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Delineating lesions and anatomical structure is important for image-guided interventions. Point-supervised medical image segmentation (PSS) has great potential to alleviate costly expert delineation labeling. However, due to the lack of precise size and boundary guidance, the effectiveness of PSS often falls short of expectations. Although recent vision foundational models, such as the medical segment anything model (MedSAM), have made significant advancements in bounding-box-prompted segmentation, it is not straightforward to utilize point annotation, and is prone to semantic ambiguity. In this preliminary study, we introduce an iterative framework to facilitate semantic-aware point-supervised MedSAM. Specifically, the semantic box-prompt generator (SBPG) module has the capacity to convert the point input into potential pseudo bounding box suggestions, which are explicitly refined by the prototype-based semantic similarity. This is then succeeded by a prompt-guided spatial refinement (PGSR) module that harnesses the exceptional generalizability of MedSAM to infer the segmentation mask, which also updates the box proposal seed in SBPG. Performance can be progressively improved with adequate iterations. We conducted an evaluation on BraTS2018 for the segmentation of whole brain tumors and demonstrated its superior performance compared to traditional PSS methods and on par with box-supervised methods., Comment: 2024 IEEE Nuclear Science Symposium and Medical Imaging Conference

Deep learning-based segmentation techniques have shown remarkable performance in brain segmentation, yet their success hinges on the availability of extensive labeled training data. Acquiring such vast datasets, however, poses a significant challenge in many clinical applications. To address this issue, in this work, we propose a novel 3D brain segmentation approach using complementary 2D diffusion models. The core idea behind our approach is to first mine 2D features with semantic information extracted from the 2D diffusion models by taking orthogonal views as input, followed by fusing them into a 3D contextual feature representation. Then, we use these aggregated features to train multi-layer perceptrons to classify the segmentation labels. Our goal is to achieve reliable segmentation quality without requiring complete labels for each individual subject. Our experiments on training in brain subcortical structure segmentation with a dataset from only one subject demonstrate that our approach outperforms state-of-the-art self-supervised learning methods. Further experiments on the minimum requirement of annotation by sparse labeling yield promising results even with only nine slices and a labeled background region., Comment: Extended version of "3D Segmentation of Subcortical Brain Structure with Few Labeled Data using 2D Diffusion Models" (ISMRM 2024 oral)

Multisequence Magnetic Resonance Imaging (MRI) provides a reliable diagnosis in clinical applications through complementary information within sequences. However, in practice, the absence of certain MR sequences is a common problem that can lead to inconsistent analysis results. In this work, we propose a novel unified framework for synthesizing multisequence MR images, called Hybrid Fusion GAN (HF-GAN). We introduce a hybrid fusion encoder designed to ensure the disentangled extraction of complementary and modality-specific information, along with a channel attention-based feature fusion module that integrates the features into a common latent space handling the complexity from combinations of accessible MR sequences. Common feature representations are transformed into a target latent space via the modality infuser to synthesize missing MR sequences. We have performed experiments on multisequence brain MRI datasets from healthy individuals and patients diagnosed with brain tumors. Experimental results show that our method outperforms state-of-the-art methods in both quantitative and qualitative comparisons. In addition, a detailed analysis of our framework demonstrates the superiority of our designed modules and their effectiveness for use in data imputation tasks., Comment: 11 pages, 7 figures

Diffusion-weighted MRI (DW-MRI) is used to quantitatively characterize the microscopic structure of soft tissue due to the anisotropic diffusion of water in muscle. Applications such as fiber tractography or modeling of tumor spread in soft tissue require precise detection of muscle fiber orientation, which is derived from the principal eigenvector of the diffusion tensor. For clinical applications, high image quality and high signal-to-noise ratio (SNR) of DW-MRI for fiber orientation must be balanced with an appropriate scan duration. Muscles with known structural heterogeneity, e.g. bipennate muscles such as the thigh rectus femoris, provide a natural quality benchmark to determine fiber orientation at different scan parameters. Here, we analyze DW-MR images of the thigh of a healthy volunteer at different SNRs and use PCA to identify subsets of voxels with different directions of diffusion tensor eigenvectors. We propose to use the mixing index of spatial co-localization of the clustered eigenvectors as a quality metric for fiber orientation detection. Comparing acquisitions at different SNRs, we find that high SNR results in a low mixing index, reflecting a clear separation of the two compartments of the bipennate muscle on either side of the central tendon. Because the mixing index allows joint estimation of spatial and directional noise in DW-MRI as a single parameter, it will allow future quantitative optimization of DW-MRI protocols for soft tissue.

Understanding the relationship between tongue motion patterns during speech and their resulting speech acoustic outcomes -- i.e., articulatory-acoustic relation -- is of great importance in assessing speech quality and developing innovative treatment and rehabilitative strategies. This is especially important when evaluating and detecting abnormal articulatory features in patients with speech-related disorders. In this work, we aim to develop a framework for detecting speech motion anomalies in conjunction with their corresponding speech acoustics. This is achieved through the use of a deep cross-modal translator trained on data from healthy individuals only, which bridges the gap between 4D motion fields obtained from tagged MRI and 2D spectrograms derived from speech acoustic data. The trained translator is used as an anomaly detector, by measuring the spectrogram reconstruction quality on healthy individuals or patients. In particular, the cross-modal translator is likely to yield limited generalization capabilities on patient data, which includes unseen out-of-distribution patterns and demonstrates subpar performance, when compared with healthy individuals.~A one-class SVM is then used to distinguish the spectrograms of healthy individuals from those of patients. To validate our framework, we collected a total of 39 paired tagged MRI and speech waveforms, consisting of data from 36 healthy individuals and 3 tongue cancer patients. We used both 3D convolutional and transformer-based deep translation models, training them on the healthy training set and then applying them to both the healthy and patient testing sets. Our framework demonstrates a capability to detect abnormal patient data, thereby illustrating its potential in enhancing the understanding of the articulatory-acoustic relation for both healthy individuals and patients., Comment: SPIE Medical Imaging 2024: Image Processing

