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Biomedical subjects

Britton Chance

Publications and source records attributed to Britton Chance.

At least 19 recordsLinked to original sources
PubMed2006

Simultaneous fluorometry and phosphorometry of Langendorff perfused rat heart: ex vivo animal studies.

Fluorescence imaging of intrinsic fluorophores of tissue is a powerful method to assess metabolic changes at the cellular and intracellular levels. At the same time, exogenous phosphorescent probes can be used to accurately measure intravascular tissue oxygenation. Heart failure is the leading cause of death in America. A rat heart can potentially model the human heart to study failures or other abnormalities optically. We report simultaneous fluorescence and phosphorescence measurements performed on a rat heart. We have used two different optical systems to acquire fluorescence signals of flavoprotein and nicotinamide adenine dinucleotide--the two intrinsic fluorophores of mitochondria--and the phosphorescence signal of an intravascular oxygen probe to extract intracellular and intravascular metabolism loads, respectively.

Animals↗
PubMed2006

A novel method to measure regional muscle blood flow continuously using NIRS kinetics information.

BACKGROUND: This article introduces a novel method to continuously monitor regional muscle blood flow by using Near Infrared Spectroscopy (NIRS). We demonstrate the feasibility of the new method in two ways: (1) by applying this new method of determining blood flow to experimental NIRS data during exercise and ischemia; and, (2) by simulating muscle oxygenation and blood flow values using these newly developed equations during recovery from exercise and ischemia. METHODS: Deoxy (Hb) and oxyhemoglobin (HbO2), located in the blood of the skeletal muscle, carry two internal relationships between blood flow and oxygen consumption. One is a mass transfer principle and the other describes a relationship between oxygen consumption and Hb kinetics in a two-compartment model. To monitor blood flow continuously, we transfer these two relationships into two equations and calculate the blood flow with the differential information of HbO2 and Hb. In addition, these equations are used to simulate the relationship between blood flow and reoxygenation kinetics after cuff ischemia and a light exercise. Nine healthy subjects volunteered for the cuff ischemia, light arm exercise and arm exercise with cuff ischemia for the experimental study. RESULTS: Analysis of experimental data of both cuff ischemia and light exercise using the new equations show greater blood flow (four to six times more than resting values) during recovery, agreeing with previous findings. Further, the simulation and experimental studies of cuff ischemia and light exercise agree with each other. CONCLUSION: We demonstrate the accuracy of this new method by showing that the blood flow obtained from the method agrees with previous data as well as with simulated data. We conclude that this novel continuous blood flow monitoring method can provide blood flow information non-invasively with NIRS.

Journal Article↗
PubMed2006

Skeletal muscle energetics with PNMR: personal views and historic perspectives.

This article reviews historical and current NMR approaches to describing in vivo bioenergetics of skeletal muscles in normal and diseased populations. It draws upon the first author's more than 70 years of personal experience in enzyme kinetics and the last author's physiological approaches. The development of in vivo PNMR jointly with researchers around the world is described. It is explained how non-invasive PNMR has advanced human exercise biochemistry, physiology and pathology. Further, after a brief explanation of bioenergetics with PNMR on creatine kinase, anerobic glycolysis and mitochondrial oxidative phosphorylation, some basic and controversial subjects are focused upon, and the authors' view of the subjects are offered, with questions and answers. Some of the research has been introduced in exercise physiology. Future directions of NMR on bioenergetics, as a part of system biological approaches, are indicated.

Adenosine Triphosphate↗
PubMed2006

Extended kalman filtering for the modeling and analysis of ICG pharmacokinetics in cancerous tumors using NIR optical methods.

Compartmental modeling of indocyanine green (ICG) pharmacokinetics, as measured by near infrared (NIR) techniques, has the potential to provide diagnostic information for tumor differentiation. In this paper, we present three different compartmental models to model the pharmacokinetics of ICG in cancerous tumors. We introduce a systematic and robust approach to model and analyze ICG pharmacokinetics based on the extended Kalman filtering (EKF) framework. The proposed EKF framework effectively models multiple-compartment and multiple-measurement systems in the presence of measurement noise and uncertainties in model dynamics. It provides simultaneous estimation of pharmacokinetic parameters and ICG concentrations in each compartment. Moreover, the recursive nature of the Kalman filter estimator potentially allows real-time monitoring of time varying pharmacokinetic rates and concentration changes in different compartments. Additionally, we introduce an information theoretic criteria for the best compartmental model order selection, and residual analysis for the statistical validation of the estimates. We tested our approach using the ICG concentration data acquired from four Fischer rats carrying adenocarcinoma tumor cells. Our study indicates that, in addition to the pharmacokinetic rates, the EKF model may provide parameters that may be useful for tumor differentiation.

