Dr Benemerito is a research associate at The University of Sheffield and the INSIGNEO institute for in silico medicine. Following the award of his PhD from The University of Sheffield, during which he studied the contact mechanics of the ankle joint during walking activities, he shifted fields of application to cardiovascular biomechanics. He is interested in combining deterministic techniques with statistical approaches to investigate the sensitivity of complex computational models to uncertain input parameters, and to develop methodologies that can be translated to the clinical practice with minimum modifications to existing clinical practices.

Identification of biomarkers for distal perfusion following an ischaemic event: a combined mechanistical-statistical approach

An ischaemic stroke (IS) is an occlusion of a major cerebral vessel. It often causes severe reduction to the perfusion of downstream districts and the consequent death of tissues. The effects of middle cerebral artery (MCA) occlusion are partially mitigated by the action of the leptomeningeal anastomoses (LMAs), small arterioles which provide continuity of perfusion through diversion of flow from the anterior and posterior brain districts. Extensive LMAs networks are linked to better post-IS outcomes. The action of these vessels, which are active and can be observed only during an ischaemic event, induces modifications in the blood velocities of adjacent vessels. Transcranial Doppler ultrasound (TCD) can monitor the blood velocity in these major arteries but fails in detecting signals from the LMAs and to estimate the efficacy of their action in restoring distal perfusion. 1D computational models can simulate the cerebral circulation and identify biomarkers that correlate with the level of distal perfusion. In this study we have developed a deterministic1D model of the brain circulation which includes the LMAs, and combined its predictions with the use of Gaussian Process emulators and Sobol's sensitivity analysis to identify TCD biomarkers for distal perfusion in case of MCA stroke. We identified four biomarkers related to velocity pulsatility whose values can be associated with poor perfusion in the distal MCA regions.