In this work, we aim to predict the survival time (ST) of glioblastoma (GBM) patients undergoing different treatments based on preoperative magnetic resonance (MR) scans. The personalized and precise treatment planning can be achieved by comparing the ST of different treatments. It is well established that both the current status of the patient (as represented by the MR scans) and the choice of treatment are the cause of ST. While previous related MR-based glioblastoma ST studies have focused only on the direct mapping of MR scans to ST, they have not included the underlying causal relationship between treatments and ST. To address this limitation, we propose a treatment-conditioned regression model for glioblastoma ST that incorporates treatment information in addition to MR scans. Our approach allows us to effectively utilize the data from all of the treatments in a unified manner, rather than having to train separate models for each of the treatments. Furthermore, treatment can be effectively injected into each convolutional layer through the adaptive instance normalization we employ. We evaluate our framework on the BraTS20 ST prediction task. Three treatment options are considered: Gross Total Resection (GTR), Subtotal Resection (STR), and no resection. The evaluation results demonstrate the effectiveness of injecting the treatment for estimating GBM survival., Comment: SPIE Medical Imaging 2024: Computer-Aided Diagnosis

Multimodal Magnetic Resonance (MR) Imaging plays a crucial role in disease diagnosis due to its ability to provide complementary information by analyzing a relationship between multimodal images on the same subject. Acquiring all MR modalities, however, can be expensive, and, during a scanning session, certain MR images may be missed depending on the study protocol. The typical solution would be to synthesize the missing modalities from the acquired images such as using generative adversarial networks (GANs). Yet, GANs constructed with convolutional neural networks (CNNs) are likely to suffer from a lack of global relationships and mechanisms to condition the desired modality. To address this, in this work, we propose a transformer-based modality infuser designed to synthesize multimodal brain MR images. In our method, we extract modality-agnostic features from the encoder and then transform them into modality-specific features using the modality infuser. Furthermore, the modality infuser captures long-range relationships among all brain structures, leading to the generation of more realistic images. We carried out experiments on the BraTS 2018 dataset, translating between four MR modalities, and our experimental results demonstrate the superiority of our proposed method in terms of synthesis quality. In addition, we conducted experiments on a brain tumor segmentation task and different conditioning methods., Comment: 6 pages

Magnetic Resonance Imaging with tagging (tMRI) has long been utilized for quantifying tissue motion and strain during deformation. However, a phenomenon known as tag fading, a gradual decrease in tag visibility over time, often complicates post-processing. The first contribution of this study is to model tag fading by considering the interplay between $T_1$ relaxation and the repeated application of radio frequency (RF) pulses during serial imaging sequences. This is a factor that has been overlooked in prior research on tMRI post-processing. Further, we have observed an emerging trend of utilizing raw tagged MRI within a deep learning-based (DL) registration framework for motion estimation. In this work, we evaluate and analyze the impact of commonly used image similarity objectives in training DL registrations on raw tMRI. This is then compared with the Harmonic Phase-based approach, a traditional approach which is claimed to be robust to tag fading. Our findings, derived from both simulated images and an actual phantom scan, reveal the limitations of various similarity losses in raw tMRI and emphasize caution in registration tasks where image intensity changes over time., Comment: Accepted to SPIE Medical Imaging 2024 (oral)

This work aims efficiently estimating the posterior distribution of kinetic parameters for dynamic positron emission tomography (PET) imaging given a measurement of time of activity curve. Considering the inherent information loss from parametric imaging to measurement space with the forward kinetic model, the inverse mapping is ambiguous. The conventional (but expensive) solution can be the Markov Chain Monte Carlo (MCMC) sampling, which is known to produce unbiased asymptotical estimation. We propose a deep-learning-based framework for efficient posterior estimation. Specifically, we counteract the information loss in the forward process by introducing latent variables. Then, we use a conditional variational autoencoder (CVAE) and optimize its evidence lower bound. The well-trained decoder is able to infer the posterior with a given measurement and the sampled latent variables following a simple multivariate Gaussian distribution. We validate our CVAE-based method using unbiased MCMC as the reference for low-dimensional data (a single brain region) with the simplified reference tissue model., Comment: Published on IEEE NSS&MIC

The tongue's intricate 3D structure, comprising localized functional units, plays a crucial role in the production of speech. When measured using tagged MRI, these functional units exhibit cohesive displacements and derived quantities that facilitate the complex process of speech production. Non-negative matrix factorization-based approaches have been shown to estimate the functional units through motion features, yielding a set of building blocks and a corresponding weighting map. Investigating the link between weighting maps and speech acoustics can offer significant insights into the intricate process of speech production. To this end, in this work, we utilize two-dimensional spectrograms as a proxy representation, and develop an end-to-end deep learning framework for translating weighting maps to their corresponding audio waveforms. Our proposed plastic light transformer (PLT) framework is based on directional product relative position bias and single-level spatial pyramid pooling, thus enabling flexible processing of weighting maps with variable size to fixed-size spectrograms, without input information loss or dimension expansion. Additionally, our PLT framework efficiently models the global correlation of wide matrix input. To improve the realism of our generated spectrograms with relatively limited training samples, we apply pair-wise utterance consistency with Maximum Mean Discrepancy constraint and adversarial training. Experimental results on a dataset of 29 subjects speaking two utterances demonstrated that our framework is able to synthesize speech audio waveforms from weighting maps, outperforming conventional convolution and transformer models., Comment: MICCAI 2023 (Oral presentation)

Chatbots have been studied for more than half a century. With the rapid development of natural language processing (NLP) technologies in recent years, chatbots using large language models (LLMs) have received much attention nowadays. Compared with traditional ones, modern chatbots are more powerful and have been used in real-world applications. There are however, bias and fairness concerns in modern chatbot design. Due to the huge amounts of training data, extremely large model sizes, and lack of interpretability, bias mitigation and fairness preservation of modern chatbots are challenging. Thus, a comprehensive overview on bias and fairness in chatbot systems is given in this paper. The history of chatbots and their categories are first reviewed. Then, bias sources and potential harms in applications are analyzed. Considerations in designing fair and unbiased chatbot systems are examined. Finally, future research directions are discussed.

