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J B Bassingthwaighte

Publications and source records attributed to J B Bassingthwaighte.

At least 19 recordsLinked to original sources
PubMed1992

Computationally efficient algorithms for convection-permeation-diffusion models for blood-tissue exchange.

Analysis of data on tissue depositions obtained by positron tomographic or NMR imaging, or of multiple tracer outflow dilution curves, requires fitting data with models composed of aggregates of capillary-tissue units. These units account for heterogeneities of flows and multisolute exchanges between longitudinally distributed regions across capillary and cell barriers within an organ. Because the analytic solutions to the partial differential equations require convolution integration, solutions are obtained relatively efficiently by a fast numerical method. Our approach centers on the use of a sliding fluid element algorithm for capillary convection, with the time step set equal to the length step divided by the fluid velocity. Radial fluxes by permeation between plasma, interstitial fluid, and cells and axial diffusion exchanges within each time step are calculated analytically. The method enforces mass conservation unless there is regional consumption. Solution for a 2-barrier, 3-region model, accurate to within 0.5%, are 100 to 1000 times faster than the corresponding, purely analytic solution, and over 10,000 times for a 4-region model. Applications include multiple indicator dilution studies of kinetics of transcapillary exchange and positron emission tomographic studies of the mechanisms of substrate transport into cells of organs in vivo.

Algorithms↗
PubMed1992

Triple-label beta liquid scintillation counting.

The detection of radioactive compounds by liquid scintillation has revolutionized modern biology, yet few investigators make full use of the power of this technique. Even though multiple isotope counting is considerably more difficult than single isotope counting, many experimental designs would benefit from using more than one isotope. The development of accurate isotope counting techniques enabling the simultaneous use of three beta-emitting tracers has facilitated studies in our laboratory using the multiple tracer indicator dilution technique for assessing rates of transmembrane transport and cellular metabolism. The details of sample preparation, and of stabilizing the liquid scintillation spectra of the tracers, are critical to obtaining good accuracy. Reproducibility is enhanced by obtaining detailed efficiency/quench curves for each particular set of tracers and solvent media. The numerical methods for multiple-isotope quantitation depend on avoiding error propagation (inherent to successive subtraction techniques) by using matrix inversion. Experimental data obtained from triple-label beta counting illustrate reproducibility and good accuracy even when the relative amounts of different tracers in samples of protein/electrolyte solutions, plasma, and blood are changed.

Animals↗
PubMed1992

Capillary endothelial transport of uric acid in guinea pig heart.

Much of the adenosine formed in the heart is degraded by endothelial enzymes to uric acid, which is exported across the coronary capillary endothelial cell membrane before renal excretion. Because previous experiments suggested that cell permeability for uric acid is either very high (similar to water) or very low, multiple indicator-dilution experiments were carried out to distinguish between the two possibilities. An intravascular reference tracer, 131I-labeled albumin, and an extracellular reference tracer, L-[3H]glucose, were injected together with [14C]uric acid as a bolus into the coronary inflow, while fractionating the venous outflow for 90 s. Recovery of injected uric acid averaged 99.0 +/- 2.9% (mean +/- SD, n = 12) that of L-glucose. Peak capillary extraction of L-glucose and uric acid averaged 0.38 +/- 0.032 and 0.42 +/- 0.035 (P less than 0.005) compared with albumin. Except at the peaks, the dilution curves for [14C]uric acid and L-[3H]glucose coincided closely, indicating that little uric acid was transported into cells. The dilution curves were analyzed using an axially distributed, multipathway, four region mathematical model, to estimate membrane permeability-surface area (PS) products. Since the endothelial cell PS for uric acid was low (0.12 +/- 0.09 ml.g-1.min-1), approximately 3% of the PS reported for adenosine, the possibility of flow-limited exchange for uric acid is ruled out. To estimate steady-state endothelial concentrations of uric acid in vivo, equations were developed describing electrochemical potential gradients for dissociated and undissociated forms of a weak acid. Despite endothelial production, intracellular concentrations that are lower than outside are expected because the negative membrane potential and lower cellular pH assist uric acid efflux.

Algorithms↗
PubMed1992

Contribution of labeled carbon dioxide to PET imaging of carbon-11-labeled compounds.

