Probing Water Dynamics in Acute Cerebral Ischemia by MRI

Cerebral ischemia that leads to stroke is one of the major causes of disability and death in Finland and around the world. After sustaining ischemic damage due to lack of oxygen and glucose, cerebral tissue undergoes a complex timedependent cascade of heterogeneous histopathological changes. Following an ischemic attack, patients require fast and accurate diagnostic tools to characterize their cerebral tissue state upon hospital admission. New treatment methods for stroke are being discovered and are under investigation. Therefore, to select the most appropriate treatment method for each patient a thorough overview of the ischemic tissue status is needed. Furthermore, in experimental studies a way to accurately predict tissue damage without intervention gives an opportunity to study and compare new treatment modalities. Magnetic resonance imaging (MRI) is a sensitive method to assess local changes in tissue water during ischemia. Several different MRI contrasts can be exploited to assess blood flow and perfusion, diffusion of water and changes in the water molecule environment. These biophysical and pathological changes give information about the state and progression of ischemic damage in tissue. However, each of these MRI contrasts only tells about one aspect of the complex dynamic changes that are happening during ischemia. Multiple MRI techniques in combination must be applied to attain a better overview of the status of the brain tissue. Furthermore, a significant difference in measured lesion sizes can be seen when using diffusion and perfusion MRI during early stages of acute ischemia. This highlights the difference of the contrasts as they have very different and specific temporal evolution. This discrepancy in the projected lesion size is considered the area of transition from viable to irreparably damaged tissue; an area, where changes are happening, but that can be reversed or stopped with a timely intervention. This is an important target to recognize for treatment planning to maximize the benefit and minimize the side effects of a therapeutic intervention. The aim of this study was to study acute brain ischemia in rats with advanced MRI techniques with a view to increase the understanding of changes in tissue water. We investigated the dynamic changes in MRI parameters in ischemic brain during hyperacute ischemia. Apart from the established MRI contrasts diffusion, perfusion and T2 and T1 relaxation times also more novel contrasts were utilized, such as rotating frame contrasts T and T and amide proton transfer ratio (APTR) contrasts. The rotating frame contrast techniques probe the molecular motion and the different molecular environments during stroke. APTR is connected with pH and can be used to image the changes in the acidity relating to the energy state of the tissue. The MRI parameters were measured at multiple time points to assess the temporal evolution of ischemia. This multiparametric MRI approach provided complementary information from different aspects of the ischemic pathway. Partially due to the high socio-economical impact of stroke there is active research both to prevent conditions that lead to an increased risk of stroke and to find new treatment methods to prevent further injury during ischemia. This also creates incentive to investigate more accurate methods to assess the state of stroke and the effectiveness of novel pharmaceuticals. This work demonstrated that multiparametric MRI has the potential to accurately assess and predict ischemic damage. With optimization of the imaging protocols MRI can be an indispensable tool both in pre-clinical and clinical stroke imaging. National Library of Medicine Classification: WL 355, WL 302, WN 185 Medical Subject Headings: Cerebrovascular Disorders/diagnosis; Stroke/diagnosis; Brain Ischemia/diagnosis; Cerebral Infarction/diagnosis; Cerebral Hemorrhage/diagnosis; Diagnostic Imaging; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Blood Circulation; Cerebrovascular Circulation; Hypoxia, Brain/diagnosis; Water; Lactic Acid; Hydrogen-Ion Concentration; Disease Models, Animal; Rose Bengal; Rats After spending hundreds of hours working with a pile of data ending up with only one or two small pictures and disregarding 95% of the analysis. It gives a perspective to the old saying: It is the journey not the goal.