Longitudinal alterations in cerebral perfusion following a season of adolescent contact sport participation compared to non-contact athletes.

BACKGROUND: Cerebral blood flow (CBF) change, a non-invasive marker of head injury, has yet to be thoroughly investigated as a potential consequence of repetitive head impacts (RHI) via contact sport participation in youth athletes. We examined pre-to post-season differences in relative CBF (rCBF), arterial transit time (ATT), and neurocognition between adolescent contact sport (CS; 79.4% of which were football players) and non-contact sport (NCS) athletes. METHODS: Adolescent athletes (N = 57; age = 14.70 ± 1.97) completed pre- and post-season clinical assessments and neuroimaging. Brain perfusion was evaluated using an advanced 3D pseudo-continuous ASL sequence with Hadamard encoded multiple post-labeling delays. Mixed-effect models tested group-by-time interactions for rCBF, ATT, and neurocognition. RESULTS: A significant group-by-time interaction was observed for rCBF in a cluster consisting primarily of frontal and parietal lobe regions, with regional rCBF increasing in CS and decreasing among NCS athletes. No significant interaction was observed for ATT. A significant group-by-time interaction was observed for verbal memory and visual motor speed, with NCS athletes improving and CS athletes exhibiting lower performance from pre-to post-season in comparison. CONCLUSIONS: Alterations in rCBF and variability in cognition, not purported neurovasculature changes (measured by ATT), were observed following one season of CS participation. Further study surrounding the clinical meaningfulness of these findings, as they related to adverse long-term outcomes, is needed.

Realistic non-Newtonian viscosity modelling highlights hemodynamic differences between intracranial aneurysms with and without surface blebs.

Most computational fluid dynamic (CFD) simulations of aneurysm hemodynamics assume constant (Newtonian) viscosity, even though blood demonstrates shear-thinning (non-Newtonian) behavior. We sought to evaluate the effect of this simplifying assumption on hemodynamic forces within cerebral aneurysms, especially in regions of low wall shear stress, which are associated with rupture. CFD analysis was performed for both viscosity models using 3D rotational angiography volumes obtained for 26 sidewall aneurysms (12 with blebs, 12 ruptured), and parametric models incorporating blebs at different locations (inflow/outflow zone). Mean and lowest 5% values of time averaged wall shear stress (TAWSS) computed over the dome were compared using Wilcoxon rank-sum test. Newtonian modeling not only resulted in higher aneurysmal TAWSS, specifically in areas of low flow and blebs, but also showed no difference between aneurysms with or without blebs. In contrast, for non-Newtonian analysis, bleb-bearing aneurysms showed significantly lower 5% TAWSS compared to those without (p=0.005), despite no significant difference in mean dome TAWSS (p=0.32). Non-Newtonian modeling also accentuated the differences in dome TAWSS between ruptured and unruptured aneurysms (p<0.001). Parametric models further confirmed that realistic non-Newtonian viscosity resulted in lower bleb TAWSS and higher focal viscosity, especially when located in the outflow zone. The results show that adopting shear-thinning non-Newtonian blood viscosity in CFD simulations of intracranial aneurysms uncovered hemodynamic differences induced by bleb presence on aneurysmal surfaces, and significantly improved discriminant statistics used in risk stratification. These findings underline the possible implications of using a realistic model of blood viscosity in predictive computational hemodynamics.

Wall shear stress association with rupture status in volume matched sidewall aneurysms.

OBJECTIVE: Flow induced tangential wall shear stress (WSS) is thought to be involved in aneurysm formation, growth, and rupture. Low WSS was previously associated with rupture, but definitive quantitative analyses remain scant as larger aneurysms are associated with lower WSS regardless of rupture status, and ruptured aneurysms are larger than unruptured aneurysms. Here, the intra-dome WSS was evaluated on 18 internal carotid artery aneurysms, volume matched as ruptured/unruptured pairs in order to remove the confounding effect of size dependence. METHODS: Computational fluid dynamic simulations were performed and WSS was evaluated at peak systole, end diastole, and as time averaged over the cardiac cycle. WSS logarithmic scaling was applied to refine value discrimination at extrema. Ruptured/unruptured lesions were statistically evaluated using pairwise t test analysis. The effect of size on WSS was evaluated in parametric models. RESULTS: In parametric data, there was a statistically significant negative correlation between volume and WSS values. In patient data, mean WSS was not statistically significant but low range WSS values were significantly lower for ruptured aneurysms, regardless of WSS evaluation (time averaged, peak systole, end diastole). Statistically, logarithmic WSS performed better than WSS, with minimum logarithmic WSS at end diastole being the best rupture status discriminator (p=0.001, area under the curve=0.98). Higher range and maximal WSS were not significantly significant. CONCLUSIONS: Aneurysm size is a confounding factor to WSS rupture discrimination, and volume matched analysis is necessary for unbiased evaluation. While these results lend support to the hypothesis that lower WSS induces wall changes which may be associated with rupture, it raises questions regarding the extent of this association, which requires further exploration.

