Revisiting registration-based synthesis: A focus on unsupervised MR image synthesis

Deep learning (DL) has led to significant improvements in medical image synthesis, enabling advanced image-to-image translation to generate synthetic images. However, DL methods face challenges such as domain shift and high demands for training data, limiting their generalizability and applicability. Historically, image synthesis was also carried out using deformable image registration (DIR), a method that warps moving images of a desired modality to match the anatomy of a fixed image. However, concerns about its speed and accuracy led to its decline in popularity. With the recent advances of DL-based DIR, we now revisit and reinvigorate this line of research. In this paper, we propose a fast and accurate synthesis method based on DIR. We use the task of synthesizing a rare magnetic resonance (MR) sequence, white matter nulled (WMn) T1-weighted (T1-w) images, to demonstrate the potential of our approach. During training, our method learns a DIR model based on the widely available MPRAGE sequence, which is a cerebrospinal fluid nulled (CSFn) T1-w inversion recovery gradient echo pulse sequence. During testing, the trained DIR model is first applied to estimate the deformation between moving and fixed CSFn images. Subsequently, this estimated deformation is applied to align the paired WMn counterpart of the moving CSFn image, yielding a synthetic WMn image for the fixed CSFn image. Our experiments demonstrate promising results for unsupervised image synthesis using DIR. These findings highlight the potential of our technique in contexts where supervised synthesis methods are constrained by limited training data.

Towards an accurate and generalizable multiple sclerosis lesion segmentation model using self-ensembled lesion fusion

Automatic multiple sclerosis (MS) lesion segmentation using multi-contrast magnetic resonance (MR) images provides improved efficiency and reproducibility compared to manual delineation. Current state-of-the-art automatic MS lesion segmentation methods utilize modified U-Net-like architectures. However, in the literature, dedicated architecture modifications were always required to maximize their performance. In addition, the best-performing methods have not proven to be generalizable to diverse test datasets with contrast variations and image artifacts. In this work, we developed an accurate and generalizable MS lesion segmentation model using the well-known U-Net architecture without further modification. A novel test-time self-ensembled lesion fusion strategy is proposed that not only achieved the best performance using the ISBI 2015 MS segmentation challenge data but also demonstrated robustness across various self-ensemble parameter choices. Moreover, equipped with instance normalization rather than batch normalization widely used in literature, the model trained on the ISBI challenge data generalized well on clinical test datasets from different scanners.

Harmonization-enriched domain adaptation with light fine-tuning for multiple sclerosis lesion segmentation

Deep learning algorithms utilizing magnetic resonance (MR) images have demonstrated cutting-edge proficiency in autonomously segmenting multiple sclerosis (MS) lesions. Despite their achievements, these algorithms may struggle to extend their performance across various sites or scanners, leading to domain generalization errors. While few-shot or one-shot domain adaptation emerges as a potential solution to mitigate generalization errors, its efficacy might be hindered by the scarcity of labeled data in the target domain. This paper seeks to tackle this challenge by integrating one-shot adaptation data with harmonized training data that incorporates labels. Our approach involves synthesizing new training data with a contrast akin to that of the test domain, a process we refer to as "contrast harmonization" in MRI. Our experiments illustrate that the amalgamation of one-shot adaptation data with harmonized training data surpasses the performance of utilizing either data source in isolation. Notably, domain adaptation using exclusively harmonized training data achieved comparable or even superior performance compared to one-shot adaptation. Moreover, all adaptations required only minimal fine-tuning, ranging from 2 to 5 epochs for convergence.

Rapid Brain Meninges Surface Reconstruction with Layer Topology Guarantee

The meninges, located between the skull and brain, are composed of three membrane layers: the pia, the arachnoid, and the dura. Reconstruction of these layers can aid in studying volume differences between patients with neurodegenerative diseases and normal aging subjects. In this work, we use convolutional neural networks (CNNs) to reconstruct surfaces representing meningeal layer boundaries from magnetic resonance (MR) images. We first use the CNNs to predict the signed distance functions (SDFs) representing these surfaces while preserving their anatomical ordering. The marching cubes algorithm is then used to generate continuous surface representations; both the subarachnoid space (SAS) and the intracranial volume (ICV) are computed from these surfaces. The proposed method is compared to a state-of-the-art deformable model-based reconstruction method, and we show that our method can reconstruct smoother and more accurate surfaces using less computation time. Finally, we conduct experiments with volumetric analysis on both subjects with multiple sclerosis and healthy controls. For healthy and MS subjects, ICVs and SAS volumes are found to be significantly correlated to sex (p<0.01) and age (p<0.03) changes, respectively.

