Microstructure mapping with time-dependent diffusion MRI differentiates primary central nervous system lymphoma from glioblastoma

Background Glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) are two different types of malignant brain tumors, precise preoperative differentiation is crucial for guiding optimal treatments. This study aimed to evaluate the diagnostic utility of time-dependent diffusion MRI (t _d -dMRI)-derived microstructural parameters in differentiating PCNSL from GBM and to correlate these parameters with histopathologic findings. Methods This study included 32 GBM and 19 PCNSL patients who underwent 3.0-T MRI with oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE) sequences. Microstructural parameters [intracellular volume fraction ( V _in ), cell diameter, cellularity, extracellular diffusivity ( D _ex )] were compared between groups. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of these indices. Histopathologic validation was performed by correlating t _d -dMRI parameters with hematoxylin-eosin (H&E)–stained sections. Results In enhancing tumor regions, PCNSL showed significantly lower cell diameter and D _ex , but higher V _in and cellularity than GBM (all p  < 0.001). V _in demonstrated the highest diagnostic accuracy (AUC = 0.901; sensitivity = 0.737; specificity = 0.906). No significant differences were observed in peritumoral regions. V _in correlated strongly with histopathologic nuclear volume fraction (r = 0.76; p  < 0.0001). Conclusion T _d -dMRI-derived microstructural parameters, particularly V _in , effectively differentiated PCNSL from GBM, providing a novel approach to improve preoperative diagnosis.