Blake E. Dewey

Lianrui Zuo, Yihao Liu, Yuan Xue et al.

The lack of standardization is a prominent issue in magnetic resonance (MR) imaging. This often causes undesired contrast variations in the acquired images due to differences in hardware and acquisition parameters. In recent years, image synthesis-based MR harmonization with disentanglement has been proposed to compensate for the undesired contrast variations. Despite the success of existing methods, we argue that three major improvements can be made. First, most existing methods are built upon the assumption that multi-contrast MR images of the same subject share the same anatomy. This assumption is questionable, since different MR contrasts are specialized to highlight different anatomical features. Second, these methods often require a fixed set of MR contrasts for training (e.g., both T1-weighted and T2-weighted images), limiting their applicability. Lastly, existing methods are generally sensitive to imaging artifacts. In this paper, we present Harmonization with Attention-based Contrast, Anatomy, and Artifact Awareness (HACA3), a novel approach to address these three issues. HACA3 incorporates an anatomy fusion module that accounts for the inherent anatomical differences between MR contrasts. Furthermore, HACA3 is also robust to imaging artifacts and can be trained and applied to any set of MR contrasts. HACA3 is developed and evaluated on diverse MR datasets acquired from 21 sites with varying field strengths, scanner platforms, and acquisition protocols. Experiments show that HACA3 achieves state-of-the-art performance under multiple image quality metrics. We also demonstrate the applicability and versatility of HACA3 on downstream tasks including white matter lesion segmentation and longitudinal volumetric analyses.

Lianrui Zuo, Yuan Xue, Blake E. Dewey et al.

Image quality control (IQC) can be used in automated magnetic resonance (MR) image analysis to exclude erroneous results caused by poorly acquired or artifact-laden images. Existing IQC methods for MR imaging generally require human effort to craft meaningful features or label large datasets for supervised training. The involvement of human labor can be burdensome and biased, as labeling MR images based on their quality is a subjective task. In this paper, we propose an automatic IQC method that evaluates the extent of artifacts in MR images without supervision. In particular, we design an artifact encoding network that learns representations of artifacts based on contrastive learning. We then use a normalizing flow to estimate the density of learned representations for unsupervised classification. Our experiments on large-scale multi-cohort MR datasets show that the proposed method accurately detects images with high levels of artifacts, which can inform downstream analysis tasks about potentially flawed data.

Samuel W. Remedios, Zhangxing Bian, Shuwen Wei et al.

Diffusion models are the current state-of-the-art for solving inverse problems in imaging. Their impressive generative capability allows them to approximate sampling from a prior distribution, which alongside a known likelihood function permits posterior sampling without retraining the model. While recent methods have made strides in advancing the accuracy of posterior sampling, the majority focuses on single-image inverse problems. However, for modalities such as magnetic resonance imaging (MRI), it is common to acquire multiple complementary measurements, each low-resolution along a different axis. In this work, we generalize common diffusion-based inverse single-image problem solvers for multi-image super-resolution (MISR) MRI. We show that the DPS likelihood correction allows an exactly-separable gradient decomposition across independently acquired measurements, enabling MISR without constructing a joint operator, modifying the diffusion model, or increasing network function evaluations. We derive MISR versions of DPS, DMAP, DPPS, and diffusion-based PnP/ADMM, and demonstrate substantial gains over SISR across $4\times/8\times/16\times$ anisotropic degradations. Our results achieve state-of-the-art super-resolution of anisotropic MRI volumes and, critically, enable reconstruction of near-isotropic anatomy from routine 2D multi-slice acquisitions, which are otherwise highly degraded in orthogonal views.

Zhangxing Bian, Shuwen Wei, Samuel W. Remedios et al.

