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Automated segmentation plays a pivotal role in medical image analysis and computer-assisted interventions. Despite the promising performance of existing methods based on convolutional neural networks (CNNs), they neglect useful equivariant properties for images, such as rotational and reflection equivariance. This limitation can decrease performance and lead to inconsistent predictions, especially in applications like vessel segmentation where explicit orientation is absent. While existing equivariant learning approaches attempt to mitigate these issues, they substantially increase learning cost, model size, or both. To overcome these challenges, we propose a novel application of an efficient symmetric rotation-equivariant (SRE) convolutional (SRE-Conv) kernel implementation to the U-Net architecture, to learn rotation and reflection-equivariant features, while also reducing the model size dramatically. We validate the effectiveness of our method through improved segmentation performance on retina vessel fundus imaging. Our proposed SRE U-Net not only significantly surpasses standard U-Net in handling rotated images, but also outperforms existing equivariant learning methods and does so with a reduced number of trainable parameters and smaller memory cost. The code is available at https://github.com/OnofreyLab/sre_conv_segm_isbi2025., Comment: Accepted by IEEE ISBI 2025

Monte-Carlo (MC) Dropout provides a practical solution for estimating predictive distributions in deterministic neural networks. Traditional dropout, applied within the signal space, may fail to account for frequency-related noise common in medical imaging, leading to biased predictive estimates. A novel approach extends Dropout to the frequency domain, allowing stochastic attenuation of signal frequencies during inference. This creates diverse global textural variations in feature maps while preserving structural integrity -- a factor we hypothesize and empirically show is contributing to accurately estimating uncertainties in semantic segmentation. We evaluated traditional MC-Dropout and the MC-frequency Dropout in three segmentation tasks involving different imaging modalities: (i) prostate zones in biparametric MRI, (ii) liver tumors in contrast-enhanced CT, and (iii) lungs in chest X-ray scans. Our results show that MC-Frequency Dropout improves calibration, convergence, and semantic uncertainty, thereby improving prediction scrutiny, boundary delineation, and has the potential to enhance medical decision-making., Comment: Accepted by IEEE ISBI 2025 4-page paper. Code for the implementation is available at https://github.com/talze/frequency-dropout

Convolutional neural networks (CNNs) are essential tools for computer vision tasks, but they lack traditionally desired properties of extracted features that could further improve model performance, e.g., rotational equivariance. Such properties are ubiquitous in biomedical images, which often lack explicit orientation. While current work largely relies on data augmentation or explicit modules to capture orientation information, this comes at the expense of increased training costs or ineffective approximations of the desired equivariance. To overcome these challenges, we propose a novel and efficient implementation of the Symmetric Rotation-Equivariant (SRE) Convolution (SRE-Conv) kernel, designed to learn rotation-invariant features while simultaneously compressing the model size. The SRE-Conv kernel can easily be incorporated into any CNN backbone. We validate the ability of a deep SRE-CNN to capture equivariance to rotation using the public MedMNISTv2 dataset (16 total tasks). SRE-Conv-CNN demonstrated improved rotated image classification performance accuracy on all 16 test datasets in both 2D and 3D images, all while increasing efficiency with fewer parameters and reduced memory footprint. The code is available at https://github.com/XYPB/SRE-Conv., Comment: Accepted by IEEE ISBI 2025 4-page paper

Brain positron emission tomography (PET) imaging is broadly used in research and clinical routines to study, diagnose, and stage Alzheimer's disease (AD). However, its potential cannot be fully exploited yet due to the lack of portable motion correction solutions, especially in clinical settings. Head motion during data acquisition has indeed been shown to degrade image quality and induces tracer uptake quantification error. In this study, we demonstrate that it also biases machine learning-based AD classification. We start by proposing a binary classification algorithm solely based on PET images. We find that it reaches a high accuracy in classifying motion corrected images into cognitive normal or AD. We demonstrate that the classification accuracy substantially decreases when images lack motion correction, thereby limiting the algorithm's effectiveness and biasing image interpretation. We validate these findings in cohorts of 128 $^{11}$C-UCB-J and 173 $^{18}$F-FDG scans, two tracers highly relevant to the study of AD. Classification accuracies decreased by 10% and 5% on 20 $^{18}$F-FDG and 20 $^{11}$C-UCB-J testing cases, respectively. Our findings underscore the critical need for efficient motion correction methods to make the most of the diagnostic capabilities of PET-based machine learning., Comment: 5 pages

