The 'Sphere': A Dedicated Bifurcation Aneurysm Flow-Diverter Device.

We present flow-based results from the early stage design cycle, based on computational modeling, of a prototype flow-diverter device, known as the 'Sphere', intended to treat bifurcation aneurysms of the cerebral vasculature. The device is available in a range of diameters and geometries and is constructed from a single loop of NITINOL(®) wire. The 'Sphere' reduces aneurysm inflow by means of a high-density, patterned, elliptical surface that partially occludes the aneurysm neck. The device is secured in the healthy parent vessel by two armatures in the shape of open loops, resulting in negligible disruption of parent or daughter vessel flow. The device is virtually deployed in six anatomically accurate bifurcation aneurysms: three located at the Basilar tip and three located at the terminus bifurcation of the Internal Carotid artery (at the meeting of the middle cerebral and anterior cerebral arteries). Both steady state and transient flow simulations reveal that the device presents with a range of aneurysm inflow reductions, with mean flow reductions falling in the range of 30.6-71.8% across the different geometries. A significant difference is noted between steady state and transient simulations in one geometry, where a zone of flow recirculation is not captured in the steady state simulation. Across all six aneurysms, the device reduces the WSS magnitude within the aneurysm sac, resulting in a hemodynamic environment closer to that of a healthy vessel. We conclude from extensive CFD analysis that the 'Sphere' device offers very significant levels of flow reduction in a number of anatomically accurate aneurysm sizes and locations, with many advantages compared to current clinical cylindrical flow-diverter designs. Analysis of the device's mechanical properties and deployability will follow in future publications

Human arachnoid granulations Part I: a technique for quantifying area and distribution on the superior surface of the cerebral cortex

<p>Abstract</p> <p>Background</p> <p>The arachnoid granulations (AGs) are herniations of the arachnoid membrane into the dural venous sinuses on the surface of the brain. Previous morphological studies of AGs have been limited in scope and only one has mentioned surface area measurements. The purpose of this study was to investigate the topographic distribution of AGs on the superior surface of the cerebral cortex.</p> <p>Methods</p> <p><it>En face </it>images were taken of the superior surface of 35 formalin-fixed human brains. AGs were manually identified using Adobe Photoshop, with a pixel location containing an AG defined as 'positive'. A set of 25 standard fiducial points was marked on each hemisphere for a total of 50 points on each image. The points were connected on each hemisphere to create a segmented image. A standard template was created for each hemisphere by calculating the average position of the 25 fiducial points from all brains. Each segmented image was mapped to the standard template using a linear transformation. A topographic distribution map was produced by calculating the proportion of AG positive images at each pixel in the standard template. The AG surface area was calculated for each hemisphere and for the total brain superior surface. To adjust for different brain sizes, the proportional involvement of AGs was calculated by dividing the AG area by the total area.</p> <p>Results</p> <p>The total brain average surface area of AGs was 78.53 ± 13.13 mm²(n = 35) and average AG proportional involvement was 57.71 × 10^-4± 7.65 × 10^-4. Regression analysis confirmed the reproducibility of AG identification between independent researchers with r²= 0.97. The surface AGs were localized in the parasagittal planes that coincide with the region of the lateral lacunae.</p> <p>Conclusion</p> <p>The data obtained on the spatial distribution and <it>en face </it>surface area of AGs will be used in an <it>in vitro </it>model of CSF outflow. With an increase in the number of samples, this analysis technique can be used to study the relationship between AG surface area and variables such as age, race and gender.</p

Elevated Uptake of Plasma Macromolecules by Regions of Arterial Wall Predisposed to Plaque Instability in a Mouse Model

Atherosclerosis may be triggered by an elevated net transport of lipid-carrying macromolecules from plasma into the arterial wall. We hypothesised that whether lesions are of the thin-cap fibroatheroma (TCFA) type or are less fatty and more fibrous depends on the degree of elevation of transport, with greater uptake leading to the former. We further hypothesised that the degree of elevation can depend on haemodynamic wall shear stress characteristics and nitric oxide synthesis. Placing a tapered cuff around the carotid artery of apolipoprotein E -/- mice modifies patterns of shear stress and eNOS expression, and triggers lesion development at the upstream and downstream cuff margins; upstream but not downstream lesions resemble the TCFA. We measured wall uptake of a macromolecular tracer in the carotid artery of C57bl/6 mice after cuff placement. Uptake was elevated in the regions that develop lesions in hyperlipidaemic mice and was significantly more elevated where plaques of the TCFA type develop. Computational simulations and effects of reversing the cuff orientation indicated a role for solid as well as fluid mechanical stresses. Inhibiting NO synthesis abolished the difference in uptake between the upstream and downstream sites. The data support the hypothesis that excessively elevated wall uptake of plasma macromolecules initiates the development of the TCFA, suggest that such uptake can result from solid and fluid mechanical stresses, and are consistent with a role for NO synthesis. Modification of wall transport properties might form the basis of novel methods for reducing plaque rupture

Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas)