Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments

Abstract Hyperspectral imaging (HSI) technologies have been used extensively in medical research, targeting various biological phenomena and multiple tissue types. Their high spectral resolution over a wide range of wavelengths enables acquisition of spatial information corresponding to different light-interacting biological compounds. This review focuses on the application of HSI to monitor brain tissue metabolism and hemodynamics in life sciences. Different approaches involving HSI have been investigated to assess and quantify cerebral activity, mainly focusing on: (1) mapping tissue oxygen delivery through measurement of changes in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin; and (2) the assessment of the cerebral metabolic rate of oxygen (CMRO2) to estimate oxygen consumption by brain tissue. Finally, we introduce future perspectives of HSI of brain metabolism, including its potential use for imaging optical signals from molecules directly involved in cellular energy production. HSI solutions can provide remarkable insight in understanding cerebral tissue metabolism and oxygenation, aiding investigation on brain tissue physiological processes.

[1]  Liang Gao,et al.  Compact Image Slicing Spectrometer (ISS) for hyperspectral fluorescence microscopy. , 2009, Optics express.

[2]  Jürgen Popp,et al.  Hyperspectral unmixing of Raman micro-images for assessment of morphological and chemical parameters in non-dried brain tumor specimens , 2013, Analytical and Bioanalytical Chemistry.

[3]  Chein-I. Chang.  Hyperspectral Imaging: Techniques for Spectral Detection and Classification , 2003 .

[4]  Irene Georgakoudi,et al.  Optical imaging using endogenous contrast to assess metabolic state. , 2012, Annual review of biomedical engineering.

[5]  Qingming Luo,et al.  Simultaneous detection of hemodynamics, mitochondrial metabolism and light scattering changes during cortical spreading depression in rats based on multi-spectral optical imaging , 2013, NeuroImage.

[6]  R. Yolken,et al.  Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress , 2004, Molecular Psychiatry.

[7]  Liang Gao,et al.  Development of image mappers for hyperspectral biomedical imaging applications. , 2010, Applied optics.

[8]  Y. Kosugi,et al.  Blood vessel detection and artery-vein differentiation using hyperspectral imaging , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[9]  A. Grinvald,et al.  Interactions Between Electrical Activity and Cortical Microcirculation Revealed by Imaging Spectroscopy: Implications for Functional Brain Mapping , 1996, Science.

[10]  Anita Mahadevan-Jansen,et al.  Liquid-crystal tunable filter spectral imaging for brain tumor demarcation. , 2007, Applied optics.

[11]  B. Schoener,et al.  Intracellular Oxidation-Reduction States in Vivo , 1962, Science.

[12]  Ilias Tachtsidis,et al.  Reduction of Cytochrome c Oxidase During Vasovagal Hypoxia-Ischemia in Human Adult Brain: A Case Study , 2013, Advances in experimental medicine and biology.

[13]  Richard Lucas,et al.  Hyperspectral Sensors and Applications , 2004 .

[14]  J. Briers,et al.  Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. , 2001, Physiological measurement.

[15]  J. Beach,et al.  Hyperspectral imaging for measurement of oxygen saturation in the optic nerve head. , 2004, Investigative ophthalmology & visual science.

[16]  B. Hoogwerf,et al.  Evaluation of Diabetic Foot Ulcer Healing With Hyperspectral Imaging of Oxyhemoglobin and Deoxyhemoglobin , 2009, Diabetes Care.

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

[18]  U. Lindauer,et al.  Neurovascular Coupling in Rat Brain Operates Independent of Hemoglobin Deoxygenation , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  R. Auer,et al.  Hypoxia, hyperoxia, ischemia, and brain necrosis , 2000, Neurology.

[20]  Yukio Kosugi,et al.  Hyperspectral Imaging: a New Modality in Surgery , 2009 .

[21]  M. Govender,et al.  A review of hyperspectral remote sensing and its application in vegetation and water resource studies , 2009 .

[22]  William E. Roper,et al.  Hyperspectral imaging applied to medical diagnoses and food safety , 2003, SPIE Defense + Commercial Sensing.

[23]  Liang Gao,et al.  Optical hyperspectral imaging in microscopy and spectroscopy – a review of data acquisition , 2015, Journal of biophotonics.

[24]  Eustace L. Dereniak,et al.  Snapshot hyperspectral imaging , 2001 .

[25]  Wafik S El-Deiry,et al.  Spectral imaging-based methods for quantifying autophagy and apoptosis , 2011, Cancer biology & therapy.

[26]  J E Shook,et al.  Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans. , 1990, Journal of applied physiology.