Accurate uncertainty estimation is crucial for deploying neural networks in risk-sensitive applications such as medical diagnosis. Monte Carlo Dropout is a widely used technique for approximating predictive uncertainty by performing stochastic forward passes with dropout during inference. However, using static dropout rates across all layers and inputs can lead to suboptimal uncertainty estimates, as it fails to adapt to the varying characteristics of individual inputs and network layers. Existing approaches optimize dropout rates during training using labeled data, resulting in fixed inference-time parameters that cannot adjust to new data distributions, compromising uncertainty estimates in Monte Carlo simulations. In this paper, we propose Rate-In, an algorithm that dynamically adjusts dropout rates during inference by quantifying the information loss induced by dropout in each layer's feature maps. By treating dropout as controlled noise injection and leveraging information-theoretic principles, Rate-In adapts dropout rates per layer and per input instance without requiring ground truth labels. By quantifying the functional information loss in feature maps, we adaptively tune dropout rates to maintain perceptual quality across diverse medical imaging tasks and architectural configurations. Our extensive empirical study on synthetic data and real-world medical imaging tasks demonstrates that Rate-In improves calibration and sharpens uncertainty estimates compared to fixed or heuristic dropout rates without compromising predictive performance. Rate-In offers a practical, unsupervised, inference-time approach to optimizing dropout for more reliable predictive uncertainty estimation in critical applications., Comment: Updated author affiliation

Magnetic Resonance Spectroscopic Imaging (MRSI) is a non-invasive imaging technique for studying metabolism and has become a crucial tool for understanding neurological diseases, cancers and diabetes. High spatial resolution MRSI is needed to characterize lesions, but in practice MRSI is acquired at low resolution due to time and sensitivity restrictions caused by the low metabolite concentrations. Therefore, there is an imperative need for a post-processing approach to generate high-resolution MRSI from low-resolution data that can be acquired fast and with high sensitivity. Deep learning-based super-resolution methods provided promising results for improving the spatial resolution of MRSI, but they still have limited capability to generate accurate and high-quality images. Recently, diffusion models have demonstrated superior learning capability than other generative models in various tasks, but sampling from diffusion models requires iterating through a large number of diffusion steps, which is time-consuming. This work introduces a Flow-based Truncated Denoising Diffusion Model (FTDDM) for super-resolution MRSI, which shortens the diffusion process by truncating the diffusion chain, and the truncated steps are estimated using a normalizing flow-based network. The network is conditioned on upscaling factors to enable multi-scale super-resolution. To train and evaluate the deep learning models, we developed a 1H-MRSI dataset acquired from 25 high-grade glioma patients. We demonstrate that FTDDM outperforms existing generative models while speeding up the sampling process by over 9-fold compared to the baseline diffusion model. Neuroradiologists' evaluations confirmed the clinical advantages of our method, which also supports uncertainty estimation and sharpness adjustment, extending its potential clinical applications., Comment: Accepted by Medical Image Analysis (MedIA)

Contrastive Language-Image Pre-training (CLIP) shows promise in medical image analysis but requires substantial data and computational resources. Due to these restrictions, existing CLIP applications in medical imaging focus mainly on modalities like chest X-rays that have abundant image-report data available, leaving many other important modalities under-explored. Here, we propose the first adaptation of the full CLIP model to mammography, which presents significant challenges due to labeled data scarcity, high-resolution images with small regions of interest, and data imbalance. We first develop a specialized supervision framework for mammography that leverages its multi-view nature. Furthermore, we design a symmetric local alignment module to better focus on detailed features in high-resolution images. Lastly, we incorporate a parameter-efficient fine-tuning approach for large language models pre-trained with medical knowledge to address data limitations. Our multi-view and multi-scale alignment (MaMA) method outperforms state-of-the-art baselines for three different tasks on two large real-world mammography datasets, EMBED and RSNA-Mammo, with only 52% model size compared with the largest baseline., Comment: This work is also the basis of the overall best solution for the MICCAI 2024 CXR-LT Challenge

