Neurovascular coupling: in vivo optical techniques for functional brain imaging

Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology.

[1]  Fritjof Helmchen,et al.  Two-Photon Functional Imaging of Neuronal Activity , 2009 .

[2]  Tzyy-Ping Jung,et al.  Biosensor Technologies for Augmented Brain–Computer Interfaces in the Next Decades , 2012, Proceedings of the IEEE.

[3]  K. Svoboda,et al.  Principles of Two-Photon Excitation Microscopy and Its Applications to Neuroscience , 2006, Neuron.

[4]  S. Tong,et al.  Laser speckle contrast imaging of cerebral blood flow in freely moving animals. , 2011, Journal of biomedical optics.

[5]  A. Villringer,et al.  Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study. , 1994, Circulation research.

[6]  Y. Hoshi Functional near-infrared spectroscopy: potential and limitations in neuroimaging studies. , 2005, International review of neurobiology.

[7]  David A. Boas,et al.  Coupling between somatosensory evoked potentials and hemodynamic response in the rat , 2008, NeuroImage.

[8]  Douglas J. Fox,et al.  Laser speckle contrast imaging of cerebral blood flow in humans during neurosurgery: a pilot clinical study. , 2010, Journal of biomedical optics.

[9]  Marco Ferrari,et al.  A brief review on the history of human functional near-infrared spectroscopy (fNIRS) development and fields of application , 2012, NeuroImage.

[10]  W. Kuschinsky,et al.  Interdependency of local capillary density, blood flow, and metabolism in rat brains. , 1986, The American journal of physiology.

[11]  Lihong V. Wang,et al.  In vivo dark-field reflection-mode photoacoustic microscopy. , 2005, Optics letters.

[12]  Jesse V Jokerst,et al.  Photoacoustic imaging of mesenchymal stem cells in living mice via silica-coated gold nanorods. , 2012, ACS nano.

[13]  Junjie Yao,et al.  In vivo photoacoustic imaging of transverse blood flow by using Doppler broadening of bandwidth. , 2010, Optics letters.

[14]  Jun Suzurikawa,et al.  Voltage-sensitive-dye imaging of microstimulation-evoked neural activity through intracortical horizontal and callosal connections in cat visual cortex. , 2009, Journal of neural engineering.

[15]  C. Iadecola Neurovascular regulation in the normal brain and in Alzheimer's disease , 2004, Nature Reviews Neuroscience.

[16]  I. Y. Petrov,et al.  Optoacoustic monitoring of cerebral venous blood oxygenation though intact scalp in large animals , 2012, Optics express.

[17]  F. Chavane,et al.  Voltage-sensitive dye imaging: Technique review and models , 2010, Journal of Physiology-Paris.

[18]  Laurie D. Burns,et al.  High-speed, miniaturized fluorescence microscopy in freely moving mice , 2008, Nature Methods.

[19]  Patrick Jenny,et al.  Vascular Graph Model to Simulate the Cerebral Blood Flow in Realistic Vascular Networks , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  N. Thakor,et al.  Contrast-enhanced imaging of cerebral vasculature with laser speckle. , 2007, Applied optics.

[21]  Kartikeya Murari,et al.  High spatiotemporal resolution imaging of the neurovascular response to electrical stimulation of rat peripheral trigeminal nerve as revealed by in vivo temporal laser speckle contrast , 2009, Journal of Neuroscience Methods.

[22]  Davide Contini,et al.  Deep and surface hemodynamic signal from functional time resolved transcranial near infrared spectroscopy compared to skin flowmotion , 2012, Comput. Biol. Medicine.

[23]  R. Keynes,et al.  Opacity changes in stimulated nerve , 1949, The Journal of physiology.

[24]  Lihong V. Wang,et al.  In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure. , 2011, Optics letters.

[25]  Jan Laufer,et al.  In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy. , 2012, Journal of biomedical optics.

[26]  P. Beard Biomedical photoacoustic imaging , 2011, Interface Focus.

[27]  Daniel Pope,et al.  Study of the cortical representation of whisker directional deflection using voltage-sensitive dye optical imaging , 2010, NeuroImage.

[28]  Jyh-Yeong Chang,et al.  Transcranial Imaging of Functional Cerebral Hemodynamic Changes in Single Blood Vessels using in vivo Photoacoustic Microscopy , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[29]  Anna Devor,et al.  Two-photon Laser Scanning Microscopy as a Tool to Study Cortical Vasodynamics under Normal and Ischemic Conditions Institutional Affiliations , 2022 .

