F. Lauwers

A Novel Three-Dimensional Computer-Assisted Method for a Quantitative Study of Microvascular Networks of the Human Cerebral Cortex

Objective: Detailed information on microvascular network anatomy is a requirement for understanding several aspects of microcirculation, including oxygen transport, distributions of pressure, and wall shear stress in microvessels, regulation of blood flow, and interpretation of hemodynamically based functional imaging methods, but very few quantitative data on the human brain microcirculation are available. The main objective of this study is to propose a new method to analyze this microcirculation.

Morphometry of the human cerebral cortex microcirculation: General characteristics and space-related profiles

Studies on human brain microcirculation have thus far yielded few quantitative data, preventing the closest possible interpretation of functional imaging methods such as fMRI and PET that necessarily rely on robustly delineated morphology of haemodynamic systems. Inadequate data in this area can lead to severe underestimation of the spatial specificity of the BOLD response. We took thick sections of Indian ink injected human brain and, using confocal laser microscopy and a novel three-dimensional computer-assisted method we extracted and analyzed hundreds of thousands of vascular segments within a large area of cortex. From this database the global densities, the statistical distributions of diameters and lengths were analysed, separating the tree-like and the net-like parts of the microcirculation. Furthermore, our analysis included variations in volume density along the cortical depth and along vectors parallel to the cortical surface. These morphometric parameters are all key requirements for a sound model of cerebral microcirculation.

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network: Part I: Methodology and baseline flow

Hemodynamically based functional neuroimaging techniques, such as BOLD fMRI and PET, provide indirect measures of neuronal activity. The quantitative relationship between neuronal activity and the measured signals is not yet precisely known, with uncertainties remaining about the relative contribution by their metabolic and hemodynamic components. Empirical observations have demonstrated the importance of the latter component and suggested that micro-vascular anatomy has a potential influence. The recent development of a 3D computer-assisted method for micro-vascular cerebral network analysis has produced a large quantitative library on the microcirculation of the human cerebral cortex (Cassot et al., 2006), which can be used to investigate the hemodynamic component of brain activation through fluid dynamic modeling. 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.

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: Flow variations induced by global or localized modifications of arteriolar diameters

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 Grubbs 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 (<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.

Branching patterns for arterioles and venules of the human cerebral cortex

Branching patterns of microvascular networks influence vascular resistance and allow control of peripheral flow distribution. The aim of this paper was to analyze these branching patterns in human cerebral cortex. Digital three-dimensional images of the microvascular network were obtained from thick sections of India ink-injected human brain by confocal laser microscopy covering a large zone of secondary cortex. A novel segmentation method was used to extract the skeletons of 228 vascular trees (152 arterioles and 76 venules) and measure the diameter at every vertex. The branching patterns (area ratios and angles of bifurcations) of nearly 10,000 bifurcations of cortical vascular trees were analyzed, establishing their statistical properties and structural variations as a function of the vessel nature (arterioles versus venules), the parent vessel topological order or the bifurcation type. We also describe their connectivity and discuss the relevance of the assumed optimal design of vascular branching to account for the complex nature of microvascular architecture. The functional implications of some of these structural variations are considered. The branching patterns established from a large database of a human organ contributes to a better understanding of the bifurcation design and provides an essential reference both for diagnosis and for a future large reconstruction of cerebral microvascular network.

Anatomic variations of the renal vessels: focus on the precaval right renal artery

The aim of this study was to determine the prevalence of precaval right renal artery and to investigate the distribution of renal arteries and veins. We discuss a theory of development of renal vascular variants. We retrospectively reviewed 120 arterial phase contrast material-enhanced spiral computerized tomography scans of the abdomen (1- to 2-mm section thickness) performed during a two-month period. Forty percent of the study group (48 patients) had one artery and one vein on each side, with typical course. There was a 9.17% prevalence of precaval right renal artery: 10 patients had a lower pole accessory artery in precaval position and one patient had the main and the accessory arteries that pass anterior to the inferior vena cava. In these cases, associated variations of renal vessels were higher than in the patients without precaval artery variant. There were multiple arteries in 28.3% of the right kidneys and in 26.7% of the left ones. Variants of the right renal vein consisted in multiple veins in 20% (24 cases). We detected no case of multiple left renal veins, but we described variations of its course (circum- or retroaortic vein) in 9.17% (11 cases). Twenty-six patients (21.7%) had associated variations of the renal pedicle. The current technical support allows for a minimally invasive study of vessels anatomy. In our study the prevalence of a precaval right renal artery appears to be higher than previously reported (9.17%). Knowledge on anatomical variations of right renal artery and associated renal vessels variations has major clinical implications.

