Non-invasive assessment of cerebral microcirculation with diffuse optics and coherent hemodynamics spectroscopy

We describe the general principles and initial results of coherent hemodynamics spectroscopy (CHS), which is a new technique for the quantitative assessment of cerebral hemodynamics on the basis of dynamic near-infrared spectroscopy (NIRS) measurements. The two components of CHS are (1) dynamic measurements of coherent cerebral hemodynamics in the form of oscillations at multiple frequencies (frequency domain) or temporal transients (time domain), and (2) their quantitative analysis with a dynamic mathematical model that relates the concentration and oxygen saturation of hemoglobin in tissue to cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2). In particular, CHS can provide absolute measurements and dynamic monitoring of CBF, and quantitative measures of cerebral autoregulation. We report initial results of CBF measurements in hemodialysis patients, where we found a lower CBF (54 ± 16 ml/(100 g-min)) compared to a group of healthy controls (95 ± 11 ml/(100 g-min)). We also report CHS measurements of cerebral autoregulation, where a quantitative index of autoregulation (its cutoff frequency) was found to be significantly greater in healthy subjects during hyperventilation (0.034 ± 0.005 Hz) than during normal breathing (0.017 ± 0.002 Hz). We also present our approach to depth resolved CHS, based on multi-distance, frequency-domain NIRS data and a two-layer diffusion model, to enhance sensitivity to cerebral tissue. CHS offers a potentially powerful approach to the quantitative assessment and continuous monitoring of local brain perfusion at the microcirculation level, with prospective brain mapping capabilities of research and clinical significance.

[1]  R. Panerai Transcranial Doppler for evaluation of cerebral autoregulation , 2009, Clinical Autonomic Research.

[2]  D. S. Williams,et al.  Magnetic resonance imaging of perfusion using spin inversion of arterial water. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Thompson,et al.  Cerebral perfusion CT: technique and clinical applications. , 2004, Radiology.

[4]  T G Robinson,et al.  Continuous estimates of dynamic cerebral autoregulation during transient hypocapnia and hypercapnia. , 2010, Journal of applied physiology.

[5]  Atsushi Maki,et al.  Spontaneous oscillation of oxy- and deoxy- hemoglobin changes with a phase difference throughout the occipital cortex of newborn infants observed using non-invasive optical topography , 2000, Neuroscience Letters.

[6]  D Gur,et al.  Stable xenon CT cerebral blood flow imaging: rationale for and role in clinical decision making. , 1991, AJNR. American journal of neuroradiology.

[7]  Sergio Fantini,et al.  Optical Characterization of Two-Layered Turbid Media for Non-Invasive, Absolute Oximetry in Cerebral and Extracerebral Tissue , 2013, PloS one.

[8]  B. Rosen,et al.  High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis , 1996, Magnetic resonance in medicine.

[9]  I. Kanno,et al.  Arterial fraction of cerebral blood volume in humans measured by positron emission tomography , 2001, Annals of nuclear medicine.

[10]  Alwin Kienle,et al.  Light diffusion in N-layered turbid media: frequency and time domains. , 2010, Journal of biomedical optics.

[11]  R. Aaslid,et al.  Cerebral autoregulation dynamics in humans. , 1989, Stroke.

[12]  E Gratton,et al.  Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique. , 1994, Applied optics.

[13]  R. Aaslid,et al.  Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. , 1982, Journal of neurosurgery.

[14]  N. Lassen,et al.  Regional cerebral blood flow in man determined by intra-arterial injection of radioactive inert gas. , 1966, Circulation research.

[15]  D. Delpy,et al.  COTSIDE MEASUREMENT OF CEREBRAL BLOOD FLOW IN ILL NEWBORN INFANTS BY NEAR INFRARED SPECTROSCOPY , 1988, The Lancet.

[16]  Cornelius Weiller,et al.  Oscillatory cerebral hemodynamics—the macro- vs. microvascular level , 2006, Journal of the Neurological Sciences.

[17]  E. Sveinsdottir,et al.  Regional Cerebral low in Man Determined by Intral‐artrial Injection of Radioactive Inert Gas , 1966 .

[18]  Sergio Fantini,et al.  Bilateral near-infrared monitoring of the cerebral concentration and oxygen-saturation of hemoglobin during right unilateral electro-convulsive therapy , 2003, Brain Research.

