Among the many parameters that can be analyzed by this method, the capillary size, the frequency distributions of diameters and lengths, the fractal nature of these networks, and the depth-related density of vessels are all vital features for an adequate model of cerebral microcirculation.

No abstract

OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible. This is an author-deposited version published in: http://oatao. For this purpose, we perform the first simulations of blood flow in an anatomically accurate large human intra-cortical vascular network (~10000 segments), using a 1D non-linear model taking account of the complex rheological properties of blood flow in microcirculation. This model predicts blood pressure, blood flow and hematocrit distributions, as well as volumes of functional vascular territories, and regional flow at voxel and network scales. First, the influence of the prescribed boundary conditions (BCs) on the baseline flow structure is investigated, highlighting relevant lower-and upper-bound BCs. Independent of these BCs, large heterogeneities of baseline flow from vessel to vessel and from voxel to voxel, are demonstrated. These heterogeneities are controlled by the architecture of the intra-cortical vascular network. In particular, a correlation between the blood flow and the proportion of vascular volume occupied by arterioles or venules, at voxel scale, is highlighted. Then, the extent of venous contamination downstream to the sites of neuronal activation is investigated, demonstrating a linear relationship between the catchment surface of the activated area and the diameter of the intra-cortical draining vein.

No abstract

OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible. In a companion paper (Lorthois et al., Neuroimage, in press), we perform the first simulations of blood flow in an anatomically accurate large human intra-cortical vascular network (~10000 segments), using a 1D non-linear model taking into account the complex rheological properties of blood flow in microcirculation. This model predicts blood pressure, blood flow and hematocrit distributions, volumes of functional vascular territories, regional flow at voxel and network scales, etc. Using the same approach, we study flow reorganizations induced by global arteriolar vasodilations (an isometabolic global increase in cerebral blood flow). For small to moderate global vasodilations, the relationship between changes in volume and changes in flow is in close agreement with Grubb's law, providing a quantitative tool for studying the variations of its exponent with underlying vascular architecture. A significant correlation between blood flow and vascular structure at the voxel scale, practically unchanged with respect to baseline, is demonstrated. Furthermore, the effects of localized arteriolar vasodilations, representative of a local increase in metabolic demand, are analyzed. In particular, localized vasodilations induce flow changes, including vascular steal, in the neighboring arteriolar trunks at small distances (b 300 μm), while their influence in the neighboring veins is much larger (about 1 mm), which provides an estimate of the vascular point spread function. More generally, for the first time, the hemodynamic component of various functional neuroimaging techniques has been isolated from metabolic and neuronal components, and a direct relationship with several known characteristics of the BOLD signal has been demonstrated. IntroductionThere is increasing recognition that, by its structural implication in neuro-vascular coupling, underlying vascular architecture is a key player in hemodynamically based functional imaging techniques (including fMRI and PET) (Harrison et al., 2002;d'Esposito et al., 2003;Logothetis and Wandell, 2004;Lauwers et al., 2008;Weber et al., 2008). In particular, the spatial resolution and specificity of such techniques are bound to the density of blood capillary vasculature and blood flow regulating structures (Harel et al., 2006). This is especially important in the context of high field fMRI Harel et al., 2006), because, despite a dramatic increase in the theoretical spatial resolution obtained by using higher magnetic fields, associated with other hardware advancements, "the spatial extent of the hemodynamic response ultimately will impose a fundamental limitation on the spatial resolution of fMRI modalities" ).However, little is known about the fundamentals of the relationship between vascular structure and hemodynamic changes induced by brain activation. A growing body of evidence indicates that neurons, glia, and cerebral blood vessels, actin...

Despite the key role of the capillaries in neurovascular function, a thorough characterization of cerebral capillary network properties is currently lacking. Here, we define a range of metrics (geometrical, topological, flow, mass transfer, and robustness) for quantification of structural differences between brain areas, organs, species, or patient populations and, in parallel, digitally generate synthetic networks that replicate the key organizational features of anatomical networks (isotropy, connectedness, space-filling nature, convexity of tissue domains, characteristic size). To reach these objectives, we first construct a database of the defined metrics for healthy capillary networks obtained from imaging of mouse and human brains. Results show that anatomical networks are topologically equivalent between the two species and that geometrical metrics only differ in scaling. Based on these results, we then devise a method which employs constrained Voronoi diagrams to generate 3D model synthetic cerebral capillary networks that are locally randomized but homogeneous at the network-scale. With appropriate choice of scaling, these networks have equivalent properties to the anatomical data, demonstrated by comparison of the defined metrics. The ability to synthetically replicate cerebral capillary networks opens a broad range of applications, ranging from systematic computational studies of structure-function relationships in healthy capillary networks to detailed analysis of pathological structural degeneration, or even to the development of templates for fabrication of 3D biomimetic vascular networks embedded in tissue-engineered constructs.

SummaryThis paper presents the first application of high-resolution X-ray synchrotron tomography to the imaging of large microvascular networks in biological tissue samples. This technique offers the opportunity of analysing the full three-dimensional vascular network from the micrometre to the millimetre scale. This paper presents the specific sample preparation method and the X-ray imaging procedure. Either barium or iron was injected as contrast agent in the vascular network. The impact of the composition and concentration of the injected solution on the X-ray synchrotron tomography images has been studied. Two imaging modes, attenuation and phase contrast, are compared. Synchrotron high-resolution computed tomography offers new prospects in the three-dimensional imaging of in situ biological vascular networks.

No abstract