Deep learning applied to the segmentation of rodent brain MRI data outperforms noisy ground truth on full-fledged brain atlases

Translational magnetic resonance imaging of the rodent brain provides invaluable information for preclinical drug development. However, the automated segmentation of such images for quantitative analyses is limited compared to human brain imaging mainly due to the inferior anatomical contrast and the resulting less advanced registration and atlasing tools. Here, we investigated the potential of deep learning models for the segmentation of magnetic resonance images of rat brains into an entire set of multiple regions of interest (rather than individual loci), focusing on the development of a robust method that accommodates changes in the input based on differences in animal strain (genotype) and size. Manually generated labels are expensive, so we tested the ability of neural networks to learn brain structures from noisy but inexpensive registration-based labels, allowing very large datasets to be leveraged for training. We compared three distinct model architectures (U-Net, Attention-U-Net and DeepLab) by training them on a dataset of >10,000 magnetic resonance images of rat brains and found that each model was able to segment the entire brain into predefined sets of 29 and 58 regions, respectively, with the Attention U-Net achieving the best performance. The models canceled out unstructured label noise in the imperfect training data to provide smoother and more symmetric segmentations than registration-based labeling, and were more robust when presented with input variations, thus outperforming the noisy ground truth. Our pipeline also includes uncertainty estimation and an explainability mechanism, hence providing features essential for anomaly detection and quality assurance. In summary, our study shows that deep learning models do achieve accurate brain segmentation in high-throughput quantitative preclinical imaging without the need for expensive expert-generated labels.