New Clinical Magnetic Resonance Technologies for Capturing Brain Microstructure Alterations in Patients With Minor Stroke or Transient Ischemic Attack

Background:

Stroke and transient ischemic attack (TIA) patients are often burdened by fatigue and reduced attention span subacutely. The frequency of post-stroke fatigue is estimated to occur in 29-77% of all patients, with the highest burden often reported at 3 months post-stroke. The micro-sized structures that form the brain connection, i.e. White Matter (WM), the low blood flow, and the little collateral blood supply make the WM highly susceptible to ischemic injuries. In the case of stroke or TIA in WM, the surrounding microstructures of the are affected start losing vital nutrients, i.e. oxygen and glucose, which initiate a cascade of cellular dysfunction due to excitotoxicity. As a result, several microstructures deteriorate and degenerate, leading to neuronal damage and reduction of signal conduction. Diagnosis of stroke and TIA relies on clinical findings and imaging, where MRI has become the chosen imaging modality due to the sensitivity to detect brain lesions. However, at the later sub-acute phases of stroke and TIA, the standard clinical MRI sequences lack specificity to map microstructural degeneration/regeneration of the brain connections that project through or nearby the ischemic area. In recent years, new technologies for structural quantitative MRI have emerged that are sensitive to different microstructural features and their anisotropy organization i.e. demyelination and axonal sizes and densities. Using these new MRI methods has the potential to disentangle some of the pathological processes underlying minor stroke phases in a more quantitative way. Previously, a similar MRI study of future directions of clinical MRI technologies was applied to the Multiple Sclerosis disease (MS). The MS disease follows some of the systemic pathological degeneration effects as in minor stroke i.e. axonal degeneration and de-/remyelination. The preliminary results of that study strongly suggest e.g. that the newly introduced MRI modality improves diagnostic value by better correlation with clinical assessment. Furthermore, the combination of MRI modalities provides new insight into pathology only seen in histology.

Objectives:

1. To investigate whether new MRI methods can detect the impact of microstructure ischemic changes along brain connections e.g. neuronal degeneration.
2. To test the hypothesis that a combination of unique structural MRI measures will synergistically provide patterns of altered brain structure that give rise to excessive fatigue in patients with minor stroke or TIA.
3. To evaluate the capability of the new quantitative MRI methods to objectively assess the presence and severity of fatigue by pinpointing the relevant structural brain alterations that contribute to fatigue.

Hypothesis: