Dagan Feng

Yige Peng, Jinman Kim, Dagan Feng et al.

Multi-modality Fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) has been routinely used in the assessment of common cancers, such as lung cancer, lymphoma, and melanoma. This is mainly attributed to the fact that PET/CT combines the high sensitivity for tumor detection of PET and anatomical information from CT. In PET/CT image assessment, automatic tumor segmentation is an important step, and in recent years, deep learning based methods have become the state-of-the-art. Unfortunately, existing methods tend to over-segment the tumor regions and include regions such as the normal high uptake organs, inflammation, and other infections. In this study, we introduce a false positive reduction network to overcome this limitation. We firstly introduced a self-supervised pre-trained global segmentation module to coarsely delineate the candidate tumor regions using a self-supervised pre-trained encoder. The candidate tumor regions were then refined by removing false positives via a local refinement module. Our experiments with the MICCAI 2022 Automated Lesion Segmentation in Whole-Body FDG-PET/CT (AutoPET) challenge dataset showed that our method achieved a dice score of 0.9324 with the preliminary testing data and was ranked 1st place in dice on the leaderboard. Our method was also ranked in the top 7 methods on the final testing data, the final ranking will be announced during the 2022 MICCAI AutoPET workshop. Our code is available at: https://github.com/YigePeng/AutoPET_False_Positive_Reduction.

Mingyuan Meng, Lei Bi, Michael Fulham et al.

Image registration is a fundamental requirement for medical image analysis. Deep registration methods based on deep learning have been widely recognized for their capabilities to perform fast end-to-end registration. Many deep registration methods achieved state-of-the-art performance by performing coarse-to-fine registration, where multiple registration steps were iterated with cascaded networks. Recently, Non-Iterative Coarse-to-finE (NICE) registration methods have been proposed to perform coarse-to-fine registration in a single network and showed advantages in both registration accuracy and runtime. However, existing NICE registration methods mainly focus on deformable registration, while affine registration, a common prerequisite, is still reliant on time-consuming traditional optimization-based methods or extra affine registration networks. In addition, existing NICE registration methods are limited by the intrinsic locality of convolution operations. Transformers may address this limitation for their capabilities to capture long-range dependency, but the benefits of using transformers for NICE registration have not been explored. In this study, we propose a Non-Iterative Coarse-to-finE Transformer network (NICE-Trans) for image registration. Our NICE-Trans is the first deep registration method that (i) performs joint affine and deformable coarse-to-fine registration within a single network, and (ii) embeds transformers into a NICE registration framework to model long-range relevance between images. Extensive experiments with seven public datasets show that our NICE-Trans outperforms state-of-the-art registration methods on both registration accuracy and runtime.

Mingyuan Meng, Michael Fulham, Dagan Feng et al.

Deformable image registration aims to find a dense non-linear spatial correspondence between a pair of images, which is a crucial step for many medical tasks such as tumor growth monitoring and population analysis. Recently, Deep Neural Networks (DNNs) have been widely recognized for their ability to perform fast end-to-end registration. However, DNN-based registration needs to explore the spatial information of each image and fuse this information to characterize spatial correspondence. This raises an essential question: what is the optimal fusion strategy to characterize spatial correspondence? Existing fusion strategies (e.g., early fusion, late fusion) were empirically designed to fuse information by manually defined prior knowledge, which inevitably constrains the registration performance within the limits of empirical designs. In this study, we depart from existing empirically-designed fusion strategies and develop a data-driven fusion strategy for deformable image registration. To achieve this, we propose an Automatic Fusion network (AutoFuse) that provides flexibility to fuse information at many potential locations within the network. A Fusion Gate (FG) module is also proposed to control how to fuse information at each potential network location based on training data. Our AutoFuse can automatically optimize its fusion strategy during training and can be generalizable to both unsupervised registration (without any labels) and semi-supervised registration (with weak labels provided for partial training data). Extensive experiments on two well-benchmarked medical registration tasks (inter- and intra-patient registration) with eight public datasets show that our AutoFuse outperforms state-of-the-art unsupervised and semi-supervised registration methods.

Wei-Chien Wang, Euijoon Ahn, Dagan Feng et al.

Over the last decade, supervised deep learning on manually annotated big data has been progressing significantly on computer vision tasks. But the application of deep learning in medical image analysis was limited by the scarcity of high-quality annotated medical imaging data. An emerging solution is self-supervised learning (SSL), among which contrastive SSL is the most successful approach to rivalling or outperforming supervised learning. This review investigates several state-of-the-art contrastive SSL algorithms originally on natural images as well as their adaptations for medical images, and concludes by discussing recent advances, current limitations, and future directions in applying contrastive SSL in the medical domain.

Mingyuan Meng, Lei Bi, Michael Fulham et al.

Survival prediction is crucial for cancer patients as it provides early prognostic information for treatment planning. Recently, deep survival models based on deep learning and medical images have shown promising performance for survival prediction. However, existing deep survival models are not well developed in utilizing multi-modality images (e.g., PET-CT) and in extracting region-specific information (e.g., the prognostic information in Primary Tumor (PT) and Metastatic Lymph Node (MLN) regions). In view of this, we propose a merging-diverging learning framework for survival prediction from multi-modality images. This framework has a merging encoder to fuse multi-modality information and a diverging decoder to extract region-specific information. In the merging encoder, we propose a Hybrid Parallel Cross-Attention (HPCA) block to effectively fuse multi-modality features via parallel convolutional layers and cross-attention transformers. In the diverging decoder, we propose a Region-specific Attention Gate (RAG) block to screen out the features related to lesion regions. Our framework is demonstrated on survival prediction from PET-CT images in Head and Neck (H&N) cancer, by designing an X-shape merging-diverging hybrid transformer network (named XSurv). Our XSurv combines the complementary information in PET and CT images and extracts the region-specific prognostic information in PT and MLN regions. Extensive experiments on the public dataset of HEad and neCK TumOR segmentation and outcome prediction challenge (HECKTOR 2022) demonstrate that our XSurv outperforms state-of-the-art survival prediction methods.

Mingyuan Meng, Lei Bi, Dagan Feng et al.

Deformable image registration is a crucial step in medical image analysis for finding a non-linear spatial transformation between a pair of fixed and moving images. Deep registration methods based on Convolutional Neural Networks (CNNs) have been widely used as they can perform image registration in a fast and end-to-end manner. However, these methods usually have limited performance for image pairs with large deformations. Recently, iterative deep registration methods have been used to alleviate this limitation, where the transformations are iteratively learned in a coarse-to-fine manner. However, iterative methods inevitably prolong the registration runtime, and tend to learn separate image features for each iteration, which hinders the features from being leveraged to facilitate the registration at later iterations. In this study, we propose a Non-Iterative Coarse-to-finE registration Network (NICE-Net) for deformable image registration. In the NICE-Net, we propose: (i) a Single-pass Deep Cumulative Learning (SDCL) decoder that can cumulatively learn coarse-to-fine transformations within a single pass (iteration) of the network, and (ii) a Selectively-propagated Feature Learning (SFL) encoder that can learn common image features for the whole coarse-to-fine registration process and selectively propagate the features as needed. Extensive experiments on six public datasets of 3D brain Magnetic Resonance Imaging (MRI) show that our proposed NICE-Net can outperform state-of-the-art iterative deep registration methods while only requiring similar runtime to non-iterative methods.

Mingyuan Meng, Lei Bi, Dagan Feng et al.

Outcome prediction is crucial for head and neck cancer patients as it can provide prognostic information for early treatment planning. Radiomics methods have been widely used for outcome prediction from medical images. However, these methods are limited by their reliance on intractable manual segmentation of tumor regions. Recently, deep learning methods have been proposed to perform end-to-end outcome prediction so as to remove the reliance on manual segmentation. Unfortunately, without segmentation masks, these methods will take the whole image as input, such that makes them difficult to focus on tumor regions and potentially unable to fully leverage the prognostic information within the tumor regions. In this study, we propose a radiomics-enhanced deep multi-task framework for outcome prediction from PET/CT images, in the context of HEad and neCK TumOR segmentation and outcome prediction challenge (HECKTOR 2022). In our framework, our novelty is to incorporate radiomics as an enhancement to our recently proposed Deep Multi-task Survival model (DeepMTS). The DeepMTS jointly learns to predict the survival risk scores of patients and the segmentation masks of tumor regions. Radiomics features are extracted from the predicted tumor regions and combined with the predicted survival risk scores for final outcome prediction, through which the prognostic information in tumor regions can be further leveraged. Our method achieved a C-index of 0.681 on the testing set, placing the 2nd on the leaderboard with only 0.00068 lower in C-index than the 1st place.

Mingyuan Meng, Lei Bi, Dagan Feng et al.

In this study, we focus on brain tumor sequence registration between pre-operative and follow-up Magnetic Resonance Imaging (MRI) scans of brain glioma patients, in the context of Brain Tumor Sequence Registration challenge (BraTS-Reg 2022). Brain tumor registration is a fundamental requirement in brain image analysis for quantifying tumor changes. This is a challenging task due to large deformations and missing correspondences between pre-operative and follow-up scans. For this task, we adopt our recently proposed Non-Iterative Coarse-to-finE registration Networks (NICE-Net) - a deep learning-based method for coarse-to-fine registering images with large deformations. To overcome missing correspondences, we extend the NICE-Net by introducing dual deep supervision, where a deep self-supervised loss based on image similarity and a deep weakly-supervised loss based on manually annotated landmarks are deeply embedded into the NICE-Net. At the BraTS-Reg 2022, our method achieved a competitive result on the validation set (mean absolute error: 3.387) and placed 4th in the final testing phase (Score: 0.3544).

Yuan Yuan, Euijoon Ahn, Dagan Feng et al.

Bi-parametric magnetic resonance imaging (bpMRI) has become a pivotal modality in the detection and diagnosis of clinically significant prostate cancer (csPCa). Developing AI-based systems to identify csPCa using bpMRI can transform PCa management by improving efficiency and cost-effectiveness. However, current state-of-the-art methods using convolutional neural networks (CNNs) are limited in learning in-plane and three-dimensional spatial information from anisotropic images. Their performances also depend on the availability of large, diverse, and well-annotated bpMRI datasets. We propose a Zonal-aware Self-supervised Mesh Network (Z-SSMNet) that adaptively integrates multi-dimensional (2D/2.5D/3D) convolutions to learn dense intra-slice information and sparse inter-slice information of the anisotropic bpMRI in a balanced manner. A self-supervised learning (SSL) technique is proposed to pre-train our network using large-scale unlabeled data to learn the appearance, texture, and structure semantics of bpMRI. It aims to capture both intra-slice and inter-slice information during the pre-training stage. Furthermore, we constrained our network to focus on the zonal anatomical regions to further improve the detection and diagnosis capability of csPCa. We conducted extensive experiments on the PI-CAI dataset comprising 10000+ multi-center and multi-scanner data. Our Z-SSMNet excelled in both lesion-level detection (AP score of 0.633) and patient-level diagnosis (AUROC score of 0.881), securing the top position in the Open Development Phase of the PI-CAI challenge and maintained strong performance, achieving an AP score of 0.690 and an AUROC score of 0.909, and securing the second-place ranking in the Closed Testing Phase.

