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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]

As frequency of endovascular treatments for intracranial aneurysms increases, there is a growing need to understand the mechanisms for coil embolization failure. Computational fluid dynamics (CFD) modeling often simplifies modeling the endovascular coils as a homogeneous porous medium (PM), and focuses on the vascular wall endothelium, not considering the biomechanical environment of platelets. These assumptions limit the accuracy of computations for treatment predictions. We present a rigorous analysis using X-ray microtomographic imaging of the coils and a combination of Lagrangian (platelet) and Eulerian (endothelium) metrics. Four patient-specific, anatomically accurate in vitro flow phantoms of aneurysms are treated with the same patient-specific endovascular coils. Synchrotron tomography scans of the coil mass morphology are obtained. Aneurysmal hemodynamics are computationally simulated before and after coiling, using patient-specific velocity/pressure measurements. For each patient, we analyze the trajectories of thousands of platelets during several cardiac cycles, and calculate residence times (RTs) and shear exposure, relevant to thrombus formation. We quantify the inconsistencies of the PM approach, comparing them with coil-resolved (CR) simulations, showing the under- or overestimation of key hemodynamic metrics used to predict treatment outcomes. We fully characterize aneurysmal hemodynamics with converged statistics of platelet RT and shear stress history (SH), to augment the traditional wall shear stress (WSS) on the vascular endothelium. Incorporating microtomographic scans of coil morphology into hemodynamic analysis of coiled intracranial aneurysms, and augmenting traditional analysis with Lagrangian platelet metrics improves CFD predictions, and raises the potential for understanding and clinical translation of computational hemodynamics for intracranial aneurysm treatment outcomes. [ABSTRACT FROM AUTHOR]

Pediatric heart failure is associated with high mortality rates and is a current clinical burden. There is only one FDA approved pediatric VAD, Berlin Heart EXCOR, for treatment. Thrombo-embolic complications are a significant clinical challenge, which can lead to devastating complications such as stroke and impair efficient EXCOR function. Currently, clinicians perform largely qualitative periodic assessment of EXCOR operation by observing the motion of a rapidly moving membrane, which can be prone to human error and can lead to missing out on crucial information.In this study, we design and implement a quantitative early warning system for accurate and quantitative assessment of the EXCOR membrane, named EXCOR Membrane Motion Analyzer (EMMA). Using a combination of image analysis, computer vision and custom designed algorithm, we perform rigorous frame by frame analysis of EXCOR membrane video data. We developed specialized metrics to identify relative smoothness between successive peaks, time between peaks and overall smoothness indicators to quantify and compare between multiple cases.Our results demonstrate that EMMA can successfully identify the motion and wrinkles on each video frame and quantify the smoothness and identify the phases of each cardiac cycle. Moreover, EMMA can obtain the smoothness of each frame and the temporal evolution of membrane smoothness across all image frames for the video sequence.EMMA allows for a fast, accurate, quantitative assessment to be completed and reduces user error. This enables EMMA to be used effectively as an early warning system to rapidly identify device abnormalities. [ABSTRACT FROM AUTHOR]