Development of a portable tissue oximeter using near infra-red spectroscopy.
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Ambulatory Care↗
Biomedical subjects
B Chance
Publications and source records attributed to B Chance.
Determination of optical properties and blood oxygenation in tissue using continuous NIR light.
In this article, we introduce a simple method to characterize optical properties and blood oxygenation in tissue using spatially resolved, steady-state reflectance. The method considers multiple source-detector separations larger than 2 cm, i.e. 20 times the optical mean free path in tissue, and makes an approximation to linearize the relationship between the separation and reflectance. Simulation results show that errors of the algorithm due to the approximation are less than 10%. Using a calibration sample, we calculate from the slope and intercept the absorption and reduced scattering coefficients, mu a and mu's, of a tissue-like solution, and experimental results confirm the usefulness of the method for quantitation of haemoglobin saturation in tissue.
Algorithms↗
A dynamic phantom brain model for near-infrared spectroscopy.
This report describes the construction, fluid dynamics and optical properties of an in vitro model of the neonatal brain for testing near-infrared spectroscopy (NIRS) instruments. The brain model is a solid plastic structure containing a vascular network perfused with blood equilibrated with O2, N2 and CO2 in a closed circuit. The oxygenation state and haemoglobin concentration of the perfusate can be regulated and measured with a co-oximeter, providing a means to compare NIRS measurements of oxy-, deoxy- and total haemoglobin concentrations and haemoglobin O2 directly with a validated standard method. Fluid dynamic experiments revealed that the model's vasculature remains stable over time with minimal haemolysis. The model's optical properties were characterized by time-resolved and continuous wave NIRS between 670 and 850 nm as perfusate saturation was varied in the range 0-100%. Optical properties of the neonatal piglet brain were also determined by similar methods. No significant differences were found between the model and piglet brain in absorption coefficients, reduced scattering coefficients and optical pathlengths, indicating that the model optically simulates the piglet brain over a wide range of oxygenation states. These results demonstrate the potential utility of this dynamic phantom brain for testing NIRS instruments for accuracy and reliability.
Animals↗
A new application for near-infrared spectroscopy: detection of delayed intracranial hematomas after head injury.
Clinical studies have documented the importance of secondary brain insults in determining neurologic outcome after head injury. Delayed intracranial hematomas are one of the most easily remediable causes of secondary injury if identified early, but can cause significant disability or death if not promptly recognized and treated. Early identification and treatment of these lesions that appear or enlarge after the initial CT scan may improve neurological outcome. Serial examinations using near-infrared spectroscopy (NIRS) to detect the development of delayed hematomas were obtained in 167 patients. The difference in absorbance of light (deltaOD) at 760 nm between the normal and the hematoma side was measured serially during the first 3 days after injury. Twenty-seven (16%) of the patients developed some type of late hematoma: an intracerebral hematoma in 8 patients, an extracerebral hematoma in 6 patients, and a postoperative hematoma in 13 patients. Eighteen of the delayed hematomas caused significant mass effect and required surgical evacuation. The hematomas appeared between 2 and 72 h after admission. In 24 of the 27 patients, a significant increase (>0.3) in the deltaOD occurred prior to an increase in intracranial pressure or a change in the neurological examination, or a change on CT scan. Early diagnosis using MRS may allow early treatment and reduce secondary injury caused by delayed hematomas.
Cerebral Hemorrhage↗
Insulin, ketone bodies, and mitochondrial energy transduction.
Addition of insulin or a physiological ratio of ketone bodies to buffer with 10 mM glucose increased efficiency (hydraulic work/energy from O2 consumed) of working rat heart by 25%, and the two in combination increased efficiency by 36%. These additions increased the content of acetyl CoA by 9- to 18-fold, increased the contents of metabolites of the first third of the tricarboxylic acid (TCA) cycle 2- to 5-fold, and decreased succinate, oxaloacetate, and aspartate 2- to 3-fold. Succinyl CoA, fumarate, and malate were essentially unchanged. The changes in content of TCA metabolites resulted from a reduction of the free mitochondrial NAD couple by 2- to 10-fold and oxidation of the mitochondrial coenzyme Q couple by 2- to 4-fold. Cytosolic pH, measured using 31P-NMR spectra, was invariant at about 7.0. The total intracellular bicarbonate indicated an increase in mitochondrial pH from 7.1 with glucose to 7.2, 7.5 and 7.4 with insulin, ketones, and the combination, respectively. The decrease in Eh7 of the mitochondrial NAD couple, Eh7NAD+/NADH, from -280 to -300 mV and the increase in Eh7 of the coenzyme Q couple, Eh7Q/QH2, from -4 to +12 mV was equivalent to an increase from -53 kJ to -60 kJ/2 mol e in the reaction catalyzed by the mitochondrial NADH dehydrogenase multienzyme complex (EC 1.6.5.3). The increase in the redox energy of the mitochondrial cofactor couples paralleled the increase in the free energy of cytosolic ATP hydrolysis, delta GATP. The potential of the mitochondrial relative to the cytosolic phases, Emito/cyto, calculated from delta GATP and delta pH on the assumption of a 4 H+ transfer for each ATP synthesized, was -143 mV during perfusion with glucose or glucose plus insulin, and decreased to -120 mV on addition of ketones. Viewed in this light, the moderate ketosis characteristic of prolonged fasting or type II diabetes appears to be an elegant compensation for the defects in mitochondrial energy transduction associated with acute insulin deficiency or mitochondrial senescence.
