Abstract
Intracranial volume (ICV) segmentation, also known as brain extraction or skull-stripping, is a critical preprocessing step in analytical pipelines for studying neurodegenerative diseases in magnetic resonance imaging (MRI). While the fluid-attenuated inversion recovery (FLAIR) MRI modality has emerged as an important sequence for analyzing cerebrovascular and neurodegenerative disease, most existing automated ICV segmentation methods have been developed for T1-weighted or multi-modal inputs. Additionally, many methods have been designed using single centre data of healthy subjects and encounter difficulties using images with varying acquisition parameters and neurodegenerative pathology. In this work, we develop and evaluate 2 traditional and 8 deep learning algorithms for ICV segmentation in FLAIR MRI. Training and testing were completed on 175 vol (8317 images) from 2 dementia and 1 vascular disease cohort. A human phantom FLAIR MRI dataset from a repeatedly scanned, healthy individual was also utilized for reliability analysis. Images were acquired from 47 imaging centres with varying scanners and parameters. To measure and compare performance, we present a novel framework for evaluating the effectiveness of computer generated segmentations on multicentre datasets. The evaluation framework includes assessments of algorithm accuracy, generalization capabilities, robustness to pathology and spatial location, and volumetric measurement reliability - all important dimensions for establishing proof of effectiveness (a prerequisite to clinical translation). The top performing method was a multiple resolution U-Net (MultiResUNet), which achieved a mean Dice similarity coefficient greater than 98% and was robust across pathology levels and spatial locations. Our results confirm a FLAIR-based ICV analytical pipeline can alone be utilized for large-scale neurodegenerative disease research. The presented evaluation framework can be deployed by other researchers to assess the viability of tools proposed for automated analysis of diverse, clinical MRI datasets.