Adenocarcinoma↗
PubMed2006

Impaired exercise-induced blood volume in type 2 diabetes with or without peripheral arterial disease measured by continuous-wave near-infrared spectroscopy.

OBJECTIVE: Diabetes is a significant risk factor for peripheral arterial disease (PAD) and is associated with accelerated atherosclerosis and limb loss. However, the pathophysiology involved in PAD is unclear. This study was conducted to evaluate the hemodynamic response to exercise of patients with and without diabetes and PAD. RESEARCH DESIGN AND METHODS: The hemodynamic response in calf muscles of patients with diabetes, PAD, or both was determined using near-infrared spectroscopy (NIRS). Patients performed both a plantar-flexion and treadmill-walking exercise regimen. RESULTS: Skeletal muscle capillary blood volume expansion during exercise, as measured by NIRS, was significantly impaired in the lower extremities of diabetic patients with a normal ankle-brachial index. The relative deoxygenation and oxygenation recovery times measured by NIRS correlates significantly with the presence of PAD. CONCLUSIONS: Patients with diabetes have reduced capillary volume expansion even without PAD. This is likely due to impaired vasodilation secondary to endothelial dysfunction. Further studies are needed to determine whether pharmaceutical intervention improves the blood volume expansion in the diabetic state.

Aged↗
PubMed2005

Diffuse optical tomography with a priori anatomical information.

Diffuse optical tomography (DOT) poses a typical ill-posed inverse problem with a limited number of measurements and inherently low spatial resolution. In this paper, we propose a hierarchical Bayesian approach to improve spatial resolution and quantitative accuracy by using a priori information provided by a secondary high resolution anatomical imaging modality, such as magnetic resonance (MR) or x-ray. In such a dual imaging approach, while the correlation between optical and anatomical images may be high, it is not perfect. For example, a tumour may be present in the optical image, but may not be discernable in the anatomical image. The proposed hierarchical Bayesian approach allows incorporation of partial a priori knowledge about the noise and unknown optical image models, thereby capturing the function-anatomy correlation effectively. We present a computationally efficient iterative algorithm to simultaneously estimate the optical image and the unknown a priori model parameters. Extensive numerical simulations demonstrate that the proposed method avoids undesirable bias towards anatomical prior information and leads to significantly improved spatial resolution and quantitative accuracy.

Anatomy↗
PubMed2005

Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression.

Integrins mediate many biological processes, including tumor-induced angiogenesis and metastasis. The arginine-glycine-aspartic acid (RGD) peptide sequence is a common recognition motif by integrins in many proteins and small peptides. While evaluating a small library of RGD peptides for imaging alpha(V)beta(3) integrin (ABI)-positive tumor cell line (A549) by optical methods, we discovered that conjugating a presumably inactive linear hexapeptide GRDSPK with a near-infrared carbocyanine molecular probe (Cypate) yielded a previously undescribed bioactive ligand (Cyp-GRD) that targets ABI-positive tumors. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay with A549 cells showed that Cyp-GRD was not cytotoxic up to 100 muM in cell culture. The compound was internalized by cells, and this internalization was blocked by coincubation with a cyclic RGD peptide (cyclo[RGDfV], f is d-phenylalanine) that binds ABI with high affinity. In vivo, Cyp-GRD selectively accumulated in tumors relative to surrounding normal tissues. Blocking studies with cyclo[RGDfV] inhibited the in vivo uptake of Cyp-GRD, suggesting that both compounds target the same active site of the protein. A strong correlation between the Cyp-GRD peptide and mitochondrial NADH concentration suggests that the new molecule could also report on the metabolic status of cells ex vivo. Interestingly, neither a Cypate-labeled linear RGD peptide nor an (111)In-labeled DOTA-GRD conjugate was selectively retained in the tumor. These results clearly demonstrate the synergistic effects of Cypate and GRD peptide for molecular recognition of integrin expression and suggest the potential of using carbocyanines as optical scaffolds for designing biologically active molecules.

Animals↗
PubMed2005

Near-infrared-emissive polymersomes: self-assembled soft matter for in vivo optical imaging.

