Finding Significant Hits in Networks (FISHNET) uses prior biological knowledge, represented as gene interaction networks and gene function annotations, to identify genes that do not meet the genome-wide significance threshold but replicate, nonetheless. Its input is gene-level P-values from any source, including omicsWAS, aggregation of genome-wide association studies P-values, CRISPR screens, or differential expression analysis. It is based on the idea that genes whose P-values are low purely by chance are distributed randomly across networks and functions, so genes with suggestive P-values that cluster in densely connected subnetworks and share common functions are less likely to reflect chance and more likely to replicate. FISHNET combines network and function analysis with permutation-based P-value thresholds to identify a small set of exceptional genes that we call FISHNET genes. Applied to 11 cardiovascular risk traits, FISHNET identified 19 gene-trait relationships that missed genome-wide significance thresholds but, nonetheless, replicated in an independent cohort. The replication rate of FISHNET genes matched that of genes with lower P-values. FISHNET identified a novel association between RUNX1 expression and HDL that is supported by experimental evidence that RUNX1 promotes white fat browning, which increases HDL cholesterol levels. FISHNET also identified an association between LTB expression and BMI that is supported by experimental evidence that higher LTB expression increases BMI via activation of the LTβR pathway. Both associations failed genome-wide significance thresholds, highlighting FISHNET's ability to uncover meaningful relationships missed by traditional methods. FISHNET software is freely available at https://brentlab.github.io/fishnet/.

In clinical practice, multi-modal magnetic resonance imaging (MRI) with different contrasts is usually acquired in a single study to assess different properties of the same region of interest in the human body. The whole acquisition process can be accelerated by having one or more modalities under-sampled in the k -space. Recent research has shown that, considering the redundancy between different modalities, a target MRI modality under-sampled in the k -space can be more efficiently reconstructed with a fully-sampled reference MRI modality. However, we find that the performance of the aforementioned multi-modal reconstruction can be negatively affected by subtle spatial misalignment between different modalities, which is actually common in clinical practice. In this paper, we improve the quality of multi-modal reconstruction by compensating for such spatial misalignment with a spatial alignment network. First, our spatial alignment network estimates the displacement between the fully-sampled reference and the under-sampled target images, and warps the reference image accordingly. Then, the aligned fully-sampled reference image joins the multi-modal reconstruction of the under-sampled target image. Also, considering the contrast difference between the target and reference images, we have designed a cross-modality-synthesis-based registration loss in combination with the reconstruction loss, to jointly train the spatial alignment network and the reconstruction network. The experiments on both clinical MRI and multi-coil k -space raw data demonstrate the superiority and robustness of the multi-modal MRI reconstruction empowered with our spatial alignment network. Our code is publicly available at https://github.com/woxuankai/SpatialAlignmentNetwork.

Lumbar spondylolisthesis is one of the most common spinal diseases. It is caused by the anterior shift of a lumbar vertebrae relative to subjacent vertebrae. In current clinical practices, staging of spondylolisthesis is often conducted in a qualitative way. Although meyerding grading opens the door to stage spondylolisthesis in a more quantitative way, it relies on the manual measurement, which is time consuming and irreproducible. Thus, an automatic measurement algorithm becomes desirable for spondylolisthesis diagnosis and staging. However, there are two challenges. 1) Accurate detection of the most anterior and posterior points on the superior and inferior surfaces of each lumbar vertebrae. Due to the small size of the vertebrae, slight errors of detection may lead to significant measurement errors, hence, wrong disease stages. 2) Automatic localize and label each lumbar vertebrae is required to provide the semantic meaning of the measurement. It is difficult since different lumbar vertebraes have high similarity of both shape and image appearance. To resolve these challenges, a new auto measurement framework is proposed with two major contributions: First, a learning based spine labeling method that integrates both the image appearance and spine geometry information is designed to detect lumbar vertebrae. Second, a hierarchical method using both the population information from atlases and domain-specific information in the target image is proposed for most anterior and posterior points positioning. Validated on 258 CT spondylolisthesis patients, our method shows very similar results to manual measurements by radiologists and significantly increases the measurement efficiency.

