Unsupervised learning of spatially varying regularization for diffeomorphic image registration

Spatially varying regularization accommodates the deformation variations that may be necessary for different anatomical regions during deformable image registration. Historically, optimization-based registration models have harnessed spatially varying regularization to address anatomical subtleties. However, most modern deep learning-based models tend to gravitate towards spatially invariant regularization, wherein a homogenous regularization strength is applied across the entire image, potentially disregarding localized variations. In this paper, we propose a hierarchical probabilistic model that integrates a prior distribution on the deformation regularization strength, enabling the end-to-end learning of a spatially varying deformation regularizer directly from the data. The proposed method is straightforward to implement and easily integrates with various registration network architectures. Additionally, automatic tuning of hyperparameters is achieved through Bayesian optimization, allowing efficient identification of optimal hyperparameters for any given registration task. Comprehensive evaluations on publicly available datasets demonstrate that the proposed method significantly improves registration performance and enhances the interpretability of deep learning-based registration, all while maintaining smooth deformations.

Unique MS Lesion Identification from MRI

Unique identification of multiple sclerosis (MS) white matter lesions (WMLs) is important to help characterize MS progression. WMLs are routinely identified from magnetic resonance images (MRIs) but the resultant total lesion load does not correlate well with EDSS; whereas mean unique lesion volume has been shown to correlate with EDSS. Our approach builds on prior work by incorporating Hessian matrix computation from lesion probability maps before using the random walker algorithm to estimate the volume of each unique lesion. Synthetic images demonstrate our ability to accurately count the number of lesions present. The takeaways, are: 1) that our method correctly identifies all lesions including many that are missed by previous methods; 2) we can better separate confluent lesions; and 3) we can accurately capture the total volume of WMLs in a given probability map. This work will allow new more meaningful statistics to be computed from WMLs in brain MRIs

Unsupervised Learning of Multi-modal Affine Registration for PET/CT

Affine registration plays a crucial role in PET/CT imaging, where aligning PET with CT images is challenging due to their respective functional and anatomical representations. Despite the significant promise shown by recent deep learning (DL)-based methods in various medical imaging applications, their application to multi-modal PET/CT affine registration remains relatively unexplored. This study investigates a DL-based approach for PET/CT affine registration. We introduce a novel method using Parzen windowing to approximate the correlation ratio, which acts as the image similarity measure for training DNNs in multi-modal registration. Additionally, we propose a multi-scale, instance-specific optimization scheme that iteratively refines the DNN-generated affine parameters across multiple image resolutions. Our method was evaluated against the widely used mutual information metric and a popular optimization-based technique from the ANTs package, using a large public FDG-PET/CT dataset with synthetic affine transformations. Our approach achieved a mean Dice Similarity Coefficient (DSC) of 0.870, outperforming the compared methods and demonstrating its effectiveness in multi-modal PET/CT image registration.

From Registration Uncertainty to Segmentation Uncertainty

Understanding the uncertainty inherent in deep learning-based image registration models has been an ongoing area of research. Existing methods have been developed to quantify both transformation and appearance uncertainties related to the registration process, elucidating areas where the model may exhibit ambiguity regarding the generated deformation. However, our study reveals that neither uncertainty effectively estimates the potential errors when the registration model is used for label propagation. Here, we propose a novel framework to concurrently estimate both the epistemic and aleatoric segmentation uncertainties for image registration. To this end, we implement a compact deep neural network (DNN) designed to transform the appearance discrepancy in the warping into aleatoric segmentation uncertainty by minimizing a negative log-likelihood loss function. Furthermore, we present epistemic segmentation uncertainty within the label propagation process as the entropy of the propagated labels. By introducing segmentation uncertainty along with existing methods for estimating registration uncertainty, we offer vital insights into the potential uncertainties at different stages of image registration. We validated our proposed framework using publicly available datasets, and the results prove that the segmentation uncertainties estimated with the proposed method correlate well with errors in label propagation, all while achieving superior registration performance.

Is Registering Raw Tagged-MR Enough for Strain Estimation in the Era of Deep Learning?

Magnetic Resonance Imaging with tagging (tMRI) has long been utilized for quantifying tissue motion and strain during deformation. However, a phenomenon known as tag fading, a gradual decrease in tag visibility over time, often complicates post-processing. The first contribution of this study is to model tag fading by considering the interplay between $T_1$ relaxation and the repeated application of radio frequency (RF) pulses during serial imaging sequences. This is a factor that has been overlooked in prior research on tMRI post-processing. Further, we have observed an emerging trend of utilizing raw tagged MRI within a deep learning-based (DL) registration framework for motion estimation. In this work, we evaluate and analyze the impact of commonly used image similarity objectives in training DL registrations on raw tMRI. This is then compared with the Harmonic Phase-based approach, a traditional approach which is claimed to be robust to tag fading. Our findings, derived from both simulated images and an actual phantom scan, reveal the limitations of various similarity losses in raw tMRI and emphasize caution in registration tasks where image intensity changes over time.

