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Biomedical subjects

Britton Chance

Publications and source records attributed to Britton Chance.

At least 55 records · Page 3Linked to original sources

Microcirculatory function, tissue oxygenation, microregional redox status and ATP distribution in tumors upon localized infrared-A-hyperthermia at 42 degrees C.

Since local hyperthermia (HT) affects microenvironmental parameters, the aim of the study was to analyze the impact of 42 degrees C-HT on microcirculatory function, tumor pO2, microregional redox status and ATP distribution in experimental rat tumors. Subcutaneously growing DS-sarcomas were treated with localized HT using infrared-A radiation resulting in a mean tumor temperature of 42 degrees C. The relative red blood cell (RBC) flux in the tumor was assessed using the laser Doppler technique and the mean tumor pO2 measured continuously using O2-sensitive catheter electrodes. In a second series of experiments, the microregional distribution of the mitochondrial redox status and ATP concentration was measured. Although the average RBC flux increased by 63%, tumor pO2 rose only by approx. 6%. No distinct changes were seen in the mitochondrial redox status. The microregional distribution of the redox status as well as of the ATP concentration showed considerable heterogeneity. In conclusion, although 42 degrees C-HT leads to a distinct improvement in tumor perfusion, there is practically no change in the oxygenation status. The latter finding can be explained by an equivalent increase in the oxygen consumption rate of the cells which increases by approx. 58% at 42 degrees C compared to normothermia.

Adenosine Triphosphate↗

Muscle oxygen consumption at onset of exercise by near infrared spectroscopy in humans.

In this study, we tried to continuously measure muscle oxygen consumption (m-VO2) by near infrared spectroscopy (NIRS) without arterial occlusions. We used an intermittent isometric exercise at high intensity, which elicits a spontaneous occlusion of the blood flow to the muscle due to an increase in intramuscular pressure. Changes in muscle oxygenation and phosphocreatine (PCr) concentration were monitored in 5 subjects during an intermittent isometric exercise (5 sec. contraction/5 sec. relaxation) at 50% of maximum voluntary contraction for 3 minutes. The rate of deoxygenation was measured from the 2nd sec. to the 3rd sec. of each muscle contraction. The rate of deoxygenation at the onset of exercise followed an exponential time course with a time constant of 42.0 +/- 12.5 sec. (mean +/- SD). This value agreed with the time constant of the decrease in PCr (48.2 +/- 10.2 sec.). This result suggests that m-VO2 was successfully monitored with a time resolution of 10 sec. by NIRS during exercise without arterial occlusion.

Adult↗

Oxygenation and blood concentration changes in human subject prefrontal activation by anagram solutions.

Continued studies in cognitive function in problem solving of graded difficulties has now proceeded through several thousand tests of high school students in a six-week period last summer (2000). The optical imager used 9 sources and 23 detectors operated in time multiplex to give an image of the prefrontal region in several seconds. Thus, the image can be acquired in the state prior to activation, during and following activation. The images are acquired at two wavelengths, 750 and 850 nm, from which the changes of blood concentration (blood pooling) and relative oxygenation/deoxygenation state (metabolic activity) can be obtained and with suitable calibrations converted into micromolar changes of total Hb concentration and fractional oxygenation, respectively. The imager has a wearable pad applied to the forehead and the electronics now presents the running average of the two quantities mentioned above in the 16 voxels which cover the prefrontal region in 1 sec. Thus the protocol involves a scanning through anagrams of graded difficulty which are known to include the range of maximal activation (>3 solutions in the 30 sec test interval or are too easy (>10), or too difficult. Anagrams are presented in a sequence of three, four, five, etc. letter anagrams to the maximal level of difficulty and then back down again to the starting point. Each anagram is displayed for approximately one minute. Computer scanning of the results gives histograms of the several hundred tests per individual in the "training" interval (for three weeks) and in the post training interval about 400 tests, each for 4 levels of difficulty (3 weeks). Usually two or three complete trials per day were achieved with the result that the group of 7 students produced over 2600 test results in 2000. The histogram displays are under study to determine: a) the most fruitful voxels, b) the fraction of the total tests that appeared in those voxels, and c) the maximum signal level observed in the histogram display in units of micromolar hemoglobin. The product of these two was taken as the Figure of Merit and their displays of the 16 voxels gave patterns for trained and untrained responses. The preliminary conclusions of this study were: a) that the training effect was very large, pretraining exhibited a chaotic voxel distribution for all difficulty levels while trained students gave a higher output and activated only one or two of the 16 voxels. If the tests were too easy, too hard, i.e., an ability/difficulty mismatch, frustration or disattention gave similar chaotic patterns (7); b) a match between difficulty and ability activated only a few voxels in similar locations. Since attention and success measures appear to be of interest in school room studies, a wearable imager with local LCD display can be supplied to the Senior class of the local high school for those individuals who have already had last Summer's training in anagrams. A wearable NIR measurement of metabolic activation and blood flow may be a useful educational aid. In summary, the optical method focuses attention on cognition activated oxygenation of prefrontal cortex.