Vascular change measured with independent component analysis of dynamic susceptibility contrast MRI predicts bevacizumab response in high-grade glioma.

BACKGROUND: Standard pre- and postcontrast (T1 + C) anatomical MR imaging is proving to be insufficient for accurately monitoring bevacizumab treatment response in recurrent glioblastoma (GBM). We present a novel imaging biomarker that detects abnormal tumor vasculature exhibiting both arterial and venous perfusion characteristics. We hypothesized that a decrease in the extent of this abnormal vasculature after bevacizumab treatment would predict treatment efficacy and overall survival. METHODS: Dynamic susceptibility contrast perfusion MRI was gathered in 43 patients with high-grade glioma. Independent component analysis separated vasculature into arterial and venous components. Voxels with perfusion characteristics of both arteries and veins (ie, arterio-venous overlap [AVOL]) were measured in patients with de novo untreated GBM and patients with recurrent high-grade glioma before and after bevacizumab treatment. Treated patients were separated on the basis of an increase or decrease in AVOL volume (+/-ΔAVOL), and overall survival following bevacizumab onset was then compared between +/-ΔAVOL groups. RESULTS: AVOL in untreated GBM was significantly higher than in normal vasculature (P < .001). Kaplan-Meier survival curves revealed a greater median survival (348 days) in patients with GBM with a negative ΔAVOL after bevacizumab treatment than in patients with a positive change (197 days; hazard ratio, 2.51; P < .05). Analysis of patients with combined grade III and IV glioma showed similar results, with median survivals of 399 days and 153 days, respectively (hazard ratio, 2.71; P < .01). Changes in T1+C volume and ΔrCBV after treatment were not significantly different across +/-ΔAVOL groups, and ΔAVOL was not significantly correlated with ΔT1+C or ΔrCBV. CONCLUSIONS: The independent component analysis dynamic susceptibility contrast-derived biomarker AVOL adds additional information for determining bevacizumab treatment efficacy.

Y-stent coiling of basilar bifurcation aneurysms induces a dynamic angular vascular remodeling with alteration of the apical wall shear stress pattern.

BACKGROUND: Although wide-necked basilar bifurcation aneurysms are treated with Y-stent coiling, the effect of this intervention on vessel configuration and hemodynamics is unknown. OBJECTIVE: To investigate the immediate and delayed effects of Y-stenting using self-expanding microstents on basilar bifurcation architecture and hemodynamics. METHODS: Fifteen patients underwent basilar Y-stent coiling and imaging with rotational angiography. Vascular angles were measured between proximal P1 segments of the posterior cerebral arteries (α) and between the basilar artery and each P1 segment (ß(1,2)) in the anteroposterior and γ(1,2) sagittal planes. Patient-specific computational fluid dynamic analysis was used to estimate wall shear stress (WSS) changes with treatment. RESULTS: In the anteroposterior plane, Y-stenting significantly decreased angle α and increased ß angles immediately after stent coiling (P < .05 and P < .01, respectively) in a continued dynamic remodeling that progressed further in later months; sagittal γ angles also decreased (P < .0001). This novel stent-induced geometric progressive remodeling resulted in effective straightening and narrowing of the basilar bifurcation angle α (150.0 degrees vs 113 degrees, P < .0001) with significant correlation (r = 0.39, P < .05) between pretreatment proximal P1 angles and maximal angular change. Computational fluid dynamic analysis showed the angular remodeling led to significant narrowing of the WSS interpeak at the apex, redirecting high WSS away from the neck transition zone with native vessel toward the inert coil mass. CONCLUSION: Y-configuration stent coiling induced immediate and, more significantly, a previously undefined delayed cerebrovascular remodeling. This progressive stent-induced angular remodeling alters perianeurysmal hemodynamics, independent of the flow-diverting properties of stent struts, thus shifting the balance of hemodynamic forces affecting aneurysm development and evolution.