Restriction Spectrum Imaging Improves Risk Stratification in Patients with Glioblastoma

Abstract

Background and purpose: ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC.

Materials and methods: Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, restriction spectrum imaging-contrast-enhanced volume fraction, ADC-FLAIR volume fraction, ADC-contrast-enhanced volume fraction) and intensities (restriction spectrum imaging-FLAIR 90th percentile, restriction spectrum imaging-contrast-enhanced 90th percentile, ADC-FLAIR 10th percentile, ADC-contrast-enhanced 10th percentile) within the contrast-enhanced and FLAIR hyperintensity VOIs were calculated. The association of diffusion imaging metrics, contrast-enhanced volume, and FLAIR hyperintensity volume with progression-free survival and overall survival was evaluated by using Cox proportional hazards models.

Results: Among the diffusion metrics, restriction spectrum imaging-FLAIR volume fraction was the strongest prognostic metric of progression-free survival (P = .036) and overall survival (P = .007) in a multivariate Cox proportional hazards analysis, with higher values indicating earlier progression and shorter survival. Restriction spectrum imaging-FLAIR 90th percentile was also associated with overall survival (P = .043), with higher intensities, indicating shorter survival. None of the ADC metrics were associated with progression-free survival/overall survival. Contrast-enhanced volume exhibited a trend toward significance for overall survival (P = .063).

Conclusions: Restriction spectrum imaging-derived cellularity in FLAIR hyperintensity regions may be a more robust prognostic marker than ADC and conventional imaging for early progression and poorer survival in patients with glioblastoma. However, future studies with larger samples are needed to explore its predictive ability.

Fig 1.

Boxplots of the imaging metrics.

Fig 2.

Kaplan-Meier curves for the cohort stratified on the basis of the median values for CE_vol for PFS (A) and OS (C), and RSI-FLAIR_vf for PFS (B) and OS (D).

Fig 3.

Shown here are the axial T1-postcontrast, FLAIR, ADC, and RSI-cellularity z score maps acquired postsurgery but pre-RT for 2 patients, A and B. The VOI contours are shown in red and green for the CE and FLAIR-HI, respectively. Patient A is a 63-year-old man with a right posterior frontal GBM who underwent subtotal resection. This patient had high RSI cellularity in the FLAIR-HI region. Although there is corresponding ADC hypointensity in this region, it is subtle and inconspicuous. He had a shorter PFS and OS (PFS, 4.2 months; OS, 6.6 months) than patient B. Patient B is a 31-year-old woman with a right frontal GBM. There are no areas of high RSI cellularity or low ADC signal in the FLAIR-HI or CE region. She had a correspondingly longer PFS (PFS, 14.5 months; OS, 19.9 months).