Yuxin Xue, Yige Peng, Lei Bi et al.

Positron emission tomography (PET) is the most sensitive molecular imaging modality routinely applied in our modern healthcare. High radioactivity caused by the injected tracer dose is a major concern in PET imaging and limits its clinical applications. However, reducing the dose leads to inadequate image quality for diagnostic practice. Motivated by the need to produce high quality images with minimum low-dose, Convolutional Neural Networks (CNNs) based methods have been developed for high quality PET synthesis from its low-dose counterparts. Previous CNNs-based studies usually directly map low-dose PET into features space without consideration of different dose reduction level. In this study, a novel approach named CG-3DSRGAN (Classification-Guided Generative Adversarial Network with Super Resolution Refinement) is presented. Specifically, a multi-tasking coarse generator, guided by a classification head, allows for a more comprehensive understanding of the noise-level features present in the low-dose data, resulting in improved image synthesis. Moreover, to recover spatial details of standard PET, an auxiliary super resolution network - Contextual-Net - is proposed as a second-stage training to narrow the gap between coarse prediction and standard PET. We compared our method to the state-of-the-art methods on whole-body PET with different dose reduction factors (DRFs). Experiments demonstrate our method can outperform others on all DRF.

Mingyuan Meng, Yuxin Xue, Dagan Feng et al.

Dense prediction is a fundamental requirement for many medical vision tasks such as medical image restoration, registration, and segmentation. The most popular vision model, Convolutional Neural Networks (CNNs), has reached bottlenecks due to the intrinsic locality of convolution operations. Recently, transformers have been widely adopted for dense prediction for their capability to capture long-range visual dependence. However, due to the high computational complexity and large memory consumption of self-attention operations, transformers are usually used at downsampled feature resolutions. Such usage cannot effectively leverage the tissue-level textural information available only at the full image resolution. This textural information is crucial for medical dense prediction as it can differentiate the subtle human anatomy in medical images. In this study, we hypothesize that Multi-layer Perceptrons (MLPs) are superior alternatives to transformers in medical dense prediction where tissue-level details dominate the performance, as MLPs enable long-range dependence at the full image resolution. To validate our hypothesis, we develop a full-resolution hierarchical MLP framework that uses MLPs beginning from the full image resolution. We evaluate this framework with various MLP blocks on a wide range of medical dense prediction tasks including restoration, registration, and segmentation. Extensive experiments on six public well-benchmarked datasets show that, by simply using MLPs at full resolution, our framework outperforms its CNN and transformer counterparts and achieves state-of-the-art performance on various medical dense prediction tasks.

Yu-Xuan Chen, Dagan Feng, Hong-Bin Shen

Rigid image alignment is a fundamental task in computer vision, while the traditional algorithms are either too sensitive to noise or time-consuming. Recent unsupervised image alignment methods developed based on spatial transformer networks show an improved performance on clean images but will not achieve satisfactory performance on noisy images due to its heavy reliance on pixel value comparations. To handle such challenging applications, we report a new unsupervised difference learning (UDL) strategy and apply it to rigid image alignment. UDL exploits the quantitative properties of regression tasks and converts the original unsupervised problem to pseudo supervised problem. Under the new UDL-based image alignment pipeline, rotation can be accurately estimated on both clean and noisy images and translations can then be easily solved. Experimental results on both nature and cryo-EM images demonstrate the efficacy of our UDL-based unsupervised rigid image alignment method.

Shuchang Ye, Mingyuan Meng, Mingjian Li et al.

Segmentation of infected areas in chest X-rays is pivotal for facilitating the accurate delineation of pulmonary structures and pathological anomalies. Recently, multi-modal language-guided image segmentation methods have emerged as a promising solution for chest X-rays where the clinical text reports, depicting the assessment of the images, are used as guidance. Nevertheless, existing language-guided methods require clinical reports alongside the images, and hence, they are not applicable for use in image segmentation in a decision support context, but rather limited to retrospective image analysis after clinical reporting has been completed. In this study, we propose a self-guided segmentation framework (SGSeg) that leverages language guidance for training (multi-modal) while enabling text-free inference (uni-modal), which is the first that enables text-free inference in language-guided segmentation. We exploit the critical location information of both pulmonary and pathological structures depicted in the text reports and introduce a novel localization-enhanced report generation (LERG) module to generate clinical reports for self-guidance. Our LERG integrates an object detector and a location-based attention aggregator, weakly-supervised by a location-aware pseudo-label extraction module. Extensive experiments on a well-benchmarked QaTa-COV19 dataset demonstrate that our SGSeg achieved superior performance than existing uni-modal segmentation methods and closely matched the state-of-the-art performance of multi-modal language-guided segmentation methods.

Xiaoshuang Li, Mingyuan Meng, Zimo Huang et al.

