Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy.
Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy.



We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests.



Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002).



Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
Tyler M
TM
Seibert
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
Roshan
R
Karunamuni
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
Samar
S
Kaifi
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
Jeffrey
J
Burkeen
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
Michael
M
Connor
Department of Radiology, University of California, San Diego, La Jolla, California.
Anitha Priya
AP
Krishnan
Department of Radiology, University of California, San Diego, La Jolla, California.
Nathan S
NS
White
Department of Radiology, University of California, San Diego, La Jolla, California.
Nikdokht
N
Farid
Department of Radiology, University of California, San Diego, La Jolla, California.
Hauke
H
Bartsch
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
Vyacheslav
V
Murzin
Department of Psychiatry, University of California, San Diego, La Jolla, California.
Tanya T
TT
Nguyen
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
Vitali
V
Moiseenko
Department of Radiology, University of California, San Diego, La Jolla, California; Department of Neurosciences, University of California, San Diego, La Jolla, California.
James B
JB
Brewer
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California; Department of Psychiatry, University of California, San Diego, La Jolla, California.
Carrie R
CR
McDonald
Department of Radiology, University of California, San Diego, La Jolla, California; Department of Psychiatry, University of California, San Diego, La Jolla, California; Department of Neurosciences, University of California, San Diego, La Jolla, California.
Anders M
AM
Dale
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California. Electronic address: jhattangadi@ucsd.edu.
Jona A
JA
Hattangadi-Gluth
D000328:Adult; D000368:Aged; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy; D002540:Cerebral Cortex / Q000473:pathology* / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000009:adverse effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology* / Q000473:pathology*; D011879:Radiotherapy Dosage; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult