A Review of the Advancements in the in-vitro Modelling of Acute Ischemic Stroke and Its Treatment

Abstract

In-vitro neurovascular models of large vessel occlusions (LVOs) causing acute ischemic stroke (AIS) are used extensively for pre-clinical testing of new treatment devices. They enable physicians and engineers to examine device performance and the response of the occlusion to further advance design solutions for current unmet clinical needs. These models also enable physicians to train on basic skills, to try out new devices and new procedural approaches, and for the stroke team to practice workflows together in the comfort of a controlled environment in a non-clinical setting. Removal of the occlusive clot in its entirety is the primary goal of the endovascular treatment of LVOs via mechanical thrombectomy (MT) and the medical treatment via thrombolysis. In MT, recanalization after just one pass is associated with better clinical outcomes than procedures that take multiple passes to achieve the same level of recanalization, commonly known as first pass effect (FPE). To achieve this, physicians and engineers are continually investigating new devices and treatment approaches. To distinguish between treatment devices in the pre-clinical setting, test models must also be optimized and expanded become more nuanced and to represent challenging patient cohorts that could be improved through new technology or better techniques. The aim of this paper is to provide a perspective review of the recent advancements in the in-vitro modeling of stroke and to outline how these models need to advance further in future. This review provides an overview of the various in-vitro models used for the modeling of AIS and compares the advantages and limitations of each. In-vitro models remain an extremely useful tool in the evaluation and design of treatment devices, and great strides have been made to improve replication of physiological conditions. However, further advancement is still required to represent the expanding indications for thrombectomy and thrombolysis, and the generation of new thrombectomy devices, to ensure that smaller treatment effects are captured.

Therapeutic Polymer-Based Cannabidiol Formulation: Tackling Neuroinflammation Associated with Ischemic Events in the Brain

“…To overcome some of the limitations described above, NPCBD was tested in a complex model involving all of the relevant cell populations found in the in vivo scenario. Various in vitro models have been used over the last three decades to mimic stroke . The OGD model has proved to be the most reliable and reproducible. , However, it is not possible to fully reproduce in vitro the high complexity found in the poststroke brain tissue.…”

“…Stroke presents a highly complex pathophysiology . The innate immune system is activated after ischemic insult due to the accumulation of cell debris and dying neurons.…”

Evaluating the accuracy of cerebrovascular computational fluid dynamics modeling through time-resolved experimental validation

“…When analyzing EVT, such as endovascular aspiration and thrombectomy, it is most relevant to accurately resolve the transient arterial pressure for two reasons. First, the pressure difference from the artery to the aspiration catheter tip alters the aspiration flow 29 , and second, cerebral artery pressure substantially influences the force required during endovascular thrombectomy 11 . In conclusion, stationary outlet BCs should be avoided when modeling transient hemodynamics in the intracranial arteries.…”

“…An established EVT technique for the treatment of ischemic stroke is thrombectomy, the mechanical removal of blood clots from the occluded vessel. It was indicated that the force required during thrombectomy in cerebral vessels is substantially influenced by the arterial pressure gradient across the clot 11 ; hence, physiologically relevant pressures have to be accurately modeled. Few studies investigated transient flows and pressures in patient-specific compliant phantoms of the cerebral arteries with complete Circle of Willis (CoW) anatomies 12 , 13 .…”

“…Computational fluid dynamics (CFD) of 3D models allow insight into local hemodynamics and account for the complex anatomy of the cerebral arteries, but the reliability of such models depends on the scale of validation. Since the acquisition of detailed in-vivo data is challenging, it is crucial to validate in-silico models with results from in-vitro models 11 . It is known that boundary conditions (BCs) of the in-silico models strongly influence the hemodynamic results.…”