Despite the great promise that machine learning has offered in many fields of medicine, it has also raised concerns about potential biases and poor generalization across genders, age distributions, races and ethnicities, hospitals, and data acquisition equipment and protocols. In the current study, and in the context of three brain diseases, we provide evidence which suggests that when properly trained, machine learning models can generalize well across diverse conditions and do not necessarily suffer from bias. Specifically, by using multistudy magnetic resonance imaging consortia for diagnosing Alzheimer’s disease, schizophrenia, and autism spectrum disorder, we find that well-trained models have a high area-under-the-curve (AUC) on subjects across different subgroups pertaining to attributes such as gender, age, racial groups and different clinical studies and are unbiased under multiple fairness metrics such as demographic parity difference, equalized odds difference, equal opportunity difference, etc. We find that models that incorporate multisource data from demographic, clinical, genetic factors, and cognitive scores are also unbiased. These models have a better predictive AUC across subgroups than those trained only with imaging features, but there are also situations when these additional features do not help.

Multiple sclerosis (MS) lesions occupy a small fraction of the brain volume, and are heterogeneous with regards to shape, size and locations, which poses a great challenge for training deep learning based segmentation models. We proposed a new geometric loss formula to address the data imbalance and exploit the geometric property of MS lesions. We showed that traditional region-based and boundary-aware loss functions can be associated with the formula. We further develop and instantiate two loss functions containing first-and second-order geometric information of lesion regions to enforce regularization on optimizing deep segmentation models. Experimental results on two MS lesion datasets with different scales, acquisition protocols and resolutions demonstrated the superiority of our proposed methods compared to other stateof-the-art methods.

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