Fangxu Xing

Xiaofeng Liu, Fangxu Xing, Nadya Shusharina et al. · cmu, harvard

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.

Xiaofeng Liu, Chaehwa Yoo, Fangxu Xing et al. · cmu, harvard

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.

Xiaofeng Liu, Fangxu Xing, Jia You et al. · cmu, harvard

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.

Zhangxing Bian, Fangxu Xing, Jinglun Yu et al.

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

Xiaofeng Liu, Chaehwa Yoo, Fangxu Xing et al.

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.

Xiaofeng Liu, Fangxu Xing, Hanna K. Gaggin et al.

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.

Xiaofeng Liu, Fangxu Xing, Georges El Fakhri et al.

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.

Xiaofeng Liu, Fangxu Xing, Maureen Stone et al.

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.

Zhangxing Bian, Shuwen Wei, Yihao Liu et al.

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.

Xiaofeng Liu, Fangxu Xing, Jerry L. Prince et al.

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.

Xiaofeng Liu, Fangxu Xing, Jerry L. Prince et al.

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.

Jihoon Cho, Suhyun Ahn, Beomju Kim et al.

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.

Jyun-Ping Kao, Shinyeong Rho, Shahar Lazarev et al.

Early diagnosis of attention-deficit/hyperactivity disorder (ADHD) in children plays a crucial role in improving outcomes in education and mental health. Diagnosing ADHD using neuroimaging data, however, remains challenging due to heterogeneous presentations and overlapping symptoms with other conditions. To address this, we propose a novel parameter-efficient transfer learning approach that adapts a large-scale 3D convolutional foundation model, pre-trained on CT images, to an MRI-based ADHD classification task. Our method introduces Low-Rank Adaptation (LoRA) in 3D by factorizing 3D convolutional kernels into 2D low-rank updates, dramatically reducing trainable parameters while achieving superior performance. In a five-fold cross-validated evaluation on a public diffusion MRI database, our 3D LoRA fine-tuning strategy achieved state-of-the-art results, with one model variant reaching 71.9% accuracy and another attaining an AUC of 0.716. Both variants use only 1.64 million trainable parameters (over 113x fewer than a fully fine-tuned foundation model). Our results represent one of the first successful cross-modal (CT-to-MRI) adaptations of a foundation model in neuroimaging, establishing a new benchmark for ADHD classification while greatly improving efficiency.

Shihua Qin, Ming Zhang, Juan Shan et al.

Bone marrow lesions (BMLs) are critical indicators of knee osteoarthritis (OA). Since they often appear as small, irregular structures with indistinguishable edges in knee magnetic resonance images (MRIs), effective detection of BMLs in MRI is vital for OA diagnosis and treatment. This paper proposes a semi-supervised local anomaly detection method using mask inpainting models for identification of BMLs in high-resolution knee MRI, effectively integrating a 3D femur bone segmentation model, a large mask inpainting model, and a series of post-processing techniques. The method was evaluated using MRIs at various resolutions from a subset of the public Osteoarthritis Initiative database. Dice score, Intersection over Union (IoU), and pixel-level sensitivity, specificity, and accuracy showed an advantage over the multiresolution knowledge distillation method-a state-of-the-art global anomaly detection method. Especially, segmentation performance is enhanced on higher-resolution images, achieving an over two times performance increase on the Dice score and the IoU score at a 448x448 resolution level. We also demonstrate that with increasing size of the BML region, both the Dice and IoU scores improve as the proportion of distinguishable boundary decreases. The identified BML masks can serve as markers for downstream tasks such as segmentation and classification. The proposed method has shown a potential in improving BML detection, laying a foundation for further advances in imaging-based OA research.

Daiqi Liu, Lukas Mulzer, Md Hasan et al.

