Paul N. Watton

Cerebral vasospasm, a prolonged constriction of cerebral arteries, is the first cause of morbidity and mortality for patients who survive hospitalisation after aneurysmal subarachnoid haemorrhage. The recent finding that stent-retrievers can successfully treat the disease has challenged the viewpoint that damage to the extracellular matrix is necessary. We apply a 3D finite element rate-based constrained mixture model (rb-CMM) to simulate vasospasm, remodelling and treatment with stents. The artery is modelled as a thick-walled fibre-reinforced constrained mixture subject to physiological pressure and axial stretch. The model accounts for distributions of collagen fibre homeostatic stretches, VSMC active response, remodelling and damage. After simulating vasospasm and subsequent remodelling of the artery to a new homeostatic state, we simulate treatment with commonly available stent-retrievers. We perform a parameter study to examine how arterial diameter and thickness affect the success of stent treatment. The model predictions on the pressure required to mechanically resolve the constriction are consistent with stent-retrievers. In agreement with clinical observations, our model predicts that stent-retrievers tend to be effective in arteries of up to 3mm diameter, but fail in larger ones. Variations in arterial wall thickness significantly affect stent pressure requirements. We have developed a novel rb-CMM that accounts for VSMC active response, remodelling and damage. Consistently with clinical observations, simulations predict that stent-retrievers can mechanically resolve vasospasm. Moreover, accounting for a patient's arterial properties is important for predicting likelihood of stent success. This in silico tool has the potential to support clinical decision-making and guide the development and evaluation of dedicated stents for personalised treatment of vasospasm.

We present a novel patient-specific fluid-solid-growth framework to model the mechanobiological state of clinically detected intracranial aneurysms (IAs) and their evolution. The artery and IA sac are modeled as thick-walled, non-linear elastic fiber-reinforced composites. We represent the undulation distribution of collagen fibers: the adventitia of the healthy artery is modeled as a protective sheath whereas the aneurysm sac is modeled to bear load within physiological range of pressures. Initially, we assume the detected IA is stable and then consider two flow-related mechanisms to drive enlargement: (1) low wall shear stress; (2) dysfunctional endothelium which is associated with regions of high oscillatory flow. Localized collagen degradation and remodelling gives rise to formation of secondary blebs on the aneurysm dome. Restabilization of blebs is achieved by remodelling of the homeostatic collagen fiber stretch distribution. This integrative mechanobiological modelling workflow provides a step towards a personalized risk-assessment and treatment of clinically detected IAs.

Background Cerebral vasospasm (CVS) following subarachnoid hemorrhage occurs in up to 70% of patients. Recently, stents have been used to successfully treat CVS. This implies that the force required to expand spastic vessels and resolve vasospasm is lower than previously thought. Objective We develop a mechanistic model of the spastic arterial wall to provide insight into CVS and predict the forces required to treat it. Material and Methods The arterial wall is modelled as a cylindrical membrane using a constrained mixture theory that accounts for the mechanical roles of elastin, collagen and vascular smooth muscle cells (VSMC). We model the pressure diameter curve prior to CVS and predict how it changes following CVS. We propose a stretch-based damage criterion for VSMC and evaluate if several commercially available stents are able to resolve vasospasm. Results The model predicts that dilatation of VSMCs beyond a threshold of mechanical failure is sufficient to resolve CVS without damage to the underlying extracellular matrix. Consistent with recent clinical observations, our model predicts that existing stents have the potential to provide sufficient outward force to successfully treat CVS and that success will be dependent on an appropriate match between stent and vessel. Conclusion Mathematical models of CVS can provide insights into biological mechanisms and explore treatment approaches. Improved understanding of the underlying mechanistic processes governing CVS and its mechanical treatment may assist in the development of dedicated stents.

Endovascular repair with parallel stent‐grafts (SG) is a challenging technique that reconstructs the luminal flow pathways by implanting parallel‐placed SGs into the vessel. After treatment, occlusion and shifting of the parallel SGs are sometimes reported, which could be fatal and difficult to be re‐operated. These issues are highly related to the local hemodynamic conditions in the stented region. In this study, a patient case treated by the octopus endograft technique (a head‐SG with three limb‐SGs) and experienced limb‐SG occlusion is studied. 3‐D models are established based on computed tomography (CT) angiography datasets pretreatment and posttreatment as well as during follow‐ups. Hemodynamic quantities such as pressure drop, wall shear stress‐related parameters, and flow division in limb‐SGs and visceral arteries are quantitatively investigated. Optimizations on the length of the head‐SG and diameter of the limb‐SGs are analyzed based on various scenarios. The results indicate that when reconstructing the flow pathways via octopus stenting, it is important to ensure the flow distribution as physiologically required with this new morphology. Position (or length) of the head‐SG and diameter of the limb‐SGs play an important role in controlling flow division, and high time average wall shear stress (TAWSS) around the head‐SG acts as a main factor for graft immigration. This study, by proposing optimization suggestions with hemodynamic analyses for a specific case, implicates that pretreatment SG scenarios may assist in wise selection and placement of the device and thus may improve long‐term effectiveness of this kind of challenging endovascular repair techniques.

In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves was evaluated in the context of the inner (lamina propria) and outer (detrusor smooth muscle) layers. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For more extensible bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria layer and detrusor smooth muscle layer was found. A second important finding was that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This change was correlated with age. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder extensibility and capacitance.

Thoracic endovascular aortic repair (TEVAR) is commonly applied in type-B aortic dissection. For patients with dissection affects descending aorta and extends downward to involve abdominal aorta and possibly iliac arteries, false lumen (FL) expansion might occur post-TEVAR. Predictions of dissection development may assist in medical decision on re-intervention or surgery. In this study, two patients are selected with similar morphological features at initial presentation but with different long-term FL development post-TEVAR (stable and enlarged FL). Patient-specific models are established for each of the follow-ups. Flow boundaries and computational validations are obtained from Doppler ultrasound velocimetry. By analyzing the hemodynamic parameters, the false-to-true luminal pressure difference (PDiff) and particle relative residence time (RRT) are found related to FL remodeling. It is found that (i) the position of the first FL flow entry is the watershed of negative-and-positive PDiff and, in long-term follow-ups, and the position of largest PDiff is consistent with that of the greatest increase of FL width; (ii) high RRT occurs at the FL proximal tip and similar magnitude of RRT is found in both stable and enlarged cases; (iii) comparing to the RRT at 7days post-TEVAR, an increase of RRT afterwards in short-term is found in the stable case while a slight decrease of this parameter is found in the enlarged case, indicating that the variation of RRT in short-term post-TEVAR might be potential to predict long-term FL remodeling.