Panoramic X-ray (PX) is a prevalent modality in dental practice for its wide availability and low cost. However, as a 2D projection image, PX does not contain 3D anatomical information, and therefore has limited use in dental applications that can benefit from 3D information, e.g., tooth angular misa-lignment detection and classification. Reconstructing 3D structures directly from 2D PX has recently been explored to address limitations with existing methods primarily reliant on Convolutional Neural Networks (CNNs) for direct 2D-to-3D mapping. These methods, however, are unable to correctly infer depth-axis spatial information. In addition, they are limited by the in-trinsic locality of convolution operations, as the convolution kernels only capture the information of immediate neighborhood pixels. In this study, we propose a progressive hybrid Multilayer Perceptron (MLP)-CNN pyra-mid network (3DPX) for 2D-to-3D oral PX reconstruction. We introduce a progressive reconstruction strategy, where 3D images are progressively re-constructed in the 3DPX with guidance imposed on the intermediate recon-struction result at each pyramid level. Further, motivated by the recent ad-vancement of MLPs that show promise in capturing fine-grained long-range dependency, our 3DPX integrates MLPs and CNNs to improve the semantic understanding during reconstruction. Extensive experiments on two large datasets involving 464 studies demonstrate that our 3DPX outperforms state-of-the-art 2D-to-3D oral reconstruction methods, including standalone MLP and transformers, in reconstruction quality, and also im-proves the performance of downstream angular misalignment classification tasks.

Xiaoshuang Li, Zimo Huang, Mingyuan Meng et al.

Panoramic X-ray (PX) is a prevalent modality in dentistry practice owing to its wide availability and low cost. However, as a 2D projection of a 3D structure, PX suffers from anatomical information loss and PX diagnosis is limited compared to that with 3D imaging modalities. 2D-to-3D reconstruction methods have been explored for the ability to synthesize the absent 3D anatomical information from 2D PX for use in PX image analysis. However, there are challenges in leveraging such 3D synthesized reconstructions. First, inferring 3D depth from 2D images remains a challenging task with limited accuracy. The second challenge is the joint analysis of 2D PX with its 3D synthesized counterpart, with the aim to maximize the 2D-3D synergy while minimizing the errors arising from the synthesized image. In this study, we propose a new method termed 3DPX - PX image analysis guided by 2D-to-3D reconstruction, to overcome these challenges. 3DPX consists of (i) a novel progressive reconstruction network to improve 2D-to-3D reconstruction and, (ii) a contrastive-guided bidirectional multimodality alignment module for 3D-guided 2D PX classification and segmentation tasks. The reconstruction network progressively reconstructs 3D images with knowledge imposed on the intermediate reconstructions at multiple pyramid levels and incorporates Multilayer Perceptrons to improve semantic understanding. The downstream networks leverage the reconstructed images as 3D anatomical guidance to the PX analysis through feature alignment, which increases the 2D-3D synergy with bidirectional feature projection and decease the impact of potential errors with contrastive guidance. Extensive experiments on two oral datasets involving 464 studies demonstrate that 3DPX outperforms the state-of-the-art methods in various tasks including 2D-to-3D reconstruction, PX classification and lesion segmentation.

Shuchang Ye, Usman Naseem, Mingyuan Meng et al.

Medical Visual Question Answering (MedVQA) is crucial for enhancing the efficiency of clinical diagnosis by providing accurate and timely responses to clinicians' inquiries regarding medical images. Existing MedVQA models suffered from modality preference bias, where predictions are heavily dominated by one modality while overlooking the other (in MedVQA, usually questions dominate the answer but images are overlooked), thereby failing to learn multimodal knowledge. To overcome the modality preference bias, we proposed a Medical CounterFactual VQA (MedCFVQA) model, which trains with bias and leverages causal graphs to eliminate the modality preference bias during inference. Existing MedVQA datasets exhibit substantial prior dependencies between questions and answers, which results in acceptable performance even if the model significantly suffers from the modality preference bias. To address this issue, we reconstructed new datasets by leveraging existing MedVQA datasets and Changed their P3rior dependencies (CP) between questions and their answers in the training and test set. Extensive experiments demonstrate that MedCFVQA significantly outperforms its non-causal counterpart on both SLAKE, RadVQA and SLAKE-CP, RadVQA-CP datasets.

Shuchang Ye, Mingyuan Meng, Mingjian Li et al.

Automated medical report generation has demonstrated the potential to significantly reduce the workload associated with time-consuming medical reporting. Recent generative representation learning methods have shown promise in integrating vision and language modalities for medical report generation. However, when trained end-to-end and applied directly to medical image-to-text generation, they face two significant challenges: i) difficulty in accurately capturing subtle yet crucial pathological details, and ii) reliance on both visual and textual inputs during inference, leading to performance degradation in zero-shot inference when only images are available. To address these challenges, this study proposes a novel multimodal dynamic traceback learning framework (DTrace). Specifically, we introduce a traceback mechanism to supervise the semantic validity of generated content and a dynamic learning strategy to adapt to various proportions of image and text input, enabling text generation without strong reliance on the input from both modalities during inference. The learning of cross-modal knowledge is enhanced by supervising the model to recover masked semantic information from a complementary counterpart. Extensive experiments conducted on two benchmark datasets, IU-Xray and MIMIC-CXR, demonstrate that the proposed DTrace framework outperforms state-of-the-art methods for medical report generation.

Mingyuan Meng, Bingxin Gu, Michael Fulham et al.

