In this paper, the variations in cerebral blood flow induced by global or localised capillary vasodilations are studied. The results demonstrate that pericyte-mediated regulation of blood flowat capillary level would be efficient for neuro-vascular coupling. By contrast to a regulation situated at the level of arterioles (Lorthois et al. 2011b), the changes in blood volume can be highly localised in space, with the potential to be as close as possible of areas of neuronal activation. However, the changes in blood flow are much more diffuse. This imposes limits on the ultimate spatial resolution of hemodynamically based brain functional imaging techniques

F. Lauwers

Hamilton NB

Lauwers F

Lorthois S

S. Lorthois

Tian P

Lorthois, Sylvie

Lauwers, Frédéric

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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.univ-toulouse.fr/Eprints ID : 9158 To link to this article : DOI: 10.1080/10255842.2012.713680 URL : http://dx.doi.org/10.1080/10255842.2012.713680 Open Archive TOULOUSE Archive Ouverte (OATAO)To cite this version : Lorthois, Sylvie and Lauwers, Frédéric Control of brain blood flow by capillaries: a simulation study in an anatomically accurate large human vascular network. (2012) Computer Methods in Biomechanics and Biomedical Engineering, vol. 15 (n° S1). pp. 66-68. ISSN 1025-5842 Control of brain blood flow by capillaries: a simulation study in an anatomically accurate largehuman vascular networkS. Lorthoisa* and F. Lauwersb,caInstitut de Me´canique des Fluides de Toulouse, UMR CNRS/INPT/UPS 5502, Toulouse, France; bDepartment of Anatomy,LSR44, Faculty of Medicine Toulouse-Purpan, Toulouse, France;cINSERM U825 Cerebral Imaging and Neurological Handicap,Toulouse, FranceKeywords: cerebral microcirculation; cerebral blood flow; neurovascular coupling; functional neuroimaging1. IntroductionBlood micro-circulation plays a central role in the localadaptation of cerebral blood flow to neural activity.A growing body of evidence indicates that neurons, gliaand cerebral blood vessels, acting as an integrated unit,have a crucial role in mediating the activation-inducedchanges in blood flow. In particular, the smooth musclecells surrounding the arterioles, and possibly pericytes,at capillary level, convert the bio-chemical signals thatoriginate from this integrated unit into changes in vasculardiameter, thus regulating blood flow bymodulating vascularresistance (Hamilton et al. 2010).However, the role of capillaries in the control ofcerebral blood flow is still controversial (Hamiltonet al. 2010). In particular, it is at present not clear whetherthe capillary dilatation experimentally observed in vivoby several groups is a passive consequence of upstreamarteriolar dilatation via an alteration in perfusion pressureor the result of an active regulation of the capillary diametervia contraction/relaxation of pericytes (Hamilton et al.2010). Answering this question by experimental meansis extremely challenging. For example, the penetrationdepth of the most recent intravital two-photon microscopytechniques (typically ,500mm) does neither allow toinvestigate the cortical layers of highest capillary density,which are located approximately in the middle third of thecortex (Lauwers et al. 2008) nor those where the fastestcapillary dilation occurs (Tian et al. 2010).Bycontrast, Hamilton et al. (2010) have pointed out thatmodelling using anatomically accurate representations ofthe intracortical vascular network will be valuable forgenerating predictions as to the likely impact of pericyte-mediated capillary diameter regulation.Our group has recently performed the first numericalsimulations of blood flow in an anatomically accurate largehuman intra-cortical vascular network (,10,000 segments),using a 1Dnon-linearmodel taking into account the complexrheological properties of blood flow in microcirculation(i.e. Fahraeus, Fahraeus–Lindquist and phase separationeffects; Lorthois et al. 2011a). This model predicts bloodpressure, blood flow and hematocrit distributions, volumesof functional vascular territories, regional flow at local,voxel and network scales, etc. Using the same approach,we have studied the flow re-organisations induced byarteriolar vasodilations, highlighting the hemodynamiccomponent of various functional neuroimaging techniques(Lorthois et al. 2011b).In this paper, the variations in cerebral blood flowinduced by global or localised capillary vasodilations arestudied.2. MethodsThe methodology for simulating blood flow in the intra-cortical vascular network of a secondary cortex regionextendingover 7.7mm2 along the lateral part of the collateralsulcus has been presented in detail and validated elsewhere(Lorthois et al. 2011a). It is used to calculate the flow andhematocrit in each segment and the pressure at each node.Of course, the computed values of these parameters dependon the boundary condition prescribed at frontiers capillarynodes, and two relevant conditions, providing a lower- andupper-bound limit to the network behaviour, have beendetermined: a zero flow condition (Case 1) and a self-consistent constant pressure condition adjusted such that thenet flux contributed by all the frontiers capillary segmentsis null (Case 2).To study the active role of intra-cortical capillaries,the diameters either of every capillary in the network(global) or of capillaries in a restricted area (localised) aremultiplied by a constant factor fvaso. This restricted area israndomly chosen in the high capillary density corticallayer, with a spatial extent in the direction parallel to thecortical surface fixed to 600mm, typically corresponding*Corresponding author. Email: lorthois@imft.frto the periodicity of the vascular organisation in the cortex(Lauwers et al. 2008).3. Results and discussionThe relative variations of the regional blood flow inducedby global capillary vasodilations as a function of fvaso aredisplayed in Figure 1 for both boundary conditionsstudied. In both cases, the results can accurately be fittedby a simple model of two resistances connected in seriesand subjected to a constant pressure drop. Despite thearchitectural and rheological complexity, the secondresistance, representing the capillary network, behavesas a single Poiseuille resistance, the variation of whichis inversely proportional to the fourth power of fvaso (seeFigure 1). In both cases, a two-fold increase in capillarydiameter increases blood flow by a factor ,5. This ismuch greater than previous estimates from the relativeimportance of capillary and arteriolar resistance in modelswith simplified network structure and rheology, where afactor between 1.18 and 2.98 had been found (Hamiltonet al. 2010). This is also greater than the increase inducedby a two-fold global vasodilation of the arteriolar trees(Lorthois et al. 2011b).However, this simple approach cannot account for theheterogeneities of flow variations throughout the network,the flow increasing by a factor ofmore than 9 in a significantproportion of vessels (data not shown).In case of local vasodilations, a general augmentationof the flow in the vasodilated area is observed (Figure 2).This augmentation is larger than above: a 2-fold increase indiameter can result in a 10-fold increase in the most centralcapillaries (see Figure 2(B)). It is generally associated witha decrease in pressure and an increase in hematocrit.Outside the vasodilated region, a ,300mm widesurrounding area exhibits a decrease in flow rate. Furtheraway, significant variations spread as far as ,1mm fromthe centre of the vasodilated region.4. ConclusionsThe above results demonstrate that pericyte-mediatedregulation of blood flow at capillary level would be efficientfor neuro-vascular coupling. By contrast to a regulationsituated at the level of arterioles (Lorthois et al. 2011b), thechanges in blood volume can be highly localised in space,with the potential to be as close as possible of areas ofneuronal activation. However, the changes in blood floware much more diffuse. This imposes limits on the ultimatespatial resolution of hemodynamically based brainfunctional imaging techniques.ReferencesHamilton NB, Attwell D, Hall CN. 2010. Pericyte-mediatedregulation of capillary diameter: a component of neurovas-cular coupling in health and disease. Front Neuroenergetics.2:1–14.Lauwers F, Cassot F, Lauwers-Cances V, Puwanarajah P,Duvernoy H. 2008. Morphometry of the human cerebralcortex microcirculation: general characteristics and space-related profiles. Neuroimage. 39:936–948.Lorthois S, Cassot F, Lauwers F. 2011a. Simulation study ofbrain blood flow regulation by intra-cortical arterioles inan anatomically accurate large human vascular network:part I: methodology and baseline flow. Neuroimage. 54:1031–1042.Figure 2. Flow rate variations in individual vessels induced by atwo-fold increase of the diameters of the capillaries situated inthe box.Figure 1. Regional blood flow normalised to its baseline valueas a function of fvaso. Symbols: numerical results; lines: bestfit according to a two-series resistance model (see insertedequation).Lorthois S, Cassot F, Lauwers F. 2011b. Simulation study ofbrain blood flow regulation by intra-cortical arterioles in ananatomically accurate large human vascular network: part II:flow variations induced by global or localised modificationsof arteriolar diameters. Neuroimage. 54:2840–2853.Tian P, Teng IC, May LD, Kurz R, Lu K, Scadeng M, HillmanEM, DeCrespigny AJ, D’Arceuil HE, Mandeville JB, et al.2010. Cortical depth-specific microvascular dilationunderlies laminar differences in blood oxygenation level-dependent functional MRI signal. Proc Natl Acad Sci USA.107:15246–152451.

