• A new method, UNISELF, is proposed to improve multiple sclerosis lesion segmentation. • UNISELF uses self-ensembled lesion fusion to improve accuracy and generalization. • UNISELF uses test-time instance normalization to address latent feature distribution shift. • UNISELF is among the top methods in the ISBI lesion segmentation challenge. • UNISELF outperforms other benchmarks on various out-of-domain test datasets. Automated segmentation of multiple sclerosis (MS) lesions using multicontrast magnetic resonance (MR) images improves efficiency and reproducibility compared to manual delineation, with deep learning (DL) methods achieving state-of-the-art performance. However, these DL-based methods have yet to simultaneously optimize in-domain accuracy and out-of-domain generalization when trained on a single source with limited data, or their performance has been unsatisfactory. To fill this gap, we propose a method called UNISELF, which achieves high accuracy within a single training domain while demonstrating strong generalizability across multiple out-of-domain test datasets. UNISELF employs a novel test-time self-ensembled lesion fusion to improve segmentation accuracy, and leverages test-time instance normalization (TTIN) of latent features to address domain shifts and missing input contrasts. Trained on the ISBI 2015 longitudinal MS segmentation challenge training dataset, UNISELF ranks among the best-performing methods on the challenge test dataset. Additionally, UNISELF outperforms all benchmark methods trained on the same ISBI training data across diverse out-of-domain test datasets with domain shifts and missing contrasts, including the public MICCAI 2016 and UMCL datasets, as well as a private multisite dataset. These test datasets exhibit domain shifts and/or missing contrasts caused by variations in acquisition protocols, scanner types, and imaging artifacts arising from imperfect acquisition. Our code is available at https://github.com/Jinwei1209/UNISELF .

Medical image harmonization aims to reduce the differences in appearance caused by scanner hardware variations to allow for consistent and reliable comparisons across devices. Harmonization based on paired images from different devices has limited applicability in real-world clinical settings. On the other hand, unpaired harmonization typically does not guarantee anatomy consistency, which is problematic because anatomical information preservation is paramount. The Schrödinger bridge framework has achieved state-of-the-art style transfer performance with natural images by matching distributions of unpaired images, but this approach can also introduce anatomy changes when applied to medical images. We show that such changes occur because the Schrödinger bridge uses the square of the Euclidean distance between images as the transport cost in an entropy-regularized optimal transport problem. Such a transport cost is not appropriate for measuring anatomical distances, as medical images with the same anatomy need not have a small Euclidean distance between them. In this paper, we propose a latent metric Schrödinger bridge (LMSB) framework to improve the anatomical consistency for the harmonization of medical images. We develop an invertible network that maps medical images into a latent Euclidean metric space where the distances among images with the same anatomy are minimized using the pullback latent metric. Within this latent space, we train a Schrödinger bridge to match distributions. We show that the proposed LMSB is superior to the direct application of a Schrödinger bridge to harmonize optical coherence tomography (OCT) images.

Dimension reduction tools preserving similarity and graph structure such as t-SNE and UMAP can capture complex biological patterns in high-dimensional data. However, these tools typically are not designed to separate effects of interest from unwanted effects due to confounders. We introduce the partial embedding (PARE) framework, which enables removal of confounders from any distance-based dimension reduction method. We then develop partial t-SNE and partial UMAP and apply these methods to genomic and neuroimaging data. For lower-dimensional visualization, our results show that the PARE framework can remove batch effects in single-cell sequencing data as well as separate clinical and technical variability in neuroimaging measures. We demonstrate that the PARE framework extends dimension reduction methods to highlight biological patterns of interest while effectively removing confounding effects.

Optical coherence tomography angiography (OCTA) is an imaging modality that can be used for analyzing retinal vasculature. Quantitative assessment of en face OCTA images requires accurate segmentation of the capillaries. Using deep learning approaches for this task faces two major challenges. First, acquiring sufficient manual delineations for training can take hundreds of hours. Second, OCTA images suffer from numerous contrast-related artifacts that are currently inherent to the modality and vary dramatically across scanners. We propose to solve both problems by learning a disentanglement of an anatomy component and a local contrast component from paired OCTA scans. With the contrast removed from the anatomy component, a deep learning model that takes the anatomy component as input can learn to segment vessels with a limited portion of the training images being manually labeled. Our method demonstrates state-of-the-art performance for OCTA vessel segmentation.

High resolution magnetic resonance (MR) images are desired in many clinical and research applications. Acquiring such images with high signal-to-noise (SNR), however, can require a long scan duration, which is difficult for patient comfort, is more costly, and makes the images susceptible to motion artifacts. A very common practical compromise for both 2D and 3D MR imaging protocols is to acquire volumetric MR images with high in-plane resolution, but lower through-plane resolution. In addition to having poor resolution in one orientation, 2D MRI acquisitions will also have aliasing artifacts, which further degrade the appearance of these images. This paper presents an approach SMORE1 based on convolutional neural networks (CNNs) that restores image quality by improving resolution and reducing aliasing in MR images.2 This approach is self-supervised, which requires no external training data because the high-resolution and low-resolution data that are present in the image itself are used for training. For 3D MRI, the method consists of only one self-supervised super-resolution (SSR) deep CNN that is trained from the volumetric image data. For 2D MRI, there is a self-supervised anti-aliasing (SAA) deep CNN that precedes the SSR CNN, also trained from the volumetric image data. Both methods were evaluated on a broad collection of MR data, including filtered and downsampled images so that quantitative metrics could be computed and compared, and actual acquired low resolution images for which visual and sharpness measures could be computed and compared. The super-resolution method is shown to be visually and quantitatively superior to previously reported methods.