Melanie A Morrison1, Sabine Mueller2, Erin Felton2, Angela Jakary1, Schuyler Stoller2, Sivakami Avadiappan1, Justin Yuan1, Annette M Molinaro3, Steve Braunstein4, Anu Banerjee2, Christopher P Hess5, Janine M Lupo6. 1. Department of Radiology and Biomedical Imaging, University of California San Francisco, USA. 2. Department of Neurology, University of California San Francisco, USA. 3. Department of Neurological Surgery, University of California San Francisco, USA; Department of Epidemiology & Biostatistics, University of California San Francisco, USA. 4. Department of Radiation Oncology, University of California San Francisco, USA. 5. Department of Radiology and Biomedical Imaging, University of California San Francisco, USA; Department of Neurology, University of California San Francisco, USA. 6. Department of Radiology and Biomedical Imaging, University of California San Francisco, USA. Electronic address: janine.lupo@ucsf.edu.
Abstract
BACKGROUND: Radiation therapy (RT) is essential to the management of many brain tumors, but has been known to lead to cognitive decline and vascular injury in the form of cerebral microbleeds (CMBs). PURPOSE: In a subset of children, adolescents, and young adults recruited from a larger trial investigating arteriopathy and stroke risk after RT, we evaluated the prevalence of CMBs after RT, examined risk factors for CMBs and cognitive impairment, and related their longitudinal development to cognitive performance changes. METHODS: Twenty-five patients (mean 17 years, range: 10-25 years) underwent 7-Tesla MRI and cognitive assessment. Nineteen patients were treated with whole-brain or focal RT 1-month to 20-years prior, while 6 non-irradiated patients with posterior-fossa tumors served as controls. CMBs were detected on 7T susceptibility-weighted imaging (SWI) using semi-automated software, a first use in this population. RESULTS: CMB detection sensitivity with 7T SWI was higher than previously reported at lower field strengths, with one or more CMBs detected in 100% of patients treated with RT at least 1-year prior. CMBs were localized to dose-targeted brain volumes with risk factors including whole-brain RT (p = 0.05), a higher RT dose (p = 0.01), increasing time since RT (p = 0.03), and younger age during RT (p = 0.01). Apart from RT dose, these factors were associated with impaired memory performance. Follow-up data in a subset of patients revealed a proportional increase in CMB count with worsening verbal memory performance (r = -0.85, p = 0.03). CONCLUSIONS: Treatment with RT during youth is associated with the chronic development of CMBs that evolve with memory impairment over time.
BACKGROUND: Radiation therapy (RT) is essential to the management of many brain tumors, but has been known to lead to cognitive decline and vascular injury in the form of cerebral microbleeds (CMBs). PURPOSE: In a subset of children, adolescents, and young adults recruited from a larger trial investigating arteriopathy and stroke risk after RT, we evaluated the prevalence of CMBs after RT, examined risk factors for CMBs and cognitive impairment, and related their longitudinal development to cognitive performance changes. METHODS: Twenty-five patients (mean 17 years, range: 10-25 years) underwent 7-Tesla MRI and cognitive assessment. Nineteen patients were treated with whole-brain or focal RT 1-month to 20-years prior, while 6 non-irradiated patients with posterior-fossa tumors served as controls. CMBs were detected on 7T susceptibility-weighted imaging (SWI) using semi-automated software, a first use in this population. RESULTS: CMB detection sensitivity with 7T SWI was higher than previously reported at lower field strengths, with one or more CMBs detected in 100% of patients treated with RT at least 1-year prior. CMBs were localized to dose-targeted brain volumes with risk factors including whole-brain RT (p = 0.05), a higher RT dose (p = 0.01), increasing time since RT (p = 0.03), and younger age during RT (p = 0.01). Apart from RT dose, these factors were associated with impaired memory performance. Follow-up data in a subset of patients revealed a proportional increase in CMB count with worsening verbal memory performance (r = -0.85, p = 0.03). CONCLUSIONS: Treatment with RT during youth is associated with the chronic development of CMBs that evolve with memory impairment over time.
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