Interpretation and medical application of laser biospeckle

Laser biospeckle is the dynamic laser speckle pattern produced by illuminating tissue with laser light. The dynamic nature of the speckle indicates the movement of particles in the tissue, particularly blood cells. Contrast analysis of laser biospeckle generates flow maps showing areas of higher or lower blood flow, for example vessels or background perfusion, and can detect changes in flow associated with inflammation, wounds or disease. This thesis presents methods of analysing laser speckle contrast, particularly a method using multiple camera exposures to generate the find the same spectral information from laser speckle fluctuations as laser Doppler, allowing quantitative measurements of flow. This work also presents a correction for spatial averaging in speckle, and confirms the validity of that correction using simulation and experiment. Spatial effects on laser speckle imaging techniques in tissues are tested experimentally. Multiple exposure speckle imaging was tested in vivo in a variety of situations, and clinically in measurements around diabetic foot ulcers. Measurements were made on three groups: patients with diabetic foot ulcers, patients with peripheral vascular disease, and normal control subjects. No difference in mean flow speed was found between the groups, but a significant difference in mean static contrast, indicating blood volume in tissue, was found.

[1]  G. Tribillon,et al.  Biological Activity Measurement on Botanical Specimen Surfaces Using a Temporal Decorrelation Effect of Laser Speckle , 1989 .

[2]  J. Tulip,et al.  A comparison of two laser-based methods for determination of burn scar perfusion: laser Doppler versus laser speckle imaging. , 2005, Burns : journal of the International Society for Burn Injuries.

[3]  Bernard Choi,et al.  Characterization of a laser speckle imaging instrument for monitoring skin blood flow dynamics , 2005, SPIE BiOS.

[4]  Héctor Rabal,et al.  Numerical model for dynamic speckle: an approach using the movement of the scatterers , 2003 .

[5]  Vyacheslav Kalchenko,et al.  Visualisation of blood and lymphatic vessels with increasing exposure time of the detector , 2013 .

[6]  Gert E. Nilsson,et al.  Evaluation of a Laser Doppler Flowmeter for Measurement of Tissue Blood Flow , 1980, IEEE Transactions on Biomedical Engineering.

[7]  Kevin R. Forrester,et al.  A laser speckle imaging technique for measuring tissue perfusion , 2004, IEEE Transactions on Biomedical Engineering.

[8]  P O Byrne,et al.  A laser Doppler scanner for imaging blood flow in skin. , 1991, Journal of biomedical engineering.

[9]  Sean J. Kirkpatrick,et al.  Laser speckle contrast imaging for the quantitative assessment of flow , 2009, BiOS.

[10]  Gert E. Nilsson,et al.  A New Instrument for Continuous Measurement of Tissue Blood Flow by Light Beating Spectroscopy , 1980, IEEE Transactions on Biomedical Engineering.

[11]  A. P. Shepherd,et al.  Laser-Doppler Blood Flowmetry , 2010, Developments in Cardiovascular Medicine.

[12]  G. G. Romero,et al.  Bio-speckle activity applied to the assessment of tomato fruit ripening , 2009 .

[13]  F F de Mul,et al.  Monte Carlo simulations of laser Doppler blood flow measurements in tissue. , 1990, Applied optics.

[14]  Sean J. Kirkpatrick,et al.  What is the proper statistical model for laser speckle flowmetry? , 2008, SPIE BiOS.

[15]  Donald D Duncan,et al.  Detrimental effects of speckle-pixel size matching in laser speckle contrast imaging. , 2008, Optics letters.

[16]  J. Walkup,et al.  Statistical optics , 1986, IEEE Journal of Quantum Electronics.

[17]  J. David Briers,et al.  Capillary-blood-flow monitoring using laser speckle contrast analysis (LASCA): improving the dynamic range , 1997, Photonics West - Biomedical Optics.

[18]  Scott L. Rudder,et al.  Hybrid ECL/DBR wavelength and spectrum stabilized lasers demonstrate high power and narrow spectral linewidth , 2006, SPIE LASE.

[19]  John Tulip,et al.  Spatially resolved diffuse reflectance for the determination of tissue optical properties and metabolic state , 2000, Photonics West - Biomedical Optics.

[20]  Evan Hirst,et al.  Measurement of directed blood flow by laser speckle , 2011, BiOS.

[21]  J. A. Pomarico,et al.  Compact device for assessment of microorganism motility , 2004 .