Control of brain blood flow by capillaries: a simulation study in an anatomically accurate large human vascular network

In this paper, the variations in cerebral blood flow induced by global or localised capillary vasodilations are

studied. The results demonstrate that pericyte-mediated regulation of blood flowat capillary level would be efficient for neuro-vascular coupling. By contrast to a regulation situated at the level of arterioles (Lorthois et al. 2011b), the changes in blood volume can be highly localised in space, with the potential to be as close as possible of areas of neuronal activation. However, the changes in blood flow are much more diffuse. This imposes limits on the ultimate spatial resolution of hemodynamically based brain functional imaging techniques

Control of brain blood flow by capillaries: a simulation

study in an anatomically accurate large human vascular

network

International audienceIn this paper, the variations in cerebral blood flow induced by global or localised capillary vasodilations are studied. The results demonstrate that pericyte-mediated regulation of blood flowat capillary level would be efficient for neuro-vascular coupling. By contrast to a regulation situated at the level of arterioles (Lorthois et al. 2011b), the changes in blood volume can be highly localised in space, with the potential to be as close as possible of areas of neuronal activation. However, the changes in blood flow are much more diffuse. This imposes limits on the ultimate spatial resolution of hemodynamically based brain functional imaging techniques

Control of brain blood flow by capillaries: a simulation study in an anatomically accurate large human vascular network

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