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Biomedical subjects

B Chance

Publications and source records attributed to B Chance.

At least 127 records · Page 7Linked to original sources

Highly sensitive object location in tissue models with linear in-phase and anti-phase multi-element optical arrays in one and two dimensions.

Based upon previous observations of low-frequency photon diffusion waves within highly scattering tissue, this paper explores the "near-field" phenomena of such waves of approximately 10-cm wavelength with 200-MHz phase modulation equipment. Multiple-element source arrays consist of laser diode sources modulated at 180 degrees out of phase with respect to the other sources. The diffusing waves originating from the out-of-phase sources give, in the midplane, an amplitude null and a sharp phase transition. These may be observed in a highly scattering intralipid medium simulating the breast or brain (0.5% intralipid), 3-5 cm from the transmitting laser diodes. In the plane containing the array, there is a high sensitivity for a small volume of a hidden absorber (indocyanine green) deep within a highly scattering medium; 20 pmol in a volume of 70 microliters can be detected. Two-dimensional arrays consisting of four or more elements in two orthogonal planes give sensitivity on both axes similar to the one-dimensional array. Measurements show that in the presence of a light-absorbing object, the amplitude null and the interference plane becomes a curved surface which is deflected toward the heterogeneity. The degree of deflection is related to the volume and the absorption characteristics of the heterogeneity and provides detection of the heterogeneity, and thereby may provide localization information for the detection of small tumors within the human breast, or stroke volumes, aneurysms, and tumors in the human brain.

Brain↗

Cognition-activated low-frequency modulation of light absorption in human brain.

Animal model studies indicate light-absorption changes of the exposed animal brain in response to visual stimulation. Here we report observations of red-light absorbance changes, attributable to repetitive blood concentration changes in response to stimulation in the human brain frontal region by a cognitive process. These responses are observed as low-frequency recurrence of changes by Fourier transform analysis and are attributed to blood concentration change stimulated by the increased metabolic rate of brain tissue in cognitive function. A simple, portable dual wavelength spectrophotometer was attached noninvasively to the human forehead to measure the low frequency and power spectra of fluctuations of absorbances attributed to variations of brain blood concentration in the frontal region. The responses are associated with brain activity in responses to problem solving of analogies presented visually that require an associative function in the frontal region. The method of subtraction of test -rest Fourier transforms minimizes the arterial pulse frequency contributions and identifies specific frequencies--for example, 0.8, 1.6, 1.8 Hz in 24 of 28 tests of nine individuals (85%). Tests in which no increased brain activity was elicited (rest-rest) showed small differences. It is concluded that low-frequency recurrences of brain activity linked to blood concentration increases can be detected in human subjects with an optical device of potentially for simplified tests of cognitive function in the 0- to 3-Hz region and with modifications for wider band recordings in localized tissue volumes by time-resolved spectroscopy.

Adolescent↗

A method to estimate the ratio of absorption coefficients of two wavelengths using phase-modulated near infrared light spectroscopy.

Near infrared spectroscopy is a very useful tool for monitoring the oxygen saturation of living tissue noninvasively. We can calculate the hemoglobin oxygen saturation within tissue, using the ratio of the absorption coefficients (mua) at two different wave lengths of light. Biological tissue has a very high effective scattering factor (mu's), which elongates an optical path length and makes it difficult to compute the mua by the conventional method using continuous light. Phase-modulated spectroscopy (PMS) measures the path length which is a complex function of the mua and mu's. To obtain the ratio for mua, we have to eliminate the effects of the mu's from the obtained value by the PMS method. In this report, we present a theory and an experimental result which show that the inverse of the squared ratio of two phase angle differences at two different separations obtained by two different light wavelengths provides a good estimate of the ratio at these wavelengths.

Algorithms↗

NMR visibility studies of N-delta proton of proximal histidine in deoxyhemoglobin in lysed and intact red cells.

Recent in vivo 1H MRS studies of muscle oxygen levels by means of myoglobin (Mb) oxygenation have necessitated an investigation of the possible contamination from deoxy-hemoglobin (Hb). To determine the contribution of Hb in these NMR measurements, we studied the NMR visibility of histidyl N-delta proton of Hb in lysed and intact RBC (red blood cell) suspensions. We found that the visibility of deoxy-Hb was significantly lower in intact RBCs (ca. 16%) than the solution form at an equivalent concentration of beta heme-iron, even though the visibility of deoxy-Hb from lysed RBC and deoxy-Mb was almost identical. Our study also shows that visibility increases with RBC swelling. Based on the difference in concentration and compartmentation, we conclude that less than 17% contribution from Hb is expected in Mb measurements in vivo. The possible mechanisms which cause the low visibility of Hb in RBCs are discussed.

