Rules-based Volumetric Segmentation of Multiparametric MRI for Response Assessment in Recurrent High-Grade Glioma

We report domain knowledge-based rules for assigning voxels in brain multiparametric MRI (mpMRI) to distinct tissuetypes based on their appearance on Apparent Diffusion Coefficient of water (ADC) maps, T1-weighted unenhanced and contrast-enhanced, T2-weighted, and Fluid-Attenuated Inversion Recovery images. The development dataset comprised mpMRI of 18 participants with preoperative high-grade glioma (HGG), recurrent HGG (rHGG), and brain metastases. External validation was performed on mpMRI of 235 HGG participants in the BraTS 2020 training dataset. The treatment dataset comprised serial mpMRI of 32 participants (total 231 scan dates) in a clinical trial of immunoradiotherapy in rHGG (NCT02313272). Pixel intensity-based rules for segmenting contrast-enhancing tumor (CE), hemorrhage, Fluid, non-enhancing tumor (Edema1), and leukoaraiosis (Edema2) were identified on calibrated, co-registered mpMRI images in the development dataset. On validation, rule-based CE and High FLAIR (Edema1 + Edema2) volumes were significantly correlated with ground truth volumes of enhancing tumor (R = 0.85;p < 0.001) and peritumoral edema (R = 0.87;p < 0.001), respectively. In the treatment dataset, a model combining time-on-treatment and rule-based volumes of CE and intratumoral Fluid was 82.5% accurate for predicting progression within 30 days of the scan date. An explainable decision tree applied to brain mpMRI yields validated, consistent, intratumoral tissuetype volumes suitable for quantitative response assessment in clinical trials of rHGG.