Magnetic Resonance Spectroscopic Imaging (MRSI) is an essential tool for quantifying metabolites in the body, but the low spatial resolution limits its clinical applications. Deep learning-based super-resolution methods provided promising results for improving the spatial resolution of MRSI, but the super-resolved images are often blurry compared to the experimentally-acquired high-resolution images. Attempts have been made with the generative adversarial networks to improve the image visual quality. In this work, we consider another type of generative model, the flow-based model, of which the training is more stable and interpretable compared to the adversarial networks. Specifically, we propose a flow-based enhancer network to improve the visual quality of super-resolution MRSI. Different from previous flow-based models, our enhancer network incorporates anatomical information from additional image modalities (MRI) and uses a learnable base distribution. In addition, we impose a guide loss and a data-consistency loss to encourage the network to generate images with high visual quality while maintaining high fidelity. Experiments on a 1H-MRSI dataset acquired from 25 high-grade glioma patients indicate that our enhancer network outperforms the adversarial networks and the baseline flow-based methods. Our method also allows visual quality adjustment and uncertainty estimation., Comment: Accepted by DGM4MICCAI 2022

Magnetic Resonance Spectroscopic Imaging (MRSI) is a valuable tool for studying metabolic activities in the human body, but the current applications are limited to low spatial resolutions. The existing deep learning-based MRSI super-resolution methods require training a separate network for each upscaling factor, which is time-consuming and memory inefficient. We tackle this multi-scale super-resolution problem using a Filter Scaling strategy that modulates the convolution filters based on the upscaling factor, such that a single network can be used for various upscaling factors. Observing that each metabolite has distinct spatial characteristics, we also modulate the network based on the specific metabolite. Furthermore, our network is conditioned on the weight of adversarial loss so that the perceptual sharpness of the super-resolved metabolic maps can be adjusted within a single network. We incorporate these network conditionings using a novel Multi-Conditional Module. The experiments were carried out on a 1H-MRSI dataset from 15 high-grade glioma patients. Results indicate that the proposed network achieves the best performance among several multi-scale super-resolution methods and can provide super-resolved metabolic maps with adjustable sharpness., Comment: Accepted by MICCAI 2022

Single-photon emission computed tomography (SPECT) is a widely applied imaging approach for diagnosis of coronary artery diseases. Attenuation maps (u-maps) derived from computed tomography (CT) are utilized for attenuation correction (AC) to improve diagnostic accuracy of cardiac SPECT. However, SPECT and CT are obtained sequentially in clinical practice, which potentially induces misregistration between the two scans. Convolutional neural networks (CNN) are powerful tools for medical image registration. Previous CNN-based methods for cross-modality registration either directly concatenated two input modalities as an early feature fusion or extracted image features using two separate CNN modules for a late fusion. These methods do not fully extract or fuse the cross-modality information. Besides, deep-learning-based rigid registration of cardiac SPECT and CT-derived u-maps has not been investigated before. In this paper, we propose a Dual-Branch Squeeze-Fusion-Excitation (DuSFE) module for the registration of cardiac SPECT and CT-derived u-maps. DuSFE fuses the knowledge from multiple modalities to recalibrate both channel-wise and spatial features for each modality. DuSFE can be embedded at multiple convolutional layers to enable feature fusion at different spatial dimensions. Our studies using clinical data demonstrated that a network embedded with DuSFE generated substantial lower registration errors and therefore more accurate AC SPECT images than previous methods., Comment: 10 pages, 4 figures, accepted at MICCAI 2022

