Measurement of Cerebral Oxidative Metabolism with Near-Infrared Spectroscopy: A Validation Study

Predicting the onset of secondary energy failure after a hypoxic–ischemic insult in newborns is critical for providing effective treatment. Measuring reductions in the cerebral metabolic rate of oxygen (CMRO2) may be one method for early detection, as hypoxia–ischemia is believed to impair oxidative metabolism. We have developed a near-infrared spectroscopy (NIRS) technique based on the Fick Principle for measuring CMRO2. This technique combines cerebral blood flow (CBF) measurements obtained using the tracer indocyanine green with measurements of the cerebral deoxy-hemoglobin (Hb) concentration. In this study, NIRS measurements of CMRO2 were compared with CMRO2 determined from the product of CBF and the cerebral arteriovenous difference in oxygen measured from blood samples. The blood samples were collected from a peripheral artery and the sagittal sinus. Eight piglets were subjected to five cerebral metabolic states created by varying the plane of anesthesia. No significant difference was found between CMRO2 measurements obtained with the two techniques at any anesthetic level (P > 0.5). Furthermore, there was a strong correlation when concomitant CMRO2 values from the two techniques were compared (R2 = 0.88, P< 0.001). This work showed that CMRO2 can be determined accurately by combining NIRS measurements of CBF and Hb. Since NIRS is safe and measurements can be obtained at the bedside, it is believed that this technique could assist in the early diagnosis of cerebral energy dysfunction after hypoxia–ischemia.

[1]  M. Wiedeman,et al.  Dimensions of Blood Vessels from Distributing Artery to Collecting Vein , 1963, Circulation research.

[2]  K. Zierler Equations for Measuring Blood Flow by External Monitoring of Radioisotopes , 1965, Circulation research.

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

[4]  B. Siesjö,et al.  Brain energy metabolism , 1978 .

[5]  M E Phelps,et al.  Validation of tomographic measurement of cerebral blood volume with C-11-labeled carboxyhemoglobin. , 1979, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  J. Astrup Energy-requiring cell functions in the ischemic brain. Their critical supply and possible inhibition in protective therapy. , 1982, Journal of neurosurgery.

[7]  E. Rubinstein,et al.  Journal of Cerebral Blood Flow and Metabolism Cerebrovascular Anatomy and Blood Flow Measurements in the Rabbit , 2022 .

[8]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[9]  J M Bland,et al.  Statistical methods for assessing agreement between two methods of clinical measurement , 1986 .

[10]  C. Poser,et al.  Arterial Behavior and Blood Circulation in the Brain , 1987 .

[11]  W. Armstead,et al.  Adrenergic and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs. , 1988, The American journal of physiology.

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

[13]  P. Albert,et al.  Models for longitudinal data: a generalized estimating equation approach. , 1988, Biometrics.

[14]  M. C. Rogers,et al.  Noninvasive determination of hemoglobin saturation in dogs by derivative near-infrared spectroscopy. , 1989, The American journal of physiology.

[15]  E. Ryding,et al.  A porcine model for sequential assessments of cerebral haemodynamics and metabolism , 1992, Acta anaesthesiologica Scandinavica.

[16]  Fredric B. Meyer Cerebral Blood Flow Metabolism , 1993 .

[17]  D. Delpy,et al.  Use of the water absorption spectrum to quantify tissue chromophore concentration changes in near-infrared spectroscopy. , 1994, Physics in medicine and biology.

[18]  J. Adams,et al.  Immunolocalization of aquaporin CHIP in the guinea pig inner ear. , 1995, The American journal of physiology.

[19]  K. Petersson,et al.  Effects of indomethacin on brain blood flow, cerebral metabolism, and sagittal sinus prostanoids after hypoxia. , 1995, The American journal of physiology.

[20]  D T Delpy,et al.  The Noninvasive Measurement of Absolute Cerebral Deoxyhemoglobin Concentration and Mean Optical Path Length in the Neonatal Brain by Second Derivative Near Infrared Spectroscopy , 1996, Pediatric Research.

[21]  G. Greisen,et al.  Near-infrared monitoring of cerebral tissue oxygen saturation and blood volume in newborn piglets. , 1997, The American journal of physiology.

[22]  I. Roberts,et al.  Measurement of Cerebral Blood Flow in Newborn Infants Using Near Infrared Spectroscopy with Indocyanine Green , 1998, Pediatric Research.

[23]  R. Craen,et al.  Dynamic CT measurement of cerebral blood flow: a validation study. , 1999, AJNR. American journal of neuroradiology.

[24]  S. Nicolson,et al.  Arterial and Venous Contributions to Near-infrared Cerebral Oximetry , 2000, Anesthesiology.

[25]  K. Blomgren,et al.  Impairment of mitochondrial respiration after cerebral hypoxia-ischemia in immature rats: relationship to activation of caspase-3 and neuronal injury. , 2000, Brain research. Developmental brain research.

[26]  D. Delpy,et al.  Oxygen dependency and precision of cytochrome oxidase signal from full spectral NIRS of the piglet brain. , 2000, American journal of physiology. Heart and circulatory physiology.

[27]  E. Cady Magnetic resonance spectroscopy in neonatal hypoxic-ischaemic insults , 2001, Child's Nervous System.

[28]  Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green. , 2001, Physics in medicine and biology.

[29]  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.

[30]  A. Villringer,et al.  Determining changes in NIR absorption using a layered model of the human head , 2001, Physics in medicine and biology.

[31]  D. Delpy,et al.  Quantitative Near Infrared Spectroscopy Measurement of Cerebral Hemodynamics in Newborn Piglets , 2002, Pediatric Research.

[32]  J. Volpe,et al.  Perinatal brain injury in the preterm and term newborn , 2002, Current opinion in neurology.

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

[34]  T. Kusaka,et al.  Quantification of cerebral oxygenation by full-spectrum near-infrared spectroscopy using a two-point method. , 2002, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[35]  D. Delpy,et al.  Noninvasive Measurement of Cerebral Blood Flow in Adults Using Near-Infrared Spectroscopy and Indocyanine Green: A Pilot Study , 2002, Journal of neurosurgical anesthesiology.

[36]  S A Spencer,et al.  The light still shines, but not that brightly? The current status of perinatal near infrared spectroscopy , 2003, Archives of disease in childhood. Fetal and neonatal edition.

[37]  Ting-Yim Lee,et al.  Near-Infrared Spectroscopy Measurement of Oxygen Extraction Fraction and Cerebral Metabolic Rate of Oxygen in Newborn Piglets , 2003, Pediatric Research.

[38]  Ling Wei,et al.  Direct Comparison of Local Cerebral Blood Flow Rates Measured by MRI Arterial Spin-Tagging and Quantitative Autoradiography in a Rat Model of Experimental Cerebral Ischemia , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[39]  A. Kanat Brain oxygenation and energy metabolism: Part 1--Biological function and pathophysiology. , 2003, Neurosurgery.

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

[41]  Masayoshi Fuse,et al.  Cardiac output and circulating blood volume analysis by pulse dye-densitometry , 1997, Journal of Clinical Monitoring.

[42]  H. Hagberg Mitochondrial Impairment in the Developing Brain After Hypoxia–Ischemia , 2004, Journal of bioenergetics and biomembranes.

[43]  Near-infrared spectroscopy measurement of cerebral oxidative metabolism: A validation study , 2005 .

[44]  Ting-Yim Lee,et al.  Near-infrared spectroscopy measurements of cerebral blood flow and oxygen consumption following hypoxia-ischemia in newborn piglets , 2006 .