A preclinical and clinical investigation into quantitative magnetic resonance imaging as a tool for estimating onset time in hyperacute ischaemic stroke

Abstract

Ischaemic stroke is a major cause of adult death and disability and is one of the most expensive neurological conditions. Currently, thrombolysis by rtPA is the only pharmacotherapy for hyperacute ischaemic stroke, and in routine practice it must be administered within 4.5 hours of symptom onset. Consequently, most patients with unknown onset time are precluded from thrombolytic therapy, despite the possibility of still being within the 4.5 hour treatment window. Unknown onset time, therefore, poses a substantial challenge in the management of hyperacute stroke patients.

Multiparametric quantitative magnetic resonance imaging (qMRI) is a potential tool for estimating stroke onset time due to its sensitivity to hydrodynamic and haemodynamic changes in the ischaemic brain. This thesis explores the potential abilities of MRI based stroke timing methods in a preclinical rat model of ischaemia and hyperacute ischaemic stroke patients. Both the preclinical and clinical results suggest that quantifying the change in the T2 relaxation time is a more accurate and reliable method for onset time estimation than measuring the intensities of signals represented in the T2-based weighted images typically acquired in clinics. Results also suggest that T2 distributional information within grey matter lesions may provide a reference-independent stroke timing method.

The translation of preclinical methods and MRI findings to stroke patients demonstrated in the thesis highlights the importance of preclinical research in identifying MRI biomarkers that could aid treatment decisions. Clinical MRI scanners can transform conventional weighted magnetic resonance images that are usually acquired and assessed visually (e.g., T2 weighted), into their ‘absolute’ parametric counterparts (e.g., T2 relaxometry maps). Exploiting this ability will enable ischaemia to be identified and onset time estimated more accurately and reliably. Ultimately, the encouraging results from this thesis warrant further investigation into the quantification of T2 for informing treatment decisions regarding hyperacute ischaemic stroke patients, in a more extensive clinical study.

Date of Award	12 May 2020
Original language	English
Awarding Institution	The University of Bristol
Supervisor	Risto Kauppinen (Supervisor) & Iain D Gilchrist (Supervisor)