TY - JOUR
T1 - MRI evaluation of the effects of whole brain radiotherapy on breast cancer brain metastasis
AU - Crowe, William
AU - Wang, Lulu
AU - Zhang, Zhongwei
AU - Varagic, Jasmina
AU - Bourland, J. Daniel
AU - Chan, Michael D.
AU - Habib, Amyn A.
AU - Zhao, Dawen
N1 - Funding Information:
This research has been supported in part by the Department of Defense Breast Cancer Idea Award [Grant number W81XWH-12-1-0317]; National Institute of Health/National Cancer Institute [Grant number R01CA194578]; Wake Forest Comprehensive Cancer Center [Grant number P30 CA01219740] and the Wells Fargo Scholar Program; AH is supported by a Merit Award from the Department of Veteran’s Affairs.
Funding Information:
This research has been supported in part by the Department of Defense Breast Cancer Idea Award [Grant number W81XWH-12-1-0317]; National Institute of Health/National Cancer Institute [Grant number R01CA194578]; Wake Forest Comprehensive Cancer Center [Grant number P30 CA01219740] and the Wells Fargo Scholar Program; AH is supported by a Merit Award from the Department of Veteran?s Affairs. We are grateful to Drs. Diane Palmieri and Patricia Steeg (CCR, NCI) for providing breast cancer MDA-MB231-Br cells. We are also grateful to Dr. Youngkyoo Jung for his assistance and technical support.
Publisher Copyright:
© 2019, © 2019 Taylor & Francis Group LLC.
PY - 2018/12/6
Y1 - 2018/12/6
N2 - Purpose: To assess early changes in brain metastasis in response to whole brain radiotherapy (WBRT) by longitudinal Magnetic Resonance Imaging (MRI). Materials and methods: Using a 7T system, MRI examinations of brain metastases in a breast cancer MDA-MD231-Br mouse model were conducted before and 24 hours after 3 daily fractionations of 4 Gy WBRT. Besides anatomic MRI, diffusion-weighted (DW) MRI and dynamic contrast-enhanced (DCE) MRI were applied to study cytotoxic effect and blood-tumor-barrier (BTB) permeability change, respectively. Results: Before treatment, high-resolution T2-weighted images revealed hyperintense multifocal lesions, many of which (∼50%) were not enhanced on T1-weighted contrast images, indicating intact BTB in the brain metastases. While no difference in the number of new lesions was observed, WBRT-treated tumors were significantly smaller than sham controls (p <.05). DW MRI detected significant increase in apparent diffusion coefficient (ADC) in WBRT tumors (p <.05), which correlated with elevated caspase 3 staining of apoptotic cells. Many lesions remained non-enhanced post WBRT. However, quantitative DCE MRI analysis showed significantly higher permeability parameter, K trans , in WBRT than the sham group (p <.05), despite marked spatial heterogeneity. Conclusions: MRI allowed non-invasive assessments of WBRT induced changes in BTB permeability, which may provide useful information for potential combination treatment.
AB - Purpose: To assess early changes in brain metastasis in response to whole brain radiotherapy (WBRT) by longitudinal Magnetic Resonance Imaging (MRI). Materials and methods: Using a 7T system, MRI examinations of brain metastases in a breast cancer MDA-MD231-Br mouse model were conducted before and 24 hours after 3 daily fractionations of 4 Gy WBRT. Besides anatomic MRI, diffusion-weighted (DW) MRI and dynamic contrast-enhanced (DCE) MRI were applied to study cytotoxic effect and blood-tumor-barrier (BTB) permeability change, respectively. Results: Before treatment, high-resolution T2-weighted images revealed hyperintense multifocal lesions, many of which (∼50%) were not enhanced on T1-weighted contrast images, indicating intact BTB in the brain metastases. While no difference in the number of new lesions was observed, WBRT-treated tumors were significantly smaller than sham controls (p <.05). DW MRI detected significant increase in apparent diffusion coefficient (ADC) in WBRT tumors (p <.05), which correlated with elevated caspase 3 staining of apoptotic cells. Many lesions remained non-enhanced post WBRT. However, quantitative DCE MRI analysis showed significantly higher permeability parameter, K trans , in WBRT than the sham group (p <.05), despite marked spatial heterogeneity. Conclusions: MRI allowed non-invasive assessments of WBRT induced changes in BTB permeability, which may provide useful information for potential combination treatment.
KW - Brain metastasis
KW - blood-tumor-barrier (BTB)
KW - diffusion-weighted (DW) MRI
KW - dynamic contrast-enhanced (DCE) MRI
KW - volume transfer coefficient Ktrans
KW - whole brain radiotherapy (WBRT)
UR - https://www.scopus.com/pages/publications/85059741665
U2 - 10.1080/09553002.2019.1554920
DO - 10.1080/09553002.2019.1554920
M3 - Article
C2 - 30499763
AN - SCOPUS:85059741665
SN - 0955-3002
VL - 95
SP - 338
EP - 346
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 3
ER -