BACKGROUND AND PURPOSE: White matter fiber tractography relies on fiber bundle orientation estimates from diffusion MR imaging. However, clinically feasible techniques such as DTI and diffusional kurtosis imaging use assumptions, which may introduce error into in vivo orientation estimates. In this study, fiber bundle orientations from DTI and diffusional kurtosis imaging are compared with diffusion spectrum imaging as a criterion standard to assess the performance of each technique. MATERIALS AND METHODS: For each subject, full DTI, diffusional kurtosis imaging, and diffusion spectrum imaging datasets were acquired during 2 independent sessions, and fiber bundle orientations were estimated by using the specific theoretic assumptions of each technique. Angular variability and angular error measures were assessed by comparing the orientation estimates. Tractography generated with each of the 3 reconstructions was also examined and contrasted. RESULTS: Orientation estimates from all 3 techniques had comparable angular reproducibility, but diffusional kurtosis imaging decreased angular error throughout the white matter compared with DTI. Diffusion spectrum imaging and diffusional kurtosis imaging enabled the detection of crossing-fiber bundles, which had pronounced effects on tractography relative to DTI. Diffusion spectrum imaging had the highest sensitivity for detecting crossing fibers; however, the diffusion spectrum imaging and diffusional kurtosis imaging tracts were qualitatively similar. CONCLUSIONS: Fiber bundle orientation estimates from diffusional kurtosis imaging have less systematic error than those from DTI, which can noticeably affect tractography. Moreover, tractography obtained with diffusional kurtosis imaging is qualitatively comparable with that of diffusion spectrum imaging. Because diffusional kurtosis imaging has a shorter typical scan time than diffusion spectrum imaging, diffusional kurtosis imaging is potentially more suitable for a variety of clinical and research applications.

Purpose: Pharmacologic ascorbate (P-AscH−) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH− with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH− in humans. Patients and Methods: The single-arm phase II clinical trial (NCT02344355) enrolled 55 subjects, with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan–Meier method and compared across patient subgroups with log-rank tests. Forty-nine of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker. Results: Median OS was estimated to be 19.6 months [90% confidence interval (CI), 15.7–26.5 months], a statistically significant increase compared with historic control patients (14.6 months). Subjects with initial T2* relaxation < 50 ms were associated with a significant increase in PFS compared with T2*-high subjects (11.2 months vs. 5.7 months, P < 0.05) and a trend toward increased OS (26.5 months vs. 17.5 months). These results were validated in preclinical in vitro and in vivo model systems. Conclusions: P-AscH− combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes. See related commentary by Nabavizadeh and Bagley, p. 255

Purpose: The purpose of this preliminary study is to apply diffusional kurtosis imaging to assess the early response of recurrent glioblastoma to bevacizumab treatment. Methods: This prospective cohort study included 10 patients who had been diagnosed with recurrent glioblastoma and scheduled to receive bevacizumab treatment. Diffusional kurtosis images were obtained from all the patients 0–7 days before (pre-bevacizumab) and 28 days after (post-bevacizumab) initiating bevacizumab treatment. The mean, 10th, and 90th percentile values were derived from the histogram of diffusional kurtosis imaging metrics in enhancing and non-enhancing lesions, selected on post-contrast T1-weighted and fluid-attenuated inversion recovery images. Correlations of imaging measures with progression-free survival and overall survival were evaluated using Spearman's rank correlation coefficient. The significance level was set at P < 0.05. Results: Higher pre-bevacizumab non-enhancing lesion volume was correlated with poor overall survival ( r = −0.65, P = 0.049). Higher post-bevacizumab mean diffusivity and axial diffusivity (D_∥, D_∥10% and D_∥90%) in non-enhancing lesions were correlated with poor progression-free survival ( r = −0.73, −0.83, −0.71 and −0.85; P < 0.05). Lower post-bevacizumab axial kurtosis (K_∥10%) in non-enhancing lesions was correlated with poor progression-free survival ( r = 0.81, P = 0.008). Conclusions: This preliminary study demonstrates that diffusional kurtosis imaging metrics allow the detection of tissue changes 28 days after initiating bevacizumab treatment and that they may provide information about tumor progression.

P-AscH- stimulates the release of iron as Fe2+ from ferritin.

Predictive power of T2* in patients receiving standard-of-care therapy.