Segmenting vocal tract articulators in real-time MRI (rtMRI) is a challenging dynamic image segmentation problem characterized by low contrast, rapid motion, and limited spatial resolution. However, while rtMRI acquisitions may provide synchronized acoustic signals, existing methods discard this information, and the few multimodal approaches that incorporate audio cannot be deployed when audio is unavailable. We propose a three-stage framework that leverages acoustic and phonological supervision during training while requiring only the rtMRI image at inference: phonological representations are converted into spatial bounding-box priors for articulator localization, visual and acoustic encoders are aligned via dual-level cross-modal contrastive pretraining, and the learned representations are fused through a cross-attention decoder, effectively transferring multimodal knowledge into a single-modality inference pipeline. Evaluated on 75-Speaker~Annot-16 and USC-TIMIT datasets, our method outperforms existing unimodal and multimodal methods, demonstrating that multimodal supervision provides transferable benefits for precise and clinically deployable vocal tract segmentation.

Yaxuan Li, Han Jiang, Yifei Ma et al.

Dynamic Magnetic Resonance Imaging (MRI) of the vocal tract has become an increasingly adopted imaging modality for speech motor studies. Beyond image signals, systematic data loss, noise pollution, and audio file corruption can occur due to the unpredictability of the MRI acquisition environment. In such cases, generating audio from images is critical for data recovery in both clinical and research applications. However, this remains challenging due to hardware constraints, acoustic interference, and data corruption. Existing solutions, such as denoising and multi-stage synthesis methods, face limitations in audio fidelity and generalizability. To address these challenges, we propose a Knowledge Enhanced Conditional Variational Autoencoder (KE-CVAE), a novel two-step "knowledge enhancement + variational inference" framework for generating speech audio signals from cine dynamic MRI sequences. This approach introduces two key innovations: (1) integration of unlabeled MRI data for knowledge enhancement, and (2) a variational inference architecture to improve generative modeling capacity. To the best of our knowledge, this is one of the first attempts at synthesizing speech audio directly from dynamic MRI video sequences. The proposed method was trained and evaluated on an open-source dynamic vocal tract MRI dataset recorded during speech. Experimental results demonstrate its effectiveness in generating natural speech waveforms while addressing MRI-specific acoustic challenges, outperforming conventional deep learning-based synthesis approaches.

Jihoon Cho, Xiaofeng Liu, Fangxu Xing et al.

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.

Zhangxing Bian, Shuwen Wei, Xiao Liang et al.

Magnetic resonance (MR) tagging is an imaging technique for noninvasively tracking tissue motion in vivo by creating a visible pattern of magnetization saturation (tags) that deforms with the tissue. Due to longitudinal relaxation and progression to steady-state, the tags and tissue brightnesses change over time, which makes tracking with optical flow methods error-prone. Although Fourier methods can alleviate these problems, they are also sensitive to brightness changes as well as spectral spreading due to motion. To address these problems, we introduce the brightness-invariant tracking estimation (BRITE) technique for tagged MRI. BRITE disentangles the anatomy from the tag pattern in the observed tagged image sequence and simultaneously estimates the Lagrangian motion. The inherent ill-posedness of this problem is addressed by leveraging the expressive power of denoising diffusion probabilistic models to represent the probabilistic distribution of the underlying anatomy and the flexibility of physics-informed neural networks to estimate biologically-plausible motion. A set of tagged MR images of a gel phantom was acquired with various tag periods and imaging flip angles to demonstrate the impact of brightness variations and to validate our method. The results show that BRITE achieves more accurate motion and strain estimates as compared to other state of the art methods, while also being resistant to tag fading.

Xiaofeng Liu, Fangxu Xing, Jiachen Zhuo et al.

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.

Daiqi Liu, Tomás Arias-Vergara, Johannes Enk et al.

Accurately segmenting articulatory structures in real-time magnetic resonance imaging (rtMRI) remains challenging, as most existing methods rely almost entirely on visual cues. Yet synchronized acoustic and phonological signals provide complementary context that can enrich visual information and improve precision. In this paper, we introduce VocSegMRI, a multimodal framework that integrates video, audio, and phonological inputs through cross-attention fusion for dynamic feature alignment. To further enhance cross-modal representation, we incorporate a contrastive learning objective that improves segmentation performance even when the audio modality is unavailable at inference. Evaluated on a sub-set of USC-75 rtMRI dataset, our approach achieves state-of-the-art performance, with a Dice score of 0.95 and a 95th percentile Hausdorff Distance (HD_95) of 4.20 mm, outperforming both unimodal and multimodal baselines. Ablation studies confirm the contributions of cross-attention and contrastive learning to segmentation precision and robustness. These results highlight the value of integrative multimodal modeling for accurate vocal tract analysis.

