Deep neural networks, including Convolutional Neural Networks (CNNs) and Visual Transformers (ViT), have achieved stunning success in medical image domain. We study thorax disease classification in this paper. Effective extraction of features for the disease areas is crucial for disease classification on radiographic images. While various neural architectures and training techniques, such as self-supervised learning with contrastive/restorative learning, have been employed for disease classification on radiographic images, there are no principled methods which can effectively reduce the adverse effect of noise and background, or non-disease areas, on the radiographic images for disease classification. To address this challenge, we propose a novel Low-Rank Feature Learning (LRFL) method in this paper, which is universally applicable to the training of all neural networks. The LRFL method is both empirically motivated by the low frequency property observed on all the medical datasets in this paper, and theoretically motivated by our sharp generalization bound for neural networks with low-rank features. In the empirical study, using a neural network such as a ViT or a CNN pre-trained on unlabeled chest X-rays by Masked Autoencoders (MAE), our novel LRFL method is applied on the pre-trained neural network and demonstrate better classification results in terms of both multiclass area under the receiver operating curve (mAUC) and classification accuracy.

The ability to classify images is dependent on having access to large labeled datasets and testing on data from the same domain that the model can train on. Classification becomes more challenging when dealing with new data from a different domain, where gathering and especially labeling a larger image dataset for retraining a classification model requires a labor-intensive human effort. Cross-domain classification frameworks were developed to handle this data domain shift problem by utilizing unsupervised image-to-image translation models to translate an input image from the unlabeled domain to the labeled domain. The problem with these unsupervised models lies in their unsupervised nature. For lack of annotations, it is not possible to use the traditional supervised metrics to evaluate these translation models to pick the best-saved checkpoint model. This paper introduces a new method called Domain-knowledge Inspired Pseudo Supervision (DIPS) which utilizes domain-informed Gaussian Mixture Models to generate pseudo annotations to enable the use of traditional supervised metrics. This method was designed specifically to support cross-domain classification applications contrary to other typically used metrics such as the FID which were designed to evaluate the model in terms of the quality of the generated image from a human-eye perspective. DIPS proves its effectiveness by outperforming various GAN evaluation metrics, including FID, when selecting the optimal saved checkpoint model. It is also evaluated against truly supervised metrics. Furthermore, DIPS showcases its robustness and interpretability by demonstrating a strong correlation with truly supervised metrics, highlighting its superiority over existing state-of-the-art alternatives. The code and data to replicate the results can be found on the official Github repository: https://github.com/Hindawi91/DIPS

Harnessing the power of deep neural networks in the medical imaging domain is challenging due to the difficulties in acquiring large annotated datasets, especially for rare diseases, which involve high costs, time, and effort for annotation. Unsupervised disease detection methods, such as anomaly detection, can significantly reduce human effort in these scenarios. While anomaly detection typically focuses on learning from images of healthy subjects only, real-world situations often present unannotated datasets with a mixture of healthy and diseased subjects. Recent studies have demonstrated that utilizing such unannotated images can improve unsupervised disease and anomaly detection. However, these methods do not utilize knowledge specific to registered neuroimages, resulting in a subpar performance in neurologic disease detection. To address this limitation, we propose Brainomaly, a GAN-based image-to-image translation method specifically designed for neurologic disease detection. Brainomaly not only offers tailored image-to-image translation suitable for neuroimages but also leverages unannotated mixed images to achieve superior neurologic disease detection. Additionally, we address the issue of model selection for inference without annotated samples by proposing a pseudo-AUC metric, further enhancing Brainomaly's detection performance. Extensive experiments and ablation studies demonstrate that Brainomaly outperforms existing state-of-the-art unsupervised disease and anomaly detection methods by significant margins in Alzheimer's disease detection using a publicly available dataset and headache detection using an institutional dataset. The code is available from https://github.com/mahfuzmohammad/Brainomaly.

Diagnosis of Alzheimer's disease (AD) at the early stage of the disease development is of great clinical importance. Current clinical assessment that relies primarily on cognitive measures proves low sensitivity and specificity. The fast growing neuroimaging techniques hold great promise. Research so far has focused on single neuroimaging modalities. However, as different modalities provide complementary measures for the same disease pathology, fusion of multi-modality data may increase the statistical power in identification of disease-related brain regions. This is especially true for early AD, at which stage the disease-related regions are most likely to be weak-effect regions that are difficult to be detected from a single modality alone. We propose a sparse composite linear discriminant analysis model (SCLDA) for identification of disease-related brain regions of early AD from multi-modality data. SCLDA uses a novel formulation that decomposes each LDA parameter into a product of a common parameter shared by all the modalities and a parameter specific to each modality, which enables joint analysis of all the modalities and borrowing strength from one another. We prove that this formulation is equivalent to a penalized likelihood with non-convex regularization, which can be solved by the DC ((difference of convex functions) programming. We show that in using the DC programming, the property of the non-convex regularization in terms of preserving weak-effect features can be nicely revealed. We perform extensive simulations to show that SCLDA outperforms existing competing algorithms on feature selection, especially on the ability for identifying weak-effect features. We apply SCLDA to the Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) images of 49 AD patients and 67 normal controls (NC). Our study identifies disease-related brain regions consistent with findings in the AD literature.

Recent advances in neuroimaging techniques provide great potentials for effective diagnosis of Alzheimer's disease (AD), the most common form of dementia. Previous studies have shown that AD is closely related to the alternation in the functional brain network, i.e., the functional connectivity among different brain regions. In this paper, we consider the problem of learning functional brain connectivity from neuroimaging, which holds great promise for identifying image-based markers used to distinguish Normal Controls (NC), patients with Mild Cognitive Impairment (MCI), and patients with AD. More specifically, we study sparse inverse covariance estimation (SICE), also known as exploratory Gaussian graphical models, for brain connectivity modeling. In particular, we apply SICE to learn and analyze functional brain connectivity patterns from different subject groups, based on a key property of SICE, called the "monotone property" we established in this paper. Our experimental results on neuroimaging PET data of 42 AD, 116 MCI, and 67 NC subjects reveal several interesting connectivity patterns consistent with literature findings, and also some new patterns that can help the knowledge discovery of AD.