Erythrocytes↗

Characterization of absorption and scattering properties of small-volume biological samples using time-resolved spectroscopy.

With time-resolved spectroscopy, we develop an experimental approach by sample substitution to measure the absorption (mu a) and reduced scattering (mu's) coefficients of small-volume biological samples. To investigate the method, small-volume control samples are substituted into a large-size host medium during increases in the absorber (or scatterer) concentration of the host. By characterizing the deviation of the spectra taken with and without the sample, we determine the matching points where the sample and surrounding medium are optically identical. We show that this method can result in correct values of the mu a and mu's for the sample within 6% error if the matching conditions for both the mu a and mu's are fully realized. The results also indicate that this method can give approximate values of the mu a and mu's in a reasonable range if either the mu a or the mu's matching between the two media is realized. This method has been applied to the studies of absorption properties of a human finger and of scattering properties of yeast.

Absorption↗

Consequences of reduced cerebral blood flow in brain development. I. Gross morphology, histology, and callosal connectivity.

Reduced blood flow produced by bilateral carotid artery occlusion (BCAO) caused multiple histopathological alterations in the cerebral cortex of developing cats. BCAO was performed in the second postnatal week. At 1 and 2 months, global structural observations were made using magnetic resonance imaging (MRI). At 3 months, neuron and glial density, extent of myelination, blood vessel distribution, and the distribution of visual callosal projecting neurons (as visualized with the retrogradely transported tracer horseradish peroxidase) were assessed by light microscopy. MRI showed lateral ventricular dilatation at 1 month in five of eight subjects, with wide-ranging severity, although at 2 months only two animals still had enlarged ventricles. Histological observations at 3 months showed that neuron density in the motor cortex, but not the occipital cortex, of BACO animals was significantly lower than that in controls. BCAO animals had more dilated small vessels, again more evident in the motor cortex than in the occipital cortex. From frontal to occipital cortex, the corpus callosum was thinned and the subcortical white matter was reduced. Even with the reduction of white matter, the number of neurons in visual areas 17 and 18 contributing a callosal projection was much higher than normal. BCAO thus altered cerebral vascularization, caused neuronal death, and reduced myelinization over an area much greater than the direct area of carotid perfusion. The excess callosal projection in these animals suggests that neonatal ischemia interferes with the normal process of axon retraction during development.

Aging↗

Consequences of reduced cerebral blood flow in brain development. II. Retardation of neurological outcome and phosphorus metabolism.

We investigated the temporal relationship of the emergence of biochemical abnormalities to the development of behavioral dysfunction to identify the central factors of ischemic neurological disorders in developing brains. To induce early ischemia, bilateral carotid artery occlusion (BCAO) was surgically performed on 21 cats at the second week of age. BCAO produces histopathological damage, including neuronal loss and thinning of white matter. 31P magnetic resonance spectroscopy was used to monitor brain oxidative metabolism, neuronal membrane growth, and myelination of the prefrontal cortex in the first 3 months. Neurological development was monitored by conducting 25 tests of reflex, motor, sensory, and integrated behavioral function. At 1 month, phosphodiester (PDE) levels, a component of membranes and myelin, were low in animals showing complete ligation. At 2 months, the growth of PDE was low (1/4 to 1/2 of normal) in BCAO animals, whereas normal animals demonstrated a 23% increase. Phosphocreatine (PCr) levels, indicated by PCr/ATP and PCr/inorganic phosphate ratios, were retarded at 2 months in completely ligated animals (1/4 of normal). Neurologically, the completely ligated animals showed retardation of general development. The retardation was most pronounced for integrative functions, including visual function, and became more pronounced later in development. The time course of emergence of the retardation generally coincided with emergence of abnormalities in phosphorous compounds. The simultaneous occurrence of several biochemical and functional abnormalities in development following early ischemic insult suggests a causal relationship between membrane and mitochondrial development and neurological function.

Adenosine Triphosphate↗

NMR and time-resolved optical studies of brain imaging.

The classical optical method of the biochemist used in so many applications to determine stoichiometry kinetics, quantitative analysis of biochemical systems which was subsequently applied to tissue studies by G.A. Millikan and others seems now to have a new lease on life provided by time and frequency resolved studies which appear to afford the essential quantification lacking in the earlier methods. The fact that localization seems possible as well may bring the optical technology into the arena of new non-invasive technology capable of high sensitivity, high resolution and rapid data acquisition.

Animals↗

Near-infrared monitoring of the cerebral circulation.