Tagged MRI enables tracking internal tissue motion non-invasively. It encodes motion by modulating anatomy with periodic tags, which deform along with tissue. However, the entanglement between anatomy, tags and motion poses significant challenges for post-processing. The existence of tags and imaging blur hinders downstream tasks such as segmenting anatomy. Tag fading, due to T1-relaxation, disrupts the brightness constancy assumption for motion tracking. For decades, these challenges have been handled in isolation and sub-optimally. In contrast, we introduce a blind and nonlinear inverse framework for tagged MRI that, for the first time, unifies these tasks: anatomical image recovery, high-resolution cine image synthesis, and motion estimation. At its core, the synergy of MR physics and generative priors enables us to blindly estimate the unknown forward imaging models and high-resolution underlying anatomy, while simultaneously tracking 3D diffeomorphic Lagrangian motion over time. Experiments on tagged brain MRI demonstrate that our approach yields high-resolution anatomy images, cine images, and more accurate motion than specialized methods.

Jinwei Zhang, Lianrui Zuo, Blake E. Dewey et al.

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/uponacceptance.

Samuel W. Remedios, Aaron Carass, Jerry L. Prince et al.

The purpose of this study is to present and compare three denoising diffusion probabilistic models (DDPMs) that generate 3D $T_1$-weighted MRI human brain images. Three DDPMs were trained using 80,675 image volumes from 42,406 subjects spanning 38 publicly available brain MRI datasets. These images had approximately 1 mm isotropic resolution and were manually inspected by three human experts to exclude those with poor quality, field-of-view issues, and excessive pathology. The images were minimally preprocessed to preserve the visual variability of the data. Furthermore, to enable the DDPMs to produce images with natural orientation variations and inhomogeneity, the images were neither registered to a common coordinate system nor bias field corrected. Evaluations included segmentation, Frechet Inception Distance (FID), and qualitative inspection. Regarding results, all three DDPMs generated coherent MR brain volumes. The velocity and flow prediction models achieved lower FIDs than the sample prediction model. However, all three models had higher FIDs compared to real images across multiple cohorts. In a permutation experiment, the generated brain regional volume distributions differed statistically from real data. However, the velocity and flow prediction models had fewer statistically different volume distributions in the thalamus and putamen. In conclusion this work presents and releases the first 3D non-latent diffusion model for brain data without skullstripping or registration. Despite the negative results in statistical testing, the presented DDPMs are capable of generating high-resolution 3D $T_1$-weighted brain images. All model weights and corresponding inference code are publicly available at https://github.com/piksl-research/medforj .

Samuel W. Remedios, Shuwen Wei, Shuo Han et al.

In clinical imaging, magnetic resonance (MR) image volumes are often acquired as stacks of 2D slices with decreased scan times, improved signal-to-noise ratio, and image contrasts unique to 2D MR pulse sequences. While this is sufficient for clinical evaluation, automated algorithms designed for 3D analysis perform poorly on multi-slice 2D MR volumes, especially those with thick slices and gaps between slices. Super-resolution (SR) methods aim to address this problem, but previous methods do not address all of the following: slice profile shape estimation, slice gap, domain shift, and non-integer or arbitrary upsampling factors. In this paper, we propose ECLARE (Efficient Cross-planar Learning for Anisotropic Resolution Enhancement), a self-SR method that addresses each of these factors. ECLARE uses a slice profile estimated from the multi-slice 2D MR volume, trains a network to learn the mapping from low-resolution to high-resolution in-plane patches from the same volume, and performs SR with anti-aliasing. We compared ECLARE to cubic B-spline interpolation, SMORE, and other contemporary SR methods. We used realistic and representative simulations so that quantitative performance against ground truth can be computed, and ECLARE outperformed all other methods in both signal recovery and downstream tasks. Importantly, as ECLARE does not use external training data it cannot suffer from domain shift between training and testing. Our code is open-source and available at https://www.github.com/sremedios/eclare.

Zejun Wu, Samuel W. Remedios, Blake E. Dewey et al.