[27]  A. Villringer,et al.  Excessive oxygen or glucose supply does not alter the blood flow response to somatosensory stimulation or spreading depression in rats , 1997, Brain Research.

[28]  Vladislav Toronov,et al.  Hyperspectral functional imaging of the human brain , 2013, Photonics West - Biomedical Optics.

[29]  S. Arridge,et al.  Estimation of optical pathlength through tissue from direct time of flight measurement , 1988 .

[30]  Y. Kosugi,et al.  Cancer detection using infrared hyperspectral imaging , 2011, Cancer science.

[31]  Robert P. Francis,et al.  Active DLP hyperspectral illumination: a noninvasive, in vivo, system characterization visualizing tissue oxygenation at near video rates. , 2011, Analytical chemistry.

[32]  David A. Boas,et al.  A Quantitative Comparison of Simultaneous BOLD fMRI and NIRS Recordings during Functional Brain Activation , 2002, NeuroImage.

[33]  Sabrina Brigadoi,et al.  Image reconstruction of oxidized cerebral cytochrome C oxidase changes from broadband near-infrared spectroscopy data , 2017, Neurophotonics.

[34]  M. Bullock,et al.  Brain Oxygenation and Energy Metabolism: Part I—Biological Function and Pathophysiology , 2002, Neurosurgery.

[35]  Costas Balas,et al.  Hyperspectral image acquisition and analysis of skin , 2003, SPIE BiOS.

[36]  Dan Savastru,et al.  Hyperspectral Imaging in the Medical Field: Present and Future , 2014 .

[37]  Katsuei Shibuki,et al.  Enduring Critical Period Plasticity Visualized by Transcranial Flavoprotein Imaging in Mouse Primary Visual Cortex , 2006, The Journal of Neuroscience.

[38]  John Klaessens,et al.  Imaging the seizure during surgery with a hyperspectral camera , 2013, Epilepsia.

[39]  M. Beal,et al.  Mitochondrial Dysfunction in Neurodegenerative Diseases , 2012, Journal of Pharmacology and Experimental Therapeutics.

[40]  S R Arridge,et al.  The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis. , 1992, Physics in medicine and biology.

[41]  Tomasz S Tkaczyk,et al.  Hyperspectral optical tomography of intrinsic signals in the rat cortex , 2015, Neurophotonics.

[42]  Paul Geladi,et al.  Techniques and applications of hyperspectral image analysis , 2007 .

[43]  Jörg Bendix,et al.  Hyperspectral imaging of mucosal surfaces in patients , 2012, Journal of biophotonics.

[44]  Dang Khoa Nguyen,et al.  Intraoperative video-rate hemodynamic response assessment in human cortex using snapshot hyperspectral optical imaging , 2016, Neurophotonics.

[45]  Tuan Vo-Dinh,et al.  Development of a multi-spectral imaging system for medical applications , 2003 .

[46]  M. Ueki,et al.  Functional Activation of Cerebral Blood Flow and Metabolism before and after Global Ischemia of Rat Brain , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[47]  Hanzhang Lu,et al.  Noninvasive quantification of whole‐brain cerebral metabolic rate of oxygen (CMRO2) by MRI , 2009, Magnetic resonance in medicine.

[48]  Michèle Allard,et al.  Brain fuel metabolism, aging, and Alzheimer's disease. , 2011, Nutrition (Burbank, Los Angeles County, Calif.).

[49]  David J Brady,et al.  Identification of fluorescent beads using a coded aperture snapshot spectral imager. , 2010, Applied optics.

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

[51]  J. Mayhew,et al.  Concurrent Optical Imaging Spectroscopy and Laser-Doppler Flowmetry: The Relationship between Blood Flow, Oxygenation, and Volume in Rodent Barrel Cortex , 2001, NeuroImage.

[52]  A. Villringer,et al.  Physical model for the spectroscopic analysis of cortical intrinsic optical signals. , 2000, Physics in medicine and biology.

[53]  M. Dewhirst,et al.  Optical imaging of tumor hypoxia dynamics. , 2010, Journal of biomedical optics.

[54]  E. Candès,et al.  Compressive fluorescence microscopy for biological and hyperspectral imaging , 2012, Proceedings of the National Academy of Sciences.

[55]  Lise L. Randeberg,et al.  Hyperspectral imaging of bruised skin , 2006, SPIE BiOS.

[56]  Eiji Okada,et al.  Estimation of optical path length factor for functional imaging of an exposed cortex by principal component analysis , 2003, European Conference on Biomedical Optics.

