Parcellation of anatomically segregated cortical and subcortical brain regions is required in diffusion MRI (dMRI) analysis for region-specific quantification and better anatomical specificity of tractography. Most current dMRI parcellation approaches compute the parcellation from anatomical MRI (T1- or T2-weighted) data, using tools such as FreeSurfer or CAT12, and then register it to the diffusion space. However, the registration is challenging due to image distortions and low resolution of dMRI data, often resulting in mislabeling in the derived brain parcellation. Furthermore, these approaches are not applicable when anatomical MRI data is unavailable. As an alternative we developed the Deep Diffusion Parcellation (DDParcel), a deep learning method for fast and accurate parcellation of brain anatomical regions directly from dMRI data. The input to DDParcel are dMRI parameter maps and the output are labels for 101 anatomical regions corresponding to the FreeSurfer Desikan-Killiany (DK) parcellation. A multi-level fusion network leverages complementary information in the different input maps, at three network levels: input, intermediate layer, and output. DDParcel learns the registration of diffusion features to anatomical MRI from the high-quality Human Connectome Project data. Then, to predict brain parcellation for a new subject, the DDParcel network no longer requires anatomical MRI data but only the dMRI data. Comparing DDParcel's parcellation with T1w-based parcellation shows higher test-retest reproducibility and a higher regional homogeneity, while requiring much less computational time. Generalizability is demonstrated on a range of populations and dMRI acquisition protocols. Utility of DDParcel's parcellation is demonstrated on tractography analysis for fiber tract identification.

We present a novel weakly-supervised framework for classifying whole slide images (WSIs). WSIs, due to their gigapixel resolution, are commonly processed by patch-wise classification with patch-level labels. However, patch-level labels require precise annotations, which is expensive and usually unavailable on clinical data. With image-level labels only, patch-wise classification would be sub-optimal due to inconsistency between the patch appearance and image-level label. To address this issue, we posit that WSI analysis can be effectively conducted by integrating information at both high magnification (local) and low magnification (regional) levels. We auto-encode the visual signals in each patch into a latent embedding vector representing local information, and down-sample the raw WSI to hardware-acceptable thumbnails representing regional information. The WSI label is then predicted with a Dual-Stream Network (DSNet), which takes the transformed local patch embeddings and multi-scale thumbnail images as inputs and can be trained by the image-level label only. Experiments conducted on three large-scale public datasets demonstrate that our method outperforms all recent state-of-the-art weakly-supervised WSI classification methods.

In this paper, we present a deep learning method, DDMReg, for accurate registration between diffusion MRI (dMRI) datasets. In dMRI registration, the goal is to spatially align brain anatomical structures while ensuring that local fiber orientations remain consistent with the underlying white matter fiber tract anatomy. DDMReg is a novel method that uses joint whole-brain and tract-specific information for dMRI registration. Based on the successful VoxelMorph framework for image registration, we propose a novel registration architecture that leverages not only whole brain information but also tract-specific fiber orientation information. DDMReg is an unsupervised method for deformable registration between pairs of dMRI datasets: it does not require nonlinearly pre-registered training data or the corresponding deformation fields as ground truth. We perform comparisons with four state-of-the-art registration methods on multiple independently acquired datasets from different populations (including teenagers, young and elderly adults) and different imaging protocols and scanners. We evaluate the registration performance by assessing the ability to align anatomically corresponding brain structures and ensure fiber spatial agreement between different subjects after registration. Experimental results show that DDMReg obtains significantly improved registration performance compared to the state-of-the-art methods. Importantly, we demonstrate successful generalization of DDMReg to dMRI data from different populations with varying ages and acquired using different acquisition protocols and different scanners.

Tractography from high-dimensional diffusion magnetic resonance imaging (dMRI) data allows brain's structural connectivity analysis. Recent dMRI studies aim to compare connectivity patterns across subject groups and disease populations to understand subtle abnormalities in the brain's white matter connectivity and distributions of biologically sensitive dMRI derived metrics. Existing software products focus solely on the anatomy, are not intuitive or restrict the comparison of multiple subjects. In this paper, we present the design and implementation of FiberStars, a visual analysis tool for tractography data that allows the interactive visualization of brain fiber clusters combining existing 3D anatomy with compact 2D visualizations. With FiberStars, researchers can analyze and compare multiple subjects in large collections of brain fibers using different views. To evaluate the usability of our software, we performed a quantitative user study. We asked domain experts and non-experts to find patterns in a tractography dataset with either FiberStars or an existing dMRI exploration tool. Our results show that participants using FiberStars can navigate extensive collections of tractography faster and more accurately. All our research, software, and results are available openly.