Blood-Brain Barrier↗

Myoglobin gene expression attenuates hepatic ischemia reperfusion injury.

BACKGROUND: Cellular functions are maintained by a continuous supply of ATP, which is supplied efficiently by mitochondrial oxidative phosphorylation. Since myoglobin, found in cardiac myocytes and red skeletal muscle, but not in the liver, facilitates oxygen diffusion under low oxygen conditions and enhances oxidative phosphorylation, this study seeks to enhance hepatic ATP levels and attenuate ischemia-reperfusion injury in rodent livers by adenovirus-mediated myoglobin expression. MATERIAL AND METHODS: After infecting Hep3B and rodent livers with adenovirus carrying CMV promoter sequences linked to the human myoglobin gene (AdCMVMyo), reverse transcriptase-PCR and immunodetection for myoglobin, and cellular and hepatic ATP levels were examined. The effect of myoglobin was evaluated in a hepatic ischemia-reperfusion model in the rat. RESULTS: Myoglobin expression was confirmed in Hep3B and rat livers after AdCMVMyo infection. The ATP levels in Hep3B cells and C57BL/6 mice livers 72 h after AdCMVMyo transfection were significantly higher than control levels and those after adenovirus-mediated beta-galactosidase transfection. Finally, expression of myoglobin attenuated ischemia-reperfusion injury in the rat liver. CONCLUSION: These results indicate that myoglobin gene transfer to the liver enhanced ATP levels both in vitro and in vivo and might be a novel strategy to reduce ischemia-reperfusion injury.

Adenosine Triphosphate↗

In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green.

We investigate the uptake of a nontargeted contrast agent by breast tumors using a continuous wave diffuse optical tomography apparatus. The instrument operates in the near-infrared spectral window and employs 16 sources and 16 detectors to collect light in parallel on the surface of the tumor-bearing breast (coronal geometry). In our protocol an extrinsic contrast agent, Indocyanine Green (ICG), was injected by bolus. Three clinical scenarios with three different pathologies were investigated. A two-compartment model was used to analyze the pharmacokinetics of ICG and preprocess the data, and diffuse optical tomography was used for imaging. Localization and delineation of the tumor was achieved in good agreement with a priori information. Moreover, different dynamical features were observed for differing pathologies. The malignant cases exhibited slower rate constants (uptake and outflow) compared to healthy tissue. These results provide further evidence that in vivo pharmacokinetics of ICG in breast tumors may be a useful diagnostic tool for differentiation of benign and malignant pathologies.

Adenocarcinoma↗

Effect of muscle oxygenation during resistance exercise on anabolic hormone response.

PURPOSE: The mechanisms that underlie the affect of acute program variables on muscle growth and strength development for strength/power athletes have been of great interest. This investigation examined the affects of two different resistance exercise protocols on muscle oxygenation, and the anabolic hormonal response to such exercise. METHODS: Eleven experienced resistance-trained male athletes performed four sets of the squat exercise using either a low-intensity, high-volume (LI; 15 repetitions at 60% one-repetition maximum [1-RM]) or high-intensity, low-volume (HI; 4 repetitions at 90% 1-RM) load. Venous blood samples were obtained before (Pre), immediate (IP), 20- (20P), and 40-min (40P) postexercise. Continuous-wave near-infrared spectroscopy was used to measure oxygen desaturation during exercise. RESULTS: No differences in muscle deoxygenation were seen between LI and HI. However, time-dependent postexercise reoxygenation was significantly different between the two exercise sessions (35.3 +/- 17.4 s vs 24.5 +/- 14.3 s in LI and HI, respectively). Testosterone and growth hormone (GH) concentrations were significantly elevated from Pre at IP, 20P, and 40P in both LI and HI. GH concentrations were higher (P<0.05) for LI than at HI at 20P and 40P. CONCLUSION: Muscle oxygen recovery kinetics appeared to be influenced by differences in the intensity and volume of exercise, and delayed reoxygenation appears to affect the GH response to exercise.

