Diffusion MRI reveals CNS microstructural alterations in DLBCL patients at risk of CNS relapse

Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) represents a clinical challenge, with risk stratification based on the CNS International Prognostic Index (CNS-IPI) potentially leading to over- and undertreatment. This study investigated whether diffusion MRI metrics could detect CNS microstructural changes associated with CNS relapse risk factors.

In this cross-sectional study 63 DLBCL patients without CNS involvement, and 11 healthy controls, underwent brain MRI including multi-shell diffusion tensor imaging, utilising restriction spectrum imaging modelling. We analysed cellularity index (CI), fractional anisotropy (FA), mean diffusivity (MD) and neurite density (ND) in white matter (WM) and CI and MD in cortical grey matter (GM). Associations with CNS-IPI, risk factors, and blood-brain barrier (BBB) permeability were assessed.

After multiple comparisons age-adjusted linear regression showed higher GM MD in patients with high CNS-IPI versus low/intermediate (mean difference: 4.33 × 10^-5, FDR-p = 0.03). Compared with controls, patients had increased GM MD (mean difference: 3.93 × 10^-5 mm²/s, FDR-p = 0.003) and reduced WM ND (mean difference: -7.36 × 10^-5, FDR-p = 0.003). Kidney/adrenal involvement (mean difference: 4.48 × 10^-5 mm²/s, FDR-p = 0.002) and advanced stage (mean difference: 3.41 × 10^-5 mm²/s, FDR-p = 0.02) were associated with higher GM MD. MD correlated positively with BBB permeability in GM (ρ = 0.46) and WM (ρ = 0.26), whereas WM FA (ρ = -0.37) and CI (ρ = -0.32) correlated inversely all p < 0.05.

DLBCL patients demonstrate subtle CNS microstructural alterations detectable by diffusion MRI, particularly in high-risk groups, suggesting potential brain vulnerability preceding clinical CNS involvement.