Sivakami Avadiappan1, Melanie A Morrison1, Angela Jakary1, Erin Felton2,3, Schuyler Stoller2, Christopher P Hess1,2, Annette M Molinaro4,5, Steve E Braunstein6, Sabine Mueller2,4,7,8, Janine M Lupo9,10. 1. Department of Radiology and Biomedical Imaging, University of California, San Francisco, Byers Hall, 1700 4th Street, Suite 303D, Box 2532, San Francisco, CA, 94158-2330, USA. 2. Department of Neurology, University of California, San Francisco, CA, USA. 3. The George Washington University School of Medicine and Health Sciences, Washington, DC, USA. 4. Department of Neurosurgery, University of California, San Francisco, CA, USA. 5. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. 6. Department of Radiation Oncology, University of California, San Francisco, CA, USA. 7. Department of Pediatrics, University of California, San Francisco, CA, USA. 8. University Children's Hospital Zurich, Zurich, Switzerland. 9. Department of Radiology and Biomedical Imaging, University of California, San Francisco, Byers Hall, 1700 4th Street, Suite 303D, Box 2532, San Francisco, CA, 94158-2330, USA. janine.lupo@ucsf.edu. 10. UCSF/UC Berkeley Graduate Program in Bioengineering, Berkeley and San Francisco, CA, USA. janine.lupo@ucsf.edu.
Abstract
PURPOSE: Although radiation therapy (RT) is a common treatment for pediatric brain tumors, it is associated with detrimental long-term effects such as impaired cognition, vascular injury, and increased stroke risk. This study aimed to develop metrics that describe vascular injury and relate them to the presence of cerebral microbleeds (CMBs) and cognitive performance scores. METHODS: Twenty-five young adult survivors of pediatric brain tumors treated with either whole-brain (n = 12), whole-ventricular (n = 7), or no RT (n = 6) underwent 7T MRI and neurocognitive testing. Simultaneously acquired MR angiography and susceptibility-weighted images were used to segment CMBs and vessels and quantify their radii and volume. RESULTS: Patients treated with whole-brain RT had significantly lower arterial volumes (p = 0.003) and a higher proportion of smaller vessels (p = 0.003) compared to the whole-ventricular RT and non-irradiated control patients. Normalized arterial volume decreased with increasing CMB count (R = - 0.66, p = 0.003), and decreasing trends were observed with time since RT and at longitudinal follow-up. Global cognition and verbal memory significantly decreased with smaller normalized arterial volume (p ≤ 0.05). CONCLUSIONS: Arterial volume is reduced with increasing CMB presence and is influenced by the total brain volume exposed to radiation. This work highlights the potential use of vascular-derived metrics as non-invasive markers of treatment-induced injury and cognitive impairment in pediatric brain tumor patients.
PURPOSE: Although radiation therapy (RT) is a common treatment for pediatric brain tumors, it is associated with detrimental long-term effects such as impaired cognition, vascular injury, and increased stroke risk. This study aimed to develop metrics that describe vascular injury and relate them to the presence of cerebral microbleeds (CMBs) and cognitive performance scores. METHODS: Twenty-five young adult survivors of pediatric brain tumors treated with either whole-brain (n = 12), whole-ventricular (n = 7), or no RT (n = 6) underwent 7T MRI and neurocognitive testing. Simultaneously acquired MR angiography and susceptibility-weighted images were used to segment CMBs and vessels and quantify their radii and volume. RESULTS: Patients treated with whole-brain RT had significantly lower arterial volumes (p = 0.003) and a higher proportion of smaller vessels (p = 0.003) compared to the whole-ventricular RT and non-irradiated control patients. Normalized arterial volume decreased with increasing CMB count (R = - 0.66, p = 0.003), and decreasing trends were observed with time since RT and at longitudinal follow-up. Global cognition and verbal memory significantly decreased with smaller normalized arterial volume (p ≤ 0.05). CONCLUSIONS: Arterial volume is reduced with increasing CMB presence and is influenced by the total brain volume exposed to radiation. This work highlights the potential use of vascular-derived metrics as non-invasive markers of treatment-induced injury and cognitive impairment in pediatric brain tumor patients.
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