BACKGROUND AND PURPOSE: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly fatal neurodegenerative disorder. The gold standard test for a positive diagnosis of definite CJD is histopathological confirmation, usually post-mortem
however, an autopsy study is not always feasible in all health settings. MATERIALS AND METHODS: We performed a cross-sectional analysis of a retrospectively enrolled cohort of patients with suspected prion disease between 2008 and 2019. Only patients with complete medical histories who fulfilled a diagnostic checklist were enrolled. The magnetic resonance imaging (MRI) sequences (T2-FLAIR and DWI) were analyzed, and the apparent diffusion coefficients (ADCs) were calculated for five regions of interest (ROIs) in each cerebral hemisphere. RESULTS: In total, 72 MRI scans were post-processed. The series included 47 cases of CJD, including 25 genetic and 22 sporadic cases, in addition to 25 age-paired controls with non-prion encephalopathies. The neostriatum showed the most significant difference in ADC values (×10 CONCLUSIONS: Quantitative ADC measurements made in the basal ganglia seem to be the most useful ante-mortem diagnostic tool for differentiating CJD from non-prion encephalopathies when cerebrospinal fluid real-time quaking-induced conversion or other specific misfolded protein detection tests are inaccessible.