Tortuosity and other vessel attributes for arterioles and venules of the human cerebral cortex

Despite its demonstrated potential in the diagnosis and/or staging of disease, especially in oncology, tortuosity has not received a formal and unambiguous clinical definition yet. Using idealized three-dimensional vessel models (wavy helices) with known characteristics, we first demonstrate that, among various possible tortuosity indices, the standard deviation of the curvature Ksd best satisfies i) scale invariance and ii) positive monotonic response with respect to the amplitude and frequency of vessel oscillations. Ksd can thus be considered as a robust measure of tortuosity. On the contrary, indices previously considered as tortuosity metrics, such as the distance factor metrics (DFM), are highly scale dependent and inappropriate for that purpose. The tortuosity and other vessel attributes (curvature, length-to-diameter ratio (LDR),…) of more than 15,000 cortical vessels are subsequently studied, establishing their statistical properties as a function of the vessel nature (arterioles versus venules) or topological order (hierarchical position). In particular, arterioles have a higher LDR than venules, but the two kinds of vessels have the same mean curvature and tortuosity. Moreover, the lower the order of the vessels, i.e. the nearer to the capillary network, the more curved and tortuous they are. These results provide an essential reference both for diagnosis and for a future large reconstruction of the cerebral microvascular network.

The vascular system of the upper eyelid. Anatomical study and clinical interest

Thorough knowledge of the vascular supply is indispensable for repair and oncologic surgery of the eyelids, and has a significant impact on the management of complex defects of this region. This anatomic study was performed with five fresh cadavers after arterial injection of coloured neoprene latex. The distribution of the vascular system of the upper eyelid was examined after dissection and photographic study. It is made up of three arcades: the preseptal arcade, the supratarsal arcade, and the marginal arcade, under the orbicularis oculi muscle. These arcades are supplied by branches of the ophthalmic artery (supraorbital artery, supratrochlear artery and medial palpebral artery) and branches of the facial artery and temporal artery. Small vertical branches arising out of these arcades provide an anastomotic network. This anatomical study aimed to describe the vascular system of the upper eyelid in order to search for constant features and to map the blood supply of the principal upper lid flaps.

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.

Frontoethmoidal meningoencephalocele: appraisal of a craniofacial surgical teaching program in Cambodia

OBJECTIVE The treatment of frontoethmoidal meningoencephaloceles (fMECs) in Cambodia was not possible before the development of a program that taught some Khmer surgeons (working at the Childrens Surgical Centre in Phnom Penh) how to surgically correct these deformities without any foreign help. The results of that teaching program are discussed in this paper. METHODS Between 2004 and 2009, both local and visiting foreign neurosurgical and craniofacial surgeons (the visitors coming twice a year) worked together to operate on 200 patients, and a report on those cases was published in 2010. In subsequent years (2010-2016), the Khmer surgeons operated on 100 patients without the presence of the visiting surgeons. In this study, the authors compare the second case series with the previously published series and the literature in terms of results and complications. The operations were performed with limited surgical materials and equipment, using a combined bicoronal and transfacial approach in most cases. Most of the patients came from very poor families. RESULTS Organizing the postoperative follow-up of these low-income patients (mean age 12 years) was probably the most challenging part of this teaching program. Nine of the patients were lost to surgical follow-up. In the other cases, cosmetic results were judged by the surgeons as worse than the patients preoperative appearance in 1 case, poor in 12 cases, average in 27, and good in 51-data that are significantly less encouraging than the results reported by the joint local/visiting teams in 2010 (p = 0.0001). Nevertheless, patients and parents tended to have a better overall opinion about the surgical results (rating the results as good in 84% of the 80 cases in which parent or patient ratings were available). Twenty postoperative complications were observed (the most common being temporary CSF leaks). The rate of immediate postoperative complications directly related to fMEC surgery was less than that in the previous series, but the difference was not statistically significant (20% vs 28.5%, p = 0.58). No death was noted in this case series (in contrast to the previous series). Social questionnaire results confirmed that fMEC correction partially improved the adverse social and educational consequences of fMEC in affected children. CONCLUSIONS In the current state of this program, the local surgeons are able to correct fMECs in their own country, without foreign assistance, with good results in a majority of patients. Such humanitarian teaching programs generally take years to achieve the initial aims.