[57]  J. Chin,et al.  Evaluation of hyperspectral technology for assessing the presence and severity of peripheral artery disease. , 2011, Journal of vascular surgery.

[58]  Peiying Liu,et al.  Quantitative assessment of global cerebral metabolic rate of oxygen (CMRO2) in neonates using MRI , 2014, NMR in biomedicine.

[59]  Costas Balas,et al.  Multi/Hyper-Spectral Imaging , 2011 .

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

[61]  Naoum P Issa,et al.  Functional Imaging of Primary Visual Cortex Using Flavoprotein Autofluorescence , 2007, The Journal of Neuroscience.

[62]  W. Webb,et al.  Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[63]  Nicola J. Robertson,et al.  Brain mitochondrial oxidative metabolism during and after cerebral hypoxia–ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near-infrared spectroscopy , 2014, NeuroImage.

[64]  Guolan Lu,et al.  Medical hyperspectral imaging: a review , 2014, Journal of biomedical optics.

[65]  M. Raichle.  Behind the scenes of functional brain imaging: a historical and physiological perspective. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Nirmala Ramanujam,et al.  Multiphoton redox ratio imaging for metabolic monitoring in vivo. , 2010, Methods in molecular biology.

[67]  J. Mansfield,et al.  Hyperspectral imaging: a new approach to the diagnosis of hemorrhagic shock. , 2006, The Journal of trauma.

[68]  R. Arridget,et al.  The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis , 1992 .

[69]  A. Villringer,et al.  Noninvasive Assessment of Changes in Cytochrome-c Oxidase Oxidation in Human Subjects during Visual Stimulation , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[70]  Y. Kosugi,et al.  Hyperspectral imaging and diagnosis of intestinal ischemia , 2008, 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[71]  Andersson,et al.  Autofluorescence of living cells , 1998, Journal of microscopy.

[72]  Avinash C. Kak,et al.  Principles of computerized tomographic imaging , 2001, Classics in applied mathematics.

[73]  Elizabeth M C Hillman,et al.  Optical brain imaging in vivo: techniques and applications from animal to man. , 2007, Journal of biomedical optics.

[74]  Gemma Bale,et al.  From Jöbsis to the present day: a review of clinical near-infrared spectroscopy measurements of cerebral cytochrome-c-oxidase , 2016, Journal of biomedical optics.

[75]  Hellmuth Obrig,et al.  Linear Aspects of Changes in Deoxygenated Hemoglobin Concentration and Cytochrome Oxidase Oxidation during Brain Activation , 2001, NeuroImage.

[76]  R. Poldrack,et al.  Can the cerebral metabolic rate of oxygen be estimated with near-infrared spectroscopy? , 2003, Physics in medicine and biology.

[77]  D T Delpy,et al.  Simulation of the point spread function for light in tissue by a Monte Carlo method. , 1987, Advances in experimental medicine and biology.

[78]  Jerilyn A. Timlin,et al.  Imaging multiple endogenous and exogenous fluorescent species in cells and tissues , 2006, SPIE BiOS.

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

[80]  Michael W. Kudenov,et al.  Review of snapshot spectral imaging technologies , 2013, Optics and Precision Engineering.

[81]  Ilias Tachtsidis,et al.  Dependence on NIRS Source-Detector Spacing of Cytochrome c Oxidase Response to Hypoxia and Hypercapnia in the Adult Brain , 2013, Advances in experimental medicine and biology.

[82]  B. Rosen,et al.  Evidence of a Cerebrovascular Postarteriole Windkessel with Delayed Compliance , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[83]  M E Raichle,et al.  Correlation Between Regional Cerebral Blood Flow and Oxidative Metabolism: In Vivo Studies in Man , 1976 .

[84]  Michael B. Sinclair,et al.  Hyperspectral confocal fluorescence imaging of cells , 2007, SPIE Optics East.

[85]  Cristina Kurachi,et al.  In vivo fluorescence hyperspectral imaging of oral neoplasia , 2009, BiOS.

[86]  H. S. de Bruijn,et al.  In vivo monitoring of protein-bound and free NADH during ischemia by nonlinear spectral imaging microscopy , 2011, Biomedical optics express.

[87]  Avraham Mayevsky,et al.  Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies. , 2007 .

[88]  B. Chance,et al.  Intracellular Oxidation-Reduction States in Vivo , 1962, Science.

[89]  R. Keep,et al.  Effects of Cerebral Ischemia on Neuronal Hemoglobin , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[90]  V. Ntziachristos,et al.  Non-invasive and quantitative near-infrared haemoglobin spectrometry in the piglet brain during hypoxic stress, using a frequency-domain multidistance instrument† , 2001, Physics in medicine and biology.

