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

Abstract

Cranial radiation therapy is associated with white matter-specific brain injury, cortical volume loss, mineralization, microangiopathy and neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia. In this retrospective cross-sectional analysis, neurocognitive testing and 3 T brain MRI's were obtained in 101 survivors treated with cranial radiation. Small focal intracerebral hemorrhages only visible on exquisitely sensitive MRI sequences were identified and localized using susceptibility weighted imaging. Modified Poisson regression was used to assess the effect of cranial radiation on cumulative number and location of microbleeds in each brain region, and multiple linear regression was used to evaluate microbleeds on neurocognitive outcomes, adjusting for age at diagnosis and sex. At least one microbleed was present in 85% of survivors, occurring more frequently in frontal lobes. Radiation dose of 24 Gy conveyed a 5-fold greater risk (95% CI 2.57-10.32) of having multiple microbleeds compared to a dose of 18 Gy. No significant difference was found in neurocognitive scores with either the absence or presence of microbleeds or their location. Greater prevalence of microbleeds in our study compared to prior reports is likely related to longer time since treatment, better sensitivity of SWI for detection of microbleeds and the use of a 3 T MRI platform.The aims of the current study were to evaluate survivors of childhood ALL during adulthood using 3 T MRI and a well-established high quality microbleed sensitive sequence to examine if relatively low doses of cranial radiation were associated with the development of microbleeds, and to investigate if the presence, frequency and/or location of microbleeds was associated with neurocognitive impairment. Scientific RepoRtS |(2020) 10:692 | https://doi.

Non-Human Primates Receiving High-Dose Total-Body Irradiation are at Risk of Developing Cerebrovascular Injury Years Postirradiation

“…Thus these sequences can be used to identify hemorrhage and necrosis with mineralization in affected subjects. The SWI sequence is routinely used in clinical practice to identify blood products and small-volume microhemorrhages in human patients, and SWI hypointensities have been reported in cancer patients receiving brain radiotherapy (73,74,77,78,(84)(85)(86)(87)(88). Use of these non-invasive, in vivo imaging protocols allows for monitoring of the progression of brain pathology longitudinally, often years prior to death, and offers the potential to map MRI abnormalities to neurologic deficits.…”

Neurotoxic Effects of Childhood Cancer Therapy and Its Potential Neurocognitive Impact

“…19 Lifestyle and chronic aging conditions such as hypertension and hypercholesterolemia may affect cognitive function more than burden of microbleeds and cerebral calcifications. 20,21 A subset of survivors who receive cranial irradiation experienced stroke-like migraine attack after radiation therapy syndrome, which presents 1-35 years after radiation with focal neurologic deficits and/or seizures, 22,23 in addition to persistent cognitive impairment. 24 Indirect injury via vascular damage and direct injury to oligodendrocytes lead to myelin loss and demyelination and manifests as leukoencephalopathy, 17 which is correlated with dose and volume of radiation.…”

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

“…Histological examination of the mineralizing microangiopathy deposits showed a strong positive stain for Ca and a weak positive stain for Fe [ 61 ], as also seen in our cases (histologies of Figure 2 and Figure 3 ). Furthermore, brain irradiation was found to cause microbleeding in survivors irradiated during childhood [ 62 ], which is likely to increase during the follow-up, and is classified as a small vessel disease [ 63 ]. Thus, microbleeding and mineralizing microangiopathy can be seen as the responsible for microcalcifications formation in the irradiated animals of our study.…”