UCSF

Abstract

INTRODUCTION

While radiation therapy (RT) remains a standard practice in the upfront treatment of high-grade gliomas and low-grade gliomas at the time of recurrence, it is often associated with long-term effects including vascular injury and cognitive decline. The former typically manifests as size-varying hemosiderin deposits in the brain called cerebral microbleeds (CMBs), and can be accompanied by changes in the surrounding white-matter (WM) microstructure. As the median survival of lower grade gliomas can be 10 years or longer with current treatment strategies, minimizing the deficits incurred through treatment becomes especially important. Prior studies have shown increases in CMB formation over time that were dependent on RT dose and were not observed in patients treated only with chemotherapy. The goal of this study was to characterize the evolution of CMBs in a much larger cohort with serial scans and relate their changes over time to alterations in WM structure.

METHODS

125 patients (age:46 ± 12) were scanned on a 7-Tesla GE scanner either once or serially for 2-8 scans. The cohort included patients treated with RT for a glioma 2 months to 27 years prior, and a subset of nonirradiated control patients. Susceptibility-weighted vascular imaging and multi-directional, multi-shell diffusion-tensor imaging were acquired. Characteristics of RT-induced CMBs were evaluated within- and across patients, correlated with clinical and treatment parameters, and related to global and local WM changes.

RESULTS

Total CMB burden increased over time and was more severe for larger irradiated volumes and frontal lobe tumors. WM fractional anisotropy and diffusivity changes initially decreased as a function of CMB burden before improving approximately 6 years post-treatment.

CONCLUSIONS

Although there was initially a direct relationship between RT-induced vasculature injury and degradation of WM microstructure, changes in WM structure appeared to be reversible over time, whereas CMBs, potential markers of vascular injury, persisted.