Tagged magnetic resonance imaging (tMRI) has been employed for decades to measure the motion of tissue undergoing deformation. However, registration-based motion estimation from tMRI is difficult due to the periodic patterns in these images, particularly when the motion is large. With a larger motion the registration approach gets trapped in a local optima, leading to motion estimation errors. We introduce a novel "momenta, shooting, and correction" framework for Lagrangian motion estimation in the presence of repetitive patterns and large motion. This framework, grounded in Lie algebra and Lie group principles, accumulates momenta in the tangent vector space and employs exponential mapping in the diffeomorphic space for rapid approximation towards true optima, circumventing local optima. A subsequent correction step ensures convergence to true optima. The results on a 2D synthetic dataset and a real 3D tMRI dataset demonstrate our method's efficiency in estimating accurate, dense, and diffeomorphic 2D/3D motion fields amidst large motion and repetitive patterns., Comment: Accepted by MICCAI Workshop 2023: Time-Series Data Analytics and Learning (MTSAIL)

Deep learning (DL) models for segmenting various anatomical structures have achieved great success via a static DL model that is trained in a single source domain. Yet, the static DL model is likely to perform poorly in a continually evolving environment, requiring appropriate model updates. In an incremental learning setting, we would expect that well-trained static models are updated, following continually evolving target domain data -- e.g., additional lesions or structures of interest -- collected from different sites, without catastrophic forgetting. This, however, poses challenges, due to distribution shifts, additional structures not seen during the initial model training, and the absence of training data in a source domain. To address these challenges, in this work, we seek to progressively evolve an ``off-the-shelf" trained segmentation model to diverse datasets with additional anatomical categories in a unified manner. Specifically, we first propose a divergence-aware dual-flow module with balanced rigidity and plasticity branches to decouple old and new tasks, which is guided by continuous batch renormalization. Then, a complementary pseudo-label training scheme with self-entropy regularized momentum MixUp decay is developed for adaptive network optimization. We evaluated our framework on a brain tumor segmentation task with continually changing target domains -- i.e., new MRI scanners/modalities with incremental structures. Our framework was able to well retain the discriminability of previously learned structures, hence enabling the realistic life-long segmentation model extension along with the widespread accumulation of big medical data., Comment: Early Accept to MICCAI 2023

Self-training is an important class of unsupervised domain adaptation (UDA) approaches that are used to mitigate the problem of domain shift, when applying knowledge learned from a labeled source domain to unlabeled and heterogeneous target domains. While self-training-based UDA has shown considerable promise on discriminative tasks, including classification and segmentation, through reliable pseudo-label filtering based on the maximum softmax probability, there is a paucity of prior work on self-training-based UDA for generative tasks, including image modality translation. To fill this gap, in this work, we seek to develop a generative self-training (GST) framework for domain adaptive image translation with continuous value prediction and regression objectives. Specifically, we quantify both aleatoric and epistemic uncertainties within our GST using variational Bayes learning to measure the reliability of synthesized data. We also introduce a self-attention scheme that de-emphasizes the background region to prevent it from dominating the training process. The adaptation is then carried out by an alternating optimization scheme with target domain supervision that focuses attention on the regions with reliable pseudo-labels. We evaluated our framework on two cross-scanner/center, inter-subject translation tasks, including tagged-to-cine magnetic resonance (MR) image translation and T1-weighted MR-to-fractional anisotropy translation. Extensive validations with unpaired target domain data showed that our GST yielded superior synthesis performance in comparison to adversarial training UDA methods., Comment: Accepted to Medical Image Analysis

Background: In medical imaging, images are usually treated as deterministic, while their uncertainties are largely underexplored. Purpose: This work aims at using deep learning to efficiently estimate posterior distributions of imaging parameters, which in turn can be used to derive the most probable parameters as well as their uncertainties. Methods: Our deep learning-based approaches are based on a variational Bayesian inference framework, which is implemented using two different deep neural networks based on conditional variational auto-encoder (CVAE), CVAE-dual-encoder and CVAE-dual-decoder. The conventional CVAE framework, i.e., CVAE-vanilla, can be regarded as a simplified case of these two neural networks. We applied these approaches to a simulation study of dynamic brain PET imaging using a reference region-based kinetic model. Results: In the simulation study, we estimated posterior distributions of PET kinetic parameters given a measurement of time-activity curve. Our proposed CVAE-dual-encoder and CVAE-dual-decoder yield results that are in good agreement with the asymptotically unbiased posterior distributions sampled by Markov Chain Monte Carlo (MCMC). The CVAE-vanilla can also be used for estimating posterior distributions, although it has an inferior performance to both CVAE-dual-encoder and CVAE-dual-decoder. Conclusions: We have evaluated the performance of our deep learning approaches for estimating posterior distributions in dynamic brain PET. Our deep learning approaches yield posterior distributions, which are in good agreement with unbiased distributions estimated by MCMC. All these neural networks have different characteristics and can be chosen by the user for specific applications. The proposed methods are general and can be adapted to other problems., Comment: Published in Medical Physics

Investigating the relationship between internal tissue point motion of the tongue and oropharyngeal muscle deformation measured from tagged MRI and intelligible speech can aid in advancing speech motor control theories and developing novel treatment methods for speech related-disorders. However, elucidating the relationship between these two sources of information is challenging, due in part to the disparity in data structure between spatiotemporal motion fields (i.e., 4D motion fields) and one-dimensional audio waveforms. In this work, we present an efficient encoder-decoder translation network for exploring the predictive information inherent in 4D motion fields via 2D spectrograms as a surrogate of the audio data. Specifically, our encoder is based on 3D convolutional spatial modeling and transformer-based temporal modeling. The extracted features are processed by an asymmetric 2D convolution decoder to generate spectrograms that correspond to 4D motion fields. Furthermore, we incorporate a generative adversarial training approach into our framework to further improve synthesis quality on our generated spectrograms. We experiment on 63 paired motion field sequences and speech waveforms, demonstrating that our framework enables the generation of clear audio waveforms from a sequence of motion fields. Thus, our framework has the potential to improve our understanding of the relationship between these two modalities and inform the development of treatments for speech disorders., Comment: SPIE Medical Imaging: Deep Dive Oral

