ABSTRACT

Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium (²H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice. Glucose uptake, measured with FDG PET, was reduced at 48 hours after tMCAO and returned to baseline value after 11 days. DMI revealed effective glucose supply as well as elevated lactate production and reduced glutamate/glutamine synthesis in the lesion area at 48 hours post-tMCAO, of which the extent was dependent on stroke severity. A further decrease in oxidative metabolism was evident after 11 days. Immunohistochemistry revealed significant glial activation in and around the lesion, which may play a role in the observed metabolic profiles. Our findings indicate that imaging (altered) active glucose metabolism in and around reperfused stroke lesions can provide substantial information on (secondary) pathophysiological changes in post-ischemic brain tissue.

Results from nanoScan® PET/CT

• reduced glucose uptake (Figure 1(b)–(d)) in the ipsilateral MCA territory at 48 hours but not at 11 days after tMCAO
• DMI showed no differences in signal from infused deuterated glucose in the lesioned hemisphere as compared to healthy control brain
• Our findings show that stroke severity modulates metabolic changes in the brain and that DMI may inform on the underlying status of the ischemic tissue, including neuronal distress, glial activation, and metabolic changes due to inflammatory processes

Figure 1. [¹⁸F]FDG PET revealed reduced glucose uptake at 48 hours but not at 11 days after stroke in the ipsilateral MCA territory. (a) Overview of the experiment. Mice underwent [¹⁸F]FDG] PET either 48 hours or 11 days after 60-minute tMCAO. (b) Mean standard uptake value (SUV) was significantly decreased in the ipsilateral hemisphere at 48 hours compared to the control group and normalised at 11 days after stroke. (c) Representative CT image showing circular ROIs in the ipsi- and contralateral MCA territories and (d) Representative [¹⁸F]FDG] PET images overlaid on CT images of the brain showing reduced glucose uptake in the MCA territory of the ipsilateral hemisphere (white arrowhead) at 48 hours but not at 11 days after tMCAO. SUV: standard uptake value; MCA: middle cerebral artery. *p < 0.05 vs. control with Kruskall-Wallis test. n = 6 for controls, n = 5 for 48 hours post-stroke and n = 4 for 11 days post-stroke mean ± SD.

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