PubMed HealthSearch

Biomedical subjects

R L Barbour

Publications and source records attributed to R L Barbour.

At least 19 recordsLinked to original sources

Comparison of finite-difference transport and diffusion calculations for photon migration in homogeneous and heterogeneous tissues.

We analyse the limits of the diffusion approximation to the time-independent equation of radiative transfer for homogeneous and heterogeneous biological media. Analytical calculations and finite-difference simulations based on diffusion theory are compared with discrete-ordinate, finite-difference transport calculations. The influence of the ratio of absorption and transport scattering coefficient (mu(a)/mu'(s)) on the accuracy of the diffusion approximation are quantified and different definitions for the diffusion coefficient, D, are discussed. We also address effects caused by void-like heterogeneities in which absorption and scattering are very small compared with the surrounding medium. Based on results for simple homogeneous and heterogeneous systems, we analyse diffusion and transport calculation of light propagation in the human brain. For these simulations we convert density maps obtained from magnetic resonance imaging (MRI) to optical-parameter maps (mu(a) and mu'(s)) of the brain. We show that diffusion theory fails to describe accurately light propagation in highly absorbing regions, such as haematoma, and void-like spaces, such as the ventricles and the subarachnoid space.

Absorption

Nonlinear effects of localized absorption perturbations on the light distribution in a turbid medium.

A theoretical model of photon propagation in a scattering medium is presented, from which algebraic formulas for the detector-reading perturbations (delta R) produced by one or two localized perturbations in the macroscopic absorption cross section (delta mu a) are derived. Examination of these shows that when delta mu a is titrated from very small to large magnitudes in one voxel, the curve traced by the corresponding delta R values is a rectangular hyperbola. Furthermore, while delta Rinfinity identical to lim delta mu a-->infinity delta R is dependent on the location of the detector with respect to the source and the voxel, the ratio delta R/ delta Rinfinity is independent of the detector location. We also find that when delta mu a is varied in two voxels simultaneously, the quantity delta R (delta mu a,1 [symbol: see text] delta mu a,2) is a bilinear rational function of the delta mu aS. These results apply not only in the case of steady-state illumination and detection but to time-harmonic measurements as well. The validity of the theoretical formulas is demonstrated by applying them to the results of selected numerical diffusion computations. Potential applications of the derived expressions to image-reconstruction problems are discussed.

Absorption

Imaging of fluorescence in highly scattering media.

Two one-speed radiation transport equations coupled by a dynamic equation for the distribution of fluorophore electronic states are used to model the migration of excitation photons and emitted fluorescence photons. The conditions for producing appreciable levels of fluorophore in the excited state are studied, with the conclusion that minimal saturation occurs under the conditions applicable to tissue imaging. This simplifies the derivation of the frequency response and of the imaging operator for a time-harmonic excitation source. Several factors known to influence the fluorescence response-the concentration, mean lifetime and quantum yield of the fluorophore, and the modulation frequency of the excitatory source-are examined. Optimal sensitivity conditions are obtained by analyzing the fluorescence source strength as a function of the mean lifetime and modulation frequency. The dependence of demodulation of the fluorescent signal on the above factors is also examined. In complementary studies, transport-theory-based operators for imaging fluorophore distributions in a highly scattering medium are derived. Experimental data were collected by irradiating a cylindrical phantom containing one or two fluorophore-filled balloons with continuous wave laser light. The reconstruction results show that qualitatively and quantitatively good images can be obtained, with embedded objects accurately located and the fluorophore concentration correctly determined.

Algorithms

Optical imaging of anatomical maps derived from magnetic resonance images using time-independent optical sources.

We present a model suitable for computing images of absorption cross sections of thick tissue structures illuminated at near infrared (NIR) wavelengths from tomographic projection data. Image reconstruction is accomplished by solving a system of linear equations derived from transport theory. Reconstruction results using different algebraic solvers are shown for anatomical maps of the breast, derived from magnetic resonance imaging data, containing two simulated pathologies, in which case qualitatively good reconstructions were obtained. Evaluation of magnetic resonance (MR) data to optimize NIR optical tomographic imaging methods and to assess the feasibility of a combined MR-optical measurement scheme is discussed.

Adipose Tissue

A wavelet-based multiresolution regularized least squares reconstruction approach for optical tomography.

