Highly integrated workflows for exploring cardiovascular conditions: Exemplars of precision medicine in Alzheimer's disease and aortic dissection

Abstract

For precision medicine to be implemented through the lens of in silico technology, it is imperative that biophysical research workflows offer insight into treatments that are specific to a particular illness and to a particular subject. The boundaries of precision medicine can be extended using multiscale, biophysics-centred workflows that consider the fundamental underpinnings of the constituents of cells and tissues and their dynamic environments. Utilising numerical techniques that can capture the broad spectrum of biological flows within complex, deformable and permeable organs and tissues is of paramount importance when considering the core prerequisites of any state-of-the-art precision medicine pipeline. In this work, a succinct breakdown of two precision medicine pipelines developed within two VPH projects are given. The first workflow is targeted on the trajectory of Alzheimer's Disease, and caters for novel hypothesis testing through a multicompartmental poroelastic model which is integrated with a high throughput imaging workflow and subject-specific blood flow variability model. The second workflow gives rise to the patient specific exploration of Aortic Dissections via a multi-scale and compliant model, harnessing imaging, CFD and dynamic boundary conditions. Results relating to the first workflow include some core outputs of the multiporoelastic modelling framework, and the representation of peri-arterial swelling and peri-venous drainage solution fields. The latter solution fields were statistically analysed for a cohort of thirty-five subjects (stratified with respect to disease status, gender and activity level). The second workflow allowed for a better understanding of complex aortic dissection cases utilising both a rigid-wall model informed by minimal and clinically common datasets as well as a moving-wall model informed by rich datasets.

Exploring neurodegenerative disorders using a novel integrated model of cerebral transport: Initial results

“…The remaining intercompartmental flux terms (v ac , v cv ) are the same as in previous studies (see for instance Vardakis et al and Guo et al). 3,47,48,54,55 Boundary conditions of the 6-MPET numerical template. In the work conducted here, the outer/inner boundary of the cerebral tissue represents the cortical surface/cerebroventricular wall respectively.…”

“…Importantly, the work presented here will form part of a broader study, which will involve the assessment of the consolidated pipeline utilising the entire Lido dataset. 3,47,48 Important limitations include the omission of crossstorage effects from the MPET formulation. 49,83 The Table 3.…”

“…The core numerical template that sits at the epicentre of this state-of-the-art precision medicine pipeline was largely developed within the VPH-Dementia Research Enabled by IT Project. 3 In this project, the focus was to extend the understanding of Alzheimer’s Disease (AD) in addition to promoting earlier differential diagnosis through a unified multiscale modelling platform that accounts for a subjects’ environment and lifestyle. In the work presented here, the original four-compartment poroelastic model presented as part of this precision medicine pipeline is extended to six-compartments.…”

“…Additionally, an imaging pipeline is used to further personalize the workflow via the acquisition of: (i) a subject-specific atlas of CSF/extracellular fluid (ECF) permeability within the cerebral parenchymal tissue; (ii), the accurate representations of the cerebroventricular geometries; and (iii), the partitioning of white and grey matter which is complemented by a field of varying parenchymal tissue stiffness. The reader is referred to 3 , 46 – 48 for further details.…”

“…The methodology behind the full implementation of the novel six compartment poroelastic model follows in the ‘Methodology’ section, which also briefly describes the extension (spatial variation of the region-specific mechanical properties of brain tissue) of a recently developed high precision workflow. 3 The results, discussion and limitations are given in the ‘Results and discussion’ section, where 6-MPET results at the level of the neurovascular unit for five separate regions of the brain (cortical grey matter, hippocampus, amygdala, thalamus and brainstem) are presented. The conclusions and perspectives for future work are given in the ‘Conclusion’ section.…”