Paula Andrea Pérez-Toro, Tomás Arias-Vergara, Fangxu Xing et al.

Understanding the relationship between vocal tract motion during speech and the resulting acoustic signal is crucial for aided clinical assessment and developing personalized treatment and rehabilitation strategies. Toward this goal, we introduce an audio-to-video generation framework for creating Real Time/cine-Magnetic Resonance Imaging (RT-/cine-MRI) visuals of the vocal tract from speech signals. Our framework first preprocesses RT-/cine-MRI sequences and speech samples to achieve temporal alignment, ensuring synchronization between visual and audio data. We then employ a modified stable diffusion model, integrating structural and temporal blocks, to effectively capture movement characteristics and temporal dynamics in the synchronized data. This process enables the generation of MRI sequences from new speech inputs, improving the conversion of audio into visual data. We evaluated our framework on healthy controls and tongue cancer patients by analyzing and comparing the vocal tract movements in synthesized videos. Our framework demonstrated adaptability to new speech inputs and effective generalization. In addition, positive human evaluations confirmed its effectiveness, with realistic and accurate visualizations, suggesting its potential for outpatient therapy and personalized simulation of vocal tract visualizations.

Bo Gao, Jianhui Wang, Xinyuan Song et al.

Current semantic segmentation models typically require a substantial amount of manually annotated data, a process that is both time-consuming and resource-intensive. Alternatively, leveraging advanced text-to-image models such as Midjourney and Stable Diffusion has emerged as an efficient strategy, enabling the automatic generation of synthetic data in place of manual annotations. However, previous methods have been limited to generating single-instance images, as the generation of multiple instances with Stable Diffusion has proven unstable. To address this limitation and expand the scope and diversity of synthetic datasets, we propose a framework \textbf{Free-Mask} that combines a Diffusion Model for segmentation with advanced image editing capabilities, allowing for the integration of multiple objects into images via text-to-image models. Our method facilitates the creation of highly realistic datasets that closely emulate open-world environments while generating accurate segmentation masks. It reduces the labor associated with manual annotation and also ensures precise mask generation. Experimental results demonstrate that synthetic data generated by \textbf{Free-Mask} enables segmentation models to outperform those trained on real data, especially in zero-shot settings. Notably, \textbf{Free-Mask} achieves new state-of-the-art results on previously unseen classes in the VOC 2012 benchmark.

Xiaofeng Liu, Helen A. Shih, Fangxu Xing et al.

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.

Xiaofeng Liu, Jerry L. Prince, Fangxu Xing et al.

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.

Xiaofeng Liu, Fangxu Xing, Jerry L. Prince et al.

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.

Xiaofeng Liu, Fangxu Xing, Thibault Marin et al.

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.

Xiaofeng Liu, Fangxu Xing, Georges El Fakhri et al.

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.

Xiaofeng Liu, Zhenhua Guo, Site Li et al.

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.

Xiaofeng Liu, Bo Hu, Linghao Jin et al.

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.

Xiaofeng Liu, Fangxu Xing, Hanna K. Gaggin et al.

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.

Xiaofeng Liu, Fangxu Xing, Maureen Stone et al.

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.

Xiaofeng Liu, Fangxu Xing, Chao Yang et al.

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.

Xiaofeng Liu, Fangxu Xing, Chao Yang et al.

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.

Xiaofeng Liu, Fangxu Xing, Jerry L. Prince et al.

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.

Xiaofeng Liu, Fangxu Xing, Georges El Fakhri et al.

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.

Xiaofeng Liu, Fangxu Xing, Chao Yang et al.

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.

Xiaofeng Liu, Xiongchang Liu, Bo Hu et al.

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.

Jonghye Woo, Fangxu Xing, Jerry L. Prince et al.

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.

Jonghye Woo, Jerry L. Prince, Maureen Stone et al.

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.

Jonghye Woo, Fangxu Xing, Maureen Stone et al.

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.