David Sherman Lecture 2012

Translational research has the aim to transform scientific discoveries into clinical applications. Molecular concepts are analyzed in in vitro experiments, tested in vivo in animal preparations, and then explored in human studies by which the applicability for clinical disease management—diagnosis, treatment, prevention—is tested. Pathophysiological studies in animal models traditionally applied invasive methods that could not be used in humans. On the other hand, the resolution capacity of modalities for functional and metabolic imaging in humans in the past did not allow detecting regional abnormalities in small experimental animals. With the advance of high-resolution tomographic devices, comparative studies of metabolic and molecular changes in pathological states could be performed noninvasively and repeatedly in animal models and in humans. Because positron emission tomography (PET) permits the quantitative determination of a large number of physiological, metabolic, and molecular variables, it was in the past and still is an appropriate tool for comparative pathophysiological studies in animal models and human disease. In the following, some examples of the role of PET for translational research in stroke are reviewed. The Concept of the Ischemic Penumbra and Identification by ImagingExperimental work on the ischemic flow thresholds of brain tissue demonstrated the existence of 2 critical levels of decreased perfusion: first, a level representing the flow threshold for reversible functional failure (functional threshold); and second, a lower threshold below which irreversible membrane failure and morphological damage occur. The range of perfusion values between those limits was called the “ischemic penumbra,”1 which was characterized by the potential for functional recovery without morphological damage provided that local blood flow can be re-established at a sufficient level. Whereas neuronal function is impaired immediately when blood flow drops below the threshold, the development of irreversible morphological damage is time-dependent. This interaction of severity and duration of ischemia in the development of irreversible cell damage was established in simultaneous recordings …