[30]  Xiaofeng Zhang,et al.  The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans , 2005, SPIE BiOS.

[31]  S. Bunce,et al.  Functional near-infrared neuroimaging , 2005, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[32]  Liad Hollender,et al.  High-Resolution In Vivo Imaging of the Neurovascular Unit during Spreading Depression , 2007, The Journal of Neuroscience.

[33]  Lihong V. Wang,et al.  Noninvasive, in vivo imaging of blood-oxygenation dynamics within the mouse brain using photoacoustic microscopy. , 2009, Journal of biomedical optics.

[34]  Vassiliy Tsytsarev,et al.  Advantages and limitations of brain imaging methods in the research of absence epilepsy in humans and animal models , 2013, Journal of Neuroscience Methods.

[35]  D. Rossi,et al.  Another BOLD role for astrocytes: coupling blood flow to neural activity , 2006, Nature Neuroscience.

[36]  J. Filosa,et al.  Calcium Dynamics in Cortical Astrocytes and Arterioles During Neurovascular Coupling , 2004, Circulation research.

[37]  Sooyoung Chung,et al.  Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex , 2005, Nature.

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

[39]  C. Stosiek,et al.  In vivo two-photon calcium imaging of neuronal networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Mikhail Inyushin,et al.  Intracellular polyamines enhance astrocytic coupling , 2012, Neuroreport.

[41]  S. Bunce,et al.  Functional near-infrared spectroscopy , 2006, IEEE Engineering in Medicine and Biology Magazine.

[42]  Nitish V. Thakor,et al.  High Resolution Cerebral Blood Flow Imaging by Registered Laser Speckle Contrast Analysis , 2010, IEEE Transactions on Biomedical Engineering.

[43]  Hidenao Fukuyama,et al.  Optical Imaging of Interaural Time Difference Representation in Rat Auditory Cortex , 2008, Front. Neuroeng..

[44]  A. Rosen,et al.  A portable near infrared spectroscopy system for bedside monitoring of newborn brain , 2005, Biomedical engineering online.

[45]  Lihong V. Wang,et al.  Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging , 2006, Nature Biotechnology.

[46]  J. Rossier,et al.  Cortical GABA Interneurons in Neurovascular Coupling: Relays for Subcortical Vasoactive Pathways , 2004, The Journal of Neuroscience.

[47]  Alexei V. Demchenko,et al.  Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo , 2013, Photonics West - Biomedical Optics.

[48]  S. Laughlin,et al.  An Energy Budget for Signaling in the Grey Matter of the Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[49]  D. Heistad,et al.  Regulation of large cerebral arteries and cerebral microvascular pressure. , 1990, Circulation research.

[50]  A. Oraevsky,et al.  Laser optoacoustic imaging system for detection of breast cancer. , 2009, Journal of biomedical optics.

[51]  Jyh-Yeong Chang,et al.  Investigation of the cerebral hemodynamic response function in single blood vessels by functional photoacoustic microscopy. , 2012, Journal of biomedical optics.

[52]  D. Houlden,et al.  Correlation between Cerebral Blood Flow, Somatosensory Evoked Potentials, CT Scan Grade and Neurological Grade in Patients with Subarachnoid Hemorrhage , 1991, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[53]  Kartikeya Murari,et al.  Design and characterization of a miniaturized epi-illuminated microscope , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[54]  W. Freeman,et al.  Synchronized Minima in ECoG Power at Frequencies Between Beta-Gamma Oscillations Disclose Cortical Singularities in Cognition , 2012 .

[55]  Mikhail Inyushin,et al.  Potassium channel activity and glutamate uptake are impaired in astrocytes of seizure‐susceptible DBA/2 mice , 2010, Epilepsia.

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

[57]  D. Attwell,et al.  Glial and neuronal control of brain blood flow , 2022 .

[58]  Junjie Yao,et al.  Transverse flow imaging based on photoacoustic Doppler bandwidth broadening. , 2010, Journal of biomedical optics.

[59]  E. Hillman,et al.  Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics. , 2009, Optics express.

[60]  S. Bodhankar,et al.  Migraine: current concepts and emerging therapies. , 2005, Vascular pharmacology.

[61]  Hao F. Zhang,et al.  Stimulated Raman photoacoustic imaging , 2010, Proceedings of the National Academy of Sciences.

[62]  Lihong V. Wang Photoacoustic imaging and spectroscopy , 2009 .