Near-infrared spectroscopy is a noninvasive bedside technique for monitoring hemoglobin saturation (HbO2%) in brain vasculature. The method linearly relates the optical signal detected from the surface of the head to HbO2%. To do so, the method relies on constant transcranial optical pathlength and light scattering as well as minimal interference by tissues overlying the brain. This study examined these premises. Optical signals from a dual-wavelength, near-infrared spectrometer were correlated with sagittal sinus HbO2% in 7 anesthetized piglets subjected to 7 different physiological conditions: normoxia, moderate and severe hypoxia, hyperoxia, hypocapnia, hypercapnic hyperoxia, and hypotension. These conditions were induced by varying the inspired O2 concentration (7-100%), ventilatory rate (5-35 breaths/min), and blood pressure (phlebotomy 20 ml/kg) to force HbO2% over a wide range (5-93%). To evaluate interference by tissues overlying the brain, correlations were repeated after the scalp and skull were rendered ischemic. Transcranial optical pathlength was measured by phase-modulated spectroscopy. Linear relationships between optical signals and sagittal sinus HbO2% were found with correlation coefficients ranging from -0.89 to -0.99 (p < 0.05) among animals; however, slope and intercept had coefficients of variability of approximately 15 and 333%, respectively. Almost identical linear expressions were observed whether scalp and skull were ischemic or perfused. Transcranial optical pathlength was constant in each animal, but ranged from 10 to 18 cm among animals. The data indicate that the assumptions underlying near infrared spectroscopy are reasonably accurate in a given animal, but that the constants for transcranial optical pathlength and light scattering are not the same in all animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Further impairment of muscle phosphate kinetics by lengthening exercise in DMD/BMD carriers. An in vivo 31P-NMR spectroscopy study.

We used phosphorus magnetic resonance spectroscopy (31P-MRS) to study the effect of exercise-induced muscle injury in the calf muscle of 7 DMD/BMD carriers and 6 non-carrier females. All subjects performed 50-80 lengthening contractions with the right calf muscles. 48 h after lengthening exercise non-carriers showed increased sensitivity to pressure in their gastrocnemius accompanied by increased T2 relaxation times and by elevated Pi/PCr ratios at rest. DMD/BMD carriers did not show any effect of lengthening exercise on these measurements. In-magnet exercise revealed in all carriers a reduced initial rate of Pi recovery and an increased time to fully recovery the resting value of intracellular pH. Lengthening exercise further decreased the initial rate of Pi recovery. Non-carriers did not show any variation attributable to lengthening exercise either during in-magnet work or during recovery from exercise. We found that lengthening exercise contractions causes: (1) less muscle injury in carriers compared to non-carriers, (2) even slower rate of Pi recovery, but (3) no effect on Pi recovery in non-carriers. The use of lengthening exercise and measurements of Pi recovery may be a useful method to evaluate the disease process in DMD/BMD.

Adolescent↗

Chemiluminescent response to PMA in isolated rat liver after in situ ischemia-reperfusion.

The median and left lateral lobes of rat liver in situ were rendered ischemic for 30 min, then blood flow reinstituted. After 1, 3, 6, 24, or 48 h, livers were removed and set up for isolated perfused organ study. Luminol enhanced chemiluminescence (LEC) was recorded from the surface of the median and left lateral lobes before and for 90 min following phorbol myristate acetate (PMA, 1.6 x 10(-8) M) perfusion. An increase in PMA induced LEC was evident at 1 h and continued to increase up to 6 h. By 24 h the magnitude of the PMA response had returned to within control values. This indicates that a large influx of inflammatory cells had occurred in the liver following the in vivo ischemia-reperfusion insult and that these cells were well fixed in the tissue and capable of mounting a very large and sustained burst of radical production on stimulation with PMA. This combined in vivo/in vitro technique is ideally suited for the assessment of interventions designed to ameliorate damage following oxidative stress.

Animals↗

Near-infrared spectroscopic localization of intracranial hematomas.

Near-infrared spectroscopy (NIRS) of the cerebral hemispheres, applied transcranially through the intact scalp and skull, was evaluated for its ability to detect the presence of an intracranial hematoma in 46 head-injured patients. In 40 patients intracranial hematomas (22 subdural, 10 epidural, eight intracerebral) were identified on computerized tomography (CT); in all 40 cases, NIRS demonstrated greater absorption of light at 760 nm on the side of the hematoma. The mean difference in optical density (OD) between the hemisphere with the hematoma and the normal hemisphere was 0.99 +/- 0.30 for epidural hematomas, 0.87 +/- 0.31 for subdural hematomas, but only 0.41 +/- 0.11 for intracerebral hematomas. In 36 patients, the asymmetry in OD resolved after surgical evacuation of the hematoma or with spontaneous resorption of the hematoma. Four patients who developed postoperative or delayed hematomas exhibited persistence of the asymmetry in OD. Six patients had only diffuse injuries and exhibited only minor differences in OD between the hemispheres, similar to 10 patients in the control group with no head injury. It appears that NIRS is useful in the initial examination of the head-injured patient, as an adjunct to CT, and in following patients postoperatively in the intensive care unit.