11CO2 is one of the major metabolites of many [11C]-labeled radiopharmaceuticals, including glucose, thymidine, acetate, amino acids, and fatty acids. Our data contradict the notion that the contribution of labeled CO2 to PET images can be disregarded because of its rapid elimination through the lungs. We have measured the retention and excretion of 11CO2 in dogs after the intravenous injection of labeled CO2/HCO3-, which had been equilibrated ex vivo with blood. Only 58% of the label was exhaled as CO2 over the first 60 min after injection, with the rest retained in the body. The injection of [11C]thymidine labeled in the ring-2 position or [11C]acetate labeled in the carboxylate position resulted in the production of large amounts of labeled CO2 with the exhalation of about 47% and 23%, respectively, of the injected label over 60 min. At 10 min after injection of either [11C]thymidine and [11C] acetate, approximately 60% to 70% of total blood activity was in labeled CO2 or bicarbonate. On the other hand, the use of [1-11C]glucose only resulted in exhalation of 5% of the injected dose and CO2/HCO3- made up less than 10% of blood activity at 10 min. Our results indicate that retention and distribution of labeled CO2 needs to be considered when interpreting PET data obtained from 11C-labeled compounds.

Acetates↗
PubMed1991

Mathematical modelling in nuclear medicine.

Modern imaging techniques can provide sequences of images giving signals proportional to the concentrations of tracers (by emission tomography), of X-ray-absorbing contrast materials (fast CT or perhaps NMR contrast), or of native chemical substances (NMR) in tissue regions at identifiable locations in 3D space. Methods for the analysis of the concentration-time curves with mathematical models describing the physiological processes and the appropriate anatomy are now available to give a quantitative portrayal of both structure and function: such is the approach to metabolic or functional imaging. One formulates a model first by defining what it should represent: this is the hypothesis. When translated into a self-consistent set of differential equations, the model becomes a mathematical model, a quantitative version of the hypothesis. This is what one would like to test against data. However, the next step is to reduce the mathematical model to a computable form; anatomically and physiologically realistic models account of the spatial gradients in concentrations within blood-tissue exchange units, while compartmental models simplify the equations by using the average concentrations. The former are known as distributed models and the latter as lumped compartmental or mixing chamber models. Since both are derived from the same ideas, the parameters are usually the same; their differences are in their ability to represent the hypothesis correctly, quantitatively, and sometimes in their computability. In this essay we review the philosophical and practical aspects of such modelling analysis for translating image sequences into physiological terms.

Computer Simulation↗
PubMed1991

Interstitial adenosine concentration during norepinephrine infusion in isolated guinea pig hearts.

This study determined the effect of norepinephrine (NE) on cardiac interstitial fluid adenosine concentration [( ADO]isf). Isolated guinea pig hearts were perfused with a Krebs-Henseleit buffer solution. Radiolabeled albumin, sucrose, and adenosine were injected under control conditions and after 3 and 20 min of NE infusion to obtain multiple indicator dilution curves that were used to determine capillary transport parameters for adenosine. These parameters together with venous adenosine concentrations were used in a mathematical model to a calculate [ADO]isf. Capillary transport parameters were not changed significantly by NE infusion. Because of uncertainty regarding two model parameters, two sets of [ADO]isf values were calculated. One set used best-fit values obtained from indicator dilution curves, and a second set used parameters chosen to provide the highest [ADO]isf values consistent with indicator dilution curves. Venous adenosine concentrations were 1.9 +/- 0.4 nM under control conditions and 243 +/- 110 and 45 +/- 25 nM after 3 and 20 min of NE infusion, respectively. Calculated [ADO]isf was 2.6-9.4, 591-1,288, and 166-324 nM, respectively, under these same conditions. We conclude that NE infusion greatly increases [ADO]isf, and adenosine is responsible for most of the vasodilation at 3 min. The subsequent fall in venous concentration is due to a fall in [ADO]isf rather than to decreased capillary permeability. Vascular resistance remained low while [ADO]isf fell, which suggests that additional vasodilators are important during maintained NE infusion.

Adenosine↗
PubMed1991

Applications of fractal analysis to physiology.

