Magnetic Resonance Imaging Assessment of the Ischemic Penumbra in Experimental Stroke

Diffusion-weighted magnetic resonance imaging (MRI) has become an established method for noninvasive evaluation of cerebral ischemia in both humans and animal models. Although the biophysical mechanism(s) underlying apparent diffusion coefficient (ADC) reduction in ischemic tissue remains poorly understood (1-4), diffusion-weighted imaging (DWI) (1) is widely recognized for its ability to noninvasively detect ischemic brain injury within minutes after its onset, whereas other conventional imaging techniques [such as T1-, T2-weighted MRI, Computed Tomography (CT)] fail to detect such injury for at least several hours (1). Brain tissues with perfusion deficits below a critical threshold level [e.g., a cerebral blood flow (CBF) value of ~20 mL/100 g/min in rat or gerbil brain] (5, 6) experience metabolic energy failure, membrane depolarization, and subsequent cellular swelling (cytotoxic edema). These changes precipitate a reduction in the ADC of brain water that is manifested as a hyperintense region on a DWI (1). Perfusion-weighted imaging (PWI) evaluates blood flow in the microcirulation of the brain and can be performed with either a bolus contrast technique or an arterial spin labeling technique (7, 8). The latter approach provides relatively higher sensitivity and allows repeated measures for increased spatial resolution, but is less widely used because it is relatively more difficult to perform. During the first few hours after stroke onset (i.e., the acute phase), the anatomic region encompassed by the DWI abnormality is typically smaller than the volume of the perfusion deficit, but it usually expands and eventually coincides with the PWI volume (6, 9). The difference in the regions of the PWI and DWI abnormality during the acute phase of stroke has been termed the “perfusion-diffusion” mismatch (PWI/DWI mismatch), and it was suggested that this region of mismatch approximates potentially salvageable ischemic tissue or the ischemic penumbra (10).