In this work, we present an unsupervised domain adaptation (UDA) method, named Panoptic Domain Adaptive Mask R-CNN (PDAM), for unsupervised instance segmentation in microscopy images. Since there currently lack methods particularly for UDA instance segmentation, we first design a Domain Adaptive Mask R-CNN (DAM) as the baseline, with cross-domain feature alignment at the image and instance levels. In addition to the image- and instance-level domain discrepancy, there also exists domain bias at the semantic level in the contextual information. Next, we, therefore, design a semantic segmentation branch with a domain discriminator to bridge the domain gap at the contextual level. By integrating the semantic- and instance-level feature adaptation, our method aligns the cross-domain features at the panoptic level. Third, we propose a task re-weighting mechanism to assign trade-off weights for the detection and segmentation loss functions. The task re-weighting mechanism solves the domain bias issue by alleviating the task learning for some iterations when the features contain source-specific factors. Furthermore, we design a feature similarity maximization mechanism to facilitate instance-level feature adaptation from the perspective of representational learning. Different from the typical feature alignment methods, our feature similarity maximization mechanism separates the domain-invariant and domain-specific features by enlarging their feature distribution dependency. Experimental results on three UDA instance segmentation scenarios with five datasets demonstrate the effectiveness of our proposed PDAM method, which outperforms state-of-the-art UDA methods by a large margin.

Unsupervised domain adaptation (UDA) for nuclei instance segmentation is important for digital pathology, as it alleviates the burden of labor-intensive annotation and domain shift across datasets. In this work, we propose a Cycle Consistency Panoptic Domain Adaptive Mask R-CNN (CyC-PDAM) architecture for unsupervised nuclei segmentation in histopathology images, by learning from fluorescence microscopy images. More specifically, we first propose a nuclei inpainting mechanism to remove the auxiliary generated objects in the synthesized images. Secondly, a semantic branch with a domain discriminator is designed to achieve panoptic-level domain adaptation. Thirdly, in order to avoid the influence of the source-biased features, we propose a task re-weighting mechanism to dynamically add trade-off weights for the task-specific loss functions. Experimental results on three datasets indicate that our proposed method outperforms state-of-the-art UDA methods significantly, and demonstrates a similar performance as fully supervised methods.

Automated detection and segmentation of individual nuclei in histopathology images is important for cancer diagnosis and prognosis. Due to the high variability of nuclei appearances and numerous overlapping objects, this task still remains challenging. Deep learning based semantic and instance segmentation models have been proposed to address the challenges, but these methods tend to concentrate on either the global or local features and hence still suffer from information loss. In this work, we propose a panoptic segmentation model which incorporates an auxiliary semantic segmentation branch with the instance branch to integrate global and local features. Furthermore, we design a feature map fusion mechanism in the instance branch and a new mask generator to prevent information loss. Experimental results on three different histopathology datasets demonstrate that our method outperforms the state-of-the-art nuclei segmentation methods and popular semantic and instance segmentation models by a large margin.

Texture classification has been extensively studied in computer vision. Recent research shows that the combination of Fisher vector (FV) encoding and convolutional neural network (CNN) provides significant improvement in texture classification over the previous feature representation methods. However, by truncating the CNN model at the last convolutional layer, the CNN-based FV descriptors would not incorporate the full capability of neural networks in feature learning. In this study, we propose that we can further transform the CNN-based FV descriptors in a neural network model to obtain more discriminative feature representations. In particular, we design a locally-transferred Fisher vector (LFV) method, which involves a multi-layer neural network model containing locally connected layers to transform the input FV descriptors with filters of locally shared weights. The network is optimized based on the hinge loss of classification, and transferred FV descriptors are then used for image classification. Our results on three challenging texture image datasets show improved performance over the state-of-the-art approaches.

We propose a new white matter atlas creation method that learns a model of the common white matter structures present in a group of subjects. We demonstrate that our atlas creation method, which is based on group spectral clustering of tractography, discovers structures corresponding to expected white matter anatomy such as the corpus callosum, uncinate fasciculus, cingulum bundles, arcuate fasciculus, and corona radiata. The white matter clusters are augmented with expert anatomical labels and stored in a new type of atlas that we call a high-dimensional white matter atlas. We then show how to perform automatic segmentation of tractography from novel subjects by extending the spectral clustering solution, stored in the atlas, using the Nystrom method. We present results regarding the stability of our method and parameter choices. Finally we give results from an atlas creation and automatic segmentation experiment. We demonstrate that our automatic tractography segmentation identifies corresponding white matter regions across hemispheres and across subjects, enabling group comparison of white matter anatomy.