We demonstrate that synthetic soft materials can extend the utility of natural vesicles, from predominantly hydrophilic reservoirs to functional colloidal carriers that facilitate the biomedical application of large aqueous-insoluble compounds. Near-infrared (NIR)-emissive polymersomes (50-nm- to 50-microm-diameter polymer vesicles) were generated through cooperative self assembly of amphiphilic diblock copolymers and conjugated multi(porphyrin)-based NIR fluorophores (NIRFs). When compared with natural vesicles comprised of phospholipids, polymersomes were uniquely capable of incorporating and uniformly distributing numerous large hydrophobic NIRFs exclusively in their lamellar membranes. Within these sequestered compartments, long polymer chains regulate the mean fluorophore-fluorophore interspatial separation as well as the fluorophore-localized electronic environment. Porphyrin-based NIRFs manifest photophysical properties within the polymersomal matrix akin to those established for these high-emission dipole strength fluorophores in organic solvents, thereby yielding uniquely emissive vesicles. Furthermore, the total fluorescence emanating from the assemblies gives rise to a localized optical signal of sufficient intensity to penetrate through the dense tumor tissue of a live animal. Robust NIR-emissive polymersomes thus define a soft matter platform with exceptional potential to facilitate deep-tissue fluorescence-based imaging for in vivo diagnostic and drug-delivery applications.

Animals↗
PubMed2005

Simulation study of breast tissue hemodynamics during pressure perturbation.

We simulated the effects of compression of the breast on blood volume and tissue oxygenation. We sought to answer the question: how does the compression during breast examination impact on the circulatory systems of the breast tissue, namely blood flow, blood pooling, and oxygen concentration? We assumed that the blood was distributed in two compartments, arterial and venous. All the parameters were expressed with oxy- and deoxyhemoglobin quantities and were measured with a non-invasive method, Near Infrared Spectroscopy (NIRS). The simulated data showed that the blood volume pool in the breast decreased due to lower arterial flow and higher venous outflow, as the breast was squeezed under 100 cm H2O with a 10 cm diameter probe (or 78 cm2). The blood volume was reversed when the pressure was released. The breast venous oxygen saturation dropped, but overall tissue saturation (presenting NIRS signal, volume weighted average saturation) was increased. The results showed that simulation can be used to obtain venous and average oxygen saturation as well as blood flow in compressed breast tissues.

Blood Volume↗
PubMed2005

Mitochondrial NADH as the bellwether of tissue O2 delivery.

It is proposed that the redox state of mitochondrial NADH will complement blood gas analysis for measuring the health and welfare of human tissues. Use of arterial oxygen saturation levels (SaO2), especially as assayed by the Nellcor instrument, has spread almost everywhere in medicine despite the fact that hypoxia of internal organs, liver, kidney, brain, pancreas, etc. is not well indicated by peripheral digital oxygenation. Indeed, there is an implied liability in the failure to infer central oxygenation from peripheral values. Near infrared (NIR) sensing of deep tissue saturation of hemoglobin (StO2) requires multi-wavelength, multi-site measurement of both absorption and scattering properties by time or frequency domain NIR methods. Corrections for underlying water and lipid absorptions can be made so that the correct value for, and saturation oh hemoglobin are obtained. Nevertheless, the significance of blood oxygen saturation, even localized to particular organs, can be questioned from the standpoint of what is the critical value of the desaturation from which the tissue can recover; for example, in the case of cortical neurons where stroke, compression ischemia, etc. cause O2 lack, this value becomes of significant clinical importance in both the brain and the spinal chord. These approaches are actively pursued and the possibility of subsurface redox state measurement in human tissues may eventually emerge as the quantitative metric of tissue metabolic state and of hypoxic stress. The great flexibility and versatility of the fast, economical and "tetherless" nature of opto-electronic technology is appropriate to the manifold challenges of neuronal function as currently measured by intrinsic signals and soon to be studiable by extrinsic signals of metabolism and electrophysiological functions.

Animals↗
PubMed2005

Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study.

