Abstract
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, Ktrans, 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.
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