Short diffusion time DWI with oscillating gradient preparation as an early MRI biomarker for radiation therapy response monitoring in glioblastoma: A pre-clinical feasibility study

Publication date: Available online 4 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Andre Bongers, Eric Hau, Han Shen
PurposeDiffusion weighted Imaging (DWI) is a promising microstructural modality for early detection of radiation treatment effects on a cellular level. However, standard clinical DWI protocols are often too insensitive as reliable radiation biomarker. Based on the hypothesis that sensitivity of clinical pulsed gradient DWI protocols (PGSE) may be impacted by their typically long effective diffusion-times (Δeff), we investigate a novel alternative approach using oscillating gradients preparation (OGSE) to obtain much shorter Δeff for tumor response monitoring by ADC mapping in a glioblastoma mouse model.Methods24 BALB/c nude mice inoculated with U87 glioblastoma cells were randomized into a control and irradiation group, which underwent a 15-day fractioned RT course with 2Gy/d. Therapy response was assessed by mapping of apparent diffusion coefficients (ADC) at 6 time points using an in-house implementation of a cos-OGSE DWI sequence with Δeff=1.25ms and compared with a standard PGSE with typical clinical diffusion time Δeff=18ms. Longitudinal ADC changes in tumor and contralateral white matter (WM) were statistically assessed using repeated-measures ANOVA and post-hoc (Sidak) testing.ResultsOn short Δeff OGSE maps tumor ADC was generally 30-50% higher than in surrounding WM. Areas correlated well with histology. Tumor identification was generally more difficult on PGSE maps due to non-significant WM/tumor contrast. During RT, OGSE maps also showed significant tumor ADC increase (∼15%) in response to radiation, consistently seen after 14Gy RT-dose. The clinical reference (PGSE) showed lower sensitivity to radiation changes and no significant response across the radiation group and timecourse could be detected.ConclusionOur short Δeff DWI method using OGSE better reflected histologically defined tumor areas and enabled more consistent and earlier detection of microstructural radiation changes than conventional methods. OGSE offers significant potential as a robust microstructural RT response biomarker potentially helping to shift important therapy decisions to earlier stages in the RT-timecourse.

Teaser

This study investigates DWI at very short diffusion times (Δeff) as a novel tool for radiotherapy monitoring and response detection in a glioblastoma mouse model. Using oscillating gradient diffusion MRI (OGSE) to overcome Δeff limits in conventional DWI we show that ADC mapping at short Δeff can detect radiation changes significantly earlier and more robustly than standard clinical DWI. We believe that short Δeff DWI is highly promising for radiotherapy monitoring on a cellular level.


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