RATIONALE AND OBJECTIVES: To demonstrate that near-infrared spectroscopy would achieve sufficient sensitivity and specificity in human breast cancer to reach ROC/AUC values in the 90s and yet to warn of the potential liabilities of introduction of a novel technology in this field. MATERIALS AND METHODS: 116 subjects from two nations (44 were cancer-verified by biopsy and histopathology) were reviewed. NIR spectroscopy of total hemoglobin and its relative oxygenation were monitored in breast cancers and compared to their contralateral breast in a 2D nomogram for diagnostic evaluation. A novel handheld NIR breast cancer detector pad with a 3-wavelength LED and 8 detectors with 4 cm separation between source and detectors was placed on the subject's breast. The method is convenient, rapid, and safe and has achieved high patient compliance with minimal patient apprehension of compression, confinement, or radioactivity. RESULTS: The absorbance increments of the cancerous region are referred to the mirror image location on the contralateral breast. The two metrics are increased hemoglobin concentration due to angiogenesis and decreased hemoglobin saturation due to hypermetabolism of the cancer. The 2D nomogram display of these two metrics shows Zone 1 contains verified cancers and Zone 2 contains noncancers. ROC evaluation of the nomogram gives 95% AUC for the two sites, Philadelphia and Leipzig. CONCLUSION: A simple, economical breast cancer detector has achieved high patient compliance and a high ROC/AUC score for a population which involved a range of tumors down to and including those of 0.8-1 cm in diameter.

Area Under Curve↗
PubMed2005

Transabdominal fetal pulse oximetry with near-infrared spectroscopy.

OBJECTIVE: The purpose of this study was to determine the feasibility of noninvasive fetal pulse oximetry in the human fetus with transabdominal continuous-wave near-infrared spectroscopy. STUDY DESIGN: The instrument has 3 wavelength light-emitting diodes (735, 805, and 850 nm) as light sources and a photomultiplier tube as a detector. This instrument was used in 6 pregnant women (>36 weeks of gestation). First, a fetal heart rate was obtained with a fetal heart rate monitor. Then, the depth of fetal tissue (head) from the maternal abdomen was determined by ultrasound examination; the distance between the optodes (light source and the detector) was set to be approximately twice the depth of the fetus (7-11 cm). The data analysis was based on the modified Beer-Lambert law and the use of optical densities at 735 and 850 nm to obtain the concentration changes of the oxyhemoglobin and deoxyhemoglobin. The saturation was expressed as the percent of oxygen saturation equal to 100 x oxyhemoglobin/(oxyhemoglobin + deoxyhemoglobin). We recorded the spectroscopy data and the fetal heart rate for approximately 3 to 10 minutes in each patient. RESULTS: The mean oxygen saturation values of each of the 6 individual fetuses ranged from 50% to 74% (overall mean saturation, 61% +/- 14.8% [SD]). CONCLUSION: This preliminary data indicate that transabdominal fetal pulse oximetry is feasible for human patient application. The measured values were similar to those that are obtained with transvaginal pulse oximetry. Future studies should correlate transabdominally obtained measurements with those measurements that are obtained by transvaginal fetal pulse oximetry.

Abdomen↗
PubMed2005

Non-PET functional imaging techniques: optical.

The strong and steady development of diffuse optical spectroscopy and tomography as new biomedical optics technologies promises to bring these optical techniques into clinical practice. This article provides a brief review of the light-tissue interaction, the instrumentation, and the theory relevant to this field. This is followed by a survey of the three main applications: brain imaging, muscle imaging, and breast imaging. Lastly, the future outlook of the technology is presented, highlighting the new promises based on recent breakthroughs.

Brain↗
PubMed2005

Fetal transabdominal pulse oximeter studies using a hypoxic sheep model.

OBJECTIVE: This study investigates the validity of transabdominal pulse oximetry using a sheep fetal hypoxia model with fetal arterial hemoglobin saturation. METHODS: Four pregnant ewes were anaesthetized and cannulated through the brachial artery to measure direct arterial blood saturation, SaO(2). Next, the transabdominal pulse oximeter was used to measure indirect measurement of the arterial saturation of the fetus, SpO(2), from the maternal abdomen. Hypoxia was induced by a balloon placed in the maternal aorta. RESULTS: There is a linear relationship between SaO(2), arterial blood saturation values of the fetus, and SpO(2), the values measured by the transabdominal pulse oximetry with a slope of 0.75 (r(2)=0.76). CONCLUSION: This information can be used to calibrate the transabdominal pulse oximeter as a measurement of fetal arterial saturation. With these results, we can advance the accurate, no-risk, noninvasive transabdominal fetal pulse oximeter for human use. This research may contribute to the more accurate diagnosis of the diseases of the fetus including Hypoxic Ischemic Encephalopathy.

Abdomen↗