This review describes approaches to the analysis of fractal properties of physiological observations. Fractals are useful to describe the natural irregularity of physiological systems because their irregularity is not truly random and can be demonstrated to have spatial or temporal correlation. The concepts of fractal analysis are introduced from intuitive, visual, and mathematical perspectives. The regional heterogeneities of pulmonary and myocardial flows are discussed as applications of spatial fractal analysis, and methods for estimating a fractal dimension from physiological data are presented. Although the methods used for fractal analyses of physiological data are still under development and will require additional validation, they appear to have great potential for the study of physiology at scales of resolution ranging from the microcirculation to the intact organism.

Animals↗
PubMed1990

Microcirculatory considerations in NMR flow imaging.

Regional flow estimation can be accomplished either by measuring the concentration of a deposited tracer whose extraction during transit through the organ is 100%, or by observing the time course of concentration of a tracer whose transport passage through the organ is flow-limited. The deposition method is simpler and applies not only to microspheres or other large particles that lodge in the microcirculation, but also to molecular markers which are trapped. It has the advantage of having substantial time in which to observe the local concentrations by external detection. In contrast, flow-limited markers must traverse the tissue without barrier limitation or other diffusional influence on the exchange. When the marker is limited strictly to the intravascular space, the transit time through the organ is short and observations must be made rapidly with a high resolution technique. An indicator which distributes throughout a large volume of distribution within the tissue has a slower washout, providing more time in which to make observations; tracer water is a suitable marker, except perhaps in the brain. For flow measurement by NMR, markers which fulfill these criteria without causing side effects are needed.

Animals↗
PubMed1990

Fractal descriptions for spatial statistics.

Measures of spatial statistics have been available for estimating means, calculating or assessing differences, estimating nearest neighbor distances, and such, but have not provided a general approach to describing variances. Because measures of heterogeneity depend upon choosing a particular element size in the domain, estimates of apparent heterogeneity are larger with high-resolution observations than with low-resolution data. Many descriptors might be used to describe the relationships between apparent heterogeneity and the size of the observed spatial elements, but we have found that fractal relationships provide concise and precise descriptions of many types of data over large ranges of element sizes. Perhaps more importantly, the fractal approaches give additional insight, such as measures of spatial correlation, and often suggest ways of approaching the underlying basis of the heterogeneity.

Animals↗
PubMed1990

Heterogeneities in regional volumes of distribution and flows in rabbit heart.

The heterogeneity of volumes of distribution in the heart influences the rates of uptake and washout of substrates and metabolites; thus it is important to evaluate their variability in the normal heart. Several tracers were injected intravenously into anesthetized adult closed-chest rabbits, and time was allowed for equilibration in the heart. Tracer microspheres were injected into the left ventricular cavity at the apex for the measurement of regional flows, the chest was opened, another set of microspheres was injected, and the heart was frozen rapidly in situ with liquid nitrogen-cooled Freon-22. Each heart was divided into 72 pieces of less than 0.1 g weight, and the tracer content of each was determined by multichannel gamma-counting and the water content by desiccation. The regional myocardial flows were (closed chest) 0.62 +/- 0.16 ml.g-1.min-1 and (open chest) 0.63 +/- 0.37 ml.g-1.min-1. The volumes of distribution (ml/g) for the 432 pieces for six rabbits, given as mean +/- SD (% coefficient of variation), were as follows: for plasma, VP = 0.11 +/- 0.03 (26%); erythrocytes, VRBC = 0.041 +/- 0.015 (37%); vascular space, VV = 0.15 +/- 0.04 (26%); extracellular space, VECF = 0.33 +/- 0.05 (15%); interstitial space, VISF = 0.21 +/- 0.03 (15%); and water space, VW -0.79 +/- 0.022 (2.8%). Regional hematocrits were 77% +/- 9% of the large-vessel hematocrits.

Animals↗
PubMed1990

Molecular and particulate depositions for regional myocardial flows in sheep.

