Abstract
The concepts of pathophysiology of ischemic brain damage as the basis for therapeutic strategies are derived from results of experiments in animal models. For their transfer into clinical application, methods are required which permit repeated noninvasive quantitative determination of regional cerebral blood flow, oxygen consumption, and energy metabolism in patients after acute ischemic stroke. The method of choice for this purpose is still positron emission tomography (PET), which can be applied for high-resolution quantitative imaging of various parameters – cerebral blood flow, oxygen consumption, and glucose metabolism, but also of molecular events and of functional states – in humans as well as small animals. In this review, some examples of PET applications for translational research in stroke are described.
One successful application of PET concerned the transfer of the concept of the penumbra into the clinical management of acute ischemic stroke. Experiments in baboons and cats in the 1970s and 1980s defined blood flow values for functional disturbance and irreversible morphological damage, which could also be established by PET in patients with acute stroke. The progression of irreversible damage, the core of ischemia, into the functionally impaired area, the penumbra, could be followed in experimental models. Also, the potential for recovery of these areas with reperfusion within a critical time window was demonstrated in these models, a result which formed the basis for thrombolysis and other reperfusion therapies. In animal models, tracers for neuronal integrity were tested which are useful for early detection of irreversible tissue damage. These tracers can help in therapeutic decisions and in the prediction of malignant course after occlusion of large arteries. In the assessment of subacute and chronic pathophysiological changes after stroke, results from animal experiments indicated the importance of neuroinflammation, which can be visualized as microglia activation, for progression of damage into areas primarily not affected by ischemia and for prognosis of functional deficits. These inflammatory changes might play an important role in increased amyloid deposition and might therefore be involved in the development of poststroke dementia. PET can also help to prove experimental concepts for improving recovery, e.g., by demonstrating the effectiveness of repetitive transcranial magnetic stimulation for inhibiting contralateral overactivated cortex areas in rehabilitation therapy.
All these examples underline the role PET has played for translational research in stroke in the last 30 years. Its impact might even be increased by the advent of combined MR/PET equipment and the introduction of more sophisticated molecular tracers into clinical application.
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Wolf-Dieter Heiss was funded by the WDH Foundation and the Marga and Walter Boll Foundation.
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Heiss, WD. (2014). PET Reveals Pathophysiology in Ischemic Stroke. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Leenders, K. (eds) PET and SPECT in Neurology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54307-4_25
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