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Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex | PLOS Computational Biology

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Author summary The brain’s astonishing cognitive capacity depends on the coordination between neurons and the cerebral circulation, a system known as the neurovascular unit. The spatial and temporal coupling between these two networks is the object of intense research. However, the concise anatomical description of the cerebral circulation has so far been intractable. This paper introduces a methodology for the in silico creation of realistic models for the entire cerebral circulation. This innovation incorporates topological data from several neuroimaging modalities covering three lengths scales as input into a computer algorithm, which assembles anatomically accurate circulatory networks. When simulating blood flow as red blood cells suspended in plasma for experimental and synthetic cortical network models, we discovered that red blood cells tend to be more concentrated in deeper layers of the cortex compared to the surface. RBC fluxes are more homogenous in deeper layers. The phenomenon of depth dependent red blood cell supply supports the notion that the intricate architecture of the cortical microcirculation serves a self-regulating function to maintain uniform oxygen perfusion to neurons. We also demonstrate the practicality of predicting blood flow patterns for the entire brain with existing computer power.

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Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the entire brain. Because of the potential significance of blood flow and oxygen supply simulations for illuminating spatiotemporal regulation inside the cortical microanatomy, there is a need to create mathematical models of the entire cerebral circulation with realistic anatomical detail. Our hypothesis is that an anatomically accurate reconstruction of the cerebrocirculatory architecture will inform about possible regulatory mechanisms of the neurovascular interface. In this article, we introduce large-scale networks of the murine cerebral circulation spanning the Circle of Willis, main cerebral arteries connected to the pial network down to the microcirculation in the capillary bed. Several multiscale models were generated from state-of-the-art neuroimaging data. Using a vascular network construction algorithm, the entire circulation of the middle cerebral artery was synthesized. Blood flow simulations indicate a consistent trend of higher hematocrit in deeper cortical layers, while surface layers with shorter vascular path lengths seem to carry comparatively lower red blood cell (RBC) concentrations. Moreover, the variability of RBC flux decreases with cortical depth. These results support the notion that plasma skimming serves a self-regulating function for maintaining uniform oxygen perfusion to neurons irrespective of their location in the blood supply hierarchy. Our computations also demonstrate the practicality of simulating blood flow for large portions of the mouse brain with existing computer resources. The efficient simulation of blood flow throughout the entire middle cerebral artery (MCA) territory is a promising milestone towards the final aim of predicting blood flow patterns for the entire brain.

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Hematocrit,Blood flow,Capillaries,Hemodynamics,Oxygen,Neuroimaging,Arterioles,Blood

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https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006549

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Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex

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Author summary The brain’s astonishing cognitive capacity depends on the coordination between neurons and the cerebral circulation, a system known as the neurovascular unit. The spatial and temporal coupling between these two networks is the object of intense research. However, the concise anatomical description of the cerebral circulation has so far been intractable. This paper introduces a methodology for the in silico creation of realistic models for the entire cerebral circulation. This innovation incorporates topological data from several neuroimaging modalities covering three lengths scales as input into a computer algorithm, which assembles anatomically accurate circulatory networks. When simulating blood flow as red blood cells suspended in plasma for experimental and synthetic cortical network models, we discovered that red blood cells tend to be more concentrated in deeper layers of the cortex compared to the surface. RBC fluxes are more homogenous in deeper layers. The phenomenon of depth dependent red blood cell supply supports the notion that the intricate architecture of the cortical microcirculation serves a self-regulating function to maintain uniform oxygen perfusion to neurons. We also demonstrate the practicality of predicting blood flow patterns for the entire brain with existing computer power.

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https://journals.plos.org/ploscompbiol/article/figure/image?id=10.1371/journal.pcbi.1006549.g009&size=inline

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Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex

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Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex

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