Optimal operating MR contrast for brain ventricle parcellation

Development of MR harmonization has enabled different contrast MRIs to be synthesized while preserving the underlying anatomy. In this paper, we use image harmonization to explore the impact of different T1-w MR contrasts on a state-of-the-art ventricle parcellation algorithm VParNet. We identify an optimal operating contrast (OOC) for ventricle parcellation; by showing that the performance of a pretrained VParNet can be boosted by adjusting contrast to the OOC.

Automated Ventricle Parcellation and Evan's Ratio Computation in Pre- and Post-Surgical Ventriculomegaly

Normal pressure hydrocephalus~(NPH) is a brain disorder associated with enlarged ventricles and multiple cognitive and motor symptoms. The degree of ventricular enlargement can be measured using magnetic resonance images~(MRIs) and characterized quantitatively using the Evan's ratio (ER). Automatic computation of ER is desired to avoid the extra time and variations associated with manual measurements on MRI. Because shunt surgery is often used to treat NPH, it is necessary that this process be robust to image artifacts caused by the shunt and related implants. In this paper, we propose a 3D regions-of-interest aware (ROI-aware) network for segmenting the ventricles. The method achieves state-of-the-art performance on both pre-surgery MRIs and post-surgery MRIs with artifacts. Based on our segmentation results, we also describe an automated approach to compute ER from these results. Experimental results on multiple datasets demonstrate the potential of the proposed method to assist clinicians in the diagnosis and management of NPH.

A latent space for unsupervised MR image quality control via artifact assessment

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.

HACA3: A Unified Approach for Multi-site MR Image Harmonization

The lack of standardization is a prominent issue in magnetic resonance (MR) imaging. This often causes undesired contrast variations due to differences in hardware and acquisition parameters. In recent years, MR harmonization using image synthesis 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 Tw-weighted and T2-weighted images must be available), which limits their applicability. Third, existing methods generally are sensitive to imaging artifacts. In this paper, we present a novel approach, Harmonization with Attention-based Contrast, Anatomy, and Artifact Awareness (HACA3), to address these three issues. We first propose an anatomy fusion module that enables HACA3 to respect the anatomical differences between MR contrasts. HACA3 is also robust to imaging artifacts and can be trained and applied to any set of MR contrasts. Experiments show that HACA3 achieves state-of-the-art performance under multiple image quality metrics. We also demonstrate the applicability of HACA3 on downstream tasks with diverse MR datasets acquired from 21 sites with different field strengths, scanner platforms, and acquisition protocols.

Disentangling A Single MR Modality

Disentangling anatomical and contrast information from medical images has gained attention recently, demonstrating benefits for various image analysis tasks. Current methods learn disentangled representations using either paired multi-modal images with the same underlying anatomy or auxiliary labels (e.g., manual delineations) to provide inductive bias for disentanglement. However, these requirements could significantly increase the time and cost in data collection and limit the applicability of these methods when such data are not available. Moreover, these methods generally do not guarantee disentanglement. In this paper, we present a novel framework that learns theoretically and practically superior disentanglement from single modality magnetic resonance images. Moreover, we propose a new information-based metric to quantitatively evaluate disentanglement. Comparisons over existing disentangling methods demonstrate that the proposed method achieves superior performance in both disentanglement and cross-domain image-to-image translation tasks.

Coordinate Translator for Learning Deformable Medical Image Registration

The majority of deep learning (DL) based deformable image registration methods use convolutional neural networks (CNNs) to estimate displacement fields from pairs of moving and fixed images. This, however, requires the convolutional kernels in the CNN to not only extract intensity features from the inputs but also understand image coordinate systems. We argue that the latter task is challenging for traditional CNNs, limiting their performance in registration tasks. To tackle this problem, we first introduce Coordinate Translator (CoTr), a differentiable module that identifies matched features between the fixed and moving image and outputs their coordinate correspondences without the need for training. It unloads the burden of understanding image coordinate systems for CNNs, allowing them to focus on feature extraction. We then propose a novel deformable registration network, im2grid, that uses multiple CoTr's with the hierarchical features extracted from a CNN encoder and outputs a deformation field in a coarse-to-fine fashion. We compared im2grid with the state-of-the-art DL and non-DL methods for unsupervised 3D magnetic resonance image registration. Our experiments show that im2grid outperforms these methods both qualitatively and quantitatively.