive appropriate dose metrics, and optimize the delivery of these treatments. Outstanding biophysical issues in OCT include the origin of the tissue signal, correlation with standard histology, optimal signal processing and display methods, opto-electronic design of the OCT imager, use of contrast agents and novel contrast mechanisms (e.g., tissue optical birefringence), and OCT’s ultimate spatial and flow resolution limit.

Selected Publications (a more complete list and corresponding PDFs are available at: 
                                     http://www.uhnres.utoronto.ca/labs/biophotonics/staff/avitkin.htm)

• Leung  MKK, Mariampillai A, Standish BA, Lee KKC, Munce NR, Vitkin IA, Yang VXD, High-power wavelength-swept laser in Littman telescope-less polygon filter and dual amplifier configuration for multichannel optical coherence tomography, Opt Lett  34 2814-2816, 2009.
• Standish BA, Lee KKC, Jin X, Smolen J, Mariampillai A, Munce NR, Wilson BC, Vitkin IA, Yang VXD, Interstitial Doppler optical coherence tomography as a local tumour necrosis predictor in photodynamic therapy of prostatic carcinoma: An in-vivo study, Cancer Res 68 9987-95, 2008. (featured article on journal cover).
• Douplik BA, Morofke D, Chiu S, Bouchelev V, Mao YI, Yang VXD, Vitkin IA, In vivo real time monitoring of vasoconstriction and vasodilation by a combined diffuse reflectance spectroscopy and Doppler optical coherence tomography approach, Lasers Surg Med40 323-31, 2008
• Mariampillai A, Standish BA, Moriyama EH, Khurana M, Munce NR, Leung MKK, Jiang J, Cable A, Wilson BC, Vitkin IA, Yang YXD, Speckle variance detection of microvasculature using swept-source optical coherence tomography, Opt Lett 33 1530-32, 2008
• Liu GY, Mariampillai A, Standish BA, Munce NR, Gu X, Vitkin IA, High power wavelength linearly swept mode locked fiber laser for OCT imaging, Opt Express 16 14095-105, 2008
• Standish BA, Jin X, Smolen J, Mariampillai A, Munce NR, Wilson BC, Vitkin IA, Yang VXD, Interstitial Doppler optical coherence tomography monitors microvascular changes during photodynamic therapy in a Dunning prostate model under varying treatment conditions, J Biomed Opt 12 034022, 2007
• Munce NR, Yang VXD, Standish BA, Qiang B, Butany J, Courtney BK, Graham JJ, Dick AJ, Strauss BH, Wright GA, Vitkin IA, Ex-vivo imaging of chronic total occlusions using forward-looking optical coherence tomography, Lasers Surg Med 39 28-35, 2007
• Morofke D, Kolios MC, Vitkin IA, Yang VXD, Wide dynamic range detection of bi-directional flow in Doppler optical coherence tomography using 2-dimensional Kasai estimator, Opt Lett 32 253-55, 2007
• Mariampillai A, Standish BA, Vitkin IA, Yang VXD, Retrospectively gated 2D blood flow  imaging at 1000 frames per second and 4D imaging at video rates with a swept source Doppler optical coherence tomography system, Opt Express 15 1627-38, 2007
• Yang VXD, Vitkin IA, Principles of Doppler optical coherence tomography, in Handbook of Optical Coherence Tomography in Cardiology, edited by Evelyn Regar, Ton van Leeuwen and Patrick Serruys (Taylor and Francis Medical, Oxford, UK), chapter 32, 2006
• Skliarenko JV, Lunt SJ, Gordon ML, Vitkin IA, Milosevic M, Hill RP, Effects of vascular disrupting agent ZD6126 on interstitial fluid pressure and cell survival in tumours, Cancer Res 66 2074-80, 2006
• Yang VXD, Himmer PA, Standish BA, Mao L, Jafari R, Munce N, Dickensheets DL, Vitkin IA, Doppler optical coherence tomography with micro-electro-mechanical membrane mirror for high-speed dynamic focus tracking, Opt Lett 31 262-64, 2006
• Yang VXD, Lui T, Standish BA, Mao L, Sinclair M, Jafari R, Munce N, Marcon NE, Kucharczyk W, Wilson BC, Vitkin IA, Interstitial Doppler optical coherence tomography, Opt Lett 30 1791-93, 2005