Adult↗

Creatine supplementation enhances anaerobic ATP synthesis during a single 10 sec maximal handgrip exercise.

Forearm muscles of twelve healthy male subjects (age = 22.3 +/- 1.1 years (mean +/- S.E.)) were examined during a 10 sec maximal dynamic handgrip exercise (Ex10) using 31-phosphorus magnetic resonance spectroscopy before and after ingestion with 30 g creatine (Cr) monohydrate or placebo per day for 14 days. Cr supplementation produced a 11.5 +/- 4.6% increase in the resting muscle phosphocreatine (PCr) concentration and a 65.0 +/- 4.2% increase in the PCr degradation during Ex10. ATP synthesis rate through PCr hydrolysis and total anaerobic ATP synthesis rate during Ex10 increased from 0.64 +/- 0.08 (pre-value) to 0.86 +/- 0.14 mmol/kg ww/sec (post-value, p < 0.05) and from 0.97 +/- 0.16 (pre-value) to 1.33 +/- 0.27 mmol/kg ww/sec (post-value, p < 0.05), respectively. An increase in total anaerobic ATP synthesis during Ex10 after Cr supplementation positively correlated with the increase in ATP synthesis through PCr hydrolysis. Cr supplementation produced a 15.1 +/- 3.8% increase in the mean power output during Ex10. There was no significant difference in the mean power output per unit of total anaerobic ATP synthesis during Ex10 between before and after Cr supplementation. ATP synthesis rate through PCr hydrolysis positively correlated with mean power output during Ex10 in all twelve subjects after treatment (r = 0.58, p < 0.05). The results suggest that Cr supplementation enhanced PCr degradation during Ex10. It is strongly indicated that an improvement in performance during Ex10 was associated with the increased PCr availability for the synthesis of ATP.

Adenosine Triphosphate↗

Delayed reoxygenation after maximal isometric handgrip exercise in high oxidative capacity muscle.

We hypothesized that after maximal short-term isometric exercise, when O(2) demand is still high and O(2) supply is not fully activated, higher oxidative capacity muscle may exhibit slower muscle reoxygenation after the exercise than low oxidative capacity muscle. Seven healthy male subjects performed a maximal voluntary isometric handgrip exercise for 10 s. The reoxygenation rate after the exercise (Reoxy-rate) in the finger flexor muscle was determined by near infrared continuous wave spectroscopy (NIRcws) while phosphocreatine (PCr) was measured simultaneously by (31)P magnetic resonance spectroscopy. Muscle oxygen consumption (muscle VO(2)) and muscle oxidative capacity were evaluated using the rate of PCr resynthesis post-exercise. The forearm blood flow (FBF) index at the end of exercise was measured using NIRcws. There was a significant positive correlation between the Reoxy-rate, which ranged between 0.53% s(-1) and 12.47% s(-1), and the time constant for PCr resynthesis, which ranged between 17.8 s and 38.3 s (r(2)=0.939, P<0.001). At the end of the exercise, muscle VO(2) exceeded the resting level by approximately 25-fold, while the FBF index exceeded the resting level by only 3-fold on average. The Reoxy-rate closely correlated with muscle VO(2) (r(2)=0.727, P<0.05), but not with the FBF index. Also, the estimated O(2) balance (muscle VO(2) index/FBF index) was negatively correlated with the Reoxy-rate (r(2)=0.820, P<0.001). These results support our hypothesis that higher oxidative capacity muscle shows slower muscle reoxygenation after maximal short-term isometric exercise because the Reoxy-rate after this type of exercise may be influenced more by muscle VO(2) than by O(2) supply.

Adaptation, Physiological↗

Adaptive calibration for object localization in turbid media with interfering diffuse photon density waves.

