RT Journal Article
SR Electronic
T1 FDG PET Imaging as A Non-invasive Method to Demonstrate Peri-infarct Depression after Stroke
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 343
OP 343
VO 59
IS supplement 1
A1 Jessica Yao
A1 Rui Zhou
A1 Jingjing Shi
A1 Hong Zhang
YR 2018
UL http://jnm.snmjournals.org/content/59/supplement_1/343.abstract
AB 343Objectives: Secondary injury persists after stroke onset, and deteriorates tissue and function outcomes in the long run. Peri-infarct depression (PID) is a validated pathological mechanism during secondary injury. As a depolarization wave spreading across the cortex, PID increases regional glucose demand and worsens supply-demand mismatch after stroke, thus expands infarct size. Peri-infarct depression emerges as a potential therapeutic target during stroke treatment. However, detection of PID with electrocorticography (ECoG) is invasive and has a restriction in further clinical practice. Taken metabolic challenge imposed by PID, we tend to monitor metabolic state of stroke brain by FDG PET imaging, and visualize metabolic stress induced by peri-infarct depression, thus provide a non-invasive method to monitor PID related injury. Method: Photochemical method is applied to induce a 1[asterisk]1mm infarction in rat cortex. After stroke, FDG PET imaging, ECoG recording, laser speckle imaging and rotarod test are performed daily for the first week, then weekly during the 2nd week to 4th week. Regional metabolic alteration is analyzed with SPM software. Immunohistochemical staining, western blot assay, and bioluminescence imaging are employed to assess metabolic state and mitochondria function. In vitro experiments on cortical neurons from embryonic day 18 rats are performed to investigate mechanism underlying metabolic change induced neuron dysfunction. Results: FDG PET imaging indicates growing regions with increased glucose uptake around infarct core during first week after stroke. The change in glucose uptake has no correlation with regional blood supply, while apparently affected by the occurrence of PID. Results of rotarod test demonstrate deteriorated neurological performance along with expanded metabolic change and increased incidents of PID. From the 2nd week after stroke, increased FDG uptake gradually decreases, and ends up with low uptake compared with healthy brain. Histological analysis indicates overall increased glycolysis, and reduced mitochondria function in brain regions with increased FDG uptake, where gliosis and increased microglia accumulation occur in chronic state. Regional metabolic alteration is mostly accompanied with overexpression of HIF1a. In vitro, 1uM DMOG is applied to elevate expression of HIF1a and induce the metabolic change in cultured neurons. With suppressed mitochondria function, neurons firstly exhibit increased intracellular calcium concentration, then neurite spines diminish and neurites degeneration. Administration of resveratrol in stroke rats at chronic phase of stroke or neurons treated with DMOG could efficiently increase mass and function of mitochondria, and improve tissue and functional consequence. Conclusion: FDG PET imaging is reliable to reflect metabolic stress imposed by peri-infarct depression. Peri-infarct depression leads to the metabolic change in neurons, including suppression of mitochondria function and overactivation of glycolysis, thus deteriorate functional and tissue consequence. The insults from PID could be alleviated by improving mitochondria function.