Animals↗
Theo's laboratory.
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History, 20th Century↗
Near-infrared measurement of cerebral oxygenation. Correlation with electroencephalographic ischemia during ventricular fibrillation.
BACKGROUND: The application of phase-modulated near-infrared techniques for measurement of the oxygen saturation of cerebral tissue requires both validation by conventional measures of cerebral oxygenation and determination of normal and abnormal values. This study was undertaken to validate phase-modulated near-infrared measurements of cerebral oxygen saturation by comparing them with electroencephalographic evidence of cerebral ischemia during implantation of cardioverting defibrillators. This comparison also yields an estimate of the ischemic threshold as measured with near-infrared techniques. METHODS: Electroencephalograms and near-infrared measurements were performed during 85 episodes of ventricular fibrillation in ten patients. Light at 754, 785, and 816 nm was modulated at 200 MHz, transmitted through the skull, and the path lengths of the reflected light were determined by measuring the phase shifts. The electroencephalogram was inspected for changes during the hypotension associated with the arrhythmia and the oxygen saturation was calculated from the near-infrared path lengths. Changes in oxygen saturation were then compared with electroencephalographic evidence of cerebral ischemia. RESULTS: The mean saturation before fibrillation was 56.5% +/- 1.2 (SEM). In 40 (47%) of the events, electroencephalographic evidence of ischemia was observed. Such changes were related to the minimum saturation observed during ventricular fibrillation (44% +/- 2.5 vs. 56% +/- 1.9 in the absence of electroencephalographic changes; P < 0.001). The ischemic threshold was estimated to be 47% saturation. The sensitivity of this technique was estimated to be 0.6, the specificity 0.84, and the predictive accuracy 0.73. CONCLUSIONS: Near-infrared measurements reflect changes in cerebral oxygenation as indicated by electroencephalographic evidence of cerebral ischemia.
Aged↗
Influence of blood vessels on the measurement of hemoglobin oxygenation as determined by time-resolved reflectance spectroscopy.
We report the development of a heterogeneous resin-tube model to study the influence of blood vessels on the apparent absorption of the system, mu a(sys), using a time-resolved technique. The experimental results show that mu a(sys) depends on the absorption inside the tubes, mu a(tube), tube diameters, and tube-to-sample volume ratios. A mathematical expression relating mu a(sys) and mu a(tube) is derived based on the experimental results and is verified by time-resolved Monte Carlo simulations for heterogeneous models. This analytical formula predicts that the apparent absorption coefficient measured on a biological organ is a volume-weighted sum of the absorption coefficients of different absorbing components. We present some apparent absorption coefficients measured in vivo in animals and humans and discuss improved algorithms that calculate the hemoglobin saturation by including background-tissue absorption and blood vessel distribution.
Blood Vessels↗
Effects of hypercapnia on ECoG and oxidative metabolism in neonatal dog brain.
The effects of hypercapnia on cerebral electrical activity and mitochondrial oxidative phosphorylation were studied in the anesthetized neonatal dog by using the electrocorticogram (ECoG) and 31P-magnetic resonance spectroscopy. Three levels of hypercapnia with arterial PCO2 values of approximately 70, 100, and 140 Torr reduced the intracellular pH of the brain from 7.11 to 6.99, 6.87, and 6.76, respectively. These levels of hypercapnia also reduced ADP concentration ([ADP]) from 21.5 to 18.1, 14.8, and 12.9 microM as well as the average ECoG power output by 20, 30, and 40%. A Michaelis-Menten relationship for the mitochondrial respiratory enzymes was fitted with [ADP] and the change in the average ECoG. The result suggests that mitochondrial respiration is regulated by [ADP] and that the in vivo Michaelis-Menten constant for ADP was 21 microM, a value close to the in vitro value. The mitochondrial maximal reaction velocity was reduced by only 10% during hypercapnia and showed no relationship with the degree of acidosis, suggesting that mitochondrial respiratory enzymes are not responsible for the inhibition of the brain electrical activity.