The amplitude cancellation method that uses dual out-of-phase sources (a phased array system) can sensitively detect and locate small objects in turbid media. The balance of these two sources is crucial to the system's detection sensitivity and accuracy. We describe a convenient method with which to adaptively calibrate the amplitudes of the two sources at each scanning position by use of low-frequency modulation of the intensity of the in-phase and the antiphase sources. We achieve accurate localization ability of the phased array system by accounting for the influence of asymmetrical boundaries and the heterogeneous background absorption. Experimental data on human breast phantoms demonstrate that localization accuracy within several millimeters has been accomplished through this method.

Calibration↗

Detection limit enhancement of fluorescent heterogeneities in turbid media by dual-interfering excitation.

We report on a quantitative comparison between the single-source and the dual-interfering-source configurations for the detection of fluorescent heterogeneities embedded in a piecewise highly scattering homogeneous fluorescent background. The study is based on simulations with analytical solutions of the frequency-domain fluorescent diffuse photon density waves and practical signal-to-noise ratio considerations. Results show that dual-interfering sources outperform single-source techniques for the detection of heterogeneities in terms of fluorophore concentration and lifetime contrast. To detect the same inhomogeneity, less concentration and lifetime contrast is required with dual-interfering sources.

Coloring Agents↗

Tricarbocyanine cholesteryl laurates labeled LDL: new near infrared fluorescent probes (NIRFs) for monitoring tumors and gene therapy of familial hypercholesterolemia.

For monitoring low-density lipoprotein receptors (LDLr) in tumors and in livers of patients with familial hypercholesterolemia (FH) treated with gene therapy, a series of tricarbocyanine cholesteryl laurates were synthesized with the cholesteryl laurate moiety serving as the lipid-chelating anchor for low-density lipoprotein (LDL). One of these conjugates, TCL17, was successfully used to label LDL to give a new NIRF, TCL17-LDL. Ex vivo biological studies on an LDLr overexpressing tumor model, human hepatoblastoma G(2) (HepG(2)), confirmed that this NIRF were internalized selectively by the tumor and detected with high sensitivity by a low-temperature 3-D redox scanner.

Animals↗

Projection access order in algebraic reconstruction technique for diffuse optical tomography.

Algebraic reconstruction technique (ART) is one of the popular image reconstruction techniques used in diffuse optical tomography (DOT). We investigate in this note the influence of the order in which data are accessed in ART. Simulations mimicking breast tissues in transmission geometry with contrast agent tumour enhancement were used to evaluate the image quality of the diverse projection access investigated. We show that by selecting proper projection access order, the convergence speed can be significantly improved when ART is used to perform DOT. Moreover, low-contrast detection is improved.

Image Processing, Computer-Assisted↗

Near infrared muscle spectroscopy in patients with Friedreich's ataxia.

Friedreich's ataxia is a progressive neurodegenerative disorder of the afferent cerebellar pathways associated with mitochondrial dysfunction at the cellular level. We have used noninvasive continuous near infrared muscle spectroscopy (NIRS) to investigate the delivery and utilization of oxygen in response to exercise in this disorder. Patients performed an incremental treadmill walking protocol in which levels of muscle deoxygenation or oxygenation were continuously measured in the medial calf muscle. The kinetics of recovery from exercise-induced deoxygenation, called the half-time of recovery (t(1/2)) were determined. The t(1/2) was prolonged in patients with Friedreich's ataxia compared with controls, and the degree of prolongation correlated with the length of the shorter GAA repeat, a genetic measure that correlates with the age of onset of disease. The t(1/2) also correlated inversely with patient age and with the maximum treadmill speed attained. Several patients also displayed features consistent with inadequate oxygen utilization by muscle. These results suggest that NIRS may be an effective tool for monitoring the biochemical and functional features of Friedreich's ataxia in parallel.

Adolescent↗

Analysis on performance and optimization of frequency-domain near-infrared instruments.

Frequency-domain near-infrared techniques have been widely used to detect the optical properties of biological tissues noninvasively. In this paper we propose an analytical model to evaluate the performance of frequency-domain instruments. Based on the diffusion equation and the transfer properties of optoelectronic components, we treat all parts, including the medium, as two-port networks and apply systematic methods to answer questions concerning frequency-domain instruments. Experiments show that this method can reasonably reflect the properties of the instrument within an accuracy of 7%. This kind of method can be used to design suitable instruments for various applications. We also analyze the selection of the instrument parameters to achieve optimal performance at an efficient cost using this analytical model.

Fiber Optic Technology↗