Anisotropic low-resolution (LR) magnetic resonance (MR) images are fast to obtain but hinder automated processing. We propose to use denoising diffusion probabilistic models (DDPMs) to super-resolve these 2D-acquired LR MR slices. This paper introduces AniRes2D, a novel approach combining DDPM with a residual prediction for 2D super-resolution (SR). Results demonstrate that AniRes2D outperforms several other DDPM-based models in quantitative metrics, visual quality, and out-of-domain evaluation. We use a trained AniRes2D to super-resolve 3D volumes slice by slice, where comparative quantitative results and reduced skull aliasing are achieved compared to a recent state-of-the-art self-supervised 3D super-resolution method. Furthermore, we explored the use of noise conditioning augmentation (NCA) as an alternative augmentation technique for DDPM-based SR models, but it was found to reduce performance. Our findings contribute valuable insights to the application of DDPMs for SR of anisotropic MR images.

Ho Hin Lee, Adam M. Saunders, Michael E. Kim et al.

Purpose: Eye morphology varies significantly across the population, especially for the orbit and optic nerve. These variations limit the feasibility and robustness of generalizing population-wise features of eye organs to an unbiased spatial reference. Approach: To tackle these limitations, we propose a process for creating high-resolution unbiased eye atlases. First, to restore spatial details from scans with a low through-plane resolution compared to a high in-plane resolution, we apply a deep learning-based super-resolution algorithm. Then, we generate an initial unbiased reference with an iterative metric-based registration using a small portion of subject scans. We register the remaining scans to this template and refine the template using an unsupervised deep probabilistic approach that generates a more expansive deformation field to enhance the organ boundary alignment. We demonstrate this framework using magnetic resonance images across four different tissue contrasts, generating four atlases in separate spatial alignments. Results: For each tissue contrast, we find a significant improvement using the Wilcoxon signed-rank test in the average Dice score across four labeled regions compared to a standard registration framework consisting of rigid, affine, and deformable transformations. These results highlight the effective alignment of eye organs and boundaries using our proposed process. Conclusions: By combining super-resolution preprocessing and deep probabilistic models, we address the challenge of generating an eye atlas to serve as a standardized reference across a largely variable population.

Anqi Feng, Zhangxing Bian, Samuel W. Remedios et al.

Accurate thalamic nuclei segmentation is crucial for understanding neurological diseases, brain functions, and guiding clinical interventions. However, the optimal inputs for segmentation remain unclear. This study systematically evaluates multiple MRI contrasts, including MPRAGE and FGATIR sequences, quantitative PD and T1 maps, and multiple T1-weighted images at different inversion times (multi-TI), to determine the most effective inputs. For multi-TI images, we employ a gradient-based saliency analysis with Monte Carlo dropout and propose an Overall Importance Score to select the images contributing most to segmentation. A 3D U-Net is trained on each of these configurations. Results show that T1 maps alone achieve strong quantitative performance and superior qualitative outcomes, while PD maps offer no added value. These findings underscore the value of T1 maps as a reliable and efficient input among the evaluated options, providing valuable guidance for optimizing imaging protocols when thalamic structures are of clinical or research interest.

Lianrui Zuo, Blake E. Dewey, Aaron Carass et al.

Accuracy and consistency are two key factors in computer-assisted magnetic resonance (MR) image analysis. However, contrast variation from site to site caused by lack of standardization in MR acquisition impedes consistent measurements. In recent years, image harmonization approaches have been proposed to compensate for contrast variation in MR images. Current harmonization approaches either require cross-site traveling subjects for supervised training or heavily rely on site-specific harmonization models to encourage harmonization accuracy. These requirements potentially limit the application of current harmonization methods in large-scale multi-site studies. In this work, we propose an unsupervised MR harmonization framework, CALAMITI (Contrast Anatomy Learning and Analysis for MR Intensity Translation and Integration), based on information bottleneck theory. CALAMITI learns a disentangled latent space using a unified structure for multi-site harmonization without the need for traveling subjects. Our model is also able to adapt itself to harmonize MR images from a new site with fine tuning solely on images from the new site. Both qualitative and quantitative results show that the proposed method achieves superior performance compared with other unsupervised harmonization approaches.

Dzung L. Pham, Yi-Yu Chou, Blake E. Dewey et al.