[91]  Ilias Tachtsidis,et al.  Relationship between brain tissue haemodynamics, oxygenation and metabolism in the healthy human adult brain during hyperoxia and hypercapnea. , 2009, Advances in experimental medicine and biology.

[92]  E. Hillman,et al.  Hyperspectral in vivo two-photon microscopy of intrinsic contrast. , 2008, Optics letters.

[93]  Bernd J Pichler,et al.  A hyperspectral fluorescence system for 3D in vivo optical imaging , 2006, Physics in medicine and biology.

[94]  S. Ogawa,et al.  Biophysical and Physiological Origins of Blood Oxygenation Level-Dependent fMRI Signals , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[95]  D. Kleinfeld,et al.  Stimulus-Induced Changes in Blood Flow and 2-Deoxyglucose Uptake Dissociate in Ipsilateral Somatosensory Cortex , 2008, The Journal of Neuroscience.

[96]  Makoto Hashizume,et al.  Intraoperative visualization of cerebral oxygenation using hyperspectral image data: a two-dimensional mapping method , 2014, International Journal of Computer Assisted Radiology and Surgery.

[97]  Izumi Nishidate,et al.  Evaluation of Cerebral Hemodynamics and Tissue Morphology of In Vivo Rat Brain Using Spectral Diffuse Reflectance Imaging , 2017, Applied spectroscopy.

[98]  Lihong V. Wang,et al.  Biomedical Optics: Principles and Imaging , 2007 .

[99]  B. Chance,et al.  Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. , 1979, The Journal of biological chemistry.

[100]  Nathan O. Kaplan,et al.  Fluorescence of Pyridine Nucleotides in Mitochondria , 1962 .

[101]  M. Smith,et al.  Spatial Distribution of Changes in Oxidised Cytochrome C Oxidase During Visual Stimulation Using Broadband Near Infrared Spectroscopy Imaging , 2016, Advances in experimental medicine and biology.

[102]  Gang Chen,et al.  Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo. , 2004, Journal of neurophysiology.

[103]  Mark S. Humayun,et al.  Hyperspectral Computed Tomographic Imaging Spectroscopy of Vascular Oxygen Gradients in the Rabbit Retina In Vivo , 2011, PloS one.

[104]  G. Dienel.  Fueling and imaging brain activation , 2012, ASN neuro.

[105]  John H. G. M. Klaessens,et al.  Hyperspectral imaging system for imaging O2Hb and HHb concentration changes in tissue for various clinical applications , 2011, BiOS.

[106]  Andrew R. Harvey,et al.  Hyperspectral imaging for the detection of retinal disease , 2002, SPIE Optics + Photonics.

[107]  K. Oh,et al.  A novel fluorescent derivative of glucose applicable to the assessment of glucose uptake activity of Escherichia coli. , 1996, Biochimica et biophysica acta.

[108]  Robert A. Lew,et al.  Advantages of intraoperative medical hyperspectral imaging (MHSI) for the evaluation of the breast cancer resection bed for residual tumor , 2005 .

[109]  Mariel G Kozberg,et al.  Neurovascular coupling and energy metabolism in the developing brain. , 2016, Progress in brain research.

[110]  D T Delpy,et al.  Near-infrared spectroscopy of the brain: relevance to cytochrome oxidase bioenergetics. , 1994, Biochemical Society transactions.

[111]  Lihong V. Wang,et al.  Monte Carlo Modeling of Light Transport in Tissues , 1995 .

[112]  Eiji Okada,et al.  Interpretation of principal components of the reflectance spectra obtained from multispectral images of exposed pig brain. , 2005, Journal of biomedical optics.

[113]  C. Sherrington,et al.  On the Regulation of the Blood‐supply of the Brain , 1890, The Journal of physiology.

[114]  E. Hillman.  Coupling mechanism and significance of the BOLD signal: a status report. , 2014, Annual review of neuroscience.

[115]  Martin Smith,et al.  Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin☆ , 2014, NeuroImage.

[116]  Warren S. Grundfest,et al.  The use of spectral imaging for the diagnosis of retinal disease , 1999, 1999 IEEE LEOS Annual Meeting Conference Proceedings. LEOS'99. 12th Annual Meeting. IEEE Lasers and Electro-Optics Society 1999 Annual Meeting (Cat. No.99CH37009).

[117]  Ilias Tachtsidis,et al.  Increase in cerebral aerobic metabolism by normobaric hyperoxia after traumatic brain injury. , 2008, Journal of neurosurgery.

