The computer-assisted analysis for better interpreting images have been longstanding issues in the medical imaging field. On the image-understanding front, recent advances in machine learning, especially, in the way of deep learning, have made a big leap to help identify, classify, and quantify patterns in medical images. Specifically, exploiting hierarchical feature representations learned solely from data, instead of handcrafted features mostly designed based on domain-specific knowledge, lies at the core of the advances. In that way, deep learning is rapidly proving to be the state-of-the-art foundation, achieving enhanced performances in various medical applications. In this article, we introduce the fundamentals of deep learning methods; review their successes to image registration, anatomical/cell structures detection, tissue segmentation, computer-aided disease diagnosis or prognosis, and so on. We conclude by raising research issues and suggesting future directions for further improvements.

For the last decade, it has been shown that neuroimaging can be a potential tool for the diagnosis of Alzheimer’s Disease (AD) and its prodromal stage, Mild Cognitive Impairment (MCI), and also fusion of different modalities can further provide the complementary information to enhance diagnostic accuracy. Here, we focus on the problems of both feature representation and fusion of multimodal information from Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). To our best knowledge, the previous methods in the literature mostly used hand-crafted features such as cortical thickness, gray matter densities from MRI, or voxel intensities from PET, and then combined these multimodal features by simply concatenating into a long vector or transforming into a higher-dimensional kernel space. In this paper, we propose a novel method for a high-level latent and shared feature representation from neuroimaging modalities via deep learning. Specifically, we use Deep Boltzmann Machine (DBM)1, a deep network with a restricted Boltzmann machine as a building block, to find a latent hierarchical feature representation from a 3D patch, and then devise a systematic method for a joint feature representation from the paired patches of MRI and PET with a multimodal DBM. To validate the effectiveness of the proposed method, we performed experiments on ADNI dataset and compared with the state-of-the-art methods. In three binary classification problems of AD vs. healthy Normal Control (NC), MCI vs. NC, and MCI converter vs. MCI non-converter, we obtained the maximal accuracies of 95.35%, 85.67%, and 74.58%, respectively, outperforming the competing methods. By visual inspection of the trained model, we observed that the proposed method could hierarchically discover the complex latent patterns inherent in both MRI and PET.

Recently, there have been great interests for computer-aided diagnosis of Alzheimer’s disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Unlike the previous methods that considered simple low-level features such as gray matter tissue volumes from MRI, and mean signal intensities from PET, in this paper, we propose a deep learning-based latent feature representation with a stacked auto-encoder (SAE). We believe that there exist latent non-linear complicated patterns inherent in the low-level features such as relations among features. Combining the latent information with the original features helps build a robust model in AD/MCI classification, with high diagnostic accuracy. Furthermore, thanks to the unsupervised characteristic of the pre-training in deep learning, we can benefit from the target-unrelated samples to initialize parameters of SAE, thus finding optimal parameters in fine-tuning with the target-related samples, and further enhancing the classification performances across four binary classification problems: AD vs. healthy normal control (HC), MCI vs. HC, AD vs. MCI, and MCI converter (MCI-C) vs. MCI non-converter (MCI-NC). In our experiments on ADNI dataset, we validated the effectiveness of the proposed method, showing the accuracies of 98.8, 90.7, 83.7, and 83.3 % for AD/HC, MCI/HC, AD/MCI, and MCI-C/MCI-NC classification, respectively. We believe that deep learning can shed new light on the neuroimaging data analysis, and our work presented the applicability of this method to brain disease diagnosis.

Combining multi-modality brain data for disease diagnosis commonly leads to improved performance. A challenge in using multi-modality data is that the data are commonly incomplete; namely, some modality might be missing for some subjects. In this work, we proposed a deep learning based framework for estimating multi-modality imaging data. Our method takes the form of convolutional neural networks, where the input and output are two volumetric modalities. The network contains a large number of trainable parameters that capture the relationship between input and output modalities. When trained on subjects with all modalities, the network can estimate the output modality given the input modality. We evaluated our method on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, where the input and output modalities are MRI and PET images, respectively. Results showed that our method significantly outperformed prior methods.