Deep learning approaches to the segmentation of magnetic resonance images have shown significant promise in automating the quantitative analysis of brain images. However, a continuing challenge has been its sensitivity to the variability of acquisition protocols. Attempting to segment images that have different contrast properties from those within the training data generally leads to significantly reduced performance. Furthermore, heterogeneous data sets cannot be easily evaluated because the quantitative variation due to acquisition differences often dwarfs the variation due to the biological differences that one seeks to measure. In this work, we describe an approach using alternating segmentation and synthesis steps that adapts the contrast properties of the training data to the input image. This allows input images that do not resemble the training data to be more consistently segmented. A notable advantage of this approach is that only a single example of the acquisition protocol is required to adapt to its contrast properties. We demonstrate the efficacy of our approaching using brain images from a set of human subjects scanned with two different T1-weighted volumetric protocols.

Yufan He, Aaron Carass, Lianrui Zuo et al.

Domain shift is a major problem for deploying deep networks in clinical practice. Network performance drops significantly with (target) images obtained differently than its (source) training data. Due to a lack of target label data, most work has focused on unsupervised domain adaptation (UDA). Current UDA methods need both source and target data to train models which perform image translation (harmonization) or learn domain-invariant features. However, training a model for each target domain is time consuming and computationally expensive, even infeasible when target domain data are scarce or source data are unavailable due to data privacy. In this paper, we propose a novel self domain adapted network (SDA-Net) that can rapidly adapt itself to a single test subject at the testing stage, without using extra data or training a UDA model. The SDA-Net consists of three parts: adaptors, task model, and auto-encoders. The latter two are pre-trained offline on labeled source images. The task model performs tasks like synthesis, segmentation, or classification, which may suffer from the domain shift problem. At the testing stage, the adaptors are trained to transform the input test image and features to reduce the domain shift as measured by the auto-encoders, and thus perform domain adaptation. We validated our method on retinal layer segmentation from different OCT scanners and T1 to T2 synthesis with T1 from different MRI scanners and with different imaging parameters. Results show that our SDA-Net, with a single test subject and a short amount of time for self adaptation at the testing stage, can achieve significant improvements.

Jacob C. Reinhold, Blake E. Dewey, Aaron Carass et al.

Image synthesis learns a transformation from the intensity features of an input image to yield a different tissue contrast of the output image. This process has been shown to have application in many medical image analysis tasks including imputation, registration, and segmentation. To carry out synthesis, the intensities of the input images are typically scaled--i.e., normalized--both in training to learn the transformation and in testing when applying the transformation, but it is not presently known what type of input scaling is optimal. In this paper, we consider seven different intensity normalization algorithms and three different synthesis methods to evaluate the impact of normalization. Our experiments demonstrate that intensity normalization as a preprocessing step improves the synthesis results across all investigated synthesis algorithms. Furthermore, we show evidence that suggests intensity normalization is vital for successful deep learning-based MR image synthesis.

Can Zhao, Aaron Carass, Blake E. Dewey et al.

High resolution magnetic resonance~(MR) imaging~(MRI) is desirable in many clinical applications, however, there is a trade-off between resolution, speed of acquisition, and noise. It is common for MR images to have worse through-plane resolution~(slice thickness) than in-plane resolution. In these MRI images, high frequency information in the through-plane direction is not acquired, and cannot be resolved through interpolation. To address this issue, super-resolution methods have been developed to enhance spatial resolution. As an ill-posed problem, state-of-the-art super-resolution methods rely on the presence of external/training atlases to learn the transform from low resolution~(LR) images to high resolution~(HR) images. For several reasons, such HR atlas images are often not available for MRI sequences. This paper presents a self super-resolution~(SSR) algorithm, which does not use any external atlas images, yet can still resolve HR images only reliant on the acquired LR image. We use a blurred version of the input image to create training data for a state-of-the-art super-resolution deep network. The trained network is applied to the original input image to estimate the HR image. Our SSR result shows a significant improvement on through-plane resolution compared to competing SSR methods.