Survival prediction is a major concern for cancer management. Deep survival models based on deep learning have been widely adopted to perform end-to-end survival prediction from medical images. Recent deep survival models achieved promising performance by jointly performing tumor segmentation with survival prediction, where the models were guided to extract tumor-related information through Multi-Task Learning (MTL). However, these deep survival models have difficulties in exploring out-of-tumor prognostic information. In addition, existing deep survival models are unable to effectively leverage multi-modality images. Empirically-designed fusion strategies were commonly adopted to fuse multi-modality information via task-specific manually-designed networks, thus limiting the adaptability to different scenarios. In this study, we propose an Adaptive Multi-modality Segmentation-to-Survival model (AdaMSS) for survival prediction from PET/CT images. Instead of adopting MTL, we propose a novel Segmentation-to-Survival Learning (SSL) strategy, where our AdaMSS is trained for tumor segmentation and survival prediction sequentially in two stages. This strategy enables the AdaMSS to focus on tumor regions in the first stage and gradually expand its focus to include other prognosis-related regions in the second stage. We also propose a data-driven strategy to fuse multi-modality information, which realizes adaptive optimization of fusion strategies based on training data during training. With the SSL and data-driven fusion strategies, our AdaMSS is designed as an adaptive model that can self-adapt its focus regions and fusion strategy for different training stages. Extensive experiments with two large clinical datasets show that our AdaMSS outperforms state-of-the-art survival prediction methods.

Bhakti Baheti, Satrajit Chakrabarty, Hamed Akbari et al.

Registration of longitudinal brain MRI scans containing pathologies is challenging due to dramatic changes in tissue appearance. Although there has been progress in developing general-purpose medical image registration techniques, they have not yet attained the requisite precision and reliability for this task, highlighting its inherent complexity. Here we describe the Brain Tumor Sequence Registration (BraTS-Reg) challenge, as the first public benchmark environment for deformable registration algorithms focusing on estimating correspondences between pre-operative and follow-up scans of the same patient diagnosed with a diffuse brain glioma. The BraTS-Reg data comprise de-identified multi-institutional multi-parametric MRI (mpMRI) scans, curated for size and resolution according to a canonical anatomical template, and divided into training, validation, and testing sets. Clinical experts annotated ground truth (GT) landmark points of anatomical locations distinct across the temporal domain. Quantitative evaluation and ranking were based on the Median Euclidean Error (MEE), Robustness, and the determinant of the Jacobian of the displacement field. The top-ranked methodologies yielded similar performance across all evaluation metrics and shared several methodological commonalities, including pre-alignment, deep neural networks, inverse consistency analysis, and test-time instance optimization per-case basis as a post-processing step. The top-ranked method attained the MEE at or below that of the inter-rater variability for approximately 60% of the evaluated landmarks, underscoring the scope for further accuracy and robustness improvements, especially relative to human experts. The aim of BraTS-Reg is to continue to serve as an active resource for research, with the data and online evaluation tools accessible at https://bratsreg.github.io/.

Yuyu Guo, Lei Bi, Dongming Wei et al.

Motion estimation is a fundamental step in dynamic medical image processing for the assessment of target organ anatomy and function. However, existing image-based motion estimation methods, which optimize the motion field by evaluating the local image similarity, are prone to produce implausible estimation, especially in the presence of large motion. In this study, we provide a novel motion estimation framework of Dense-Sparse-Dense (DSD), which comprises two stages. In the first stage, we process the raw dense image to extract sparse landmarks to represent the target organ anatomical topology and discard the redundant information that is unnecessary for motion estimation. For this purpose, we introduce an unsupervised 3D landmark detection network to extract spatially sparse but representative landmarks for the target organ motion estimation. In the second stage, we derive the sparse motion displacement from the extracted sparse landmarks of two images of different time points. Then, we present a motion reconstruction network to construct the motion field by projecting the sparse landmarks displacement back into the dense image domain. Furthermore, we employ the estimated motion field from our two-stage DSD framework as initialization and boost the motion estimation quality in light-weight yet effective iterative optimization. We evaluate our method on two dynamic medical imaging tasks to model cardiac motion and lung respiratory motion, respectively. Our method has produced superior motion estimation accuracy compared to existing comparative methods. Besides, the extensive experimental results demonstrate that our solution can extract well representative anatomical landmarks without any requirement of manual annotation. Our code is publicly available online.

Euijoon Ahn, Dagan Feng, Jinman Kim

The segmentation of medical images is a fundamental step in automated clinical decision support systems. Existing medical image segmentation methods based on supervised deep learning, however, remain problematic because of their reliance on large amounts of labelled training data. Although medical imaging data repositories continue to expand, there has not been a commensurate increase in the amount of annotated data. Hence, we propose a new spatial guided self-supervised clustering network (SGSCN) for medical image segmentation, where we introduce multiple loss functions designed to aid in grouping image pixels that are spatially connected and have similar feature representations. It iteratively learns feature representations and clustering assignment of each pixel in an end-to-end fashion from a single image. We also propose a context-based consistency loss that better delineates the shape and boundaries of image regions. It enforces all the pixels belonging to a cluster to be spatially close to the cluster centre. We evaluated our method on 2 public medical image datasets and compared it to existing conventional and self-supervised clustering methods. Experimental results show that our method was most accurate for medical image segmentation.

Yige Peng, Lei Bi, Ashnil Kumar et al.

Distant metastases (DM) refer to the dissemination of tumors, usually, beyond the organ where the tumor originated. They are the leading cause of death in patients with soft-tissue sarcomas (STSs). Positron emission tomography-computed tomography (PET-CT) is regarded as the imaging modality of choice for the management of STSs. It is difficult to determine from imaging studies which STS patients will develop metastases. 'Radiomics' refers to the extraction and analysis of quantitative features from medical images and it has been employed to help identify such tumors. The state-of-the-art in radiomics is based on convolutional neural networks (CNNs). Most CNNs are designed for single-modality imaging data (CT or PET alone) and do not exploit the information embedded in PET-CT where there is a combination of an anatomical and functional imaging modality. Furthermore, most radiomic methods rely on manual input from imaging specialists for tumor delineation, definition and selection of radiomic features. This approach, however, may not be scalable to tumors with complex boundaries and where there are multiple other sites of disease. We outline a new 3D CNN to help predict DM in STS patients from PET-CT data. The 3D CNN uses a constrained feature learning module and a hierarchical multi-modality feature learning module that leverages the complementary information from the modalities to focus on semantically important regions. Our results on a public PET-CT dataset of STS patients show that multi-modal information improves the ability to identify those patients who develop DM. Further our method outperformed all other related state-of-the-art methods.