Adenosine Diphosphate↗
Early detection of delayed traumatic intracranial hematomas using near-infrared spectroscopy.
Delayed intracranial hematomas are an important treatable cause of secondary brain injury in patients with head trauma. Early identification and treatment of these lesions, which appear or enlarge after the initial computerized tomography (CT) scan, may improve neurological outcome. Serial examinations using near-infrared spectroscopy (NIRS) to detect the development of delayed hematomas were performed in 167 patients. The difference in absorbance of light (delta OD) at 760 nm between the normal and the hematoma side was measured serially during the first 3 days after injury. Twenty-seven (16%) of the patients developed a type of late hematoma: intracerebral hematoma in eight, extracerebral hematoma in six, and postoperative hematoma in 13 patients. Eighteen of the delayed hematomas caused significant mass effect and required surgical evacuation. The hematomas appeared between 2 and 72 hours after admission. In 24 of the 27 patients, a significant increase (> 0.3) in the delta OD occurred prior to an increase in intracranial pressure, a change in the neurological examination, or a change on CT scan. A favorable outcome occurred in 67% of the patients with delayed hematomas, which suggests that early diagnosis using NIRS may allow early treatment and reduce secondary injury caused by delayed hematomas.
Adolescent↗
Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solution and applications.
We present an analytic solution for the scattering of diffuse photon density waves by spherical inhomogeneities within turbid media. The analytic result is compared to experimental measurements. Close agreement between theory and experiment permits the use of the theory to determine the properties of unknown sphere-like objects embedded in turbid media. The analytic solution is extended to encompass several problems of practical interest in imaging, including the influence of multiple sources, multiple objects, and boundaries on the characterization of spherical inhomogeneities. We also extend the solution to encompass time-domain measurements.
Algorithms↗
Spectroscopic, electrochemical, and ligand binding properties of the horse heart metmyoglobin His64-Tyr variant.
The distal histidine (E7) of horse heart myoglobin (Mb) has been replaced by tyrosine using site-specific mutagenesis. The resulting green Mb variant (His64-Tyr) was expressed in Escherichia coli JM101, isolated and purified to homogeneity. Spectrophotometric pH titrations of the variant exhibit a change in spectrum that occurs with a pKa of 4.7 (25 degrees C). The midpoint reduction potential of the variant is 20 mV (vs. SHE at pH 7, 25 degrees C). Cyanide and azide binding measurements indicate that the oxidized variant binds these anionic ligands with much greater affinity at pH 4.0 than at neutral pH. Extended X-ray absorption fine structure (EXAFS) spectroscopy establishes that the variant is six coordinate at pH 7.0 and pH 4.2. Higher shell contributions to the iron EXAFS observed at pH 7.0 are attributed to tyrosine. These contributions are absent at pH 4.2. Thus, the sixth heme iron ligand of the oxidized variant Mb at pH 7.0 is attributed to oxygen from the hydroxyl group of tyrosine and the sixth ligand present at pH 4.2 is attributed to the oxygen atom of a coordinated water. The EXAFS spectra, electronic absorption spectra, and ligand binding properties of the His64-Tyr Mb variant are consistent with the binding of Tyr-64 as the sixth heme iron ligand between pH 5 and 12 and with the replacement of Tyr-64 by a water molecule at low pH with a pKa of 4.7.
Animals↗
Bilateral carotid artery occlusion causes periventricular leukomalacia in neonatal dogs.
At 14 days of age, seven mongrel puppies were anesthetized and bilateral carotid arteries, not only the common but also the external and internal carotid arteries, were ligated with sutures. Seven sham-operated littermates served as controls. They were sacrificed at 3 months of age, and their brains were examined macro- and microscopically. Neuropathological examination revealed dilated posterior communicating and basilar arteries in bilateral carotid artery occlusion (BCAO) animals. Six out of 7 BCAO brains had uni- or multiloculated cysts in the periventricular white matter which were surrounded by a band of GFAP-positive glial cells. Scattered small areas of gliosis were found in all experimental animals. Four BCAO brains also showed ventricular dilatation. Although the cerebral cortex seemed to be intact, the periventricular white matter and the corpus callosum were reduced in width in experimental animals. Myelination in the white matter was significantly reduced in BCAO animals compared with the controls. This study directly demonstrates that cerebral hypoperfusion alone can produce periventricular leukomalacia in neonatal dogs.
Animals↗
Kinetics of ligand binding of cytochrome oxidases: a comparative study.