Adolescent↗

Phosphorus nuclear magnetic resonance: a non-invasive technique for the study of muscle bioenergetics during exercise.

Phosphorus nuclear magnetic resonance (31P NMR) spectroscopy is a non-destructive analytical laboratory technique that, due to recent technical advances, has become applicable to the study of high-energy phosphate metabolism in both animal and human extremity muscles (in vivo). 31P NMR can assay cellular phosphocreatine, ATP, inorganic phosphate, the phosphorylated glycolytic intermediates, and intra-cellular pH in either resting or exercising muscle, in a non-invasive manner. NMR uses non-perturbing levels of radio-frequency energy as its biophysical probe and can therefore safely study intact muscle in a repeated fashion while exerting no artifactual influence on ongoing metabolic processes. Compared with standard tissue biopsy and biochemical assay techniques, NMR possesses the advantages of being non-invasive, allowing serial in situ studies of the same tissue sample, and providing measurements of only active (unbound) metabolites. NMR studies of exercising muscle have yielded information regarding fatigue mechanisms at the cellular level and are helping resolve long-standing questions regarding the metabolic control of glycolysis, oxidative phosphorylation, and post-exercise phosphocreatine re-synthesis. NMR is also being utilized to measure enzymatic reaction rates in vivo. In the near future, other forms of NMR spectroscopy may also permit the non-invasive measurement of tissue glycogen and lactate content.

Animals↗

Linear correlation between acetoacetate/beta-hydroxybutyrate in arterial blood and oxidized flavoprotein/reduced pyridine nucleotide in freeze-trapped human liver tissue.

A comparison of two methods of measuring liver mitochondrial redox state demonstrated that a linear correlation exists between acetoacetate/beta-hydroxybutyrate ratio in arterial blood (arterial ketone body ratio; AKBR) and oxidized flavoprotein/reduced pyridine nucleotide in human liver tissue (FP/PN) as measured by tissue fluorescence spectroscopy, such that [FP/PN] = 0.64 + 0.49 x [AKBR] (r = 0.84, P less than 0.001). This result supports the validity of AKBR as a method of measuring the hepatic mitochondrial redox state of pyridine nucleotide using arterial blood.

3-Hydroxybutyric Acid↗

X-ray absorption fine structure study of the active site of zinc and cobalt carboxypeptidase A in their solution and crystalline forms.

A comparative study on the metal environment of Zn(II)-carboxypeptidase A (ZnCPD) and Co(II)-carboxypeptidase A (CoCPD) in their solution and crystalline forms using the X-ray absorption fine structure (XAFS) technique has been conducted. The first coordination sphere of Zn for ZnCPD in its solution state is found to consist of two distributions of atoms, with four atoms (N or O) located at an average distance of 2.03 +/- 0.01 A and one atom (N or O) located at 2.57 +/- 0.04 A. The four-atom distribution remains the same for ZnCPD in its crystalline state, but the fifth atom is found at 2.36 +/- 0.04 A. Examination of the higher coordination shell, between 2.7 and 4.2 A, reveals the presence of two imidazoles. Combined with X-ray crystallographic results, a structural model is proposed. The four atoms at an average distance of 2.03 A are assigned to the two delta 1 nitrogens of His-69 and His-196, one epsilon 1 oxygen of Glu-72, and the oxygen of a coordinated water molecule. The atom at 2.57 A for ZnCPD in solution is assigned to the epsilon 2 oxygen of Glu-72. The results for CoCPD in solution are similar with the four atoms at an average distance of 2.08 +/- 0.01 A and one atom at 2.50 +/- 0.04 A, which moves to 2.34 +/- 0.04 A in the crystalline enzyme. The intensity of the 3d "pip" peak for CoCPD is consistent with a distorted tetragonal metal geometry for the solution form of the enzyme which is converted to a more pentacoordinated metal site for the crystalline enzyme. The first shell distribution of crystalline CoCPD is quite disordered, which may be largely due to the disorder of His-69 and His-196 as indicated by higher shell analysis. Thus, the XAFS studies show that the metal coordination spheres in the zinc and cobalt enzymes are quite similar in the solution state but differ from their crystalline counterparts. The XAFS studies provide the necessary background for measurement of substrate- and inhibitor-promoted structural changes in the metal coordination sphere of the zinc and other metal-substituted carboxypeptidases in the solution state.

Animals↗