In this paper, we present a wavelet-based multigrid approach to solve the perturbation equation encountered in optical tomography. With this scheme, the unknown image, the data, as well as the weight matrix are all represented by wavelet expansions, thus yielding a multiresolution representation of the original perturbation equation in the wavelet domain. This transformed equation is then solved using a multigrid scheme, by which an increasing portion of wavelet coefficients of the unknown image are solved in successive approximations. One can also quickly identify regions of interest (ROI's) from a coarse level reconstruction and restrict the reconstruction in the following fine resolutions to those regions. At each resolution level a regularized least squares solution is obtained using the conjugate gradient descent method. This approach has been applied to continuous wave data calculated based on the diffusion approximation of several two-dimensional (2-D) test media. Compared to a previously reported one grid algorithm, the multigrid method requires substantially shorter computation time under the same reconstruction quality criterion.

Algorithms

Luminescence optical tomography of dense scattering media.

Using a set of coupled radiation transport equations, we derive image operators for luminescence optical tomography with which it is possible to reconstruct concentration and mean lifetime distribution from information obtained from dc and time-harmonic optical sources. Weight functions and detector readings were computed from analytic solutions of the diffusion equation and from numerical solutions of the transport equation by Monte Carlo methods. Detector readings were also obtained from experiments on vessels containing a balloon filled with dye embedded in an Intralipid suspension with dye in the background. Image reconstructions were performed by the conjugate gradient descent method and the simultaneous algebraic reconstruction technique with a positivity constraint. A concentration correction was developed in which the reconstructed concentration information is used in the mean-lifetime reconstruction. The results show that the target can be accurately located in both the simulated and the experimental cases, but quantitative inaccuracies are present. Observed errors include a shadowing effect in regions that have the lowest weight within the inclusion. Application of the concentration correction can significantly improve computational efficiency and reduce error in the mean-lifetime reconstructions.

Image Processing, Computer-Assisted

Regularized progressive expansion algorithm for recovery of scattering media from time-resolved data.

Reconstructions of the absorption cross sections of dense scattering media from time-resolved data are presented. A progressive expansion (PE) algorithm, similar to a layer-stripping, is developed to circumvent the underdeterminedness of the inverse problem. An overlapping scheme, which used detector readings from several consecutive time intervals, is introduced to reduce the propagation of reconstruction errors that occur at shallower depths. To reduce the sensitivity of the PE algorithm to noise a regularized progressive expansion (RPE) algorithm is proposed, which incorporates regularization techniques into the PE algorithm. The PE and the RPE algorithms are applied to the problem of image reconstruction from time-resolved data. The test media were isotropically scattering slabs containing one or two compact absorbers at different depths below the surface. The data were corrupted by additive white Gaussian noise with various strengths. The reconstruction results show that the PE and the RPE algorithms, when they are combined by proper overlapping, can effectively overcome the underdeterminedness of the inverse problem. The RPE algorithm yields reconstructions that are more accurate and more stable under the same noise level.

Algorithms

Frequency-domain optical imaging of absorption and scattering distributions by a Born iterative method.

We presents a Born; iterative method, for reconstructing optical properties of turbid media by means of frequency-domain data. The approach is based on iterative solution of a linear perturbation equation, which is derived from the integral from of the Helmholtz wave equation for photon-density waves in each iteration the total field and the associated weight matrix are recalculated based on the previous reconstructed image. We then obtain a new estimate by solving the updated perturbation equation. The forward solution, also based on a Helmholtz equation, is obtained by a multigrid finite difference method. The inversion is carried out through a Tikhonov regularized optimization process by the conjugate gradient descent method. Using this method, we first reconstruct the distribution of the complex wave numbers in a test medium, from which the absorption and the scattering distributions are then derived. Simulation results with two-dimensional test media have shown that this method can yield quantitatively (in terms of coefficient valued) as well as qualitatively (in terms of object location and shape) accurate reconstructions of absorption and scattering distributions in cases in which the first-order Born approximation cannot work well. Both full-angle and limited-angle measurement schemes have been simulated to examine the effect of the location of detectors and sources. The robustness of the algorithm to noise has also been evaluated.

Absorption

Iterative total least-squares image reconstruction algorithm for optical tomography by the conjugate gradient method.

We present an iterative total least-squares algorithm for computing images of the interior structure of highly scattering media by using the conjugate gradient method. For imaging the dense scattering media in optical tomography, a perturbation approach has been described previously [Y. Wang et al., Proc. SPIE 1641, 58 (1992); R. L. Barbour et al., in Medical Optical Tomography: Functional Imaging and Monitoring (Society of Photo-Optical Instrumentation Engineers, Bellingham, Wash., 1993), pp. 87-120], which solves a perturbation equation of the form W delta x = delta I. In order to solve this equation, least-squares or regularized least-squares solvers have been used in the past to determine best fits to the measurement data delta I while assuming that the operator matrix W is accurate. In practice, errors also occur in the operator matrix. Here we propose an iterative total least-squares (ITLS) method that minimizes the errors in both weights and detector readings. Theoretically, the total least-squares (TLS) solution is given by the singular vector of the matrix [W/ delta I] associated with the smallest singular value. The proposed ITLS method obtains this solution by using a conjugate gradient method that is particularly suitable for very large matrices. Simulation results have shown that the TLS method can yield a significantly more accurate result than the least-squares method.