Cardiac cine magnetic resonance imaging (MRI) has been used to characterize cardiovascular diseases (CVD), often providing a noninvasive phenotyping tool.~While recently flourished deep learning based approaches using cine MRI yield accurate characterization results, the performance is often degraded by small training samples. In addition, many deep learning models are deemed a ``black box," for which models remain largely elusive in how models yield a prediction and how reliable they are. To alleviate this, this work proposes a lightweight successive subspace learning (SSL) framework for CVD classification, based on an interpretable feedforward design, in conjunction with a cardiac atlas. Specifically, our hierarchical SSL model is based on (i) neighborhood voxel expansion, (ii) unsupervised subspace approximation, (iii) supervised regression, and (iv) multi-level feature integration. In addition, using two-phase 3D deformation fields, including end-diastolic and end-systolic phases, derived between the atlas and individual subjects as input offers objective means of assessing CVD, even with small training samples. We evaluate our framework on the ACDC2017 database, comprising one healthy group and four disease groups. Compared with 3D CNN-based approaches, our framework achieves superior classification performance with 140$\times$ fewer parameters, which supports its potential value in clinical use., Comment: ISBI 2023

Tagged magnetic resonance imaging~(MRI) has been used for decades to observe and quantify the detailed motion of deforming tissue. However, this technique faces several challenges such as tag fading, large motion, long computation times, and difficulties in obtaining diffeomorphic incompressible flow fields. To address these issues, this paper presents a novel unsupervised phase-based 3D motion estimation technique for tagged MRI. We introduce two key innovations. First, we apply a sinusoidal transformation to the harmonic phase input, which enables end-to-end training and avoids the need for phase interpolation. Second, we propose a Jacobian determinant-based learning objective to encourage incompressible flow fields for deforming biological tissues. Our method efficiently estimates 3D motion fields that are accurate, dense, and approximately diffeomorphic and incompressible. The efficacy of the method is assessed using human tongue motion during speech, and includes both healthy controls and patients that have undergone glossectomy. We show that the method outperforms existing approaches, and also exhibits improvements in speed, robustness to tag fading, and large tongue motion. The code is available: https://github.com/jasonbian97/DRIMET-tagged-MRI, Comment: Accepted to MIDL 2023 (oral)

Unsupervised domain adaptation (UDA) has been a vital protocol for migrating information learned from a labeled source domain to facilitate the implementation in an unlabeled heterogeneous target domain. Although UDA is typically jointly trained on data from both domains, accessing the labeled source domain data is often restricted, due to concerns over patient data privacy or intellectual property. To sidestep this, we propose "off-the-shelf (OS)" UDA (OSUDA), aimed at image segmentation, by adapting an OS segmentor trained in a source domain to a target domain, in the absence of source domain data in adaptation. Toward this goal, we aim to develop a novel batch-wise normalization (BN) statistics adaptation framework. In particular, we gradually adapt the domain-specific low-order BN statistics, e.g., mean and variance, through an exponential momentum decay strategy, while explicitly enforcing the consistency of the domain shareable high-order BN statistics, e.g., scaling and shifting factors, via our optimization objective. We also adaptively quantify the channel-wise transferability to gauge the importance of each channel, via both low-order statistics divergence and a scaling factor.~Furthermore, we incorporate unsupervised self-entropy minimization into our framework to boost performance alongside a novel queued, memory-consistent self-training strategy to utilize the reliable pseudo label for stable and efficient unsupervised adaptation. We evaluated our OSUDA-based framework on both cross-modality and cross-subtype brain tumor segmentation and cardiac MR to CT segmentation tasks. Our experimental results showed that our memory consistent OSUDA performs better than existing source-relaxed UDA methods and yields similar performance to UDA methods with source data., Comment: Published in Medical Image Analysis (extension of MICCAI paper)

Unsupervised domain adaptation (UDA) has been widely used to transfer knowledge from a labeled source domain to an unlabeled target domain to counter the difficulty of labeling in a new domain. The training of conventional solutions usually relies on the existence of both source and target domain data. However, privacy of the large-scale and well-labeled data in the source domain and trained model parameters can become the major concern of cross center/domain collaborations. In this work, to address this, we propose a practical solution to UDA for segmentation with a black-box segmentation model trained in the source domain only, rather than original source data or a white-box source model. Specifically, we resort to a knowledge distillation scheme with exponential mixup decay (EMD) to gradually learn target-specific representations. In addition, unsupervised entropy minimization is further applied to regularization of the target domain confidence. We evaluated our framework on the BraTS 2018 database, achieving performance on par with white-box source model adaptation approaches., Comment: SPIE Medical Imaging 2022: Image Processing

Unsupervised domain adaptation (UDA) has been successfully applied to transfer knowledge from a labeled source domain to target domains without their labels. Recently introduced transferable prototypical networks (TPN) further addresses class-wise conditional alignment. In TPN, while the closeness of class centers between source and target domains is explicitly enforced in a latent space, the underlying fine-grained subtype structure and the cross-domain within-class compactness have not been fully investigated. To counter this, we propose a new approach to adaptively perform a fine-grained subtype-aware alignment to improve performance in the target domain without the subtype label in both domains. The insight of our approach is that the unlabeled subtypes in a class have the local proximity within a subtype, while exhibiting disparate characteristics, because of different conditional and label shifts. Specifically, we propose to simultaneously enforce subtype-wise compactness and class-wise separation, by utilizing intermediate pseudo-labels. In addition, we systematically investigate various scenarios with and without prior knowledge of subtype numbers, and propose to exploit the underlying subtype structure. Furthermore, a dynamic queue framework is developed to evolve the subtype cluster centroids steadily using an alternative processing scheme. Experimental results, carried out with multi-view congenital heart disease data and VisDA and DomainNet, show the effectiveness and validity of our subtype-aware UDA, compared with state-of-the-art UDA methods., Comment: IEEE Transactions on Neural Networks and Learning Systems (TNNLS)

