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Van Savage

Publications and source records attributed to Van Savage.

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Improving blood vessel tortuosity measurements via highly sampled numerical integration of the Frenet-Serret equations

Measures of vascular tortuosity--how curved and twisted a vessel is--are associated with a variety of vascular diseases. Consequently, measurements of vessel tortuosity that are accurate and comparable across modality, resolution, and size are greatly needed. Yet in practice, precise and consistent measurements are problematic--mismeasurements, inability to calculate, or contradictory and inconsistent measurements occur within and across studies. Here, we present a new method of measuring vessel tortuosity that ensures improved accuracy. Our method relies on numerical integration of the Frenet-Serret equations. By reconstructing the three-dimensional vessel coordinates from tortuosity measurements, we explain how to identify and use a minimally-sufficient sampling rate based on vessel radius while avoiding errors associated with oversampling and overfitting. Our work identifies a key failing in current practices of filtering asymptotic measurements and highlights inconsistencies and redundancies between existing tortuosity metrics. We demonstrate our method by applying it to manually constructed vessel phantoms with known measures of tortuousity, and 9,000 vessels from medical image data spanning human cerebral, coronary, and pulmonary vascular trees, and the carotid, abdominal, renal, and iliac arteries.

physics.med-ph

Optimal occlusion uniformly partitions red blood cells fluxes within a microvascular network

In animals, gas exchange between blood and tissues occurs in narrow vessels, whose diameter is comparable to that of a red blood cell. Red blood cells must deform to squeeze through these narrow vessels, transiently blocking or occluding the vessels they pass through. Although the dynamics of vessel occlusion have been studied extensively, it remains an open question why microvessels need to be so narrow. We study occlusive dynamics within a model microvascular network: the embryonic zebrafish trunk. We show that pressure feedbacks created when red blood cells enter the finest vessels of the trunk act together to uniformly partition red blood cells through the microvasculature. Using mathematical models as well as direct observation, we show that these occlusive feedbacks are tuned throughout the trunk network to prevent the vessels closest to the heart from short-circuiting the network. Thus occlusion is linked with another open question of microvascular function: how are red blood cells delivered at the same rate to each micro-vessel? Our analysis shows that tuning of occlusive feedbacks increase the total dissipation within the network by a factor of 11, showing that uniformity of flows rather than minimization of transport costs may be prioritized by the microvascular network.

q-bio.TO

A path-integral approach to Bayesian inference for inverse problems using the semiclassical approximation

We demonstrate how path integrals often used in problems of theoretical physics can be adapted to provide a machinery for performing Bayesian inference in function spaces. Such inference comes about naturally in the study of inverse problems of recovering continuous (infinite dimensional) coefficient functions from ordinary or partial differential equations (ODE, PDE), a problem which is typically ill-posed. Regularization of these problems using $L^2$ function spaces (Tikhonov regularization) is equivalent to Bayesian probabilistic inference, using a Gaussian prior. The Bayesian interpretation of inverse problem regularization is useful since it allows one to quantify and characterize error and degree of precision in the solution of inverse problems, as well as examine assumptions made in solving the problem -- namely whether the subjective choice of regularization is compatible with prior knowledge. Using path-integral formalism, Bayesian inference can be explored through various perturbative techniques, such as the semiclassical approximation, which we use in this manuscript. Perturbative path-integral approaches, while offering alternatives to computational approaches like Markov-Chain-Monte-Carlo (MCMC), also provide natural starting points for MCMC methods that can be used to refine approximations. In this manuscript, we illustrate a path-integral formulation for inverse problems and demonstrate it on an inverse problem in membrane biophysics as well as inverse problems in potential theories involving the Poisson equation.

physics.data-an