The plethora of microbial oxidases revealed by photochemical action spectra (Chance, B. (1989)) Biochim. Biophys. Acta 1000, 345-347) has led to detailed identification, purification and overproduction in many species, to the point where kinetic comparison of properties seems to allow structure/function deductions. This work compares the carbon monoxide recombination of five types of oxidases obtained from various organisms. The results are plotted in an Arrhenius-type plot and suggest that the carbon monoxide ligation is a sensitive indicator of the heme environment specific for an oxidase expressed under a given oxygen concentration. This survey of the carbon monoxide recombination kinetics of naturally occurring cytochrome oxidases in whole cells shows evidence for structural control of the reaction kinetics.
Animals↗
Structure of the binuclear heme iron-copper site in the quinol-oxidizing cytochrome aa3 from Bacillus subtilis.
Cytochrome aa3-600 is a terminal quinol oxidase of Bacillus subtilis, belonging to the large family of structurally and functionally related respiratory enzymes to which the mitochondrial cytochrome c oxidase also belongs. However, the CuA center typical of the cytochrome c oxidases is lacking from cytochrome aa3-600. The presence of only one copper, viz. CuB of the binuclear heme iron-copper site, makes cytochrome aa3-600 especially suitable for XAS analysis of this structure. Cu and Fe XAS data for fully oxidized cytochrome aa3-600 indicate a structure for the binuclear site similar to that previously reported for mitochondrial cytochrome c oxidase (see Powers et al. (1981) Biophys. J. 34, 465-468). Heme Fea3 has a proximal histidine nitrogen ligand 2.10 +/- 0.02 A from the iron, and a distal S or Cl ligand at 2.36 +/- 0.03 A. The latter is also a ligand of CuB (2.21 +/- 0.02 A), and apparently forms a bridge between the two metals which are 3.70 +/- 0.06 A apart. CuB has two more close-lying ligands at 1.95 +/- 0.02 A, which are likely histidine nitrogens. The similarity between EXAFS of CuB and type 1 'blue' copper is contrasted to EPR and optical spectroscopic properties of CuB, and the nature of the bridging ligand is discussed.
Bacillus subtilis↗
An oxidative defect in metabolic myopathies: diagnosis by noninvasive tissue oximetry.
Metabolic myopathies due to a variety of enzymatic deficiencies are well recognized. The dynamics of oxygen delivery and utilization during exercise have not been observed previously in these disorders. We used a noninvasive optical technique to measure oxygen consumption in the exercising limb in normal subjects and patients with metabolic myopathies. We measured near-infrared spectra of hemoglobin in the gastrocnemius muscle during treadmill exercise in 10 normal subjects, 1 patient with cytochrome c oxidase deficiency, 2 patients with myophosphorylase deficiency, 3 patients with phosphofructokinase deficiency, and 2 patients with carnitine palmityl transferase deficiency. All normal subjects demonstrated a sustained deoxygenation during exercise, indicating an efficient utilization of delivered oxygen. The patient with cytochrome c oxidase deficiency demonstrated consistent oxygenation during exercise, indicating an underutilization of delivered oxygen. In the patients with myophosphorylase or phosphofructokinase deficiency, abnormal oxygenation during exercise indicated an oxidative defect due to a lack of pyruvate production. In the patients with myophosphorylase deficiency, changes in oxidation coincident with glucose utilization and "the second wind phenomenon" were observed. Patients with carnitine palmityl transferase deficiency demonstrated a normal deoxygenation during exercise. Noninvasive tissue oximetry during exercise demonstrates specific abnormalities in a variety of metabolic myopathies, indicating abnormal oxygen utilization, and will be a useful addition to the clinical investigation of exercise intolerance.
Adult↗
Frequency response by pulse reduction for the analysis of TRS spectra.
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Carbon↗
Optical imaging of human breast cancer.
Since an increasing number of breast cancers have been reported in recent years, there is a need for improving techniques for early detection of the breast cancer. Here we tested a time gated optical imaging technique as a tool for imaging human breast. Pulsed laser light at wavelengths of 780 and 830 nm are transmitted through human breast tissues and time spectra of the diffused light through the tissue are recorded over nanoseconds. Data from different locations are acquired and used to reconstruct a two dimensional image as a set of spectra in pixel form. The imaging consists of absorption and scattering coefficients, and the absorption coefficients at the two wavelengths are related to oxygen concentration and blood volume. The analysis of these coefficients is based upon the early arrival photons, therefore allowing construction of a better image than those from the current diaphanography. We demonstrate images of breast cancer, cysts created after lumpectomy, and consequences of radiation therapy. Results show that time gated optical imaging can image oxygen concentration in the cancerous and fibrotic breasts. Resolution of the imaging for smaller tumor size needs to be improved.
Adult↗