A spatiotemporal theory for MRI T2 relaxation time and apparent diffusion coefficient in the brain during acute ischaemia: Application and validation in a rat acute stroke model

Quantitative magnetic resonance imaging (MRI) has considerable potential in the assessment of acute brain ischaemia, the major cause of strokes. The apparent diffusion coefficient (ADC) and T2 relaxation time in particular are highly sensitive markers of ischaemia location and time progression, respectively, yet it remains challenging to relate changes in these MRI parameters to stroke timing, which is of considerable importance in making treatment choices in clinics. To gain insights into the relationship between the spatiotemporal progression of brain ischaemia and the ADC and T2 we introduce a novel mathematical model, which we complement with experimental observations from a rat model of acute stroke. Our mathematical model, called cytotoxic oedema/dissociation (CED) model, considers movement of water into the intracellular compartment, and exchange with macromolecules which are degraded/dissociated in response to cytotoxic oedema. This is sufficient to describe the different timescales of changes in ADC and T2. The CED model also identifies key parameters that direct the progress of ischaemia in brain parenchyma. It brings the direct extraction of the parametric timing of stroke from quantitative MRI closer to reality, as well as providing insight on ischaemia pathology by imaging in general. Potentials applications in clinical stroke MRI are discussed.