Yixi Xu

Shadab Ahamed, Yixi Xu, Sara Kurkowska et al.

This study addresses critical gaps in automated lymphoma segmentation from PET/CT images, focusing on issues often overlooked in existing literature. While deep learning has been applied for lymphoma lesion segmentation, few studies incorporate out-of-distribution testing, raising concerns about model generalizability across diverse imaging conditions and patient populations. We highlight the need to compare model performance with expert human annotators, including intra- and inter-observer variability, to understand task difficulty better. Most approaches focus on overall segmentation accuracy but overlook lesion-specific measures important for precise lesion detection and disease quantification. To address these gaps, we propose a clinically relevant framework for evaluating deep segmentation networks. Using this lesion measure-specific evaluation, we assess the performance of four deep networks (ResUNet, SegResNet, DynUNet, and SwinUNETR) across 611 cases from multi-institutional datasets, covering various lymphoma subtypes and lesion characteristics. Beyond standard metrics like the Dice similarity coefficient, we evaluate clinical lesion measures and their prediction errors. We also introduce detection criteria for lesion localization and propose a new detection Criterion 3 based on metabolic characteristics. We show that networks perform better on large, intense lesions with higher metabolic activity. Finally, we compare network performance to physicians via intra- and inter-observer variability analyses, demonstrating that network errors closely resemble those made by experts, i.e., the small and faint lesions remain challenging for both humans and networks. This study aims to improve automated lesion segmentation's clinical relevance, supporting better treatment decisions for lymphoma patients. The code is available at: https://github.com/microsoft/lymphoma-segmentation-dnn.

Mohammad R. Salmanpour, Amin Mousavi, Yixi Xu et al.

Purpose: This study examines the core traits of image-to-image translation (I2I) networks, focusing on their effectiveness and adaptability in everyday clinical settings. Methods: We have analyzed data from 794 patients diagnosed with prostate cancer (PCa), using ten prominent 2D/3D I2I networks to convert ultrasound (US) images into MRI scans. We also introduced a new analysis of Radiomic features (RF) via the Spearman correlation coefficient to explore whether networks with high performance (SSIM>85%) could detect subtle RFs. Our study further examined synthetic images by 7 invited physicians. As a final evaluation study, we have investigated the improvement that are achieved using the synthetic MRI data on two traditional machine learning and one deep learning method. Results: In quantitative assessment, 2D-Pix2Pix network substantially outperformed the other 7 networks, with an average SSIM~0.855. The RF analysis revealed that 76 out of 186 RFs were identified using the 2D-Pix2Pix algorithm alone, although half of the RFs were lost during the translation process. A detailed qualitative review by 7 medical doctors noted a deficiency in low-level feature recognition in I2I tasks. Furthermore, the study found that synthesized image-based classification outperformed US image-based classification with an average accuracy and AUC~0.93. Conclusion: This study showed that while 2D-Pix2Pix outperformed cutting-edge networks in low-level feature discovery and overall error and similarity metrics, it still requires improvement in low-level feature performance, as highlighted by Group 3. Further, the study found using synthetic image-based classification outperformed original US image-based methods.

Mohammad R. Salmanpour, Sajad Amiri, Sara Gharibi et al.

We investigate the connection between visual semantic features defined in PI-RADS and associated risk factors, moving beyond abnormal imaging findings, establishing a shared framework between medical and AI professionals by creating a standardized dictionary of biological/radiological RFs. Subsequently, 6 interpretable and seven complex classifiers, linked with nine interpretable feature selection algorithms (FSA) applied to risk factors, were extracted from segmented lesions in T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) multiparametric-prostate MRI sequences to predict the UCLA scores. We then utilized the created dictionary to interpret the best-predictive models. Combining T2WI, DWI, and ADC with FSAs including ANOVA F-test, Correlation Coefficient, and Fisher Score, and utilizing logistic regression, identified key features: The 90th percentile from T2WI, which captures hypo-intensity related to prostate cancer risk; Variance from T2WI, indicating lesion heterogeneity; shape metrics including Least Axis Length and Surface Area to Volume ratio from ADC, describing lesion shape and compactness; and Run Entropy from ADC, reflecting texture consistency. This approach achieved the highest average accuracy of 0.78, significantly outperforming single-sequence methods (p-value<0.05). The developed dictionary for Prostate-MRI (PM1.0) serves as a common language, fosters collaboration between clinical professionals and AI developers to advance trustworthy AI solutions that support reliable/interpretable clinical decisions.

Shadab Ahamed, Yixi Xu, Ingrid Bloise et al.

Automated slice classification is clinically relevant since it can be incorporated into medical image segmentation workflows as a preprocessing step that would flag slices with a higher probability of containing tumors, thereby directing physicians attention to the important slices. In this work, we train a ResNet-18 network to classify axial slices of lymphoma PET/CT images (collected from two institutions) depending on whether the slice intercepted a tumor (positive slice) in the 3D image or if the slice did not (negative slice). Various instances of the network were trained on 2D axial datasets created in different ways: (i) slice-level split and (ii) patient-level split; inputs of different types were used: (i) only PET slices and (ii) concatenated PET and CT slices; and different training strategies were employed: (i) center-aware (CAW) and (ii) center-agnostic (CAG). Model performances were compared using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC), and various binary classification metrics. We observe and describe a performance overestimation in the case of slice-level split as compared to the patient-level split training. The model trained using patient-level split data with the network input containing only PET slices in the CAG training regime was the best performing/generalizing model on a majority of metrics. Our models were additionally more closely compared using the sensitivity metric on the positive slices from their respective test sets.

Yixi Xu, Sumit Mukherjee, Xiyang Liu et al.

Generative machine learning models are being increasingly viewed as a way to share sensitive data between institutions. While there has been work on developing differentially private generative modeling approaches, these approaches generally lead to sub-par sample quality, limiting their use in real world applications. Another line of work has focused on developing generative models which lead to higher quality samples but currently lack any formal privacy guarantees. In this work, we propose the first formal framework for membership privacy estimation in generative models. We formulate the membership privacy risk as a statistical divergence between training samples and hold-out samples, and propose sample-based methods to estimate this divergence. Compared to previous works, our framework makes more realistic and flexible assumptions. First, we offer a generalizable metric as an alternative to the accuracy metric especially for imbalanced datasets. Second, we loosen the assumption of having full access to the underlying distribution from previous studies , and propose sample-based estimations with theoretical guarantees. Third, along with the population-level membership privacy risk estimation via the optimal membership advantage, we offer the individual-level estimation via the individual privacy risk. Fourth, our framework allows adversaries to access the trained model via a customized query, while prior works require specific attributes.

Sumit Mukherjee, Yixi Xu, Anusua Trivedi et al.

Generative Adversarial Networks (GANs) have made releasing of synthetic images a viable approach to share data without releasing the original dataset. It has been shown that such synthetic data can be used for a variety of downstream tasks such as training classifiers that would otherwise require the original dataset to be shared. However, recent work has shown that the GAN models and their synthetically generated data can be used to infer the training set membership by an adversary who has access to the entire dataset and some auxiliary information. Current approaches to mitigate this problem (such as DPGAN) lead to dramatically poorer generated sample quality than the original non--private GANs. Here we develop a new GAN architecture (privGAN), where the generator is trained not only to cheat the discriminator but also to defend membership inference attacks. The new mechanism provides protection against this mode of attack while leading to negligible loss in downstream performances. In addition, our algorithm has been shown to explicitly prevent overfitting to the training set, which explains why our protection is so effective. The main contributions of this paper are: i) we propose a novel GAN architecture that can generate synthetic data in a privacy preserving manner without additional hyperparameter tuning and architecture selection, ii) we provide a theoretical understanding of the optimal solution of the privGAN loss function, iii) we demonstrate the effectiveness of our model against several white and black--box attacks on several benchmark datasets, iv) we demonstrate on three common benchmark datasets that synthetic images generated by privGAN lead to negligible loss in downstream performance when compared against non--private GANs.

Yixi Xu, Xiao Wang

This paper presents a general framework for norm-based capacity control for $L_{p,q}$ weight normalized deep neural networks. We establish the upper bound on the Rademacher complexities of this family. With an $L_{p,q}$ normalization where $q\le p^*$, and $1/p+1/p^{*}=1$, we discuss properties of a width-independent capacity control, which only depends on depth by a square root term. We further analyze the approximation properties of $L_{p,q}$ weight normalized deep neural networks. In particular, for an $L_{1,\infty}$ weight normalized network, the approximation error can be controlled by the $L_1$ norm of the output layer, and the corresponding generalization error only depends on the architecture by the square root of the depth.

Yixi Xu, Jean Honorio, Xiao Wang

In this paper, we propose a compositional nonparametric method in which a model is expressed as a labeled binary tree of $2k+1$ nodes, where each node is either a summation, a multiplication, or the application of one of the $q$ basis functions to one of the $p$ covariates. We show that in order to recover a labeled binary tree from a given dataset, the sufficient number of samples is $O(k\log(pq)+\log(k!))$, and the necessary number of samples is $Ω(k\log (pq)-\log(k!))$. We further propose a greedy algorithm for regression in order to validate our theoretical findings through synthetic experiments.