Deep learning has become the method of choice to tackle real-world problems in different domains, partly because of its ability to learn from data and achieve impressive performance on a wide range of applications. However, its success usually relies on two assumptions: (i) vast troves of labeled datasets are required for accurate model fitting, and (ii) training and testing data are independent and identically distributed. Its performance on unseen target domains, thus, is not guaranteed, especially when encountering out-of-distribution data at the adaptation stage. The performance drop on data in a target domain is a critical problem in deploying deep neural networks that are successfully trained on data in a source domain. Unsupervised domain adaptation (UDA) is proposed to counter this, by leveraging both labeled source domain data and unlabeled target domain data to carry out various tasks in the target domain. UDA has yielded promising results on natural image processing, video analysis, natural language processing, time-series data analysis, medical image analysis, etc. In this review, as a rapidly evolving topic, we provide a systematic comparison of its methods and applications. In addition, the connection of UDA with its closely related tasks, e.g., domain generalization and out-of-distribution detection, has also been discussed. Furthermore, deficiencies in current methods and possible promising directions are highlighted., Comment: APSIPA Transactions on Signal and Information Processing

Objective: Soft-tissue sarcoma spreads preferentially along muscle fibers. We explore the utility of deriving muscle fiber orientations from diffusion tensor MRI (DT-MRI) for defining the boundary of the clinical target volume in muscle tissue. Approach: We recruited eight healthy volunteers to acquire MR images of the left and right thigh. The imaging session consisted of (a) two MRI spin-echo-based scans, T1- and T2-weighted; (b) a diffusion weighted (DW) spin-echo-based scan using an echo planar acquisition with fat suppression. The thigh muscles were auto-segmented using CNN. DT-MRI data was used as a geometry encoding input to solve the anisotropic Eikonal equation with Hamiltonian Fast-Marching method. The isosurfaces of the solution modeled the CTV boundary. Main results: The auto-segmented muscles of the thigh agreed with manually delineated with the Dice score ranging from 0.8 to 0.94 for different muscles. Anisotropy of the isosurfaces was compared across muscles with different anatomical orientations within a thigh, between muscles in left and right thighs of each subject, and between different subjects. Analysis showed a high degree of consistency across all comparisons. The distance from the GTV to the isosurface and the eigenvalues ratio are two controlling parameters for the extent and shape of the CTV. Significance: Our feasibility study with healthy volunteers shows the promise of using muscle fiber orientations derived from diffusion weighted MRI data for automated generation of anisotropic CTV boundary in soft tissue sarcoma. Our contribution is significant as it is expected to lead to the improvements in the treatment outcomes of soft-tissue sarcoma patients undergoing radiotherapy and decrease amputation rate for a subset of patients. We expect such improvements to have a strong positive impact for the cancer centers with small volume of sarcoma patients.

Unsupervised domain adaptation (UDA) has been vastly explored to alleviate domain shifts between source and target domains, by applying a well-performed model in an unlabeled target domain via supervision of a labeled source domain. Recent literature, however, has indicated that the performance is still far from satisfactory in the presence of significant domain shifts. Nonetheless, delineating a few target samples is usually manageable and particularly worthwhile, due to the substantial performance gain. Inspired by this, we aim to develop semi-supervised domain adaptation (SSDA) for medical image segmentation, which is largely underexplored. We, thus, propose to exploit both labeled source and target domain data, in addition to unlabeled target data in a unified manner. Specifically, we present a novel asymmetric co-training (ACT) framework to integrate these subsets and avoid the domination of the source domain data. Following a divide-and-conquer strategy, we explicitly decouple the label supervisions in SSDA into two asymmetric sub-tasks, including semi-supervised learning (SSL) and UDA, and leverage different knowledge from two segmentors to take into account the distinction between the source and target label supervisions. The knowledge learned in the two modules is then adaptively integrated with ACT, by iteratively teaching each other, based on the confidence-aware pseudo-label. In addition, pseudo label noise is well-controlled with an exponential MixUp decay scheme for smooth propagation. Experiments on cross-modality brain tumor MRI segmentation tasks using the BraTS18 database showed, even with limited labeled target samples, ACT yielded marked improvements over UDA and state-of-the-art SSDA methods and approached an "upper bound" of supervised joint training., Comment: MICCAI 2022 (early accept)

Understanding the underlying relationship between tongue and oropharyngeal muscle deformation seen in tagged-MRI and intelligible speech plays an important role in advancing speech motor control theories and treatment of speech related-disorders. Because of their heterogeneous representations, however, direct mapping between the two modalities -- i.e., two-dimensional (mid-sagittal slice) plus time tagged-MRI sequence and its corresponding one-dimensional waveform -- is not straightforward. Instead, we resort to two-dimensional spectrograms as an intermediate representation, which contains both pitch and resonance, from which to develop an end-to-end deep learning framework to translate from a sequence of tagged-MRI to its corresponding audio waveform with limited dataset size.~Our framework is based on a novel fully convolutional asymmetry translator with guidance of a self residual attention strategy to specifically exploit the moving muscular structures during speech.~In addition, we leverage a pairwise correlation of the samples with the same utterances with a latent space representation disentanglement strategy.~Furthermore, we incorporate an adversarial training approach with generative adversarial networks to offer improved realism on our generated spectrograms.~Our experimental results, carried out with a total of 63 tagged-MRI sequences alongside speech acoustics, showed that our framework enabled the generation of clear audio waveforms from a sequence of tagged-MRI, surpassing competing methods. Thus, our framework provides the great potential to help better understand the relationship between the two modalities., Comment: MICCAI 2022 (early accept, Oral Presentation ~3%)

Cycle reconstruction regularized adversarial training -- e.g., CycleGAN, DiscoGAN, and DualGAN -- has been widely used for image style transfer with unpaired training data. Several recent works, however, have shown that local distortions are frequent, and structural consistency cannot be guaranteed. Targeting this issue, prior works usually relied on additional segmentation or consistent feature extraction steps that are task-specific. To counter this, this work aims to learn a general add-on structural feature extractor, by explicitly enforcing the structural alignment between an input and its synthesized image. Specifically, we propose a novel input-output image patches self-training scheme to achieve a disentanglement of underlying anatomical structures and imaging modalities. The translator and structure encoder are updated, following an alternating training protocol. In addition, the information w.r.t. imaging modality can be eliminated with an asymmetric adversarial game. We train, validate, and test our network on 1,768, 416, and 1,560 unpaired subject-independent slices of tagged and cine magnetic resonance imaging from a total of twenty healthy subjects, respectively, demonstrating superior performance over competing methods., Comment: SPIE Medical Imaging: Image Processing (Oral presentation)

