Imaging the physiological evolution of the ischemic penumbra in acute ischemic stroke

We review the hemodynamic, metabolic and cellular parameters affected during early ischemia and their changes as a function of approximate cerebral blood flow (CBF) thresholds. These parameters underlie the current practical definition of an ischemic penumbra, namely metabolically affected but still viable brain tissue. Such tissue is at risk of infarction under continuing conditions of reduced CBF, but can be rescued through timely intervention. This definition will be useful in clinical diagnosis only if imaging techniques exist that can rapidly, and with sufficient accuracy, visualize the existence of a mismatch between such a metabolically affected area and regions that have suffered cell depolarization. Unfortunately, clinical data show that defining the outer boundary of the penumbra based solely on perfusion-related thresholds may not be sufficiently accurate. Also, thresholds for CBF and cerebral blood volume (CBV) differ for white and gray matter and evolve with time for both inner and outer penumbral boundaries. As such, practical penumbral imaging would involve parameters in which the physiology is immediately displayed in a manner independent of baseline CBF or CBF threshold, namely pH, oxygen extraction fraction (OEF), diffusion constant and mean transit time (MTT). Suitable imaging technologies will need to meet this requirement in a 10–20 min exam.