Algorithms

Ferrylmyoglobin formation induced by acute magnesium deficiency in perfused rat heart causes cardiac failure.

The oxidation states of intracellular myoglobin and cytochrome oxidase aa3 were monitored by reflectance spectrophotometry in isolated perfused rat hearts subjected to an acutely magnesium deficient environment. After exposure to low extracellular [Mg2+]o (i.e., 0.3 mM) for 30 min, more than 80% of the oxymyoglobin converted to its deoxygenated form. The level of reduced cytochrome oxidase aa3 also increased about 80% in low [Mg2+]o. The deoxymyoglobin was converted further to a species identified as ferrylmyoglobin by its reaction with Na2S to form ferrous sulfmyoglobin which was optically visible. This process, set into motion by acute Mg deficiency, resulted from a direct accessibility of the exogenous peroxide to the cytosolic protein. The results suggest that a pathway leading to cardiac tissue damage, induced by magnesium deficiency, is probably involved in the generation of a ferrylmyoglobin radical which could be prevented by addition of ascorbate, which is known to be a one-electron reductant of this hypervalent form of myoglobin. In further studies, we also investigated whether addition of different concentrations of ascorbic acid (AA) to the perfusate could enhance myocardial function after exposure to low [Mg2+]o perfusion. Four concentrations of AA (0.5, 1, 5, 10 mM) were tested, and the results indicate that they exert their effects in a concentration-dependent manner; 1 mM AA was the most effective dose in improving aortic output in a Mg-deficient heart. Ferrylmyoglobin formation was found to be formed considerably before intracellular release of either creatine phosphokinase or lactic dehydrogenase. These studies may have wide implications as a new mechanism by which low extracellular Mg2+ can induce myocardial injury and subsequent cardiac failure.

Animals

Characterization of a new ion selective electrode for ionized magnesium in whole blood, plasma, serum, and aqueous samples.

Results from a novel ion selective electrode (ISE) for ionized magnesium (Mg2+) correlate well with atomic absorption spectroscopy on aqueous solutions containing from 0.1-3.0 mmol MgCl2/L. Day to day precision (coefficient of variation) of the electrode on protein-based controls is < 4%; aqueous-based controls < 6%. The new ISE is selective for Mg2+ with a selectivity constant for Ca2+ (KMgCa) of 8 x 10(-2). Adding pathophysiologic concentrations of Cd2+, Ca2+, Cu2+, Fe3+, K+, Na+, or Zn2+ to serum and aqueous solutions gave negligible to minimal changes in measured Mg2+. Ligand binding studies in aqueous solution indicate that pathophysiologic concentrations of different anions (e.g. heparin, lactate, bicarbonate, phosphate, acetate and sulfate) bind to Mg2+, effectively reducing its concentration in solution. Likewise, silicon (as either found in Vacuutainer tubes or as chlorosilane) failed to exert any significant effect on measured Mg2+. Addition of Intralipid (up to 500 mg/dL) gave negligible to minimal changes in Mg2+. Mg2+ measurements on whole blood, plasma, and serum for a given human subject's samples are virtually identical, at least within the reference range for Mg2+. Typically, Mg2+ is 71% of TMg, but varies from subject to subject; i.e. Mg2+ cannot be predicted from TMg. Clinical studies revealed that the Mg2+/TMg ratio could be remarkably consistent in sequential samples (e.g., throughout the course of coronary bypass surgery) taken from one patient, but that this ratio could differ dramatically from the ratio in sequential samples taken from another. Mg2+ is held within a narrow range (0.53-0.67 mmol/L) in normal, healthy subjects when compared to TMg (0.70-0.96 mmol/L).

Adult

Low extracellular magnesium induces intracellular free Mg deficits, ischemia, depletion of high-energy phosphates and cardiac failure in intact working rat hearts: a 31P-NMR study.