In general image recognition problems, discriminative information often lies in local image patches. For example, most human identity information exists in the image patches containing human faces. The same situation stays in medical images as well. "Bodypart identity" of a transversal slice-which bodypart the slice comes from-is often indicated by local image information, e.g., a cardiac slice and an aorta arch slice are only differentiated by the mediastinum region. In this work, we design a multi-stage deep learning framework for image classification and apply it on bodypart recognition. Specifically, the proposed framework aims at: 1) discover the local regions that are discriminative and non-informative to the image classification problem, and 2) learn a image-level classifier based on these local regions. We achieve these two tasks by the two stages of learning scheme, respectively. In the pre-train stage, a convolutional neural network (CNN) is learned in a multi-instance learning fashion to extract the most discriminative and and non-informative local patches from the training slices. In the boosting stage, the pre-learned CNN is further boosted by these local patches for image classification. The CNN learned by exploiting the discriminative local appearances becomes more accurate than those learned from global image context. The key hallmark of our method is that it automatically discovers the discriminative and non-informative local patches through multi-instance deep learning. Thus, no manual annotation is required. Our method is validated on a synthetic dataset and a large scale CT dataset. It achieves better performances than state-of-the-art approaches, including the standard deep CNN.

Conventional learning-based methods for segmenting prostate in CT images ignore the relations among the low-level features by assuming all these features are independent. Also, their feature selection steps usually neglect the image appearance changes in different local regions of CT images. To this end, we present a novel semi-automatic learning-based prostate segmentation method in this article. For segmenting the prostate in a certain treatment image, the radiation oncologist will be first asked to take a few seconds to manually specify the first and last slices of the prostate. Then, prostate is segmented with the following two steps: (i) Estimation of 3D prostate-likelihood map to predict the likelihood of each voxel being prostate by employing the coupled feature representation, and the proposed Spatial-COnstrained Transductive LassO (SCOTO); (ii) Multi-atlases based label fusion to generate the final segmentation result by using the prostate shape information obtained from both planning and previous treatment images. The major contribution of the proposed method mainly includes: (i) incorporating radiation oncologist's manual specification to aid segmentation, (ii) adopting coupled features to relax previous assumption of feature independency for voxel representation, and (iii) developing SCOTO for joint feature selection across different local regions. The experimental result shows that the proposed method outperforms the state-of-the-art methods in a real-world prostate CT dataset, consisting of 24 patients with totally 330 images, all of which were manually delineated by the radiation oncologist for performance evaluation. Moreover, our method is also clinically feasible, since the segmentation performance can be improved by just requiring the radiation oncologist to spend only a few seconds for manual specification of ending slices in the current treatment CT image.

In this paper, we propose a new framework for tackling face recognition problem. The face recognition problem is formulated as groupwise deformable image registration and feature matching problem. The main contributions of the proposed method lie in the following aspects: (1) Each pixel in a facial image is represented by an anatomical signature obtained from its corresponding most salient scale local region determined by the survival exponential entropy (SEE) information theoretic measure. (2) Based on the anatomical signature calculated from each pixel, a novel Markov random field based groupwise registration framework is proposed to formulate the face recognition problem as a feature guided deformable image registration problem. The similarity between different facial images are measured on the nonlinear Riemannian manifold based on the deformable transformations. (3) The proposed method does not suffer from the generalizability problem which exists commonly in learning based algorithms. The proposed method has been extensively evaluated on four publicly available databases: FERET, CAS-PEAL-R1, FRGC ver 2.0, and the LFW. It is also compared with several state-of-the-art face recognition approaches, and experimental results demonstrate that the proposed method consistently achieves the highest recognition rates among all the methods under comparison.