[63]  T. Takano,et al.  Signaling at the Gliovascular Interface , 2003, The Journal of Neuroscience.

[64]  S. Coons,et al.  Intraoperative Confocal Microscopy for Brain Tumors: A Feasibility Analysis in Humans , 2011, Neurosurgery.

[65]  Bilal Khan,et al.  Spatiotemporal relations of primary sensorimotor and secondary motor activation patterns mapped by NIR imaging , 2011, Biomedical optics express.

[66]  P. Niederer,et al.  Evaluation of brain toxicity following near infrared light exposure after indocyanine green dye injection , 2002, Journal of Neuroscience Methods.

[67]  D. Boas,et al.  Resting state functional connectivity of the whole head with near-infrared spectroscopy , 2010, Biomedical optics express.

[68]  Lihong V. Wang,et al.  In vivo imaging of subcutaneous structures using functional photoacoustic microscopy , 2007, Nature Protocols.

[69]  Junjie Yao,et al.  Photoacoustic microscopy of microvascular responses to cortical electrical stimulation. , 2011, Journal of biomedical optics.

[70]  T. Schwartz,et al.  Dynamic Neurovascular Coupling and Uncoupling during Ictal Onset, Propagation, and Termination Revealed by Simultaneous In Vivo Optical Imaging of Neural Activity and Local Blood Volume , 2012, Cerebral cortex.

[71]  Lihong V. Wang,et al.  Photoacoustic Tomography: In Vivo Imaging from Organelles to Organs , 2012, Science.

[72]  Lois E. H. Smith,et al.  Oxygen-induced retinopathy in the mouse. , 1994, Investigative ophthalmology & visual science.

[73]  Nitish V. Thakor,et al.  Random process estimator for laser speckle imaging of cerebral blood flow , 2009, Optics express.

[74]  R. Aldrich,et al.  Local potassium signaling couples neuronal activity to vasodilation in the brain , 2006, Nature Neuroscience.

[75]  K. Breese,et al.  Nitric oxide mediates vasodilatation in response to activation of N-methyl-D-aspartate receptors in brain. , 1993, Circulation research.

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

[77]  B. MacVicar,et al.  Calcium transients in astrocyte endfeet cause cerebrovascular constrictions , 2004, Nature.

[78]  G. Moore,et al.  The clinical use of fluorescein in neurosurgery; the localization of brain tumors. , 1948, Journal of neurosurgery.

[79]  Junjie Yao,et al.  In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose analog , 2012, Journal of Neuroscience Methods.

[80]  Mikhail Inyushin,et al.  Visualization of implanted GL261 glioma cells in living mouse brain slices using fluorescent 4-(4-(dimethylamino)-styryl)-N-methylpyridinium iodide (ASP+). , 2012, BioTechniques.

[81]  Peter Vajkoczy,et al.  Intraoperative monitoring of cerebral blood flow by laser speckle contrast analysis. , 2009, Neurosurgical focus.

[82]  Wei Shi,et al.  Real-time handheld optical-resolution photoacoustic microscopy. , 2011, Optics express.

[83]  A. Hudetz,et al.  Blood Flow in the Cerebral Capillary Network: A Review Emphasizing Observations with Intravital Microscopy , 1997, Microcirculation.

[84]  P. Shinnick‐Gallagher,et al.  Regulation of Synaptic Transmission by CRF Receptors , 2006, Reviews in the neurosciences.

[85]  Sonya Bahar,et al.  Imaging cortical electrical stimulation in vivo: fast intrinsic optical signal versus voltage-sensitive dyes. , 2008, Optics letters.

[86]  Hao F. Zhang,et al.  Combined photoacoustic microscopy and optical coherence tomography can measure metabolic rate of oxygen , 2011, Biomedical optics express.

[87]  A. Grinvald,et al.  Imaging Cortical Dynamics at High Spatial and Temporal Resolution with Novel Blue Voltage-Sensitive Dyes , 1999, Neuron.

[88]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[89]  Nitish V Thakor Highlights: Transcranial Imaging of Functional Cerebral Hemodynamic Changes in Single Blood Vessels , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[90]  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.

[91]  W. Denk,et al.  In vivo two-photon voltage-sensitive dye imaging reveals top-down control of cortical layers 1 and 2 during wakefulness , 2008, Proceedings of the National Academy of Sciences.

[92]  Nitish V Thakor,et al.  Optogenetic-guided cortical plasticity after nerve injury , 2011, Proceedings of the National Academy of Sciences.

