Structural magnetic resonance imaging (sMRI) has been widely used for computer-aided diagnosis of neurodegenerative disorders, e.g., Alzheimer's disease (AD), due to its sensitivity to morphological changes caused by brain atrophy. Recently, a few deep learning methods (e.g., convolutional neural networks, CNNs) have been proposed to learn task-oriented features from sMRI for AD diagnosis, and achieved superior performance than the conventional learning-based methods using hand-crafted features. However, these existing CNN-based methods still require the pre-determination of informative locations in sMRI. That is, the stage of discriminative atrophy localization is isolated to the latter stages of feature extraction and classifier construction. In this paper, we propose a hierarchical fully convolutional network (H-FCN) to automatically identify discriminative local patches and regions in the whole brain sMRI, upon which multi-scale feature representations are then jointly learned and fused to construct hierarchical classification models for AD diagnosis. Our proposed H-FCN method was evaluated on a large cohort of subjects from two independent datasets (i.e., ADNI-1 and ADNI-2), demonstrating good performance on joint discriminative atrophy localization and brain disease diagnosis.

In the field of computer-aided Alzheimer's disease (AD) diagnosis, jointly identifying brain diseases and predicting clinical scores using magnetic resonance imaging (MRI) have attracted increasing attention since these two tasks are highly correlated. Most of existing joint learning approaches require hand-crafted feature representations for MR images. Since hand-crafted features of MRI and classification/regression models may not coordinate well with each other, conventional methods may lead to sub-optimal learning performance. Also, demographic information (e.g., age, gender, and education) of subjects may also be related to brain status, and thus can help improve the diagnostic performance. However, conventional joint learning methods seldom incorporate such demographic information into the learning models. To this end, we propose a deep multi-task multi-channel learning (DM2L) framework for simultaneous brain disease classification and clinical score regression, using MRI data and demographic information of subjects. Specifically, we first identify the discriminative anatomical landmarks from MR images in a data-driven manner, and then extract multiple image patches around these detected landmarks. We then propose a deep multi-task multi-channel convolutional neural network for joint classification and regression. Our DM2L framework can not only automatically learn discriminative features for MR images, but also explicitly incorporate the demographic information of subjects into the learning process. We evaluate the proposed method on four large multi-center cohorts with 1984 subjects, and the experimental results demonstrate that DM2 L is superior to several state-of-the-art joint learning methods in both the tasks of disease classification and clinical score regression.

Structural magnetic resonance imaging (MRI) is a very popular and effective technique used to diagnose Alzheimer's disease (AD). The success of computer-aided diagnosis methods using structural MRI data is largely dependent on the two time-consuming steps: 1) nonlinear registration across subjects, and 2) brain tissue segmentation. To overcome this limitation, we propose a landmark-based feature extraction method that does not require nonlinear registration and tissue segmentation. In the training stage, in order to distinguish AD subjects from healthy controls (HCs), group comparisons, based on local morphological features, are first performed to identify brain regions that have significant group differences. In general, the centers of the identified regions become landmark locations (or AD landmarks for short) capable of differentiating AD subjects from HCs. In the testing stage, using the learned AD landmarks, the corresponding landmarks are detected in a testing image using an efficient technique based on a shape-constrained regression-forest algorithm. To improve detection accuracy, an additional set of salient and consistent landmarks are also identified to guide the AD landmark detection. Based on the identified AD landmarks, morphological features are extracted to train a support vector machine (SVM) classifier that is capable of predicting the AD condition. In the experiments, our method is evaluated on landmark detection and AD classification sequentially. Specifically, the landmark detection error (manually annotated versus automatically detected) of the proposed landmark detector is 2.41 mm, and our landmark-based AD classification accuracy is 83.7%. Lastly, the AD classification performance of our method is comparable to, or even better than, that achieved by existing region-based and voxel-based methods, while the proposed method is approximately 50 times faster.

One of the major challenges in anatomical landmark detection, based on deep neural networks, is the limited availability of medical imaging data for network learning. To address this problem, we present a two-stage task-oriented deep learning method to detect large-scale anatomical landmarks simultaneously in real time, using limited training data. Specifically, our method consists of two deep convolutional neural networks (CNN), with each focusing on one specific task. Specifically, to alleviate the problem of limited training data, in the first stage, we propose a CNN based regression model using millions of image patches as input, aiming to learn inherent associations between local image patches and target anatomical landmarks. To further model the correlations among image patches, in the second stage, we develop another CNN model, which includes a) a fully convolutional network that shares the same architecture and network weights as the CNN used in the first stage and also b) several extra layers to jointly predict coordinates of multiple anatomical landmarks. Importantly, our method can jointly detect large-scale (e.g., thousands of) landmarks in real time. We have conducted various experiments for detecting 1200 brain landmarks from the 3D T1-weighted magnetic resonance images of 700 subjects, and also 7 prostate landmarks from the 3D computed tomography images of 73 subjects. The experimental results show the effectiveness of our method regarding both accuracy and efficiency in the anatomical landmark detection.

Breast tumor segmentation based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a challenging problem and an active area of research. Particular challenges, similarly as in other segmentation problems, include the class-imbalance problem as well as confounding background in DCE-MR images. To address these issues, we propose a mask-guided hierarchical learning (MHL) framework for breast tumor segmentation via fully convolutional networks (FCN). Specifically, we first develop an FCN model to generate a 3D breast mask as the region of interest (ROI) for each image, to remove confounding information from input DCE-MR images. We then design a two-stage FCN model to perform coarse-to-fine segmentation for breast tumors. Particularly, we propose a Dice-Sensitivity-like loss function and a reinforcement sampling strategy to handle the class-imbalance problem. To precisely identify locations of tumors that underwent a biopsy, we further propose an FCN model to detect two landmarks located at two nipples. We finally select the biopsied tumor based on both identified landmarks and segmentations. We validate our MHL method on 272 patients, achieving a mean Dice similarity coefficient (DSC) of 0.72 which is comparable to mutual DSC between expert radiologists. Using the segmented biopsied tumors, we also demonstrate that the automatically generated masks can be applied to radiogenomics and can identify luminal A subtype from other molecular subtypes with the similar accuracy with the analysis based on semi-manual tumor segmentation.

Most automated techniques for brain disease diagnosis utilize hand-crafted (e.g., voxel-based or region-based) biomarkers from structural magnetic resonance (MR) images as feature representations. However, these hand-crafted features are usually high-dimensional or require regions-of-interest defined by experts. Also, because of possibly heterogeneous property between the hand-crafted features and the subsequent model, existing methods may lead to sub-optimal performances in brain disease diagnosis. In this paper, we propose a landmark-based deep feature learning (LDFL) framework to automatically extract patch-based representation from MRI for automatic diagnosis of Alzheimer's disease. We first identify discriminative anatomical landmarks from MR images in a data-driven manner, and then propose a convolutional neural network for patch-based deep feature learning. We have evaluated the proposed method on subjects from three public datasets, including the Alzheimer's disease neuroimaging initiative (ADNI-1), ADNI-2, and the minimal interval resonance imaging in alzheimer's disease (MIRIAD) dataset. Experimental results of both tasks of brain disease classification and MR image retrieval demonstrate that the proposed LDFL method improves the performance of disease classification and MR image retrieval.