Risk factors of radiotherapy-induced cerebral microbleeds and serial analysis of their size compared with white matter changes: A 7T MRI study in 113 adult patients with brain tumors.

BACKGROUND: Although radiation therapy (RT) contributes to survival benefit in many brain tumor patients, it has also been associated with long-term brain injury. Cerebral microbleeds (CMBs) represent an important manifestation of radiation-related injury.

PURPOSE: To characterize the change in size and number of CMBs over time and to evaluate their relationship to white matter structural integrity as measured using diffusion MRI indices.

STUDY TYPE: Longitudinal, retrospective, human cohort.

POPULATION: In all, 113 brain tumor patients including patients treated with focal RT (n = 91, 80.5%) and a subset of nonirradiated controls (n = 22, 19.5%).

FIELD STRENGTH/SEQUENCE: Single and multiecho susceptibility-weighted imaging (SWI) and multiband, shell, and direction diffusion tensor imaging (DTI) at 7 T.

ASSESSMENT: Patients were scanned either once or serially. CMBs were detected and quantified on SWI images using a semiautomated approach. Local and global fractional anisotropy (FA) were measured from DTI data for a subset of 35 patients.

STATISTICAL TESTS: Potential risk factors for CMB development were determined by multivariate linear regression and using linear mixed-effect models. Longitudinal FA was quantitatively and qualitatively evaluated for trends.

RESULTS: All patients scanned at 1 or more years post-RT had CMBs. A history of multiple surgical resections was a risk factor for development of CMBs. The total number and volume of CMBs increased by 18% and 11% per year, respectively, although individual CMBs decreased in volume over time. Simultaneous to these microvascular changes, FA decreased by a median of 6.5% per year. While the majority of nonirradiated controls had no CMBs, four control patients presented with fewer than five CMBs.

DATA CONCLUSION: Identifying patients who are at the greatest risk for CMB development, with its likely associated long-term cognitive impairment, is an important step towards developing and piloting preventative and/or rehabilitative measures for patients undergoing RT.

LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1133-1138.