[93]  Shangbin Chen,et al.  Simultaneous, live imaging of cortical spreading depression and associated cerebral blood flow changes, by combining voltage-sensitive dye and laser speckle contrast methods , 2009, NeuroImage.

[94]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[95]  M. C. Angulo,et al.  Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation , 2003, Nature Neuroscience.

[96]  Amiram Grinvald,et al.  VSDI: a new era in functional imaging of cortical dynamics , 2004, Nature Reviews Neuroscience.

[97]  Lihong V. Wang Multiscale photoacoustic microscopy and computed tomography. , 2009, Nature photonics.

[98]  H Wayland,et al.  Erythrocyte velocity measurement in microvessels by a two-slit photometric method. , 1967, Journal of applied physiology.

[99]  A. Dale,et al.  Coupling of Total Hemoglobin Concentration, Oxygenation, and Neural Activity in Rat Somatosensory Cortex , 2003, Neuron.

[100]  Lun-De Liao,et al.  Novel Trends in Biosensors Used for Electroencephalography Measurements in Neurocognitive Engineering Applications , 2012 .

[101]  Mark A. Anastasio,et al.  Photoacoustic tomography through a whole adult human skull with a photon recycler , 2012, Journal of biomedical optics.

[102]  Olli Gröhn,et al.  Coupling between simultaneously recorded BOLD response and neuronal activity in the rat somatosensory cortex , 2008, NeuroImage.

[103]  Eui Hyun Kim,et al.  Application of intraoperative indocyanine green videoangiography to brain tumor surgery , 2011, Acta Neurochirurgica.

[104]  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.

[105]  A Villringer,et al.  Three-Dimensional Reconstruction of the Rat Brain Cortical Microcirculation in vivo , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[106]  Shirley M Coyle,et al.  Brain–computer interface using a simplified functional near-infrared spectroscopy system , 2007, Journal of neural engineering.

[107]  J. Rossier,et al.  Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum , 2006, The Journal of Neuroscience.

[108]  Lihong V. Wang,et al.  Tutorial on Photoacoustic Microscopy and Computed Tomography , 2008, IEEE Journal of Selected Topics in Quantum Electronics.

[109]  M. Ducros,et al.  The Relationship between Blood Flow and Neuronal Activity in the Rodent Olfactory Bulb , 2007, The Journal of Neuroscience.

[110]  O. Garaschuk,et al.  Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo , 2006, Nature Protocols.

[111]  Anders M. Dale,et al.  A vascular anatomical network model of the spatio-temporal response to brain activation , 2008, NeuroImage.

[112]  Monica Fabiani,et al.  Fast Optical Imaging of Human Brain Function , 2010, Front. Hum. Neurosci..

[113]  T. Takano,et al.  Astrocyte-mediated control of cerebral blood flow , 2006, Nature Neuroscience.

[114]  A. Dale,et al.  Frontiers in Optical Imaging of Cerebral Blood Flow and Metabolism , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[115]  Michael M Haglund,et al.  Imaging of Intrinsic Optical Signals in Primate Cortex during Epileptiform Activity , 2007, Epilepsia.

[116]  D. Kleinfeld,et al.  Suppressed Neuronal Activity and Concurrent Arteriolar Vasoconstriction May Explain Negative Blood Oxygenation Level-Dependent Signal , 2007, The Journal of Neuroscience.

[117]  Emmanuel Bossy,et al.  Photoacoustic-guided ultrasound therapy with a dual-mode ultrasound array. , 2012, Journal of biomedical optics.

[118]  Chin-Teng Lin,et al.  Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy , 2010, NeuroImage.

[119]  Phillip B. Jones,et al.  A Multicompartment Vascular Model for Inferring Baseline and Functional Changes in Cerebral Oxygen Metabolism and Arterial Dilation , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[120]  W. Denk,et al.  Two-photon imaging to a depth of 1000 microm in living brains by use of a Ti:Al2O3 regenerative amplifier. , 2003, Optics letters.

[121]  V. Pieribone,et al.  A Fluorescent, Genetically-Encoded Voltage Probe Capable of Resolving Action Potentials , 2012, PloS one.

[122]  Konstantin I Maslov,et al.  Living Brain Optical Imaging: Technology, Methods and Applications. , 2012, Journal of neuroscience and neuroengineering.

[123]  Junjie Yao,et al.  Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo , 2013, NeuroImage.

[124]  J. Briers,et al.  Laser speckle contrast imaging for measuring blood flow , 2007 .