1031 - Regional Thalamic Atrophy, Diffusion Changes, and Neurocognitive Performance after Fractionated Brain Radiation Therapy
Presenter(s)
H. Nguyen1,2, R. Karunamuni3, A. C. Puett4, J. S. Kohli5, E. M. Qiao2, A. B. Hopper2, K. R. Tringale2, C. McDonald5, and J. A. Hattangadi-Gluth2; 1University of California San Diego School of Medicine, La Jolla, CA, 2Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 3Research Service, VA San Diego Healthcare System, San Diego, CA, 4UC San Diego, La Jolla, CA, 5Department of Psychiatry, University of California San Diego, La Jolla, CA
Purpose/Objective(s): The thalamus is a diencephalic gray matter structure composed of distinct nuclei that relay sensorimotor signals to support higher-order cognitive networks. We evaluated whether volumetric and diffusion changes in thalamic regions predicted neurocognitive performance across multiple domains after radiation therapy (RT).
Materials/Methods: Adults with primary brain tumors (n = 110) on a prospective clinical trial received fractionated brain RT (IMRT or proton therapy). MRI and diffusion tensor imaging were obtained at baseline and 3, 6, 12, 18, and 24-months post-RT, while a neurocognitive battery was performed at baseline and 3, 6, and 12-months post-RT. Automated parcellation segmented the thalamus and grouped individual subfields into six bilateral composite regions: anterior, lateral, ventral, intralaminar, medial, and posterior. Using volume and mean diffusivity (MD; higher values indicate injury) as biomarkers, linear-mixed effects models assessed (1) longitudinal change, (2) dose-response, and (3) associations with neurocognitive performance, adjusting for censored volume, age, and sex. All findings below are statistically significant (p < 0.05 vs baseline, FDR-corrected for multiple comparisons.
Results: Total thalamic volume decreased progressively from 3 to 24 months post-RT (-1.7%, -3.0%, -3.4%, -4.5%, and -5.1%), while thalamic MD significantly increased at 3, 18, and 24-months post-RT. All composite thalamic regions demonstrated significant longitudinal atrophy at multiple time points, and all but three regions exhibited significant MD increases at multiple time points. Dose-dependent MD increase was limited to the left posterior thalamus at 3 months (p = .002) and 18 months (p = .001). Preserved volumes of multiple thalamic regions were associated with better performance on the Wisconsin Card Sorting Test (WCST), Delis–Kaplan Executive Function System Color-Word Interference (DKEFS-CWI) test, Brief Visuospatial Memory Test (BVMT), and dominant-hand Pegboard test. Higher MD in multiple thalamic regions was associated with worse DKEFS Trail Making (DKEFS-TM), Wechsler Memory Scale–III (WMS-III), Wechsler Adult Intelligence Scale (WAIS), and BVMT performance.
Conclusion: Fractionated RT is associated with sustained thalamic atrophy and increased MD, with dose-dependent MD effects limited to the left posterior thalamus. Higher MD was associated with poorer neurocognitive performance across measures of processing speed (DKEFS-TM, WAIS) and memory (WMS-III, BVMT), whereas preserved thalamic volumes were associated with better performance on measures of cognitive flexibility and inhibition (WCST, DKEFS-CWI), visuospatial memory (BVMT), and fine motor dexterity (dominant-hand Pegboard). Dose constraints to selective thalamic regions may preserve domain-specific neurocognitive function.