[22]  Astro Ltd,et al.  Combined application of dynamic light scattering imaging and fluorescence intravital microscopy in vascular biology , 2010 .

[23]  B. Pogue,et al.  Tutorial on diffuse light transport. , 2008, Journal of biomedical optics.

[24]  R. Nossal,et al.  Model for laser Doppler measurements of blood flow in tissue. , 1981, Applied optics.

[25]  Bernard Choi,et al.  Impact of velocity distribution assumption on simplified laser speckle imaging equation. , 2008, Optics express.

[26]  Bengt Fagrell Peripheral Vascular Diseases , 1990 .

[27]  Marcelo Trivi,et al.  Differentiation of the drying time of paints by dynamic speckle interferometry , 2009 .

[28]  Roberto A. Braga,et al.  Biospeckle laser spectral analysis under Inertia Moment, Entropy and Cross-Spectrum methods , 2009 .

[29]  Anna Devor,et al.  Determination of optimal exposure time for imaging of blood flow changes with laser speckle contrast imaging. , 2005, Applied optics.

[30]  A. M. Enes,et al.  Biological feature isolation by wavelets in biospeckle laser images , 2007 .

[31]  W. J. Tom,et al.  Robust flow measurement with multi-exposure speckle imaging. , 2008, Optics express.

[32]  Xiaowei Liu,et al.  Effects of gemfibrozil on outcome after permanent middle cerebral artery occlusion in mice , 2009, Brain Research.

[33]  Andreas R. Luft,et al.  Imaging the development of an ischemic core following photochemically induced cortical infarction in rats using Laser Speckle Contrast Analysis (LASCA) , 2006, NeuroImage.

[34]  L. W. Winchester,et al.  Measurement of retinal blood velocity , 2006, SPIE BiOS.

[35]  Phillip B. Jones,et al.  Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia. , 2008, Journal of biomedical optics.

[36]  Douglas J. Durian,et al.  Investigating non-Gaussian scattering processes by using nth-order intensity correlation functions , 1999 .

[37]  J. Tulip,et al.  Endoscopic laser speckle imaging of tissue blood flow: Applications in the human knee , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[38]  O. B. Thompson,et al.  Spectral density and tissue perfusion from speckle contrast measurements , 2008, SPIE BiOS.

[39]  Héctor Rabal,et al.  Dynamic speckle processing using wavelets based entropy , 2005 .

[40]  Evan Hirst,et al.  Is there a difference between laser speckle and laser Doppler in depth sensitivity? , 2011, BiOS.

[41]  Ton van Leeuwen,et al.  Twente Optical Perfusion Camera: system overview and performance for video rate laser Doppler perfusion imaging. , 2009, Optics express.

[42]  J. Tulip,et al.  Comparison of laser speckle and laser Doppler perfusion imaging: Measurement in human skin and rabbit articular tissue , 2002, Medical and Biological Engineering and Computing.

[43]  Quantitative blood flow measurements with Multi-Exposure Speckle contrast imaging , 2008, 2008 Conference on Lasers and Electro-Optics and 2008 Conference on Quantum Electronics and Laser Science.

[44]  G. A. Holloway,et al.  An Instrument to Measure Cutaneous Blood Flow Using the Doppler Shift of Laser Light , 1978, IEEE Transactions on Biomedical Engineering.

[45]  Karin Wårdell,et al.  Laser Doppler perfusion,monitoring and imaging , 2003 .

[46]  J. Goodman Speckle Phenomena in Optics: Theory and Applications , 2020 .

[47]  Noninvasive Blood Flow Imaging for Real-Time Feedback During Laser Therapy of Port Wine Stain Birthmarks , 2008 .

[48]  M. Moskowitz,et al.  Dynamic Imaging of Cerebral Blood Flow Using Laser Speckle , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[49]  J. D. Briers,et al.  A note on the statistics of laser speckle patterns added to coherent and incoherent uniform background fields, and a possible application for the case of incoherent addition , 1975 .

[50]  A. Dale,et al.  Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. , 2003, Optics letters.

[51]  Marcelo Trivi Dynamic Speckle: Origin and Features , 2008 .

[52]  Yang Zhao,et al.  Point-wise and Whole-field Laser Speckle Intensity Fluctuation Measurements Applied to Botanical Specimens , 1997 .

[53]  O. B. Thompson,et al.  Measuring Doppler-like power spectra and dermal perfusion using laser speckle contrast with multiple exposures , 2010, BiOS.

[54]  G. Holloway,et al.  Laser Doppler measurement of cutaneous blood flow. , 1977, The Journal of investigative dermatology.

[55]  Bernard Choi,et al.  Magnetomotive laser speckle imaging. , 2010, Journal of biomedical optics.

[56]  Roberto A. Braga,et al.  Detection of fungi in beans by the laser biospeckle technique , 2005 .

[57]  Evan Hirst,et al.  Correction for spatial averaging in laser speckle contrast analysis , 2011, Biomedical optics express.

[58]  J. D. Briers,et al.  The statistics of fluctuating speckle patterns produced by a mixture of moving and stationary scatterers , 1978 .

[59]  G. Nilsson,et al.  Laser Doppler perfusion imaging by dynamic light scattering , 1993, IEEE Transactions on Biomedical Engineering.

[60]  Igor Meglinski,et al.  Online object oriented Monte Carlo computational tool for the needs of biomedical optics , 2011, Biomedical optics express.

[61]  A. F. Fercher,et al.  Laser Speckle Technique For The Visualization Of Retinal Blood Flow , 1983, Other Conferences.

[62]  Bernard Choi,et al.  Linear response range characterization and in vivo application of laser speckle imaging of blood flow dynamics. , 2006, Journal of biomedical optics.

[63]  Héctor Rabal,et al.  Analysis of bacterial chemotactic response using dynamic laser speckle. , 2009, Journal of biomedical optics.

[64]  Donald D Duncan,et al.  The copula: a tool for simulating speckle dynamics. , 2008, Journal of the Optical Society of America. A, Optics, image science, and vision.

[65]  R Marchesini,et al.  A phantom with tissue‐like optical properties in the visible and near infrared for use in photomedicine , 2001, Lasers in surgery and medicine.

[66]  Ulrich Dirnagl,et al.  Functional imaging with Laser Speckle Contrast Analysis: Vascular compartment analysis and correlation with Laser Doppler Flowmetry and somatosensory evoked potentials , 2006, Brain Research.

[67]  Mike Andrews,et al.  Measurement of dynamic scattering beneath stationary layers using multiple-exposure laser speckle contrast analysis , 2013, Photonics West - Biomedical Optics.

[68]  C. Riva,et al.  Laser Doppler measurements of blood flow in capillary tubes and retinal arteries. , 1972, Investigative ophthalmology.

[69]  J. Goodman Some effects of target-induced scintillation on optical radar performance , 1965 .

[70]  Erwin Hondebrink,et al.  Time domain algorithm for accelerated determination of the first order moment of photo current fluctuations in high speed laser Doppler perfusion imaging , 2009, Medical & Biological Engineering & Computing.

[71]  Béla Hopp,et al.  Real correlation time measurement in laser speckle contrast analysis using wide exposure time range images. , 2009, Applied optics.

[72]  O. B. Thompson,et al.  Spatial and temporal effects in speckle perfusion measurement , 2009, BiOS.

[73]  Donald D Duncan,et al.  Can laser speckle flowmetry be made a quantitative tool? , 2008, Journal of the Optical Society of America. A, Optics, image science, and vision.

[74]  Rolf B. Saager,et al.  Multilayer silicone phantoms for the evaluation of quantitative optical techniques in skin imaging , 2010, BiOS.

[75]  J. D. Briers,et al.  Laser speckle contrast analysis (LASCA) for blood flow visualization: improved image processing , 1998, Photonics West - Biomedical Optics.

[76]  Erwin Hondebrink,et al.  Experimental comparison of perfusion imaging systems using multi-exposure laser speckle, single-exposure laser speckle, and full-field laser Doppler , 2012, Other Conferences.

[77]  G J Tearney,et al.  Determination of Teflon thickness with laser speckle. I. Potential for burn depth diagnosis. , 1996, Applied optics.

[78]  J D Briers,et al.  Laser speckle contrast analysis (LASCA): a nonscanning, full-field technique for monitoring capillary blood flow. , 1996, Journal of biomedical optics.

[79]  V. V. Tuchin,et al.  Towards the nature of biological zero in the dynamic light scattering diagnostic modalities , 2013 .

[80]  Paul McNamara,et al.  Comparison of instruments for investigation of microcirculatory blood flow and red blood cell concentration. , 2009, Journal of biomedical optics.