(2) Tissue polarimetry: Polarization properties of light are widely used in science, technology and industry for detailed examinations of materials (ellipsometry, nondestructive evaluation, remote sensing).  However, polarized light uses in biomedicine are severely compromised by tissue multiple scattering which depolarizes the light.  We are developing experimental and theoretical methods to enable tissue polarimetry, by maximizing the detection of polarization-preserving photons, accounting for the effects of multiple scattering, and deriving intrinsic tissue polarization metrics (e.g, linear birefringence, circular birefringence, depolarization) from the measured polarimetric data.  These methods are used to study the anisotropic (birefringent) nature of cardiac tissues, and its alterations following a heart attack and then following stem-cell-based regenerative treatments.  In addition, the potential to detect small values of optical activity (circular birefringence) may offer a way to non-invasively quantify the concentration of optically active (chiral) tissue metabolites such as glucose.  Non-invasive glucose monitoring in diabetic patients continues to be a major unsolved problem in clinical medicine, and our ability to extract small chiral asymmetries from the measured tissue polarization signals suggests a promising route towards a possible solution. Cancer applications are also possible, in that pathologic tissue often exhibits altered extracellular matrix microstructure that may have a distinct polarization signature.  These and other applications will benefit from improved technologies, and we are investigating experimental (polarization modulation with synchronous detection, imaging and spectroscopic extensions, faster data acquisition, tissue probe development) and theoretical (polarization-sensitive Monte Carlo simulation, polar decomposition of tissue Mueller matrix) refinements to our tissue polarimetry platform. 

Selected Publications (a more complete list and corresponding PDFs are available at: 
                                     http://www.uhnres.utoronto.ca/labs/biophotonics/staff/avitkin.htm)

• Ghosh N, Wood MFG, Vitkin IA, Polarimetry in turbid, birefringent, optically active media: A Monte Carlo study of Mueller matrix decomposition in the backscattering geometry, J Appl Phys 105 102023-8, 2009
• Ghosh N, Wood MFG, Li S, Weisel R, Wilson BC, Li R-K, Vitkin IA, Mueller matrix decomposition for polarized light assessment of complex turbid media such as biological tissues, J Biophoton 2 145-56, 2009
• Wood MFG, Ghosh N, Moriyama EH, Wilson BC, Vitkin IA,  Proof-of-principle demonstration of a Mueller matrix decomposition method for polarized light-based tissue characterization in vivo, J Biomed Opt 14 014029-4, 2009
• Wilson BC, Vitkin IA, Matthews DL, The potential of biophotonic techniques in stem cell tracking and monitoring of tissue regeneration applied to cardiac stem cell therapy, J Biophoton 3 1-13, 2009
• Guo X, Wood MFG, Vitkin IA, A Monte Carlo study of penetration depth and sampling volume of polarized light in turbid media, Opt Communic 281 380-87, 2008
• Wood MFG, Côté D, Vitkin IA, Combined optical intensity and polarization methodology for analyte concentration determination in simulated optically clear and turbid biological media, J Biomed Opt 13 044037, 2008
• Wood MFG, Guo X, Vitkin IA, Polarized light propagation in multiply scattering media exhibiting both linear birefringence and optical activity: Monte Carlo model and experimental methodology, J Biomed Opt 12 14029, 2007
• Côté D, Vitkin IA, Robust concentration determination of optically active molecules in turbid media with validated 3-D polarization sensitive Monte Carlo simulation, Opt Express 13 148-63, 2005
• Côté D, Vitkin IA, Balanced detection for low-noise precision polarimetric measurements of optically-active, multiply-scattering tissue phantoms, J Biomed Opt 9 213-20, 2004

