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

Glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) are two distinct malignant brain tumors, and precise preoperative differentiation is crucial for guiding optimal treatments. This study aimed to evaluate the diagnostic value of time-dependent diffusion MRI (td-dMRI)-derived microstructural parameters in differentiating PCNSL from GBM and to correlate these parameters with histopathologic findings. 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 (Vin), cell diameter, cellularity, extracellular diffusivity (Dex) were compared between the two groups. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of these parameters. The DeLong test was applied to compare AUC values across parameters. Ridge regression was applied for variable selection, followed by logistic regression to construct a combined diagnostic model. Histopathological validation was performed by correlating td-dMRI parameters with hematoxylin-eosin (H sensitivity = 0.737; specificity = 0.906), which was significantly higher than diameter and Dex (all p < 0.05). No significant differences were observed in AUC values between Vin and other ADC-derived parameters, such as ADC0 Hz (AUC = 0.864; sensitivity = 0.895; specificity = 0.781). Ridge regression identified Vin and cellularity as potential independent predictors. However, no statistically robust combined diagnostic model could be established owing to insignificant combined regression results. No significant differences were observed in peritumoral regions. Additionally, Vin showed a strong positive correlation with histopathological nuclei fraction (r = 0.76; p < 0.001). Among all td-dMRI-derived microstructural parameters, Vin achieves the highest AUC and serves as a promising biomarker for the preoperative differential diagnosis between GBM and PCNSL.