Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis

Changes in blood flow can induce arterial remodeling. Intimal cells sense flow and send signals to the media to initiate remodeling. However, the nature of such intima-media signaling is not fully understood. To identify potential signals, New Zealand white rabbits underwent bilateral carotid ligation to increase flow in the basilar artery or sham surgery (n = 2 ligated, n = 2 sham). Flow was measured by transcranial Doppler ultrasonography, vessel geometry was determined by 3D angiography, and hemodynamics were quantified by computational fluid dynamics. 24 h post-surgery, the basilar artery and terminus were embedded for sectioning. Intima and media were separately microdissected from the sections, and whole transcriptomes were obtained by RNA-seq. Correlation analysis of expression across all possible intima-media gene pairs revealed potential remodeling signals. Carotid ligation increased flow in the basilar artery and terminus and caused differential expression of 194 intimal genes and 529 medial genes. 29,777 intima-media gene pairs exhibited correlated expression. 18 intimal genes had > 200 medial correlates and coded for extracellular products. Gene ontology of the medial correlates showed enrichment of organonitrogen metabolism, leukocyte activation/immune response, and secretion/exocytosis processes. This demonstrates correlative expression analysis of intimal and medial genes can reveal novel signals that may regulate flow-induced arterial remodeling.

Dural venous system: angiographic technique and correlation with ex vivo investigations

BackgroundThe dural vasculature plays a key role in several important conditions, including dural fistulas and subdural collections. While in vivo investigations of intrinsic dural arterial angioarchitecture are rare, no angiographic studies of dural venous drainage exist to our knowledge.ObjectiveTo describe methods by which dural venous drainage might be visualized with current angiographic equipment and technique, and to correlate our results with existing ex vivo literature.MethodsDigital subtraction angiography and 3D angiography (rotational and Dyna CT) of dural neurovasculature were acquired in the context of subdural hematoma embolization and normal dura. Protocols for visualization of dural venous drainage were established, and findings correlated with ex vivo studies.ResultsMeningeal arteries supply both the skull and dura. Normal dural enhancement is accentuated by the presence of hypervascular membranes. Intrinsic meningeal veins/sinuses parallel outer layer arteries with well-known tram-tracking appearance. Dura adjacent to main arterial trunks drains via skull base foramina into the pterygopalatine venous plexus, or via emissary veins into the temporalis venous plexus. Dura near the sinuses drains into venous pouches adjacent to the sinus, before emptying into the sinus proper—possibly the same pouches implicated in the angioarchitecture of dural fistulas. Finally, posterior temporoparietal convexity dura, situated in a watershed-like region between middle and posterior meningeal territories, frequently empties into diploic and emissary veins of the skull. Wide variation in balance is expected between these three routes. Drainage patterns appear to correlate with venous embryologic investigations of Padget and ex vivo studies in adults.ConclusionsContinued attention to dural venous drainage may prove useful in the diagnosis and management of dural-based vascular diseases.

Effective accuracy of stereoelectroencephalography: robotic 3D versus Talairach orthogonal approaches

OBJECTIVEStereoelectroencephalography (SEEG) was first developed in the 1950s by Jean Talairach using 2D angiography and a frame-based, orthogonal approach through a metallic grid. Since then, various other frame-based and frameless techniques have been described. In this study the authors sought to compare the traditional orthogonal Talairach 2D angiographic approach with a frame-based 3D robotic procedure that included 3D angiographic interoperative imaging guidance. MRI was used for both procedures during surgery, but MRI preplanning was done only in the robotic 3D technique.METHODSAll study patients suffered from drug-resistant focal epilepsy and were treated at the same center by the same neurosurgical team. Fifty patients who underwent the 3D robotic procedure were compared to the same number of historical controls who had previously been successfully treated with the Talairach orthogonal procedure. The effectiveness and absolute accuracy, as well as safety, of the two procedures were compared. Moreover, in the 3D robotic group, the reliability of the preoperative MRI to avoid vascular structures was evaluated by studying the rate of trajectory modification following the coregistration of the intraoperative 3D angiographic data onto the preoperative MRI-based trajectory plans.RESULTSEffective accuracy (96.5% vs 13.7%) and absolute accuracy (1.15 mm vs 4.00 mm) were significantly higher in the 3D robotic group than in the Talairach orthogonal group. Both procedures showed excellent safety results (no major complications). The rate of electrode modification after 3D angiography was 43.8%, and it was highest for frontal and insular locations.CONCLUSIONSThe frame-based, 3D angiographic, robotic procedure described here provided better accuracy for SEEG implantations than the traditional Talairach approach. This study also highlights the potential safety advantage of trajectory planning using intraoperative frame-based 3D angiography over preoperative MRI alone.

P4131Abnormal flow pattern in the main pulmonary artery of Marfan patients is related to local dilation

Introduction Marfan syndrome (MFS) is a hereditary connective tissue disorder caused by mutation in the FBN1 gene. Main pulmonary artery (MPA) dilation is very prevalent in MFS patients. Indeed, the old Ghent nosology considered main pulmonary artery (MPA) dilation as diagnostic criterion of MFS patients. Although clinical complications related to pulmonary dilation in MFS are rare, this may potentially lead to MPA dissection or be a marker of vascular disease in MFS. Studies regarding potential causes of MPA dilation in MFS patients are very scarce. Purpose Through 4D flow CMR, we aimed to assess whether flow abnormalities exist in the MPA of MFS patients and their relation to local diameter. Methods Fifty-five consecutive Marfan syndrome adults (MFS) and 22 healthy volunteers (HV) were prospectively enrolled. All subjects underwent non-contrast-enhanced 4D flow-MRI, obtaining 4D flow field and a 3D angiography. The MPA was segmented from the 3D angiography, and the segmentation was used to mask 4D velocity data. Four, equidistant analysis planes were placed in the MPA between the pulmonary valve and the pulmonary artery bifurcation. Common descriptors of large arteries hemodynamics were computed at each plane: maximum velocity, systolic flow reversal ratio (a descriptor of the amount of systolic backward flow) and circumferentially-averaged axial and circumferential wall shear stress (WSS). Pulmonary artery diameters were measured on axial images. MPA dilation was defined as a diameter larger than 27 mm in women and 29 mm in men. Systolic (SBP) and diastolic (DBP) systemic blood pressure were measured at the brachial artery with a calibrated cuff immediately after the scan. Results Compared with HV, MFS patients presented similar age, BSA, SBP and maximum blood velocity, but had larger MPA diameter (27.8 vs 25.1 mm, p<0.001) and higher DBP (75.5 vs 66.8 mmHg, p=0.003). According to the used threshold, 45% (27) of MFS patients had MPA dilation. Compared with HV, Marfan patients presented an increased systolic flow reversal ratio in the proximal part of the MPA (Figure 1). In MFS patients axial WSS was reduced in central sections of the MPA, while the circumferential component was not difference with respect to HV. All these flow abnormalities were also present in the subset of 28 MFS patients without pulmonary artery dilation. In multivariable analysis, MPA diameter was independently related to age (B=0.056; p=0.032), sex (B=−2.3; p=0.02) and axial (B=6.4; p=0.039) and circumferential (B=33.9; p<0.001) WSS. Figure 1 Conclusions Dilation of the main pulmonary artery is prevalent in Marfan syndrome patients. Abnormal increase in systolic vortexes and reduction in axial WSS were present in dilated and non-dilated MPA in MFS patients. Axial and circumferential WSS were independently related to MPA diameter. The eventual predictive role of abnormal pulmonary flow pattern in pulmonary artery dilation in MFS patients remain to be established Acknowledgement/Funding Instituto de Salud Carlos III (PI14/0106), La Maratό de TV3 (20151330), CIBERCV and FP7/People (267128)

How patient specific are patient-specific computational models of cerebral aneurysms? An overview of sources of error and variability

Computational modeling of cerebral aneurysms, derived from clinical 3D angiography, has become widespread over the past 15 years. While such “image-based” or “patient-specific” models have shown promise for the assessment of rupture risk, much debate remains about their reliability in light of necessary modeling assumptions and incomplete or uncertain model input parameters derived from the clinic. The aims of this review were to walk through the various steps of this so-called patient-specific modeling pipeline and to highlight evidence supporting those steps that we can or cannot rely on. The relative importance of the different sources of error and variability on hemodynamic predictions is summarized, with recommendations to standardize for those that can be avoided and to pay closer attention those to that cannot.