Chronic Imaging of Cortical Blood Flow using Multi-Exposure Speckle Imaging

Chronic imaging of cerebral blood flow (CBF) is an important tool for investigating vascular remodeling after injury such as stroke. Although techniques such as Laser Speckle Contrast Imaging (LSCI) have emerged as valuable tools for imaging CBF in acute experiments, their utility for chronic measurements or cross-animal comparisons has been limited. Recently, an extension to LSCI called Multi-Exposure Speckle Imaging (MESI) was introduced that increases the quantitative accuracy of CBF images. In this paper, we show that estimates of chronic blood flow are better with MESI than with traditional LSCI. We evaluate the accuracy of the MESI flow estimates using red blood cell (RBC) photographic tracking as an absolute flow calibration in mice over several days. The flow measures computed using the MESI and LSCI techniques were found to be on average 10% and 24% deviant (n = 9 mice), respectively, compared with RBC velocity changes. We also map CBF dynamics after photo-thrombosis of selected cortical microvasculature. Correlations of flow dynamics with RBC tracking were closer with MESI (r = 0.88) than with LSCI (r = 0.65) up to 2 weeks from baseline. With the increased quantitative accuracy, MESI can provide a platform for studying the efficacy of stroke therapies aimed at flow restoration.

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

[2]  R. Busto,et al.  Induction of reproducible brain infarction by photochemically initiated thrombosis , 1985, Annals of neurology.

[3]  David J. Pine,et al.  Diffusing-wave spectroscopy in a shear flow , 1990 .

[4]  D. Hatchell,et al.  Photodynamic retinal vascular thrombosis. Rate and duration of vascular occlusion. , 1991, Investigative ophthalmology & visual science.

[5]  G. Maret Diffusing-Wave Spectroscopy , 1997 .

[6]  D. Boas,et al.  Spatially varying dynamical properties of turbid media probed with diffusing temporal light correlation , 1997 .

[7]  E. Sekizuka,et al.  Measurement of RBC velocities in the rat pial arteries with an image-intensified high-speed video camera system. , 1998, Microvascular research.

[8]  D. Kleinfeld,et al.  Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[9]  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.

[10]  Rudolf Fahlbusch,et al.  Laser Doppler Flowmetry Mapping of Cerebrocortical Microflow: Characteristics and Limitations , 2002, NeuroImage.

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

[12]  M. Moskowitz,et al.  Laser Speckle Flowmetry for the Study of Cerebrovascular Physiology in Normal and Ischemic Mouse Cortex , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  J. Detre,et al.  Spatiotemporal Quantification of Cerebral Blood Flow during Functional Activation in Rat Somatosensory Cortex using Laser-Speckle Flowmetry , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

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

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

[16]  Anders M. Dale,et al.  Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex , 2005, NeuroImage.

[17]  Li Zhang,et al.  Imaging cerebral blood flow through the intact rat skull with temporal laser speckle imaging. , 2006, Optics letters.

[18]  Phillip B. Jones,et al.  Vasoconstrictive Neurovascular Coupling during Focal Ischemic Depolarizations , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  D. Kleinfeld,et al.  Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion , 2006, PLoS biology.

[20]  A. Dunn,et al.  Evaluation of Laser Speckle Flowmetry for Imaging Cortical Perfusion in Experimental Stroke Studies: Quantitation of Perfusion and Detection of Peri-Infarct Depolarisations , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  T. Murphy,et al.  Extensive Turnover of Dendritic Spines and Vascular Remodeling in Cortical Tissues Recovering from Stroke , 2007, The Journal of Neuroscience.

[22]  T. Murphy,et al.  Imaging the Impact of Cortical Microcirculation on Synaptic Structure and Sensory-Evoked Hemodynamic Responses In Vivo , 2007, PLoS biology.

[23]  David A Boas,et al.  Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia. , 2007, Brain : a journal of neurology.

[24]  A. Dunn,et al.  Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex. , 2006, Brain : a journal of neurology.

[25]  Andrew K. Dunn,et al.  Efficient Processing of Laser Speckle Contrast Images , 2008, IEEE Transactions on Medical Imaging.

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

[27]  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.

[28]  T. Duong,et al.  Temporal statistical analysis of laser speckle images and its application to retinal blood-flow imaging. , 2008, Optics express.

[29]  Gert Cauwenberghs,et al.  Rapid determination of particle velocity from space-time images using the Radon transform , 2010, Journal of Computational Neuroscience.

[30]  T. Murphy,et al.  Plasticity during stroke recovery: from synapse to behaviour , 2009, Nature Reviews Neuroscience.

[31]  J. Krupiński,et al.  Angiogenesis, Neurogenesis and Neuroplasticity in Ischemic Stroke , 2010, Current cardiology reviews.

[32]  I. Winship,et al.  Laser Speckle Contrast Imaging of Collateral Blood Flow during Acute Ischemic Stroke , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[33]  Yutaka Tomita,et al.  RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size , 2010, Brain Research.

[34]  Paul Lemaillet,et al.  Absolute blood velocity measured with a modified fundus camera. , 2010, Journal of biomedical optics.

[35]  D. Boas,et al.  Laser speckle contrast imaging in biomedical optics. , 2010, Journal of biomedical optics.

[36]  Anna W. Roe Imaging the brain with optical methods , 2010 .

[37]  Andrew K. Dunn,et al.  Quantitative imaging of ischemic stroke through thinned skull in mice with Multi Exposure Speckle Imaging , 2010, Biomedical optics express.

[38]  Nozomi Nishimura,et al.  Limitations of collateral flow after occlusion of a single cortical penetrating arteriole , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[39]  Andrew K. Dunn,et al.  Laser Speckle Contrast Imaging of Cerebral Blood Flow , 2011, Annals of Biomedical Engineering.

[40]  Kartikeya Murari,et al.  Multiexposure laser speckle contrast imaging of the angiogenic microenvironment. , 2011, Journal of biomedical optics.

[41]  D. Kleinfeld,et al.  Two-Photon Microscopy as a Tool to Study Blood Flow and Neurovascular Coupling in the Rodent Brain , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  Béla Hopp,et al.  Evaluation of laser-speckle contrast image analysis techniques in the cortical microcirculation of piglets. , 2012, Microvascular research.

[43]  E. Arsava,et al.  Can Restoring Incomplete Microcirculatory Reperfusion Improve Stroke Outcome after Thrombolysis? , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[44]  Nozomi Nishimura,et al.  In vivo two-photon excited fluorescence microscopy reveals cardiac- and respiration-dependent pulsatile blood flow in cortical blood vessels in mice. , 2012, American journal of physiology. Heart and circulatory physiology.