Lesions or organ boundaries visible through medical imaging data are often ambiguous, thus resulting in significant variations in multi-reader delineations, i.e., the source of aleatoric uncertainty. In particular, quantifying the inter-observer variability of manual annotations with Magnetic Resonance (MR) Imaging data plays a crucial role in establishing a reference standard for various diagnosis and treatment tasks. Most segmentation methods, however, simply model a mapping from an image to its single segmentation map and do not take the disagreement of annotators into consideration. In order to account for inter-observer variability, without sacrificing accuracy, we propose a novel variational inference framework to model the distribution of plausible segmentation maps, given a specific MR image, which explicitly represents the multi-reader variability. Specifically, we resort to a latent vector to encode the multi-reader variability and counteract the inherent information loss in the imaging data. Then, we apply a variational autoencoder network and optimize its evidence lower bound (ELBO) to efficiently approximate the distribution of the segmentation map, given an MR image. Experimental results, carried out with the QUBIQ brain growth MRI segmentation datasets with seven annotators, demonstrate the effectiveness of our approach., Comment: SPIE Medical Imaging 2022 (Oral)

Unsupervised domain adaptation (UDA) between two significantly disparate domains to learn high-level semantic alignment is a crucial yet challenging task.~To this end, in this work, we propose exploiting low-level edge information to facilitate the adaptation as a precursor task, which has a small cross-domain gap, compared with semantic segmentation.~The precise contour then provides spatial information to guide the semantic adaptation. More specifically, we propose a multi-task framework to learn a contouring adaptation network along with a semantic segmentation adaptation network, which takes both magnetic resonance imaging (MRI) slice and its initial edge map as input.~These two networks are jointly trained with source domain labels, and the feature and edge map level adversarial learning is carried out for cross-domain alignment. In addition, self-entropy minimization is incorporated to further enhance segmentation performance. We evaluated our framework on the BraTS2018 database for cross-modality segmentation of brain tumors, showing the validity and superiority of our approach, compared with competing methods., Comment: Accepted to ISBI 2022

Background and purpose: The delineation of the gross tumor volume (GTV) is a critical step for radiation therapy treatment planning. The delineation procedure is typically performed manually which exposes two major issues: cost and reproducibility. Delineation is a time-consuming process that is subject to inter- and intra-observer variability. While methods have been proposed to predict GTV contours, typical approaches ignore variability and therefore fail to utilize the valuable confidence information offered by multiple contours. Materials and methods: In this work we propose an automatic GTV contouring method for soft-tissue sarcomas from X-ray computed tomography (CT) images, using deep learning by integrating inter- and intra-observer variability in the learned model. Sixty-eight patients with soft tissue and bone sarcomas were considered in this evaluation, all underwent pre-operative CT imaging used to perform GTV delineation. Four radiation oncologists and radiologists performed three contouring trials each for all patients. We quantify variability by defining confidence levels based on the frequency of inclusion of a given voxel into the GTV and use a deep convolutional neural network to learn GTV confidence maps. Results: Results were compared to confidence maps from the four readers as well as ground-truth consensus contours established jointly by all readers. The resulting continuous Dice score between predicted and true confidence maps was 87% and the Hausdorff distance was 14 mm. Conclusion: Results demonstrate the ability of the proposed method to predict accurate contours while utilizing variability and as such it can be used to improve clinical workflow.

In this work, we propose an adversarial unsupervised domain adaptation (UDA) approach with the inherent conditional and label shifts, in which we aim to align the distributions w.r.t. both $p(x|y)$ and $p(y)$. Since the label is inaccessible in the target domain, the conventional adversarial UDA assumes $p(y)$ is invariant across domains, and relies on aligning $p(x)$ as an alternative to the $p(x|y)$ alignment. To address this, we provide a thorough theoretical and empirical analysis of the conventional adversarial UDA methods under both conditional and label shifts, and propose a novel and practical alternative optimization scheme for adversarial UDA. Specifically, we infer the marginal $p(y)$ and align $p(x|y)$ iteratively in the training, and precisely align the posterior $p(y|x)$ in testing. Our experimental results demonstrate its effectiveness on both classification and segmentation UDA, and partial UDA., Comment: Accepted to ICCV 2021

In this work, we propose a domain generalization (DG) approach to learn on several labeled source domains and transfer knowledge to a target domain that is inaccessible in training. Considering the inherent conditional and label shifts, we would expect the alignment of $p(x|y)$ and $p(y)$. However, the widely used domain invariant feature learning (IFL) methods relies on aligning the marginal concept shift w.r.t. $p(x)$, which rests on an unrealistic assumption that $p(y)$ is invariant across domains. We thereby propose a novel variational Bayesian inference framework to enforce the conditional distribution alignment w.r.t. $p(x|y)$ via the prior distribution matching in a latent space, which also takes the marginal label shift w.r.t. $p(y)$ into consideration with the posterior alignment. Extensive experiments on various benchmarks demonstrate that our framework is robust to the label shift and the cross-domain accuracy is significantly improved, thereby achieving superior performance over the conventional IFL counterparts., Comment: 30th International Joint Conference on Artificial Intelligence (IJCAI) 2021

