In functional neuroimaging, neurovascular coupling is used to generate maps of hemodynamic changes that are assumed to be surrogates of regional neural activation. The aim of this study was to characterize the microvascular system of the primate cortex as a basis for understanding the constraints imposed on a region's hemodynamic response by the vascular architecture, density, as well as area- and layer-specific variations. In the macaque visual cortex, an array of anatomical techniques has been applied, including corrosion casts, immunohistochemistry, and cytochrome oxidase (COX) staining. Detailed measurements of regional vascular length density, volume fraction, and surface density revealed a similar vascularization in different visual areas. Whereas the lower cortical layers showed a positive correlation between the vascular and cell density, this relationship was very weak in the upper layers. Synapse density values taken from the literature also displayed a very moderate correlation with the vascular density. However, the vascular density was strongly correlated with the steady-state metabolic demand as measured by COX activity. This observation suggests that although the number of neurons and synapses determines an upper bound on an area's integrative capacity, its vascularization reflects the neural activity of those subpopulations that represent a "default" mode of brain steady state.

At its most fundamental level, cerebral blood flow (CBF) may be modeled as fluid flow driven through a network of resistors by pressure gradients. The composition of the blood as well as the cross-sectional area and length of a vessel are the major determinants of its resistance to flow. Here, we introduce a vascular graph modeling framework based on these principles that can compute blood pressure, flow and scalar transport in realistic vascular networks. By embedding the network in a computational grid representative of brain tissue, the interaction between the two compartments can be captured in a truly three-dimensional manner and may be applied, among others, to simulate oxygen extraction from the vessels. Moreover, we have devised an upscaling algorithm that significantly reduces the computational expense and eliminates the need for detailed knowledge on the topology of the capillary bed. The vascular graph framework has been applied to investigate the effect of local vascular dilation and occlusion on the flow in the surrounding network.

The cerebrovascular system continuously delivers oxygen and energy substrates to the brain, which is one of the organs with the highest basal energy requirement in mammals. Discontinuities in the delivery lead to fatal consequences for the brain tissue. A detailed understanding of the structure of the cerebrovascular system is important for a multitude of (patho-)physiological cerebral processes and many noninvasive functional imaging methods rely on a signal that originates from the vasculature. Furthermore, neurodegenerative diseases often involve the cerebrovascular system and could contribute to neuronal loss. In this review, we focus on the cortical vascular system. In the first part, we present the current knowledge of the vascular anatomy. This is followed by a theory of topology and its application to vascular biology. We then discuss possible interactions between cerebral blood flow and vascular topology, before summarizing the existing body of the literature on quantitative cerebrovascular topology.

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Recent studies suggest that pericytes around capillaries are contractile and able to alter the diameter of capillaries. To investigate the effects of capillary dilation on network dynamics, we performed simulations in artificial capillary networks of different sizes and complexities. The unequal partition of hematocrit at diverging bifurcations was modeled by assuming that each red blood cell (RBC) enters the branch with the faster instantaneous flow. Network simulations with and without RBCs were performed to investigate the effect of local dilations. The results showed that the increase in flow rate due to capillary dilation was less when the effects of RBCs are included. For bifurcations with sufficient RBCs in the parent vessel and nearly equal flows in the branches, the flow rate in the dilated branch did not increase. Instead, a self-regulation of flow was observed due to accumulation of RBCs in the dilated capillary. A parametric study was performed to examine the dependence on initial capillary diameter, dilation factor, and tube hematocrit. Furthermore, the conditions needed for an efficient self-regulation mechanism are discussed. The results support the hypothesis that RBCs play a significant role for the fluid dynamics in capillary networks and that it is crucial to consider the blood flow rate and the distribution of RBCs to understand the supply of oxygen in the vasculature. Furthermore, our results suggest that capillary dilation/constriction offers the potential of being an efficient mechanism to alter the distribution of RBCs locally and hence could be important for the local regulation of oxygen delivery.

We propose a computational simulation framework for describing cancer-therapeutic transport in the lung. A discrete vascular graph model (VGM) is coupled to a double-continuum model (DCM) to determine the amount of administered therapeutic agent that will reach the cancer cells. An alveolar cell carcinoma is considered. The processes in the bigger blood vessels (arteries, arterioles, venules and veins) are described by the VGM. The processes in the alveolar capillaries and the surrounding tissue are represented by a continuum approach for porous media. The system of equations of the coupled discrete/continuum model contains terms that account for degradation processes of the therapeutic agent, the reduction of the number of drug molecules by the lymphatic system and the interaction of the drug with the tissue cells. The functionality of the coupled discrete/continuum model is demonstrated in example simulations using simplified pulmonary vascular networks, which are designed to show-off the capabilities of the model rather than being physiologically accurate.

Two-photon microscopy is a powerful method in biomedical research that allows functional and anatomical imaging at a subcellular resolution in vivo. The technique is seriously hampered by absorption and scattering of light by blood, which prevents imaging through large vessels. Here, we demonstrate in the rat cerebral cortex that blood replacement by perfluorocarbon emulsion, a compound also used in human critical care medicine, yields superior image quality, while preserving neuronal integrity. Shadows of large superficial vessels disappear completely and cells can be imaged underneath them. For the first time, it is possible to image complete populations of neurons and astrocytes in the upper layers of neocortex in vivo.

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