Abstract

BackgroundCerebral stroke is a severe and frequent condition that requires rapid and reliable diagnosis. If administered shortly after the first symptoms manifest themselves, IV thrombolysis has been shown to increase the functional prognosis by restoring brain reperfusion. However, a better understanding of the pathophysiology of stroke should help to identify potential new therapeutic targets. Stroke is known to induce an inflammatory brain reaction that involves overexpression of the 18-kDa translocator protein (TSPO) in glial cells and infiltrated leukocytes, which can be visualised by positron emission tomography (PET). We aimed to evaluate post-stroke neuroinflammation using the PET TSPO radioligand 18 F-DPA-714.MethodsNine patients underwent 18 F-DPA-714 PET and magnetic resonance imaging (MRI) between 8 and 18 days after the ictus. Co-registration of MRI and PET images was used to define three volumes of interest (VOIs): core infarction, contralateral region, and cerebellum ipsilateral to the stroke lesion. Time activity curves were obtained from each VOI, and ratios of mean and maximum activities between the VOIs were calculated.ResultsWe observed an increased uptake of 18 F-DPA-714 co-localised with the infarct tissue and extension beyond the region corresponding to the damage in the blood brain barrier. No correlation was identified between 18 F-DPA-714 uptake and infarct volume. 18 F-DPA-714 uptake in ischemic lesion (mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood) slowly decreased from 10 min pi to the end of the PET acquisition, remaining higher than that in both contralateral region and ipsilateral cerebellum.ConclusionOur results show that 18 F-DPA-714 uptake after acute ischemia is mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood. We also demonstrated that the kinetics of 18 F-DPA-714 differs in injured tissue compared to normal tissue. Therefore, 18 F-DPA-714 may be useful in assessing the extent of neuroinflammation associated with acute stroke and could also help to predict clinical outcomes and functional recovery, as well as to assess therapeutic strategies, such as the use of neuroprotective/anti-inflammatory drugs.

Highlights

  • Cerebral stroke is a severe and frequent condition that requires rapid and reliable diagnosis

  • Our results show that 18 F-DPA-714 uptake after acute ischemia is mainly associated with translocator protein (TSPO) expression in the infarct area and in the surrounding neighbourhood

  • We demonstrated that the binding ratio of 18 F-DPA714 was higher when the contralateral volumes of interest (VOIs) was used as a reference region, compared to when the cerebellum was used as a reference region

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Summary

Introduction

Cerebral stroke is a severe and frequent condition that requires rapid and reliable diagnosis. 18 F-DPA-714 uptake in ischemic lesion (mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood) slowly decreased from 10 min pi to the end of the PET acquisition, remaining higher than that in both contralateral region and ipsilateral cerebellum. Ischemic stroke is a diagnostic and therapeutic priority; Cerebral ischemia rapidly evolves to necrosis and a peri-necrosis area of ischemic penumbra, in which the brain tissue is still viable for a few hours. This cerebral tissue can be preserved if treatment is initiated quickly to restore the cerebral blood flow. The infarcted area has been shown to expand in 24 h after the occlusion of a cerebral artery [10,11]

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