Abstract
The concept of the ischemic penumbra was formulated based on animal experiments showing functional impairment and electrophysiological disturbances with decreasing flow to the brain below defined values (the threshold for function) and irreversible tissue damage with blood supply further decreased (the threshold for infarction). The perfusion range between these thresholds was termed “penumbra”, and restitution of flow above the functional threshold was able to reverse the deficits without permanent damage. In further experiments the dependency of the development of irreversible lesions on the interaction of severity and duration of critically reduced blood flow was established, proofing that the lower the flow the shorter the time for efficient reperfusion. As a consequence infarction develops from the core of ischemia to the areas of less severe hypoperfusion. The translation of this experimental concept as the basis for efficient treatment of stroke requires non-invasive methods by which regional flow and energy metabolism can be repeatedly investigated to demonstrate penumbra tissue, which can benefit from therapeutic interventions. Positron emission tomography (PET) allows the quantification of regional cerebral blood flow, the regional oxygen extraction fraction and the regional metabolic rate for oxygen. By these variables a clear definition of irreversible tissue damage and of critically perfused but potentially salvageable tissue (i.e. the penumbra) can be achieved in stroke patients. However, PET is a research tool and its complex logistics limit clinical routine applications. As a widely applicable clinical tool perfusion/diffusion weighted magnetic resonance imaging (PW/DW-MRI) is used, and the “mismatch” between the PW- and the DW-abnormalities served as an indicator of the penumbra. However, comparative studies of PW/DW-MRI and PET pointed to an overestimation of the core of irreversible infarction as well as of the penumbra by MRI modalities. Some of these discrepancies can be explained by unselective application of relative perfusion thresholds, which might be improved by more complex analytical procedures. Heterogeneity of the MRI signatures used for the definition of the mismatch are also responsible for disappointing results in the application of PW/DW-MRI for the selection of patients for clinical trials. As long as a validation of the mismatch selection paradigm is lacking its use as a surrogate marker of outcome is limited.
- Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.