(3) Opto-thermal therapies / optical fiber sensors: Thermal therapies using laser, microwave, or ultrasound energy sources offer several potential advantages for the treatment of solid tumours, for example in the brain or prostate. They are minimally invasive because they employ thin interstitial sources (optical fibers, microwave antennas, ultrasound applicators) to heat the target volume, obviating the need for extensive surgery; they can preserve the underlying tissue architecture; and the dividing line between thermally necrosed and viable tissue is sharp, making it possible to spare surrounding normal tissue if the treatment volume conforms to the 3D shape of the tumour. One important but poorly understood issue is the biophysics of thermal lesion formation. This requires extensive experimental measurements and three-dimensional modeling of energy propagation, temperature increases, and damage kinetics; in particular, the effects of blood flow and changing tissue properties (which makes the treatment process highly dynamic and variable) are being examined. The progress of thermal therapy can be monitored via magnetic resonance or ultrasound imaging, enabling the physician to alter the treatment in real time as required; however, these methods are expensive and often impractical. We are interested in using intestitial point optical measurements (fluence or radiance) to infer the important events during the course of thermal therapy, such as the onset of coagulation, the three-dimensional extend and location of the coagulation boundary, and the undesirable (and hopefully avoidable) occurrence of tissue charring. The clinical utility of optical monitoring as a practical feedback / control method for interstitial thermal therapy is currently being examined.

Selected Publications (a more complete list and corresponding PDFs are available at: 
                                     http://www.uhnres.utoronto.ca/labs/biophotonics/staff/avitkin.htm)

• Chin LCL, Lloyd B, Whelan WM, Vitkin IA, Interstitial point radiance spectroscopy, J Appl Phys 105 102025-11, 2009
• Chin LCL, Whelan WM, Vitkin IA, Determination of the optical properties of turbid media using relative interstitial radiance measurements: Monte Carlo study, experimental verification and sensitivity analysis, J Biomed Opt 12 036706, 2007
• Rink A, Lewis DF, Varma S, Vitkin IA, Jaffray DA, Temperature and hydration effects on absorbance spectra and radiation sensitivity of a radiochromic medium, Med Phys 35 4545-55, 2008
• Chin LCL, Whelan WM, Vitkin IA, Perturbative diffusion theory formalism for interpreting temporal light intensity changes during laser interstitial thermal therapy:  implications for point optical monitoring of coagulation boundary dynamics, Phys Med Biol52 1659-74, 2007
• Chin LCL, Whelan WM, Vitkin IA, Information content of point radiance measurements in turbid media:  Implications for interstitial optical property quantification, Appl Opt 45 2101-14, 2006
• Rink A, Vitkin IA, Jaffray DA, Suitability of radiochromic medium for real-time optical measurements of ionizing radiation dose, Med Phys 32 1140-55, 2005
• Rink A, Vitkin IA, Jaffray DA, Characterization and real-time optical measurements of the ionizing radiation dose response for a new radiochromic medium, Med Phys 32 2510-16, 2005
• Whelan WM, Davidson S, Chin LCL, Vitkin IA, Strategy for monitoring laser thermal therapy via changes in opto-thermal properties of heated tissues, Intern J Thermophys 26 233-41, 2005
• Davidson S, Vitkin IA, Whelan WM, Characterization of measurement artifacts in fluoroptic temperature sensors: Implications for laser thermal therapy at 810 nm, Lasers Surg Med 36 289-96, 2005
  
• Chin LCL, Wilson BC, Whelan WM, Vitkin IA, Radiance monitoring of the extent of tissue coagulation during laser interstitial thermal therapy, Opt Lett 29 259-61, 2004
  
  

General Interest:
Selected Publications (a more complete list is available at: http://www.uhnres.utoronto.ca/labs/biophotonics/staff/avitkin.htm)

• Vitkin IA, Shedding some light on the blue veins enigma, Optics & Photonics News 8 (6), 39-42, 1998

• Vitkin IA, Polarized light, optical activity, and the asymmetry of life, Optics & Photonics News 7 (7), 30-3, 1996

Link to Pubmed Publications

Graduate Students:

• Sanaz Alali
• Marika Archambault-Wallenberg - Polarimetry and non-linear microscopy for characterizing tissue anisotropy (MSc)
• Bahar Davoudi - Optical coherence tomography for microstructural and microvascular assessment of tissue toxicity following abdominal radiotherapy (PhD)
• Michael Leung - Optical coherence tomography: technology development and microvascular response monitoring in radiotherapy (MSc)
• Adrian Mariampillai - Algorithm development for sensitive detection of tissue microcirculation using optical coherence tomography (PhD)
• Michael Wood - Tissue polarimetry: Monte Carlo model development and biomedical applications in cardiology (PhD)
  
  

Post-doctoral Fellow(s):

• Dr. Nirmalya Ghosh – Mueller matrix decomposition for extracting individual biological metrics from tissue polarimetry signals