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Background: Vascular cognitive impairment and dementia results from blood components passing through disrupted blood brain barriers (BBBs). Current treatments can reduce further progress of neuronal damage but do not treat the primary cause. Instead, these treatments typically aim to temporarily disrupt the BBB. Alternatively, this study computationally assessed the feasibility of delivering carbon monoxide (CO) from ultrasound-sensitive microbubbles (MBs) as a strategy to promote BBB repair and integrity. CO can interact with heme-containing compounds within cells and promote cell growth. However, careful dose control is critical for safety and efficacy because CO also binds at high affinity to hemoglobin (Hb). Methods: Ultrasound activation was simulated at the internal carotid artery, and CO released from the resulting MB rupture was tracked along the shortest path to the BBB for several activation times and doses. The CO dose available to brain capillary endothelial cells (BCECs) was predicted by considering hemodynamics, mass transport, and binding kinetics. Results: The half-life of CO binding to Hb indicated that CO is available to interact with BCECs for several cardiac cycles. Further, MB and COHb concentrations would not be near toxic levels and free Hb would be available. The axisymmetric model indicated that biologically-relevant CO concentrations will be available to BCECs, and these levels can be sustained with controlled ultrasound activation. A patient-specific geometry shows that while vessel tortuosity provides a heterogeneous response, a relevant CO concentration could still be achieved. Conclusions: This computational study demonstrates feasibility of the CO / MB strategy, and that controlled delivery is important for viability of this strategy. [ABSTRACT FROM AUTHOR]

Stroke has become the main cause of mortality and morbidity in patients treated with Left Ventricular Assist Devices (LVADs). The hemodynamics of the left ventricle are altered by the implantation of an LVAD, with the increase of thrombogenic flow patterns, such as stagnation regions. Time-resolved stereo particle image velocimetry (Stereo-PIV) measurements of the flow inside a patient-specific model of the left ventricle (LV) implanted with an LVAD were performed. The effects of LVAD speed, peripheral resistance and afterload were investigated. The impact of activating the LVAD pulsatility mode (periodic speed modulation) was also evaluated. Analysis of the velocity measurements in two orthogonal planes revealed stagnation zones which may be favorable to thrombus formation. Increasing LVAD speed, despite increasing the flow rate through the inflow cannula, does not automatically result in smaller stagnation regions. These results demonstrated the strong interdependence of peripheral resistance, afterload and flow through the LVAD. As a consequence, the pulsatility mode showed very limited effect on overall flow rate. However, it did reduce the size of high stagnation areas. This study showed how LVAD speed, peripheral resistance and afterload impact the complex intraventricular flow patterns in a ventricle implanted with an LVAD and quantify their thrombogenic risk. [ABSTRACT FROM AUTHOR]

Flow-diverting stents (FDS) are used to treat cerebral aneurysms. They promote the formation of a stable thrombus within the aneurysmal sac and, if successful, isolate the aneurysmal dome from mechanical stresses to prevent rupture. Platelet activation, a mechanism necessary for thrombus formation, is known to respond to biomechanical stimuli, particularly to the platelets' residence time and shear stress exposure. Currently, there is no reliable method for predicting FDS treatment outcomes, either a priori or after the procedure. Eulerian computational fluid dynamic (CFD) studies of aneurysmal flow have searched for predictors of endovascular treatment outcome; however, the hemodynamics of thrombus formation cannot be fully understood without considering the platelets' trajectories and their mechanics-triggered activation. Lagrangian analysis of the fluid mechanics in the aneurysmal vasculature provides novel metrics by tracking the platelets' residence time (RT) and shear history (SH). Eulerian and Lagrangian parameters are compared for 19 patient-specific cases, both pre- and post-treatment, to assess the degree of change caused by the FDS and subsequent treatment efficacy. [ABSTRACT FROM AUTHOR]