Diffusion and contrast-enhancement MRI phenotypes associated with immune checkpoint inhibitor exposure and with immune cell infiltration in brain metastases.
Francesco Sanvito, Gianluca Nocera, Zexi Wang, Eileen Shiuan, Lu Sun, Sonoko Oshima, Asher Kim, Irina Kryukov, Guowen Shao, Nicholas S Cho, Noriko Salamon, Benjamin M Ellingson, Robert Prins, Won Kim, Jingwen Yao
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引用次数: 0
Abstract
Background: MRI-derived apparent diffusion coefficient (ADC) and contrast-enhancement (CE) may represent non-invasive biomarkers to evaluate microstructural tissue changes and histopathological immune cell infiltration induced by immune checkpoint inhibitors (ICI).
Methods: 125 lesions across 93 patients were analyzed. ADC (reflecting water diffusivity) and CE T1-subtraction maps (reflecting blood-brain barrier permeability) tumor values were used for bivariate histograms of ADC and CE, and to quantify voxel fractions belonging to highADC-highCE and lowADC-lowCE quadrants. The association between ICI exposure and voxel frequency in ADC-CE quadrants was evaluated with multivariate mixed-effects models accounting for corticosteroid exposure and other variables. In a subset of patients (n=23), the association between immune cell counts (CD45+ cell density) from tissue samples and ADC-CE phenotypes was tested.
Results: ICI and corticosteroid exposure were associated with distinct ADC-CE phenotypes on bivariate histograms. ICI-exposed lesions showed significantly higher voxel frequency in the highADC-highCE quadrant (p<0.001) and lower voxel frequency in the lowADC-lowCE quadrant (p<0.01), compared to ICI-naïve lesions. Multivariate analyses confirmed that ICI exposure was an independent determinant of higher voxel frequency in the highADC-highCE quadrant (p=0.001) and lower voxel frequency in the lowADC-lowCE quadrant (p=0.01) in absence of corticosteroid treatment. Corticosteroid usage significantly influenced the relationship between ADC-CE phenotypes and ICI exposure. Voxel frequency in ADC-CE quadrants was correlated with CD45+ cell density in histopathology (partial ρ=0.56 p=0.01 for highADC-highCE, partial ρ=-0.64 p<0.01 for lowADC-lowCE).
Conclusions: ADC-CE phenotypes are associated with ICI exposure and immune cell infiltration in BM, representing potential non-invasive markers to monitor ICI-induced pathophysiological changes.
期刊介绍：
Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field.
The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.
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