Microstructural MRI combined with metabolic MRI to evaluate the progression-free survival of patients with glioblastoma at the early follow-up after tumor treating fields: a pilot study

Background

Non-invasive assessment of treatment response in Tumor Treating Fields (TTFields) and exploration of progression-free survival (PFS) by imaging techniques remains a major challenge.

Objectives

This exploratory pilot study investigated the feasibility of using time-dependent diffusion MRI (t_d-dMRI) combined with chemical exchange saturation transfer (CEST) MRI to assess the TTFields treatment efficacy and explore associations with PFS in postoperative glioblastoma (GBM) patients.

Methods

This study employed t_d-dMRI and CEST techniques to scan patients before and 1–6 months after receiving TTFields or temozolomide treatment between May 2023 and November 2024. Microstructural metrics, including Diameter, intracellular volume fraction (V_in), Cellularity index and extracellular diffusivity (D_ex), were calculated using the IMPULSED method. Multiple metabolic parameters were derived through magnetization transfer ratio asymmetry analysis and pH-weighted analysis. Longitudinal changes in these parameters were analyzed using linear mixed-effects models (LMM), with sensitivity analysis conducted via the Mann-Whitney U test. Spearman correlation analysis assessed relationships between parameters and PFS.

Results

Ten patients were included (age range 29–74 years; 8 men). The TTFields group showed a trend toward greater early reduction in cellularity index at first follow‑up. LMM analysis showed different dynamic evolution trends in Diameter (F = 5.042, P = 0.035) and pH-weighted values (F = 5.291, P = 0.055) between the progression and non-progression groups. At the third month post-treatment, the Diameter in the progression group increased from baseline, while it decreased in the non-progression group (estimated value = 3.17, 95% CI: 0.29–6.06, P = 0.036). Sensitivity analyses supported these descriptive between‑group differences. Correlation analysis showed that at the third month post-treatment, the change in diameter was associated with the pH-weighted change (r = 0.697, P = 0.025). During the early treatment phase, both the change in diameter and the pH-weighted change relative to baseline showed negative associations with patient PFS (r = -0.636, P = 0.048; r = -0.697, P = 0.025).

Conclusions

This exploratory pilot study suggested that combining t_d-dMRI with CEST MRI may help describe microstructural and metabolic changes that could be associated with TTFields efficacy during early treatment. Changes in Diameter and pH-weighted values, both in trend and magnitude, showed correlations with patient PFS. These observations support further exploratory investigations in larger cohorts to clarify the role of multiparametric MRI in evaluating early TTFields‑associated changes and prognosis.

Critical relevance statement

Early assessment of the efficacy of TTFields for GBM is key to individualized therapy, but challenges remain. This exploratory pilot study combined microstructural and metabolic MRI to describe early longitudinal changes linked to TTFields response. The preliminary findings provided initial insights that may inform future larger-scale studies aimed at better understanding treatment response in GBM patients.

Clinical trial number

Not applicable.