The deposition of microspheres in small tissue regions is not strictly flow dependent. In comparison with the soluble flow marker 2-iododesmethylimipramine (IDMI), deposition of 16.5-microns microspheres was mildly but systematically biased into high flow regions of rabbit hearts (Bassingthwaighte JB, Malone MA, Moffett T-C, King RB, Little SE, Link JM, Krohn KA. Am J Physiol 1987;253 (Heart Circ Physiol 22):H184-H193). To examine the possibility of bias in larger hearts, a similar study was undertaken in sheep. 141Ce- and 103Ru-labeled 16.5-microns microspheres in one syringe and 125I- and 131I-DMI in another syringe were injected simultaneously into the left atrium of five open-chest sheep while obtaining reference blood samples from the femoral artery. In six other sheep, one microsphere type and one IDMI were used. Hearts were removed 1 minute after injection, cut into approximately 254 pieces averaging 217 mg, and regional deposition densities calculated for each tracer from the isotopic counts. Correlations in the five animals between the two differently labeled IDMIs and between the two microspheres were both greater than or equal to 0.98. In all 11 sheep, scatter plots of microsphere deposition densities versus IDMI densities showed that differences between microspheres and IDMI had substantially more scatter (0.84 less than r less than 0.98) but were not random. Microsphere depositions tended to be lower than IDMI depositions in low flow regions and higher in high flow regions, in accord with the expected bias that at a bifurcation a microsphere is most likely to enter the branch with higher flow. There was less bias ascribable to endomyocardial/epicardial maldistribution. Thus, while microsphere depositions appear to err systematically with respect to flow when the regions of interest are small enough that the diameters of their arterioles are only a few times those of the microspheres, microspheres are, in sheep as in rabbits, adequate for estimating regional flows.

Animals↗
PubMed1990

Iodophenylpentadecanoic acid-myocardial blood flow relationship during maximal exercise with coronary occlusion.

Imaging 123I-labeled iodophenylpentadecanoic acid (IPPA) uptake and clearance from the myocardium following exercise has been advocated as a means of detecting myocardial ischemia because fatty acid deposition is enhanced and clearance prolonged in regions of low flow. However, normal regional myocardial blood flows are markedly heterogeneous, and it is not known how this heterogeneity affects regional metabolism or substrate uptake and thus image interpretation. In five instrumented dogs running at near maximal workload on a treadmill, 131I-labeled IPPA and 15-micron 46Sc microspheres were injected into the left atrium after 30 sec of circumflex coronary artery occlusion. Microsphere and IPPA activity were determined in 250 mapped pieces of myocardium of approximately 400 mg. Myocardial blood flows (from microspheres) ranged from 0.05 to 7.6 ml/min/g. Deposition of IPPA was proportional to regional flows (r = 0.83) with an average retention of 25%. The mean endocardial-epicardial ratio for IPPA (0.90 +/- 0.43) was similar to that for microspheres (0.94 +/- 0.47; p = 0.08). Thus, initial IPPA deposition during treadmill exercise increases in proportion to regional myocardial blood flow over a range of flows from very low to five times normal.

Animals↗
PubMed1989

Temporal fluctuations in regional myocardial flows.

Considerable spatial heterogeneity has been observed in regional myocardial blood flow in isolated hearts and in both anesthetized and conscious animals. In order to study how local blood flow varies with time, the data obtained by King et al. (1985) from ten awake, healthy baboons were analyzed to estimate the role of temporal fluctuations. Four to six distributions of regional flows were estimated at intervals of 4 min to 27 h, using 15 mu diameter microspheres and dividing each heart into 204 locatable pieces (average piece mass = 0.17 g). The technique averages over the 40 s of the injection giving no measure of fluctuations over a few seconds. The temporal variation in regional blood flow, expressed as the relative dispersion (SD/mean) of the temporally separated measurements about the mean flow for each piece and corrected for methodological noise, was 12% for the whole heart (10828 observations). For the left ventricle, the temporal variation was 10% (8806 observations), for the right ventricle 14% (1455 observations), and for the atria 22% (567 observations). On a relative basis, temporal fluctuation was greatest in regions having low flows. Since the magnitude of the changes in flow distributions was the same after 4 min as it was in several hours, we conclude that much of the "twinkling" is a high frequency phenomenon occurring over seconds to a few minutes. Further, it is concluded that regional myocardial blood flow in conscious primates is relatively stable with time, temporal fluctuations causing only about one third of the variation between regions.

Animals↗