A Precision Medicine Framework for Personalized Simulation of Hemodynamics in Cerebrovascular Disease

Abstract

Introduction Cerebrovascular disease is a major public health challenge. An important biomarker is cerebral hemodynamics. To measure cerebral hemodynamics, however, only invasive, potentially harmful or time-to-treatment prolonging methods are available. We present a simulation-based alternative which allows calculation of cerebral hemodynamics based on the individual vessel configuration of a patient derived from structural vessel imaging. Methods We implemented a framework allowing annotation of extracted brain vessels from structural imaging followed by 0-dimensional lumped modelling of cerebral hemodynamics. For annotation, a 3D-graphical user interface (GUI) was implemented. For 0D-simulation, we used a modified nodal analysis (MNA), which was adapted for easy implementation by code. The code was written in-house in java. The simulation GUI allows inspection of simulation results, identification of vulnerable areas, simulation of changes due to different systemic blood pressures. Moreover, sensitivity analysis was implemented allowing the live simulation of changes of variables such as vessel lumen to simulate procedures and disease courses. In two exemplary patients, simulation results were compared to dynamic-susceptibility-weighted-contrast-enhanced magnetic-resonance(DSC-MR) perfusion imaging. Results The successful implementation of the framework allowing individualized annotation and simulation of patients is presented. In two exemplary patients, both the simulation as well as DSC-MRI showed the same results pertaining to the identification of areas vulnerable to ischemia. Sensitivity analysis allows the individualized simulation of changes in vessel lumen and the effect on hemodynamics. Discussion We present the first precision medicine pipeline for cerebrovascular disease which allows annotation of the arterial vasculature derived from structural vessel imaging followed by personalized simulation of brain hemodynamics. This paves the way for further development of precision medicine in stroke using novel biomarkers and might make the application of harmful and complex perfusion methods obsolete for certain use cases in the future.

A precision medicine framework for personalized simulation of hemodynamics in cerebrovascular disease

“…To record occlusion next to the type of vessel is important for the following simulation step, as subsequently the simulation will ignore segments with this flag. A video footage of the annotation process was uploaded to zenodo [ 22 ].…”

“…This work was published previously on the MedRxiv pre-print server [39]. We acknowledge Kim Mouridsen and Mikkel Bo Hansen from the Centre for Functionally Integrative Neuroscience (CFIN) from Aarhus University, Denmark, for providing the pgui perfusion software (V1.0) for research purposes.…”

Hybrid modelling for stroke care: Review and suggestions of new approaches for risk assessment and simulation of scenarios

“…models describing glucose- and insulin interplay on the whole-body level ( Dalla Man et al, 2007 ). Another example is blood pressures and flows, which can be described by either zero-dimensional Differential-Algebraic Equations (DAEs), or partial differential equations (PDEs) ( Casas et al, 2017 , Casas et al, 2018 , Frey et al, 2020 ). Generally, data can also represent intracellular concentrations of metabolites and proteins, which may be described by ODE models that are based on metabolic and signalling pathways ( Brännmark et al, 2013 , Brännmark et al, 2017 , Nyman et al, 2014 ).…”

A Precision Medicine Framework for Personalized Simulation of Hemodynamics in Cerebrovascular Disease

“…A video footage of the annotation process was uploaded to zenodo. 22 The Simulation Module The simulation itself consists of a graphical user interface, that is divided functionally in the toolbar ( Figure 4B I.), the simulation area ( Figure 4B II. ), the pressure selection area (4B III.)…”