Accurate prostate segmentation in CT images is a significant yet challenging task for image guided radiotherapy. In this paper, a novel semi-automated prostate segmentation method is presented. Specifically, to segment the prostate in the current treatment image, the physician first takes a few seconds to manually specify the first and last slices of the prostate in the image space. Then, the prostate is segmented automatically by the proposed two steps: (i) The first step of prostate-likelihood estimation to predict the prostate likelihood for each voxel in the current treatment image, aiming to generate the 3-D prostate-likelihood map by the proposed Spatial-COnstrained Transductive LassO (SCOTO), (ii) The second step of multi-atlases based label fusion to generate the final segmentation result by using the prostate shape information obtained from the planning and previous treatment images. The experimental result shows that the proposed method outperforms several state-of-the-art methods on prostate segmentation in a real prostate CT dataset, consisting of 24 patients with 330 images. Moreover, it is also clinically feasible since our method just requires the physician to spend a few seconds on manual specification of the first and last slices of the prostate.

In this paper, we propose a new prostate computed tomography (CT) segmentation method for image guided radiation therapy. The main contributions of our method lie in the following aspects. 1) Instead of using voxel intensity information alone, patch-based representation in the discriminative feature space with logistic sparse LASSO is used as anatomical signature to deal with low contrast problem in prostate CT images. 2) Based on the proposed patch-based signature, a new multi-atlases label fusion method formulated under sparse representation framework is designed to segment prostate in the new treatment images, with guidance from the previous segmented images of the same patient. This method estimates the prostate likelihood of each voxel in the new treatment image from its nearby candidate voxels in the previous segmented images, based on the nonlocal mean principle and sparsity constraint. 3) A hierarchical labeling strategy is further designed to perform label fusion, where voxels with high confidence are first labeled for providing useful context information in the same image for aiding the labeling of the remaining voxels. 4) An online update mechanism is finally adopted to progressively collect more patient-specific information from newly segmented treatment images of the same patient, for adaptive and more accurate segmentation. The proposed method has been extensively evaluated on a prostate CT image database consisting of 24 patients where each patient has more than 10 treatment images, and further compared with several state-of-the-art prostate CT segmentation algorithms using various evaluation metrics. Experimental results demonstrate that the proposed method consistently achieves higher segmentation accuracy than any other methods under comparison.

There are two main issues that make nonrigid image registration a challenging task. First, voxel intensity similarity may not be necessarily equivalent to anatomical similarity in the image correspondence searching process. Second, during the imaging process, some interferences such as unexpected rotations of input volumes and monotonic gray-level bias fields can adversely affect the registration quality. In this paper, a new feature-based nonrigid image registration method is proposed. The proposed method is based on a new type of image feature, namely, uniform spherical region descriptor (USRD), as signatures for each voxel. The USRD is rotation and monotonic gray-level transformation invariant and can be efficiently calculated. The registration process is therefore formulated as a feature matching problem. The USRD feature is integrated with the Markov random field labeling framework in which energy function is defined for registration. The energy function is then optimized by the α-expansion algorithm. The proposed method has been compared with five state-of-the-art registration approaches on both the simulated and real 3-D databases obtained from the BrainWeb and Internet Brain Segmentation Repository, respectively. Experimental results demonstrate that the proposed method can achieve high registration accuracy and reliable robustness behavior.

Automatic segmentation of prostate in CT images plays an important role in medical image analysis and image guided radiation therapy. It remains as a challenging problem mainly due to three issues: First, the image contrast between the prostate and its surrounding tissues is low in prostate CT images and no obvious boundaries can be observed. Second, the unpredictable prostate motion causes large position variations of the prostate in the treatment images scanned at different treatment days. Third, the uncertainty of the existence of bowel gas in treatment images significantly changes the image appearance even for images taken from the same patient. To address these issues, in this paper we are motivated to propose a feature based learning framework for accurate prostate localization in CT images. The main contributions of the proposed method lie in the following aspects: (1) Anatomical features are extracted from input images and adopted as signatures for each voxel. The most robust and informative features are identified by the feature selection process to help localize the prostate. (2) Regions with salient features but irrelevant to the localization of prostate, such as regions filled with bowel gas are automatically filtered out by the proposed method. (3) An online update mechanism is adopted in this paper to adaptively combine both population information and patient-specific information to localize the prostate. The proposed method is evaluated on a CT prostate dataset of 24 patients to localize the prostate, where each patient has more than 10 longitudinal images scanned at different treatment times. It is also compared with several state-of- the-art prostate localization algorithms in CT images, and the experimental results demonstrate that the proposed method achieves the highest localization accuracy among all the methods under comparison.