[19]  D. Boas,et al.  Double-layer estimation of intra- and extracerebral hemoglobin concentration with a time-resolved system. , 2008, Journal of biomedical optics.

[20]  M. Mintun,et al.  Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. , 1983, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  Ronney B Panerai,et al.  Cerebral hemodynamics: concepts of clinical importance. , 2012, Arquivos de neuro-psiquiatria.

[22]  Donald S. Williams,et al.  Perfusion imaging , 1992, Magnetic resonance in medicine.

[23]  Sergio Fantini,et al.  Validation of a novel hemodynamic model for coherent hemodynamics spectroscopy (CHS) and functional brain studies with fNIRS and fMRI , 2014, NeuroImage.

[24]  I. Roberts,et al.  Estimation of cerebral blood flow with near infrared spectroscopy and indocyanine green , 1993, The Lancet.

[25]  Philip N. Ainslie,et al.  Blood pressure regulation IX: cerebral autoregulation under blood pressure challenges , 2013, European Journal of Applied Physiology.

[26]  Martin Wolf,et al.  Noninvasive determination of the optical properties of adult brain: near-infrared spectroscopy approach. , 2004, Journal of biomedical optics.

[27]  J. Volpe,et al.  Near Infrared Spectroscopy Detects Cerebral Ischemia during Hypotension in Piglets , 1998, Pediatric Research.

[28]  D. Newell,et al.  Comparison of static and dynamic cerebral autoregulation measurements. , 1995, Stroke.

[29]  D. Delpy,et al.  Quantification of adult cerebral hemodynamics by near-infrared spectroscopy. , 1994, Journal of applied physiology.

[30]  Davide Contini,et al.  Time domain functional NIRS imaging for human brain mapping , 2014, NeuroImage.

[31]  S. Kety,et al.  THE DETERMINATION OF CEREBRAL BLOOD FLOW IN MAN BY THE USE OF NITROUS OXIDE IN LOW CONCENTRATIONS , 1945 .

[32]  Sergio Fantini,et al.  A new hemodynamic model shows that temporal perturbations of cerebral blood flow and metabolic rate of oxygen cannot be measured individually using functional near-infrared spectroscopy , 2014, Physiological measurement.

[33]  Céline Fouard,et al.  A Novel Three‐Dimensional Computer‐Assisted Method for a Quantitative Study of Microvascular Networks of the Human Cerebral Cortex , 2006, Microcirculation.

[34]  M. Patterson,et al.  Noninvasive determination of the optical properties of two-layered turbid media , 1998 .

[35]  V. Rajan,et al.  Review of methodological developments in laser Doppler flowmetry , 2009, Lasers in Medical Science.

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

[37]  Peter Herscovitch,et al.  Brain blood flow measured with intravenous H/sub 2//sup 15/O. I. Theory and error analysis , 1983 .

[38]  Sergio Fantini,et al.  Cerebral Autoregulation in the Microvasculature Measured with Near-Infrared Spectroscopy , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[39]  Sergio Fantini,et al.  Reduced speed of microvascular blood flow in hemodialysis patients versus healthy controls: a coherent hemodynamics spectroscopy study , 2014, Journal of biomedical optics.

[40]  Y Yonekura,et al.  Extraction and retention of technetium-99m-ECD in human brain: dynamic SPECT and oxygen-15-water PET studies. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[41]  R. Panerai Assessment of cerebral pressure autoregulation in humans - a review of measurement methods , 1998, Physiological measurement.

[42]  Sergio Fantini,et al.  Practical steps for applying a new dynamic model to near-infrared spectroscopy measurements of hemodynamic oscillations and transient changes: implications for cerebrovascular and functional brain studies. , 2014, Academic radiology.

[43]  Tianne Numan,et al.  Static autoregulation in humans: a review and reanalysis. , 2014, Medical engineering & physics.

[44]  Sergio Fantini,et al.  Dynamic model for the tissue concentration and oxygen saturation of hemoglobin in relation to blood volume, flow velocity, and oxygen consumption: Implications for functional neuroimaging and coherent hemodynamics spectroscopy (CHS) , 2014, NeuroImage.

[45]  Olaf B. Paulson,et al.  The Retention of [99mTc]-d,l-HM-PAO in the Human Brain after Intracarotid Bolus Injection: A Kinetic Analysis , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[46]  A. Villringer,et al.  Spontaneous Low Frequency Oscillations of Cerebral Hemodynamics and Metabolism in Human Adults , 2000, NeuroImage.