Many medical datasets have recently been created for medical image segmentation tasks, and it is natural to question whether we can use them to sequentially train a single model that (1) performs better on all these datasets, and (2) generalizes well and transfers better to the unknown target site domain. Prior works have achieved this goal by jointly training one model on multi-site datasets, which achieve competitive performance on average but such methods rely on the assumption about the availability of all training data, thus limiting its effectiveness in practical deployment. In this paper, we propose a novel multi-site segmentation framework called incremental-transfer learning (ITL), which learns a model from multi-site datasets in an end-to-end sequential fashion. Specifically, "incremental" refers to training sequentially constructed datasets, and "transfer" is achieved by leveraging useful information from the linear combination of embedding features on each dataset. In addition, we introduce our ITL framework, where we train the network including a site-agnostic encoder with pre-trained weights and at most two segmentation decoder heads. We also design a novel site-level incremental loss in order to generalize well on the target domain. Second, we show for the first time that leveraging our ITL training scheme is able to alleviate challenging catastrophic forgetting problems in incremental learning. We conduct experiments using five challenging benchmark datasets to validate the effectiveness of our incremental-transfer learning approach. Our approach makes minimal assumptions on computation resources and domain-specific expertise, and hence constitutes a strong starting point in multi-site medical image segmentation.

In PET/CT imaging, CT is used for PET attenuation correction (AC). Mismatch between CT and PET due to patient body motion results in AC artifacts. In addition, artifact caused by metal, beam-hardening and count-starving in CT itself also introduces inaccurate AC for PET. Maximum likelihood reconstruction of activity and attenuation (MLAA) was proposed to solve those issues by simultaneously reconstructing tracer activity ($\lambda$-MLAA) and attenuation map ($\mu$-MLAA) based on the PET raw data only. However, $\mu$-MLAA suffers from high noise and $\lambda$-MLAA suffers from large bias as compared to the reconstruction using the CT-based attenuation map ($\mu$-CT). Recently, a convolutional neural network (CNN) was applied to predict the CT attenuation map ($\mu$-CNN) from $\lambda$-MLAA and $\mu$-MLAA, in which an image-domain loss (IM-loss) function between the $\mu$-CNN and the ground truth $\mu$-CT was used. However, IM-loss does not directly measure the AC errors according to the PET attenuation physics, where the line-integral projection of the attenuation map ($\mu$) along the path of the two annihilation events, instead of the $\mu$ itself, is used for AC. Therefore, a network trained with the IM-loss may yield suboptimal performance in the $\mu$ generation. Here, we propose a novel line-integral projection loss (LIP-loss) function that incorporates the PET attenuation physics for $\mu$ generation. Eighty training and twenty testing datasets of whole-body 18F-FDG PET and paired ground truth $\mu$-CT were used. Quantitative evaluations showed that the model trained with the additional LIP-loss was able to significantly outperform the model trained solely based on the IM-loss function., Comment: Accepted at MICCAI 2019

Computed tomography (CT) is a widely used imaging modality for medical diagnosis and treatment. In electroencephalography (EEG), CT imaging is necessary for co-registering with magnetic resonance imaging (MRI) and for creating more accurate head models for the brain electrical activity due to better representation of bone anatomy. Unfortunately, CT imaging exposes patients to potentially harmful sources of ionizing radiation. Image synthesis methods present a solution for avoiding extra radiation exposure. In this paper, we perform image synthesis to create a realistic, synthetic CT image from MRI of the same subject, and we present a comparison of different image synthesis techniques. Using a dataset of 30 paired MRI and CT image volumes, our results compare image synthesis using deep neural network regression, state-of-the-art adversarial deep learning, as well as atlas-based synthesis utilizing image registration. We also present a novel synthesis method that combines multi-atlas registration as a prior to deep learning algorithms, in which we perform a weighted addition of synthetic CT images, derived from atlases, to the output of a deep neural network to obtain a residual type of learning. In addition to evaluating the quality of the synthetic CT images, we also demonstrate that image synthesis methods allow for more accurate bone segmentation using the synthetic CT imaging than would otherwise be possible by segmenting the bone in the MRI directly.