TY - JOUR
T1 - Cognitive and Imaging Differences After Proton and Photon Whole Brain Irradiation in a Preclinical Model
AU - Tang, Tien T.
AU - Zawaski, Janice A.
AU - Kesler, Shelli
AU - Beamish, Christine A.
AU - Inoue, Taeko
AU - Perez, Emma C.
AU - Bronk, Lawrence
AU - Poenisch, Falk
AU - Briere, Tina M.
AU - Sabek, Omaima M.
AU - Grosshans, David R.
AU - Waleed Gaber, M.
N1 - Funding Information:
This work was supported by a grant from the National Cancer Institute (1R01CA208535) (D.R.G.) and the Cancer Prevention Research Institute of Texas (RP130573CPRIT) (M.W.G.).
Funding Information:
The authors thank Texas Children's Hospital for use of the Small Animal Imaging Facility. This work was supported by a grant from the National Cancer Institute (1R01CA208535) (D.R.G.) and the Cancer Prevention Research Institute of Texas (RP130573CPRIT) (M.W.G.).
Publisher Copyright:
© 2021 The Authors
PY - 2022/2/1
Y1 - 2022/2/1
N2 - PURPOSE: Compared with photon cranial radiation therapy (X-CRT), proton cranial radiation therapy (P-CRT) offers potential advantages in limiting radiation-induced sequalae in the treatment of pediatric brain tumors. This study aims to identify cognitive, functional magnetic resonance and positron emission tomography imaging markers and molecular differences between the radiation modalities.METHODS AND MATERIALS: Juvenile rats received a single faction of 10 Gy (relative biological effectiveness-weighted dose) delivered with 6 MV X-CRT or at the midspread out Bragg peak of a 100 MeV P-CRT beam. At 3, 6, and 12 months post-CRT, executive function was measured using 5-choice serial reaction time task. At ∼12 months post-CRT, animals were imaged with
18F-Flurodeoxy-glucose positron emission tomography imaging followed by functional ex vivo magnetic resonance imaging and stained for markers of neuroinflammation.
RESULTS: Irradiated animals had cognitive impairment with a higher number of omissions and lower incorrect and premature responses compared with sham (P ≤ .05). The accuracy of the animals' X-CRT was less than that of sham (P ≤ .001). No significant difference in rates of cognitive change were found between the radiation modalities. At 12 months post-CRT, glucose metabolism was significantly higher than sham in X-CRT (P = .04) but not P-CRT. Using diffusion tensor imaging, P-CRT brains were found to have higher white matter volume and fiber lengths compared with sham (P < .03). Only X-CRT animals had higher apparent diffusion coefficient values compared with sham (P = .04). P-CRT animals had more connectomic changes compared with X-CRT. Correlative analysis identified several imaging features with cognitive performance. Furthermore, microgliosis (P < .05), astrogliosis (P < .01), and myelin thinning (P <.05) were observed in both radiation modalities, with X-CRT showing slightly more inflammation.CONCLUSIONS: Both P-CRT and X-CRT lead to neurocognitive changes compared with sham. Although no significant difference was observed in neuroinflammation between the irradiated groups, differences were found in late-term glucose metabolism and brain connectome. Our results indicate that despite relative biological effectiveness weighting of the proton dose there are still differential effects which warrants further investigation.
AB - PURPOSE: Compared with photon cranial radiation therapy (X-CRT), proton cranial radiation therapy (P-CRT) offers potential advantages in limiting radiation-induced sequalae in the treatment of pediatric brain tumors. This study aims to identify cognitive, functional magnetic resonance and positron emission tomography imaging markers and molecular differences between the radiation modalities.METHODS AND MATERIALS: Juvenile rats received a single faction of 10 Gy (relative biological effectiveness-weighted dose) delivered with 6 MV X-CRT or at the midspread out Bragg peak of a 100 MeV P-CRT beam. At 3, 6, and 12 months post-CRT, executive function was measured using 5-choice serial reaction time task. At ∼12 months post-CRT, animals were imaged with
18F-Flurodeoxy-glucose positron emission tomography imaging followed by functional ex vivo magnetic resonance imaging and stained for markers of neuroinflammation.
RESULTS: Irradiated animals had cognitive impairment with a higher number of omissions and lower incorrect and premature responses compared with sham (P ≤ .05). The accuracy of the animals' X-CRT was less than that of sham (P ≤ .001). No significant difference in rates of cognitive change were found between the radiation modalities. At 12 months post-CRT, glucose metabolism was significantly higher than sham in X-CRT (P = .04) but not P-CRT. Using diffusion tensor imaging, P-CRT brains were found to have higher white matter volume and fiber lengths compared with sham (P < .03). Only X-CRT animals had higher apparent diffusion coefficient values compared with sham (P = .04). P-CRT animals had more connectomic changes compared with X-CRT. Correlative analysis identified several imaging features with cognitive performance. Furthermore, microgliosis (P < .05), astrogliosis (P < .01), and myelin thinning (P <.05) were observed in both radiation modalities, with X-CRT showing slightly more inflammation.CONCLUSIONS: Both P-CRT and X-CRT lead to neurocognitive changes compared with sham. Although no significant difference was observed in neuroinflammation between the irradiated groups, differences were found in late-term glucose metabolism and brain connectome. Our results indicate that despite relative biological effectiveness weighting of the proton dose there are still differential effects which warrants further investigation.
KW - Animals
KW - Brain/pathology
KW - Cognition/radiation effects
KW - Cranial Irradiation/adverse effects
KW - Diffusion Tensor Imaging/methods
KW - Protons
KW - Rats
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U2 - 10.1016/j.ijrobp.2021.09.005
DO - 10.1016/j.ijrobp.2021.09.005
M3 - Article
C2 - 34509550
AN - SCOPUS:85116873369
SN - 0360-3016
VL - 112
SP - 554
EP - 564
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -