Vacuoles related to tissue neuron-astrocyte ratio and infiltration of macrophages/monocytes contribute to hyperintense brain signals on diffusion-weighted magnetic resonance imaging in sporadic Creutzfeldt-Jakob disease

Background: Radiological features in patients with sporadic Creutzfeldt-Jakob disease (sCJD) are hyperintensity of the cerebral cortex and the basal ganglia displayed by diffusion-weighted magnetic resonance imaging (DW-MRI). We performed a quantitative study on neuropathological and radiological findings.Methods: Patient 1 received a definite diagnosis of MM1-type sCJD, while patient 2 received a definite diagnosis of MM1 + 2-type sCJD. Two DW-MRI scans were performed on each patient. DW-MRI was either taken the day before or on the day of the patient's death, and several hyperintense or isointense areas were marked as a region of interest (ROI). Mean signal intensity of the ROI was measured. Pathological quantitative assessments of the vacuoles, astrocytosis, infiltration of monocytes/macrophages, and proliferation of microglia was performed. Vacuole load (% area vacuole), glial fibrillary acidic protein (GFAP), CD68, and Iba-1 load were calculated. We defined spongiform change index (SCI) to indicate vacuoles related to a tissue neuron-astrocyte ratio. We assessed the correlation of intensity of the last DW-MRI and the pathological findings as well as association of changes of the signal intensity on the sequential images and the pathological findings.Result: We observed a strong positive correlation between SCI and DW-MRI intensity. In the analysis using serial DW-MRI and pathological findings, we found that CD68 load was significantly larger in areas where signal in-tensity decreased, as compared to those areas where hyperintensity remained unchanged.Conclusion: DW-MRI intensity in sCJD is associated with the ratio of neuron to astrocyte in the vacuoles and the infiltration of macrophages and/or monocytes.