Mathematical synthesis of the cortical circulation for the whole mouse brain-part II: Microcirculatory closure.

Recent advancements in multiphoton imaging and vascular reconstruction algorithms have increased the amount of data on cerebrovascular circulation for statistical analysis and hemodynamic simulations. Experimental observations offer fundamental insights into capillary network topology but mainly within a narrow field of view typically spanning a small fraction of the cortical surface (less than 2%). In contrast, larger-resolution imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), have whole-brain coverage but capture only larger blood vessels, overlooking the microscopic capillary bed. To integrate data acquired at multiple length scales with different neuroimaging modalities and to reconcile brain-wide macroscale information with microscale multiphoton data, we developed a method for synthesizing hemodynamically equivalent vascular networks for the entire cerebral circulation. This computational approach is intended to aid in the quantification of patterns of cerebral blood flow and metabolism for the entire brain. In part I, we described the mathematical framework for image-guided generation of synthetic vascular networks covering the large cerebral arteries from the circle of Willis through the pial surface network leading back to the venous sinuses. Here in part II, we introduce novel procedures for creating microcirculatory closure that mimics a realistic capillary bed. We demonstrate our capability to synthesize synthetic vascular networks whose morphometrics match empirical network graphs from three independent state-of-the-art imaging laboratories using different image acquisition and reconstruction protocols. We also successfully synthesized twelve vascular networks of a complete mouse brain hemisphere suitable for performing whole-brain blood flow simulations. Synthetic arterial and venous networks with microvascular closure allow whole-brain hemodynamic predictions. Simulations across all length scales will potentially illuminate organ-wide supply and metabolic functions that are inaccessible to models reconstructed from image data with limited spatial coverage.