Assessment of cardiovascular disease (CVD) with cine magnetic resonance imaging (MRI) has been used to non-invasively evaluate detailed cardiac structure and function. Accurate segmentation of cardiac structures from cine MRI is a crucial step for early diagnosis and prognosis of CVD, and has been greatly improved with convolutional neural networks (CNN). There, however, are a number of limitations identified in CNN models, such as limited interpretability and high complexity, thus limiting their use in clinical practice. In this work, to address the limitations, we propose a lightweight and interpretable machine learning model, successive subspace learning with the subspace approximation with adjusted bias (Saab) transform, for accurate and efficient segmentation from cine MRI. Specifically, our segmentation framework is comprised of the following steps: (1) sequential expansion of near-to-far neighborhood at different resolutions; (2) channel-wise subspace approximation using the Saab transform for unsupervised dimension reduction; (3) class-wise entropy guided feature selection for supervised dimension reduction; (4) concatenation of features and pixel-wise classification with gradient boost; and (5) conditional random field for post-processing. Experimental results on the ACDC 2017 segmentation database, showed that our framework performed better than state-of-the-art U-Net models with 200$\times$ fewer parameters in delineating the left ventricle, right ventricle, and myocardium, thus showing its potential to be used in clinical practice., Comment: 43rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2021)

Unsupervised domain adaptation (UDA) aims to transfer knowledge learned from a labeled source domain to an unlabeled and unseen target domain, which is usually trained on data from both domains. Access to the source domain data at the adaptation stage, however, is often limited, due to data storage or privacy issues. To alleviate this, in this work, we target source free UDA for segmentation, and propose to adapt an ``off-the-shelf" segmentation model pre-trained in the source domain to the target domain, with an adaptive batch-wise normalization statistics adaptation framework. Specifically, the domain-specific low-order batch statistics, i.e., mean and variance, are gradually adapted with an exponential momentum decay scheme, while the consistency of domain shareable high-order batch statistics, i.e., scaling and shifting parameters, is explicitly enforced by our optimization objective. The transferability of each channel is adaptively measured first from which to balance the contribution of each channel. Moreover, the proposed source free UDA framework is orthogonal to unsupervised learning methods, e.g., self-entropy minimization, which can thus be simply added on top of our framework. Extensive experiments on the BraTS 2018 database show that our source free UDA framework outperformed existing source-relaxed UDA methods for the cross-subtype UDA segmentation task and yielded comparable results for the cross-modality UDA segmentation task, compared with a supervised UDA methods with the source data., Comment: To appear in MICCAI 2021

Self-training based unsupervised domain adaptation (UDA) has shown great potential to address the problem of domain shift, when applying a trained deep learning model in a source domain to unlabeled target domains. However, while the self-training UDA has demonstrated its effectiveness on discriminative tasks, such as classification and segmentation, via the reliable pseudo-label selection based on the softmax discrete histogram, the self-training UDA for generative tasks, such as image synthesis, is not fully investigated. In this work, we propose a novel generative self-training (GST) UDA framework with continuous value prediction and regression objective for cross-domain image synthesis. Specifically, we propose to filter the pseudo-label with an uncertainty mask, and quantify the predictive confidence of generated images with practical variational Bayes learning. The fast test-time adaptation is achieved by a round-based alternative optimization scheme. We validated our framework on the tagged-to-cine magnetic resonance imaging (MRI) synthesis problem, where datasets in the source and target domains were acquired from different scanners or centers. Extensive validations were carried out to verify our framework against popular adversarial training UDA methods. Results show that our GST, with tagged MRI of test subjects in new target domains, improved the synthesis quality by a large margin, compared with the adversarial training UDA methods., Comment: MICCAI 2021 (early accept <13%)

Deformable registration of magnetic resonance images between patients with brain tumors and healthy subjects has been an important tool to specify tumor geometry through location alignment and facilitate pathological analysis. Since tumor region does not match with any ordinary brain tissue, it has been difficult to deformably register a patients brain to a normal one. Many patient images are associated with irregularly distributed lesions, resulting in further distortion of normal tissue structures and complicating registration's similarity measure. In this work, we follow a multi-step context-aware image inpainting framework to generate synthetic tissue intensities in the tumor region. The coarse image-to-image translation is applied to make a rough inference of the missing parts. Then, a feature-level patch-match refinement module is applied to refine the details by modeling the semantic relevance between patch-wise features. A symmetry constraint reflecting a large degree of anatomical symmetry in the brain is further proposed to achieve better structure understanding. Deformable registration is applied between inpainted patient images and normal brains, and the resulting deformation field is eventually used to deform original patient data for the final alignment. The method was applied to the Multimodal Brain Tumor Segmentation (BraTS) 2018 challenge database and compared against three existing inpainting methods. The proposed method yielded results with increased peak signal-to-noise ratio, structural similarity index, inception score, and reduced L1 error, leading to successful patient-to-normal brain image registration., Comment: Published at MICCAI Brainles 2020

Multimodal MRI provides complementary and clinically relevant information to probe tissue condition and to characterize various diseases. However, it is often difficult to acquire sufficiently many modalities from the same subject due to limitations in study plans, while quantitative analysis is still demanded. In this work, we propose a unified conditional disentanglement framework to synthesize any arbitrary modality from an input modality. Our framework hinges on a cycle-constrained conditional adversarial training approach, where it can extract a modality-invariant anatomical feature with a modality-agnostic encoder and generate a target modality with a conditioned decoder. We validate our framework on four MRI modalities, including T1-weighted, T1 contrast enhanced, T2-weighted, and FLAIR MRI, from the BraTS'18 database, showing superior performance on synthesis quality over the comparison methods. In addition, we report results from experiments on a tumor segmentation task carried out with synthesized data., Comment: Published in IEEE International Symposium on Biomedical Imaging (ISBI) 2021 for Oral presentation

Tagged magnetic resonance imaging (MRI) is a widely used imaging technique for measuring tissue deformation in moving organs. Due to tagged MRI's intrinsic low anatomical resolution, another matching set of cine MRI with higher resolution is sometimes acquired in the same scanning session to facilitate tissue segmentation, thus adding extra time and cost. To mitigate this, in this work, we propose a novel dual-cycle constrained bijective VAE-GAN approach to carry out tagged-to-cine MR image synthesis. Our method is based on a variational autoencoder backbone with cycle reconstruction constrained adversarial training to yield accurate and realistic cine MR images given tagged MR images. Our framework has been trained, validated, and tested using 1,768, 416, and 1,560 subject-independent paired slices of tagged and cine MRI from twenty healthy subjects, respectively, demonstrating superior performance over the comparison methods. Our method can potentially be used to reduce the extra acquisition time and cost, while maintaining the same workflow for further motion analyses., Comment: Accepted to IEEE International Symposium on Biomedical Imaging (ISBI) 2021