In this paper, a new scheme to address the face recognition problem is proposed. Different from traditional face recognition approaches which represent each facial image by a single feature vector as the classification problem, the proposed method establishes a new way to formulate the face recognition problem as a deformable image registration problem. The main contributions of the paper lie in the following aspects: (i) Each pixel is represented by an anatomical feature signature calculated from its corresponding best scale salient region by using a new salient region detector based on the survival exponential entropy (SEE); (ii) The face recognition problem is formulated as a deformable image registration problem, the deformation model is represented by a Markov random field (MRF) labeling framework. Explicit pixel correspondence is established by the deformation framework. (iii) The survival exponential entropy based normalized mutual information (SEE-NMI) is proposed and integrated with the MRF based deformation model as the similarity measure to reflect the similarity between two facial images. The proposed method is evaluated on the FERET and FRGC version 2 databases and compared with several state-of-the-art face recognition approaches. Experimental results show that the proposed method achieves the highest recognition rate among all the compared approaches.

This paper proposes a new texture classification approach. There are two main contributions in the proposed method. First, input texture images are transformed to the composite Fourier domain (CFD) by using both the local and global Fourier transforms. The composite Fourier domain is rotation invariant and preserves the contextual information for the texture images in the original spatial domain. Second, the null-space based linear discriminant analysis (nLDA) is adopted to find the optimal representations of the texture images in the composite Fourier domain. This paper proposes a systematic way to cooperate subspace learning methods for texture classification in the frequency domain, which cannot be directly applied in the spatial domain for texture classification. The proposed method is evaluated on both the Brodatz and CUReT databases and compared with several state-of-the-art texture classification approaches. Experimental results show that the proposed method achieves the highest classification rate among all the compared methods.

A new feature based nonrigid image registration method for magnetic resonance (MR) brain images is presented in this paper. Each image voxel is represented by a rotation invariant feature vector, which is computed by passing the input image volumes through a new bank of symmetric alpha stable (SalphaS) filters. There are three main contributions presented in this paper. First, this work is motivated by the fact that the frequency spectrums of the brain MR images often exhibit non-Gaussian heavy-tail behavior which cannot be satisfactorily modeled by the conventional Gabor filters. To this end, we propose the use of SalphaS filters to model such behavior and show that the Gabor filter is a special case of the SalphaS filter. Second, the maximum response orientation (MRO) selection criterion is designed to extract rotation invariant features for registration tasks. The MRO selection criterion also significantly reduces the number of dimensions of feature vectors and therefore lowers the computation time. Third, in case the segmentations of the input image volumes are available, the Fisher's separation criterion (FSC) is introduced such that the discriminating power of different feature types can be directly compared with each other before performing the registration process. Using FSC, weights can also be assigned automatically to different voxels in the brain MR images. The weight of each voxel determined by FSC reflects how distinctive and salient the voxel is. Using the most distinctive and salient voxels at the initial stage to drive the registration can reduce the risk of being trapped in the local optimum during image registration process. The larger the weight, the more important the voxel. With the extracted feature vectors and the associated weights, the proposed method registers the source and the target images in a hierarchical multiresolution manner. The proposed method has been intensively evaluated on both simulated and real 3-D datasets obtained from BrainWeb and Internet Brain Segmentation Repository (IBSR), respectively, and compared with HAMMER, an extended version of HAMMER based on local histograms (LHF), FFD, Demons, and the Gabor filter based registration method. It is shown that the proposed method achieves the highest registration accuracy among the five widely used image registration methods.

