Early ADC changes in risk-model-defined brain regions precede contrast-enhancing lesions after proton therapy for low-grade glioma.

BACKGROUND

Contrast-enhancing brain lesions (CEBLs) are a challenging late effect of proton therapy (PT) in low-grade glioma (LGG), typically detected after blood-brain barrier disruption. Diffusion-weighted imaging (DWI) and derived apparent diffusion coefficient (ADC) metrics can reveal early microstructural alterations preceding this disruption. Their diagnostic value can be enhanced by combining it with voxel-wise risk-modelling, such as the Probability of Lesion Origin (POLO) model, which maps spatial susceptibility to radiation-induced damage. This pilot study investigates the feasibility of combining longitudinal DWI with POLO-based risk stratification to characterize regional tissue response trajectories after PT in patients with and without CEBL.

METHODS

Twenty LGG-patients treated with PT were retrospectively analyzed: ten developed CEBLs (CEBL⁺) and ten remained lesion-free (CEBL-). Longitudinal ADC-volume-histogram metrics (ADC20%, ADCmean, ADCmedian) were extracted from POLO-defined high-risk (HR) and low-risk (LR) volumes. Temporal evolution was quantified using coefficients of variation and slopes.

RESULTS

CEBL⁺ patients exhibited higher ADC values, greater temporal variability, and steeper increases over time, especially within HR regions. For ADC20%, HR values exceeded LR in CEBL⁺, while no HR-LR difference was observed in CEBL⁻. The HR-LR ADC20% difference distinguished CEBL⁺ from CEBL⁻ patients as early as six months post-treatment, yielding AUCs of 0.70-0.79 across quarterly timepoints.

CONCLUSIONS

Risk-model-informed interpretation of DWI, considering localized information on anticipated biological damage, demonstrates the potential for quantitative assessment of post-treatment tissue dynamics. Early HR-LR ADC divergence, particularly in ADC20%, may serve as an imaging biomarker for monitoring radiation-induced tissue changes after PT, supporting post-treatment imaging surveillance.