Yige Peng, Lei Bi, Michael Fulham et al.

'Radiomics' is a method that extracts mineable quantitative features from radiographic images. These features can then be used to determine prognosis, for example, predicting the development of distant metastases (DM). Existing radiomics methods, however, require complex manual effort including the design of hand-crafted radiomic features and their extraction and selection. Recent radiomics methods, based on convolutional neural networks (CNNs), also require manual input in network architecture design and hyper-parameter tuning. Radiomic complexity is further compounded when there are multiple imaging modalities, for example, combined positron emission tomography - computed tomography (PET-CT) where there is functional information from PET and complementary anatomical localization information from computed tomography (CT). Existing multi-modality radiomics methods manually fuse the data that are extracted separately. Reliance on manual fusion often results in sub-optimal fusion because they are dependent on an 'expert's' understanding of medical images. In this study, we propose a multi-modality neural architecture search method (MM-NAS) to automatically derive optimal multi-modality image features for radiomics and thus negate the dependence on a manual process. We evaluated our MM-NAS on the ability to predict DM using a public PET-CT dataset of patients with soft-tissue sarcomas (STSs). Our results show that our MM-NAS had a higher prediction accuracy when compared to state-of-the-art radiomics methods.

Yuyu Guo, Lei Bi, Euijoon Ahn et al.

Dynamic medical imaging is usually limited in application due to the large radiation doses and longer image scanning and reconstruction times. Existing methods attempt to reduce the dynamic sequence by interpolating the volumes between the acquired image volumes. However, these methods are limited to either 2D images and/or are unable to support large variations in the motion between the image volume sequences. In this paper, we present a spatiotemporal volumetric interpolation network (SVIN) designed for 4D dynamic medical images. SVIN introduces dual networks: first is the spatiotemporal motion network that leverages the 3D convolutional neural network (CNN) for unsupervised parametric volumetric registration to derive spatiotemporal motion field from two-image volumes; the second is the sequential volumetric interpolation network, which uses the derived motion field to interpolate image volumes, together with a new regression-based module to characterize the periodic motion cycles in functional organ structures. We also introduce an adaptive multi-scale architecture to capture the volumetric large anatomy motions. Experimental results demonstrated that our SVIN outperformed state-of-the-art temporal medical interpolation methods and natural video interpolation methods that have been extended to support volumetric images. Our ablation study further exemplified that our motion network was able to better represent the large functional motion compared with the state-of-the-art unsupervised medical registration methods.

Zehui Yao, Boyan Zhang, Zhiyong Wang et al.

Generative adversarial networks (GANs) have demonstrated great success in generating various visual content. However, images generated by existing GANs are often of attributes (e.g., smiling expression) learned from one image domain. As a result, generating images of multiple attributes requires many real samples possessing multiple attributes which are very resource expensive to be collected. In this paper, we propose a novel GAN, namely IntersectGAN, to learn multiple attributes from different image domains through an intersecting architecture. For example, given two image domains $X_1$ and $X_2$ with certain attributes, the intersection $X_1 \cap X_2$ denotes a new domain where images possess the attributes from both $X_1$ and $X_2$ domains. The proposed IntersectGAN consists of two discriminators $D_1$ and $D_2$ to distinguish between generated and real samples of different domains, and three generators where the intersection generator is trained against both discriminators. And an overall adversarial loss function is defined over three generators. As a result, our proposed IntersectGAN can be trained on multiple domains of which each presents one specific attribute, and eventually eliminates the need of real sample images simultaneously possessing multiple attributes. By using the CelebFaces Attributes dataset, our proposed IntersectGAN is able to produce high quality face images possessing multiple attributes (e.g., a face with black hair and a smiling expression). Both qualitative and quantitative evaluations are conducted to compare our proposed IntersectGAN with other baseline methods. Besides, several different applications of IntersectGAN have been explored with promising results.

Euijoon Ahn, Ashnil Kumar, Dagan Feng et al.

Medical image analysis using supervised deep learning methods remains problematic because of the reliance of deep learning methods on large amounts of labelled training data. Although medical imaging data repositories continue to expand there has not been a commensurate increase in the amount of annotated data. Hence, we propose a new unsupervised feature learning method that learns feature representations to then differentiate dissimilar medical images using an ensemble of different convolutional neural networks (CNNs) and K-means clustering. It jointly learns feature representations and clustering assignments in an end-to-end fashion. We tested our approach on a public medical dataset and show its accuracy was better than state-of-the-art unsupervised feature learning methods and comparable to state-of-the-art supervised CNNs. Our findings suggest that our method could be used to tackle the issue of the large volume of unlabelled data in medical imaging repositories.

Euijoon Ahn, Ashnil Kumar, Dagan Feng et al.