This paper proposes a new face recognition method. There are two novelties in the proposed method. First, a new saliency measure function is designed to detect the most salient regions in facial images and determine their corresponding best scales. Second, a new type of image feature, called local gradient orientation binary pattern (LGOBP) is proposed, which captures the neighborhood gradient orientation information which is not considered in the conventional local binary patterns (LBP) to give more discriminant power. LGOBPs are extracted from the most salient regions selected by the proposed saliency measure function. The proposed method is evaluated on the FRGC version 2 database by comparing it with several widely used methods. Experimental results show that the proposed method achieves the highest recognition rate among all the compared methods.

This paper proposes a novel approach to extract image features for texture classification. The proposed features are robust to image rotation, less sensitive to histogram equalization and noise. It comprises of two sets of features: dominant local binary patterns (DLBP) in a texture image and the supplementary features extracted by using the circularly symmetric Gabor filter responses. The dominant local binary pattern method makes use of the most frequently occurred patterns to capture descriptive textural information, while the Gabor-based features aim at supplying additional global textural information to the DLBP features. Through experiments, the proposed approach has been intensively evaluated by applying a large number of classification tests to histogram-equalized, randomly rotated and noise corrupted images in Outex, Brodatz, Meastex, and CUReT texture image databases. Our method has also been compared with six published texture features in the experiments. It is experimentally demonstrated that the proposed method achieves the highest classification accuracy in various texture databases and image conditions.

In this paper, based on the SalphaS distributions, we design SalphaS filters and use the filters as a new feature extraction method for non-rigid medical image registration. In brain MR images, the energy distributions of different frequency bands often exhibit heavy-tailed behavior. Such non-Gaussian behavior is essential for non-rigid image registration but cannot be satisfactorily modeled by the conventional Gabor filters. This leads to unsatisfactory modeling of voxels located at the salient regions of the images. To this end, we propose the SalphaS filters for modeling the heavy-tailed behavior of the energy distributions of brain MR images, and show that the Gabor filter is a special case of the SalphaS filter. The maximum response orientation selection criterion is defined for each frequency band to achieve rotation invariance. In our framework, if the brain MR images are already segmented, each voxel can be automatically assigned a weighting factor based on the Fisher's separation criterion and it is shown that the registration performance can be further improved. The proposed method has been compared with the free-form-deformation based method, Demons algorithm and a method using Gabor features by conducting non-rigid image registration experiments. It is observed that the proposed method achieves the best registration accuracy among all the compared methods in both the simulated and real datasets obtained from the BrainWeb and IBSR respectively.

In this paper, we propose a new feature extraction method, which is robust against rotation and histogram equalization for texture classification. To this end, we introduce the concept of advanced local binary patterns (ALBP), which reflects the local dominant structural characteristics of different kinds of textures. In addition, to extract the global spatial distribution feature of the ALBP patterns, we incooperate ALBP with the aura matrix measure as the second layer to analyze texture images. The proposed method has three novel contributions, (a) The proposed ALBP approach captures the most essential local structure characteristics of texture images (i.e. edges, corners); (b) the proposed method extracts global information by using Aura matrix measure based on the spatial distribution information of the dominant patterns produced by ALBP; and (c) the proposed method is robust to rotation and histogram equalization. The proposed approach has been compared with other widely used texture classification techniques and evaluated by applying classification tests to randomly rotated and histogram equalized images in two different texture databases: Brodatz and CUReT. The experimental results show that the classification accuracy of the proposed method exceeds the ones obtained by other image features.

This paper proposes a novel facial expression recognition approach based on two sets of features extracted from the face images: texture features and global appearance features. The first set is obtained by using the extended local binary patterns in both intensity and gradient maps and computing the Tsallis entropy of the Gabor filtered responses. The second set of features is obtained by performing null-space based linear discriminant analysis on the training face images. The proposed method is evaluated by extensive experiments on the JAFFE database, and compared with two widely used facial expression recognition approaches. Experimental results show that the proposed approach maintains high recognition rate in a wide range of resolution levels and outperforms the other alternative methods.