[118]  G. Crelier,et al.  Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[119]  Karsten Rebner,et al.  Hyperspectral Imaging: A Review of Best Practice, Performance and Pitfalls for in-line and on-line Applications , 2012 .

[120]  Shailendra Joshi,et al.  Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging , 2014, Journal of biomedical optics.

[121]  Alex J Walsh,et al.  In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts. , 2014, Biomedical optics express.

[122]  L. O. Svaasand,et al.  Hyperspectral imaging of atherosclerotic plaques in vitro. , 2011, Journal of biomedical optics.

[123]  I. Tachtsidis,et al.  Optimal wavelength combinations for near-infrared spectroscopic monitoring of changes in brain tissue hemoglobin and cytochrome c oxidase concentrations. , 2015, Biomedical optics express.

[124]  S. Jacques.  Optical properties of biological tissues: a review , 2013, Physics in medicine and biology.

[125]  Label-free microscopy: spectral imaging of multiphoton-excited cellular autofluorescence , 2012 .

[126]  Hans C Gerritsen,et al.  Design and implementation of a sensitive high-resolution nonlinear spectral imaging microscope. , 2008, Journal of biomedical optics.

[127]  D L Farkas,et al.  Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope. , 1997, Biophysical journal.

[128]  David A Boas,et al.  Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism. , 2015, Biomedical optics express.

[129]  D. Delpy,et al.  Performance comparison of several published tissue near-infrared spectroscopy algorithms. , 1995, Analytical biochemistry.

[130]  T. Wiesel,et al.  Functional architecture of cortex revealed by optical imaging of intrinsic signals , 1986, Nature.

[131]  M. Mintun,et al.  Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. , 1984, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[132]  Ying Zheng,et al.  Increased Oxygen Consumption Following Activation of Brain: Theoretical Footnotes Using Spectroscopic Data from Barrel Cortex , 2001, NeuroImage.

[133]  Daniel W. Wilson,et al.  Snapshot hyperspectral imaging in ophthalmology. , 2007, Journal of biomedical optics.

[134]  Hellmuth Obrig,et al.  Cytochrome-c-oxidase redox changes during visual stimulation measured by near-infrared spectroscopy cannot be explained by a mere cross talk artefact , 2004, NeuroImage.

[135]  Michael R. Keenan,et al.  Multivariate Analysis of Spectral Images Composed of Count Data , 2007 .

[136]  R. C. Benson,et al.  Cellular autofluorescence--is it due to flavins? , 1979, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[137]  Nicholas B. MacKinnon,et al.  Hyperspectral and Multispectral Imaging in Dermatology , 2016 .

[138]  Anna Devor,et al.  Sensitivity of neural-hemodynamic coupling to alterations in cerebral blood flow during hypercapnia. , 2009, Journal of biomedical optics.

[139]  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.

[140]  Chrysanthe Preza,et al.  Computational hyperspectral interferometry for studies of brain function: proof of concept. , 2006, Applied optics.

[141]  M. Duchen,et al.  Ca(2+)-dependent changes in the mitochondrial energetics in single dissociated mouse sensory neurons. , 1992, The Biochemical journal.

[142]  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.

[143]  F. Jöbsis.  Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. , 1977, Science.

[144]  S. Kety,et al.  THE GENERAL METABOLISM OF THE BRAIN IN VIVO , 1957 .

[145]  A. Villringer,et al.  Near infrared spectroscopy (NIRS): A new tool to study hemodynamic changes during activation of brain function in human adults , 1993, Neuroscience Letters.

[146]  Moshe Levi,et al.  Identification of cholesterol crystals in plaques of atherosclerotic mice using hyperspectral CARS imaging , 2011, Journal of Lipid Research.

[147]  David A Boas,et al.  Cortical Spreading Depression Impairs Oxygen Delivery and Metabolism in Mice , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[148]  M. Singer,et al.  In Vivo Imaging of Flavoprotein Fluorescence During Hypoxia Reveals the Importance of Direct Arterial Oxygen Supply to Cerebral Cortex Tissue , 2015, Advances in experimental medicine and biology.

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

[150]  R. Buxton,et al.  A Model for the Coupling between Cerebral Blood Flow and Oxygen Metabolism during Neural Stimulation , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[151]  Szu-Yu Chen,et al.  Non-de-scanned parallel recording two-photon hyperspectral microscopy with high spectral and spatial resolution. , 2014, Biomedical optics express.

[152]  R. Gillies,et al.  Systemic effects of shock and resuscitation monitored by visible hyperspectral imaging. , 2003, Diabetes technology & therapeutics.