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

Abstract

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 2019;50:868–877.

Cerebral microbleeds in adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiation

“…Morrison et al, however, found no association between maximum radiation dose to the brain and microbleed development in adult brain tumor patients 15 . Similarly, in a previous study of 90 children treated with cranial radiation for a mixture of CNS tumors and leukemias, no significant difference in cerebrovascular abnormalities were found between patients treated with low (18 Gy) or high (at least 32 Gy) doses of CRT 4 .…”

“…Similar to our study, Neu et al, using SWI on a 3 T MRI platform, found that 36 of 40 (90%) of brain tumor survivors treated with cranial radiation had microbleeds at a mean of 13.5 years after diagnosis 14 and the total number of microbleeds correlated with greater whole brain radiation dose and time since diagnosis. A recent study of 113 adult brain tumor patients treated with cranial radiation who received serial SWI's at 7 T were found to have an 18% increase in volume and 11% increase in number of microbleeds per year 15 .…”

“…The difference between our findings and those of Morrison et al may be related to our survivors' exposure to radiation as children as opposed to adulthood in the Morrison study. Interestingly, Morris et al found that multiple neurosurgical resections conveyed a greater risk for the development of microbleeds 15 . This may also explain the differences seen between brain tumor and ALL survivors.…”

Quantifying effects of radiotherapy-induced microvascular injury; review of established and emerging brain MRI techniques

“…In a recent study deploying T2*-weighted and SWI sequences (1,5T or 3T), the prevalence was as high as 90% after a mean observational period of 13,5 years [52]. Using 7T MRI this number is much higher with CMBs being found in up to 100% of patients [53]. CMBs might be detected as soon as 3-4 months after radiotherapy onset, with a latency of up to 9 years (mean 33 months) [54], therefore representing both early-delayed and late-delayed injury.…”

Emerging Use of Ultra-High-Field 7T MRI in the Study of Intracranial Vascularity: State of the Field and Future Directions

“…Another study of 7T SWI in 113 patients having undergone focal radiation found a 100% incidence of at least 1 microbleed 2 years following radiation. 21 Belliveau et al 19 further demonstrated the increased ability of 7T to detect radiation-related cerebral microbleeds using SWI, apparent transverse relaxation, and quantitative susceptibility mapping. Bian et al 23 found significantly more cerebral microbleeds in 7/10 patients with gliomas who underwent radiation therapy using 7T SWI compared with 3T SWI.…”