The accuracy and robustness of image classification with supervised deep learning are dependent on the availability of large-scale, annotated training data. However, there is a paucity of annotated data available due to the complexity of manual annotation. To overcome this problem, a popular approach is to use transferable knowledge across different domains by: 1) using a generic feature extractor that has been pre-trained on large-scale general images (i.e., transfer-learned) but which not suited to capture characteristics from medical images; or 2) fine-tuning generic knowledge with a relatively smaller number of annotated images. Our aim is to reduce the reliance on annotated training data by using a new hierarchical unsupervised feature extractor with a convolutional auto-encoder placed atop of a pre-trained convolutional neural network. Our approach constrains the rich and generic image features from the pre-trained domain to a sophisticated representation of the local image characteristics from the unannotated medical image domain. Our approach has a higher classification accuracy than transfer-learned approaches and is competitive with state-of-the-art supervised fine-tuned methods.

Lei Bi, Yuyu Guo, Qian Wang et al.

Automated segmentation of the optic cup and disk on retinal fundus images is fundamental for the automated detection / analysis of glaucoma. Traditional segmentation approaches depend heavily upon hand-crafted features and a priori knowledge of the user. As such, these methods are difficult to be adapt to the clinical environment. Recently, deep learning methods based on fully convolutional networks (FCNs) have been successful in resolving segmentation problems. However, the reliance on large annotated training data is problematic when dealing with medical images. If a sufficient amount of annotated training data to cover all possible variations is not available, FCNs do not provide accurate segmentation. In addition, FCNs have a large receptive field in the convolutional layers, and hence produce coarse outputs of boundaries. Hence, we propose a new fully automated method that we refer to as a dual-stage fully convolutional networks (DSFCN). Our approach leverages deep residual architectures and FCNs and learns and infers the location of the optic cup and disk in a step-wise manner with fine-grained details. During training, our approach learns from the training data and the estimated results derived from the previous iteration. The ability to learn from the previous iteration optimizes the learning of the optic cup and the disk boundaries. During testing (prediction), DSFCN uses test (input) images and the estimated probability map derived from previous iterations to gradually improve the segmentation accuracy. Our method achieved an average Dice co-efficient of 0.8488 and 0.9441 for optic cup and disk segmentation and an area under curve (AUC) of 0.9513 for glaucoma detection.

Ashnil Kumar, Michael Fulham, Dagan Feng et al.

The analysis of multi-modality positron emission tomography and computed tomography (PET-CT) images for computer aided diagnosis applications requires combining the sensitivity of PET to detect abnormal regions with anatomical localization from CT. Current methods for PET-CT image analysis either process the modalities separately or fuse information from each modality based on knowledge about the image analysis task. These methods generally do not consider the spatially varying visual characteristics that encode different information across the different modalities, which have different priorities at different locations. For example, a high abnormal PET uptake in the lungs is more meaningful for tumor detection than physiological PET uptake in the heart. Our aim is to improve fusion of the complementary information in multi-modality PET-CT with a new supervised convolutional neural network (CNN) that learns to fuse complementary information for multi-modality medical image analysis. Our CNN first encodes modality-specific features and then uses them to derive a spatially varying fusion map that quantifies the relative importance of each modality's features across different spatial locations. These fusion maps are then multiplied with the modality-specific feature maps to obtain a representation of the complementary multi-modality information at different locations, which can then be used for image analysis. We evaluated the ability of our CNN to detect and segment multiple regions with different fusion requirements using a dataset of PET-CT images of lung cancer. We compared our method to baseline techniques for multi-modality image fusion and segmentation. Our findings show that our CNN had a significantly higher foreground detection accuracy (99.29%, p < 0.05) than the fusion baselines and a significantly higher Dice score (63.85%) than recent PET-CT tumor segmentation methods.

Lei Bi, Dagan Feng, Jinman Kim

Segmentation of skin lesions is considered as an important step in computer aided diagnosis (CAD) for automated melanoma diagnosis. In recent years, segmentation methods based on fully convolutional networks (FCN) have achieved great success in general images. This success is primarily due to the leveraging of large labelled datasets to learn features that correspond to the shallow appearance as well as the deep semantics of the images. However, the dependence on large dataset does not translate well into medical images. To improve the FCN performance for skin lesion segmentations, researchers attempted to use specific cost functions or add post-processing algorithms to refine the coarse boundaries of the FCN results. However, the performance of these methods is heavily reliant on the tuning of many parameters and post-processing techniques. In this paper, we leverage the state-of-the-art image feature learning method of generative adversarial network (GAN) for its inherent ability to produce consistent and realistic image features by using deep neural networks and adversarial learning concept. We improve upon GAN such that skin lesion features can be learned at different level of complexities, in a controlled manner. The outputs from our method is then augmented to the existing FCN training data, thus increasing the overall feature diversity. We evaluated our method on the ISIC 2018 skin lesion segmentation challenge dataset and showed that it was more accurate and robust when compared to the existing skin lesion segmentation methods.

Haozhe Jia, Yang Song, Donghao Zhang et al.

Advanced deep learning methods have been developed to conduct prostate MR volume segmentation in either a 2D or 3D fully convolutional manner. However, 2D methods tend to have limited segmentation performance, since large amounts of spatial information of prostate volumes are discarded during the slice-by-slice segmentation process; and 3D methods also have room for improvement, since they use isotropic kernels to perform 3D convolutions whereas most prostate MR volumes have anisotropic spatial resolution. Besides, the fully convolutional structural methods achieve good performance for localization issues but neglect the per-voxel classification for segmentation tasks. In this paper, we propose a 3D Global Convolutional Adversarial Network (3D GCA-Net) to address efficient prostate MR volume segmentation. We first design a 3D ResNet encoder to extract 3D features from prostate scans, and then develop the decoder, which is composed of a multi-scale 3D global convolutional block and a 3D boundary refinement block, to address the classification and localization issues simultaneously for volumetric segmentation. Additionally, we combine the encoder-decoder segmentation network with an adversarial network in the training phrase to enforce the contiguity of long-range spatial predictions. Throughout the proposed model, we use anisotropic convolutional processing for better feature learning on prostate MR scans. We evaluated our 3D GCA-Net model on two public prostate MR datasets and achieved state-of-the-art performances.