Deep learning has great potential for accurate detection and classification of diseases with medical imaging data, but the performance is often limited by the number of training datasets and memory requirements. In addition, many deep learning models are considered a "black-box," thereby often limiting their adoption in clinical applications. To address this, we present a successive subspace learning model, termed VoxelHop, for accurate classification of Amyotrophic Lateral Sclerosis (ALS) using T2-weighted structural MRI data. Compared with popular convolutional neural network (CNN) architectures, VoxelHop has modular and transparent structures with fewer parameters without any backpropagation, so it is well-suited to small dataset size and 3D imaging data. Our VoxelHop has four key components, including (1) sequential expansion of near-to-far neighborhood for multi-channel 3D data; (2) subspace approximation for unsupervised dimension reduction; (3) label-assisted regression for supervised dimension reduction; and (4) concatenation of features and classification between controls and patients. Our experimental results demonstrate that our framework using a total of 20 controls and 26 patients achieves an accuracy of 93.48$\%$ and an AUC score of 0.9394 in differentiating patients from controls, even with a relatively small number of datasets, showing its robustness and effectiveness. Our thorough evaluations also show its validity and superiority to the state-of-the-art 3D CNN classification methods. Our framework can easily be generalized to other classification tasks using different imaging modalities.

Recent advances in unsupervised domain adaptation (UDA) show that transferable prototypical learning presents a powerful means for class conditional alignment, which encourages the closeness of cross-domain class centroids. However, the cross-domain inner-class compactness and the underlying fine-grained subtype structure remained largely underexplored. In this work, we propose to adaptively carry out the fine-grained subtype-aware alignment by explicitly enforcing the class-wise separation and subtype-wise compactness with intermediate pseudo labels. Our key insight is that the unlabeled subtypes of a class can be divergent to one another with different conditional and label shifts, while inheriting the local proximity within a subtype. The cases of with or without the prior information on subtype numbers are investigated to discover the underlying subtype structure in an online fashion. The proposed subtype-aware dynamic UDA achieves promising results on medical diagnosis tasks., Comment: Accepted to AAAI 2021

Intelligible speech is produced by creating varying internal local muscle groupings -- i.e., functional units -- that are generated in a systematic and coordinated manner. There are two major challenges in characterizing and analyzing functional units.~First, due to the complex and convoluted nature of tongue structure and function, it is of great importance to develop a method that can accurately decode complex muscle coordination patterns during speech. Second, it is challenging to keep identified functional units across subjects comparable due to their substantial variability. In this work, to address these challenges, we develop a new deep learning framework to identify common and subject-specific functional units of tongue motion during speech.~Our framework hinges on joint deep graph-regularized sparse non-negative matrix factorization (NMF) using motion quantities derived from displacements by tagged Magnetic Resonance Imaging. More specifically, we transform NMF with sparse and graph regularizations into modular architectures akin to deep neural networks by means of unfolding the Iterative Shrinkage-Thresholding Algorithm to learn interpretable building blocks and associated weighting map. We then apply spectral clustering to common and subject-specific weighting maps from which we jointly determine the common and subject-specific functional units. Experiments carried out with simulated datasets show that the proposed method achieved on par or better clustering performance over the comparison methods. Experiments carried out with in vivo tongue motion data show that the proposed method can determine the common and subject-specific functional units with increased interpretability and decreased size variability., Comment: Accepted by Medical Image Analysis

Muscle coordination patterns of lingual behaviors are synergies generated by deforming local muscle groups in a variety of ways. Functional units are functional muscle groups of local structural elements within the tongue that compress, expand, and move in a cohesive and consistent manner. Identifying the functional units using tagged-Magnetic Resonance Imaging (MRI) sheds light on the mechanisms of normal and pathological muscle coordination patterns, yielding improvement in surgical planning, treatment, or rehabilitation procedures. Here, to mine this information, we propose a matrix factorization and probabilistic graphical model framework to produce building blocks and their associated weighting map using motion quantities extracted from tagged-MRI. Our tagged-MRI imaging and accurate voxel-level tracking provide previously unavailable internal tongue motion patterns, thus revealing the inner workings of the tongue during speech or other lingual behaviors. We then employ spectral clustering on the weighting map to identify the cohesive regions defined by the tongue motion that may involve multiple or undocumented regions. To evaluate our method, we perform a series of experiments. We first use two-dimensional images and synthetic data to demonstrate the accuracy of our method. We then use three-dimensional synthetic and \textit{in vivo} tongue motion data using protrusion and simple speech tasks to identify subject-specific and data-driven functional units of the tongue in localized regions., Comment: Accepted at IEEE TMI (https://ieeexplore.ieee.org/document/8467354)

Quantitative measurement of functional and anatomical traits of 4D tongue motion in the course of speech or other lingual behaviors remains a major challenge in scientific research and clinical applications. Here, we introduce a statistical multimodal atlas of 4D tongue motion using healthy subjects, which enables a combined quantitative characterization of tongue motion in a reference anatomical configuration. This atlas framework, termed Speech Map, combines cine- and tagged-MRI in order to provide both the anatomic reference and motion information during speech. Our approach involves a series of steps including (1) construction of a common reference anatomical configuration from cine-MRI, (2) motion estimation from tagged-MRI, (3) transformation of the motion estimations to the reference anatomical configuration, and (4) computation of motion quantities such as Lagrangian strain. Using this framework, the anatomic configuration of the tongue appears motionless, while the motion fields and associated strain measurements change over the time course of speech. In addition, to form a succinct representation of the high-dimensional and complex motion fields, principal component analysis is carried out to characterize the central tendencies and variations of motion fields of our speech tasks. Our proposed method provides a platform to quantitatively and objectively explain the differences and variability of tongue motion by illuminating internal motion and strain that have so far been intractable. The findings are used to understand how tongue function for speech is limited by abnormal internal motion and strain in glossectomy patients., Comment: Accepted at Journal of Computer Methods in Biomechanics and Biomedical Engineering