Abstract
Introduction: Neuroinflammation plays a major role in post-stroke neuronal injury. Previous studies applied 18F-THK-5351 tau PET to identify the existence of neuroinflammation after infarction. Meanwhile, post-stroke microstructural degradation of white matter (WM) fibers can be observed using fixel-based analysis (FBA) of diffusion MRI (dMRI). We integrate 18F-THK-5351 tau PET and FBA-dMRI in ischemic stroke patients to investigate the relationship between poststroke neuroinflammation process and WM fiber alterations. Methods: 33 patients with lacunar infarcts received 18F-THK-5351 PET and dMRI (Siemens Biograph mMR PET-MR 3 Tesla scanner) at 3 months poststroke. 27 age-matched healthy controls were recruited. The reference region of 18F-THK-5351 PET was set at cerebellar cortex. FBA-dMRI metrics included microstructural fiber density (FD), fiber cross-section (FC, macrostructural morphometry), and combined-FD/FC (FDC, the overall fiber bundle connectivity). Clinical severity assessments included infarction volume, NIHSS, BI, and mRS. The whole-brain fixel-wise statistical analysis used the general linear model. Correlation anlaysis was for FBA metrics and clinical severity. Non-parametric testing >5000 permutations was used for multiple comparisons, p <0.05 using a strong family-wise error control as statistical significance. Results: All patients had lacunar infarcts at internal capsule, including 19 left and 14 right lacunes. The mean age was 64.9±7.7 in patients v.s. 61.3±9.4 in controls ( p =0.47). FBA-dMRI showed significant reductions in FD, FC, and FDC at corticospinal tract in patients compared to the controls. Tau PET demonstrated the highest uptake of 18F-THK-5351 at ischemia core. The spatial patterns of 18F-THK-5351 retention were highly consistent with the fixel metrics reduction distributions (Figure 1). Infarct volumes and clinical severity significantly negatively correlated with the fixel measures in patients. Larger infarct volume or more severity corresponds to lower FBA value (Figure 2). Conclusions: Integrating 18F-THK-5351 PET and FBA-dMRI demonstrates fiber-specific WM reductions associated with the neuroinflammation process, showing consistent spatial patterns between neuroinflammation and WM degeneration in stroke patients. Tract-specific WM reductions correlated with infarct volume and functional outcomes 3 month poststroke. Our findings have implications for understanding the mechanisms underlying functional impairment after ischemic stroke.
Published Version
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