Euijoon Ahn, Jinman Kim, Ashnil Kumar et al.

The availability of large-scale annotated image datasets and recent advances in supervised deep learning methods enable the end-to-end derivation of representative image features that can impact a variety of image analysis problems. Such supervised approaches, however, are difficult to implement in the medical domain where large volumes of labelled data are difficult to obtain due to the complexity of manual annotation and inter- and intra-observer variability in label assignment. We propose a new convolutional sparse kernel network (CSKN), which is a hierarchical unsupervised feature learning framework that addresses the challenge of learning representative visual features in medical image analysis domains where there is a lack of annotated training data. Our framework has three contributions: (i) We extend kernel learning to identify and represent invariant features across image sub-patches in an unsupervised manner. (ii) We initialise our kernel learning with a layer-wise pre-training scheme that leverages the sparsity inherent in medical images to extract initial discriminative features. (iii) We adapt a multi-scale spatial pyramid pooling (SPP) framework to capture subtle geometric differences between learned visual features. We evaluated our framework in medical image retrieval and classification on three public datasets. Our results show that our CSKN had better accuracy when compared to other conventional unsupervised methods and comparable accuracy to methods that used state-of-the-art supervised convolutional neural networks (CNNs). Our findings indicate that our unsupervised CSKN provides an opportunity to leverage unannotated big data in medical imaging repositories.

Lei Bi, Jinman Kim, Ashnil Kumar et al.

Positron emission tomography (PET) image synthesis plays an important role, which can be used to boost the training data for computer aided diagnosis systems. However, existing image synthesis methods have problems in synthesizing the low resolution PET images. To address these limitations, we propose multi-channel generative adversarial networks (M-GAN) based PET image synthesis method. Different to the existing methods which rely on using low-level features, the proposed M-GAN is capable to represent the features in a high-level of semantic based on the adversarial learning concept. In addition, M-GAN enables to take the input from the annotation (label) to synthesize the high uptake regions e.g., tumors and from the computed tomography (CT) images to constrain the appearance consistency and output the synthetic PET images directly. Our results on 50 lung cancer PET-CT studies indicate that our method was much closer to the real PET images when compared with the existing methods.

Lei Bi, Jinman Kim, Ashnil Kumar et al.

Automatic segmentation of liver lesions is a fundamental requirement towards the creation of computer aided diagnosis (CAD) and decision support systems (CDS). Traditional segmentation approaches depend heavily upon hand-crafted features and a priori knowledge of the user. As such, these methods are difficult to adopt within a clinical environment. Recently, deep learning methods based on fully convolutional networks (FCNs) have been successful in many segmentation problems primarily because they leverage a large labelled dataset to hierarchically learn the features that best correspond to the shallow visual appearance as well as the deep semantics of the areas to be segmented. However, FCNs based on a 16 layer VGGNet architecture have limited capacity to add additional layers. Therefore, it is challenging to learn more discriminative features among different classes for FCNs. In this study, we overcome these limitations using deep residual networks (ResNet) to segment liver lesions. ResNet contain skip connections between convolutional layers, which solved the problem of the training degradation of training accuracy in very deep networks and thereby enables the use of additional layers for learning more discriminative features. In addition, we achieve more precise boundary definitions through a novel cascaded ResNet architecture with multi-scale fusion to gradually learn and infer the boundaries of both the liver and the liver lesions. Our proposed method achieved 4th place in the ISBI 2017 Liver Tumor Segmentation Challenge by the submission deadline.

Lei Bi, Jinman Kim, Euijoon Ahn et al.

Malignant melanoma has one of the most rapidly increasing incidences in the world and has a considerable mortality rate. Early diagnosis is particularly important since melanoma can be cured with prompt excision. Dermoscopy images play an important role in the non-invasive early detection of melanoma [1]. However, melanoma detection using human vision alone can be subjective, inaccurate and poorly reproducible even among experienced dermatologists. This is attributed to the challenges in interpreting images with diverse characteristics including lesions of varying sizes and shapes, lesions that may have fuzzy boundaries, different skin colors and the presence of hair [2]. Therefore, the automatic analysis of dermoscopy images is a valuable aid for clinical decision making and for image-based diagnosis to identify diseases such as melanoma [1-4]. Deep residual networks (ResNets) has achieved state-of-the-art results in image classification and detection related problems [5-8]. In this ISIC 2017 skin lesion analysis challenge [9], we propose to exploit the deep ResNets for robust visual features learning and representations.

Siqi Liu, Sidong Liu, Sonia Pujol et al.

We present a longitudinal MR simulation framework which simulates the future neurodegenerative progression by outputting the predicted follow-up MR image and the voxel-based morphometry (VBM) map. This framework expects the patients to have at least 2 historical MR images available. The longitudinal and cross-sectional VBM maps are extracted to measure the affinity between the target subject and the template subjects collected for simulation. Then the follow-up simulation is performed by resampling the latest available target MR image with a weighted sum of non-linear transformations derived from the best-matched templates. The leave-one-out strategy was used to compare different simulation methods. Compared to the state-of-the-art voxel-based method, our proposed morphometry-based simulation achieves better accuracy in most cases.