[81]  M. Stern,et al.  In vivo evaluation of microcirculation by coherent light scattering , 1975, Nature.

[82]  Wiley Interscience,et al.  Endoscopic laser imaging of tissue perfusion: New instrumentation and technique , 2003, Lasers in surgery and medicine.

[83]  O. Thompson,et al.  Tissue perfusion measurements: multiple-exposure laser speckle analysis generates laser Doppler-like spectra. , 2010, Journal of biomedical optics.

[84]  J. David Briers,et al.  Laser Doppler and time-varying speckle: a reconciliation , 1996 .

[85]  D. Durian,et al.  Speckle-visibility spectroscopy: A tool to study time-varying dynamics , 2005, cond-mat/0506081.

[86]  Anastasios Bezerianos,et al.  Imaging the Cerebral Blood Flow With Enhanced Laser Speckle Contrast Analysis (eLASCA) by Monotonic Point Transformation , 2009, IEEE Transactions on Biomedical Engineering.

[87]  Robert F. Bonner,et al.  Principles of Laser-Doppler Flowmetry , 1990 .

[88]  Roberto A. Braga,et al.  Assessment of Seed Viability by Laser Speckle Techniques , 2003 .

[89]  J. Briers,et al.  Flow visualization by means of single-exposure speckle photography , 1981 .

[90]  Mikiya Muramatsu,et al.  Comparative study of analysis methods in biospeckle phenomenon , 2008 .

[91]  Chao Zhou,et al.  Characterization of periinfarct flow transients with laser speckle and Doppler after middle cerebral artery occlusion in the rat , 2009, Journal of neuroscience research.

[92]  J. D. Briers,et al.  Wavelength dependence of intensity fluctuations in laser speckle patterns from biological specimens , 1975 .

[93]  Shanbao Tong,et al.  Influences of hypothermia on the cortical blood supply by laser speckle imaging. , 2009, IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[94]  Vyacheslav Kalchenko,et al.  In vivo characterization of tumor and tumor vascular network using multi‐modal imaging approach , 2011, Journal of biophotonics.

[95]  J. Goodman Statistical Properties of Laser Speckle Patterns , 1963 .

[96]  A. F. Fercher,et al.  Retinal Blood Flow Visualization by Means of Laser Speckle , 1982 .

[97]  T. Monahan Microvascular Changes in the Diabetic Foot , 2012 .

[98]  Mikiya Muramatsu,et al.  Application of biospeckle phenomenon on monitoring of leavening process in breadmaking , 2008 .

[99]  M. K. Andrews,et al.  Effective frequency sensitivity of laser speckle contrast measurements , 2013, Photonics West - Biomedical Optics.

[100]  J. D. Briers,et al.  Quasi real-time digital version of single-exposure speckle photography for full-field monitoring of velocity or flow fields , 1995 .

[101]  G. Nilsson,et al.  Signal processor for laser Doppler tissue flowmeters , 1984, Medical and Biological Engineering and Computing.

[102]  D A Benaron,et al.  Tissue Optics , 1997, Science.

[103]  A. Welch,et al.  A review of the optical properties of biological tissues , 1990 .

[104]  Vyacheslav Kalchenko,et al.  Label free in vivo laser speckle imaging of blood and lymph vessels. , 2012, Journal of biomedical optics.

[105]  Zhijia Yuan,et al.  Quantification of cocaine-induced cortical blood flow changes using laser speckle contrast imaging and Doppler optical coherence tomography. , 2009, Applied optics.

[106]  Joseph W. Goodman,et al.  Probability density function of the sum of N partially correlated speckle patterns , 1975 .

[107]  Toshimitsu Asakura,et al.  Dynamic properties of speckled speckles with relation to velocity measurements of a diffuse object , 1989 .

[108]  Ton van Leeuwen,et al.  Burn imaging with a whole field laser Doppler perfusion imager based on a CMOS imaging array. , 2009, Burns : journal of the International Society for Burn Injuries.

[109]  Sean J. Kirkpatrick,et al.  Algorithms for simulation of speckle (laser and otherwise) , 2008, SPIE BiOS.

[110]  Bernard Choi,et al.  Laser speckle imaging for monitoring blood flow dynamics in the in vivo rodent dorsal skin fold model. , 2004, Microvascular research.

[112]  Sean J. Kirkpatrick,et al.  Spatio-temporal algorithms for processing laser speckle imaging data , 2008, SPIE BiOS.