Hemodynamic and 31P-NMR spectroscopic studies were performed on intact, perfused working rat hearts exposed to low (0.3 mM) extracellular Mg([Mg2+]o). Low [Mg2+]o perfusion resulted in rapid and significant falls in cardiac output, coronary flow, stroke volume, developed pressure and the rate-pressure product. Concomitant with this O2 consumption decreased and lactate production increased. Hearts perfused with 0.3 mM, instead of 1.2 mM, [Mg2+]o exhibited significant reductions in [ATP], [PCr], intracellular free Mg ([Mg2+]i), and pHi; a marked rise in intracellular Pi corresponding to a precipitous fall in the cytosolic phosphorylation potential was seen. Reintroduction of 1.2 mM [Mg2+]o failed to reestablish either normal hemodynamics, or high-energy phosphates and intracellular Pi, suggesting irreversible myocyte injury. These observations are consistent with the tenet that low [Mg2+]o can result in marked reduction in oxygen and substrate delivery to the cardiac myocytes, probably as a result of coronary vasoconstriction.

Animals

Ionized and total magnesium levels in cyclosporin-treated renal transplant recipients: relationship with cholesterol and cyclosporin levels.

1. Ionized magnesium, measured using a newly developed ion-selective electrode, total magnesium, and ionized and total calcium were evaluated in 39 stable, long-term, cyclosporin-treated renal transplant recipients and compared with those of age-matched, non-transplanted control subjects. Total cholesterol, cyclosporin trough level, serum creatinine, time after-transplant and the ratio of ionized calcium to ionized magnesium were also measured in renal transplant recipients and the relationships between these variables and ionized and total magnesium were evaluated. 2. Renal transplant recipients exhibited marked deficits in ionized magnesium, with a mean value of 0.54 +/- 0.01 mmol/l as compared with 0.61 +/- 0.006 mmol/l for normal control subjects (P < or = 0.05), with a more moderate deficit in total magnesium. Values for ionized and total calcium did not differ. By stepwise linear multiple regression analysis, ionized magnesium was significantly related to cyclosporin trough level and total cholesterol but not to serum creatinine, time after transplant or the dose of cyclosporin. Ionized magnesium correlated inversely with cyclosporin trough level and directly with total cholesterol. The ratio of ionized calcium to ionized magnesium was elevated in renal transplant recipients when compared with control subjects and correlated positively with the cyclosporin trough level. 3. Deficits in ionized magnesium are common during the late post-transplant period in cyclosporin-treated renal transplant recipients. Ionized magnesium may be a more sensitive clinical parameter than total magnesium in this population, in whom total magnesium may be only mildly decreased in the setting of a severe deficit in ionized magnesium. 4. Ionized magnesium correlates with the cyclosporin level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Optical spectroscopy and cerebral vascular effects of alcohol in the intact brain: effects on tissue deoxyhemoglobin, blood content, and reduced cytochrome oxidase.

Dose-response effects of acute ethanol infusions were studied, noninvasively, in the unopened brain to examine the hypothesis that ethanol can induce stroke-like events as a consequence of cerebral vasospasm and tissue ischemia. By using a single sending and receiving fiber, an optical backscatter measurement (500-800 nm) was used to monitor the levels of deoxyhemoglobin (DH), reduced cytochrome oxidase (rCO), and relative tissue blood content in a closed cranium preparation. Anesthetized rats were prepared by cannulating a branch of the internal carotid artery and subjected to either bolus infusions (1.25 or 2.5 microM ethanol in Ringers/g tissue) or to constant infusions of 5 or 10% ethanol at various rates (0.30-2.92 microM/g/min). To facilitate optical penetration, a portion of the left parietal cranium was shaved to a translucent appearance. Results showed that low, bolus doses of ethanol typically produced a slight increase (5-10%) in the oxyhemoglobin signal, indicating that vasodilation had probably occurred. Higher doses, however, produced a prompt and significant reduction in the hemoglobin signal, increased levels of DH, and a rise in rCO suggesting a vasoconstrictor response leading to ischemia had occurred, followed by recovery within 3-5 min. Constant infusions of ethanol produced a similar cerebral vascular response, in a dose-related manner, but of a more sustained nature. At levels of 50-60% of the maximum bolus dose, the effect was more pronounced, accompanied by an increase in the levels of rCO (by 50-90%). Control experiments using identical volumes/flow rates of Ringers solution produced no significant alterations in the optical spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholic Intoxication

Effects of sodium lactate infusion on cisternal lactate and carbon dioxide levels in nonhuman primates.

OBJECTIVE: To further the understanding of lactate-induced panic in patients with panic disorder, the authors examined cisternal lactate and carbon dioxide levels in nonhuman primates after infusions of sodium lactate comparable to those used in studies of human beings. METHOD: CSF and venous blood lactate, pH, PCO2, PO2, and bicarbonate were measured in five ketamine-anesthetized nonhuman primates, without mechanical ventilation, before and after they underwent infusions of sodium lactate. In addition, the same measurements were made for three of the five subjects who were given saline infusions. RESULTS: Despite the development of the characteristic peripheral biochemical effects of infused sodium lactate--increased lactate and bicarbonate levels and metabolic alkalosis--no increases in central lactate or carbon dioxide levels were observed. Saline infusions produced no biochemical effects on venous and cisternal measures. CONCLUSIONS: The results of this study are in keeping with previous findings of nonpermeability of the blood-brain barrier to anionic compounds such as lactate. They therefore support theories of lactate panic based on cognitive and/or brainstem misevaluation of peripheral somatic sensations.

Animals

Development of bioartificial liver: bilirubin conjugation in Gunn rats.

We developed a novel bioartificial liver using microcarrier-attached hepatocytes and a bioreactor. The bioreactor consists of an intracapillary chamber made up of porous (0.2 micron) cellulose acetate hollow fibers enclosed in a polycarbonate module forming an extracapillary chamber. Cryopreserved (-80 degrees C, 3 weeks) microcarrier-attached hepatocytes (3-4 X 10(7] were inoculated into the extracapillary chamber. The bioartificial liver, containing either microcarrier hepatocytes (n = 6) or microcarriers alone (n = 5); was attached to adult Gunn rats via cannulas in the aorta and inferior vena cava. Bile samples were collected before and at hourly intervals after attachment to the bioartificial liver. The same animal model was used to demonstrate de novo conjugation of free bilirubin by the bioartificial liver (n = 3) following systemic administration of unconjugated [3H]bilirubin. Bile was analyzed for bilirubin mono- and diglucuronides by high-performance liquid chromatography and confirmed by digestion with beta-glucuronidase and cochromatography with normal rat bile. A progressive increase in the concentration of bilirubin monoglucuronide and bilirubin diglucuronide in bile was seen as early as 30 min and lasted up to 4 hr following attachment to a bioartificial liver containing microcarrier hepatocytes (3.53 +/- 0.68 to 8.07 +/- 0.85 microM; P less than 0.01). Approximately 22% of the radiolabeled bilirubin excreted in bile was seen in the form of bilirubin conjugates, no radioactivity was seen in the free bilirubin fraction. In conclusion, we developed a bioartificial liver using microcarrier hepatocytes which carry out an important differentiated liver function which results in partial correction of a specific metabolic liver defect, i.e., conjugation of bilirubin.

Animals

Magnesium dietary intake modulates blood lipid levels and atherogenesis.

In this study, we have examined the effects of variation in dietary Mg on the atherogenic process. Oral supplementation of rabbits fed a high cholesterol diet (1% or 2%) with the Mg salt magnesium aspartate hydrochloride (Magnesiocard) (i) lowers the level of serum cholesterol and triglycerides in normal (25-35%) as well as atherosclerotic (20-40%) animals and (ii) attenuates the atherosclerotic process markedly. In addition, we found that dietary deficiency of Mg augments atherogenesis markedly and stimulates (or activates) macrophages of the reticuloendothelial system. Evidence is presented to indicate that the hypercholesterolemic state may cause the loss of Mg from soft tissues to the serum, thereby masking an underlying Mg deficiency.

Animals

Intraperitoneal transplantation of microcarrier-attached enterocytes in rats.

The purpose of this study was to determine whether enterocyte transplantation could be used to correct a specific genetic metabolic defect. Bilirubin uridine diphosphoglucuronyl transferase (UDPGT) activity has been demonstrated in normal rat intestinal mucosa. We hypothesized that normal rat enterocyte transplantation may restore the ability of Gunn rats, which lack bilirubin UDPGT, to conjugate bilirubin. Small intestine was resected from normal Wistar rat donors. Enterocytes were harvested and suspended in Dulbecco's modified Eagle's medium with 10 percent fetal calf serum. Isolated enterocytes were attached to collagen-coated dextran microcarriers and transplanted into congeneic Gunn rat recipients. Recipient rats underwent bile duct cannulation after transplantation, and bile was analyzed for bilirubin glucuronides by high-pressure liquid chromatography. Fifty percent of the transplanted rats showed a significant increase in the concentration of bilirubin monoglucuronide and diglucuronide in their bile 4 and 7 days posttransplantation. Recipient rats had well vascularized microcarrier-enterocyte aggregates in the peritoneal cavity. Our method for intraperitoneal transplantation of isolated enterocytes in rats could potentially be used to correct specific enzymatic and metabolic defects.

Animals