Advanced diffusion imaging reveals microstructural characteristics of primary CNS lymphoma, allowing differentiation from glioblastoma

Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL from GBM with conventional MRI can be challenging when atypical imaging features are present. We employed advanced dMRI for non-invasive characterization of the microstructure of PCNSL and differentiation from GBM as the most frequent primary brain malignancy. Multiple dMRI metrics including DTI, NODDI and DMI were extracted from the contrast-enhancing tumor component in 10 PCNSL and 10 age-matched GBM on 3T MRI. Imaging findings were correlated with cell density and axonal markers obtained from histopathology. We found significantly increased intraaxonal volume fractions (V-intra, ICVF) and microFA in PCNSL compared to GBM (all p<0.001). In contrast, mean (MD) and axial diffusivity (aD), and microADC (all p<0.001), and also free water fractions (V-CSF, V-ISO) were significantly lower in PCNSL (all p<0.01). ROC analysis revealed high predictive values regarding the presence of a PCNSL for MD, aD, microADC, V-intra, ICVF, microFA, V-CSF and V-ISO (AUC in all >0.840, highest for MD and ICVF with an AUC of 0.960). Comparative histopathology between PCNSL and GBM revealed a significantly increased cell density in PCNSL and the presence of axonal remnants in a higher proportion of samples. Advanced diffusion imaging enables the characterization of the microstructure of PCNSL and reliably distinguishes PCNSL from GBM. Both imaging and histopathology revealed a relatively increased cell density and a preserved axonal microstructure in PCNSL.