MomentaMorph: Unsupervised Spatial-Temporal Registration with Momenta, Shooting, and Correction

Tagged magnetic resonance imaging (tMRI) has been employed for decades to measure the motion of tissue undergoing deformation. However, registration-based motion estimation from tMRI is difficult due to the periodic patterns in these images, particularly when the motion is large. With a larger motion the registration approach gets trapped in a local optima, leading to motion estimation errors. We introduce a novel "momenta, shooting, and correction" framework for Lagrangian motion estimation in the presence of repetitive patterns and large motion. This framework, grounded in Lie algebra and Lie group principles, accumulates momenta in the tangent vector space and employs exponential mapping in the diffeomorphic space for rapid approximation towards true optima, circumventing local optima. A subsequent correction step ensures convergence to true optima. The results on a 2D synthetic dataset and a real 3D tMRI dataset demonstrate our method's efficiency in estimating accurate, dense, and diffeomorphic 2D/3D motion fields amidst large motion and repetitive patterns.

A Survey on Deep Learning in Medical Image Registration: New Technologies, Uncertainty, Evaluation Metrics, and Beyond

Over the past decade, deep learning technologies have greatly advanced the field of medical image registration. The initial developments, such as ResNet-based and U-Net-based networks, laid the groundwork for deep learning-driven image registration. Subsequent progress has been made in various aspects of deep learning-based registration, including similarity measures, deformation regularizations, and uncertainty estimation. These advancements have not only enriched the field of deformable image registration but have also facilitated its application in a wide range of tasks, including atlas construction, multi-atlas segmentation, motion estimation, and 2D-3D registration. In this paper, we present a comprehensive overview of the most recent advancements in deep learning-based image registration. We begin with a concise introduction to the core concepts of deep learning-based image registration. Then, we delve into innovative network architectures, loss functions specific to registration, and methods for estimating registration uncertainty. Additionally, this paper explores appropriate evaluation metrics for assessing the performance of deep learning models in registration tasks. Finally, we highlight the practical applications of these novel techniques in medical imaging and discuss the future prospects of deep learning-based image registration.

Deep Learning Guided Autonomous Retinal Surgery using a Robotic Arm, Microscopy, and iOCT Imaging

Recent technological advancements in retinal surgery has led to the modern operating room consisting of a surgical robot, microscope, and intraoperative optical coherence tomography (iOCT). The integration of these tools raises the fundamental question of how to effectively combine them to enable surgical autonomy. In this work, we address this question by developing a unified framework that enables real-time autonomous surgical workflows utilizing the aforementioned devices. To achieve this, we make the following contributions: (1) we develop a novel imaging system that integrates microscopy and iOCT in real-time, accomplished by dynamically tracking the surgical instrument via a small iOCT scanning region (e.g. B-scan), which was not previously possible; (2) implementing various convolutional neural networks (CNN) that automatically segment and detect task-relevant information for surgical autonomy; (3) enabling surgeons to intuitively select goal waypoints within both the microscope and iOCT views through simple mouse-click interactions; (4) integrating model predictive control (MPC) for real-time trajectory generation that respects kinematic constraints to ensure patient safety. We show the utility of our system by tackling subretinal injection (SI), a challenging procedure that involves inserting a microneedle below the retinal tissue for targeted drug delivery, a task surgeons find challenging due to requiring tens-of-micrometers of accuracy and precise depth perception. We validate our system by conducting 30 successful SI trials on pig eyes, achieving needle insertion accuracy of $26 \pm 12 \mu m$ to various subretinal goals and duration of $55 \pm 10.8$ seconds. Preliminary comparisons to a human operator performing SI in robot-assisted mode highlight the enhanced safety of our system.

On Finite Difference Jacobian Computation in Deformable Image Registration

Producing spatial transformations that are diffeomorphic has been a central problem in deformable image registration. As a diffeomorphic transformation should have positive Jacobian determinant $|J|$ everywhere, the number of voxels with $|J|<0$ has been used to test for diffeomorphism and also to measure the irregularity of the transformation. For digital transformations, $|J|$ is commonly approximated using central difference, but this strategy can yield positive $|J|$'s for transformations that are clearly not diffeomorphic -- even at the voxel resolution level. To show this, we first investigate the geometric meaning of different finite difference approximations of $|J|$. We show that to determine diffeomorphism for digital images, use of any individual finite difference approximations of $|J|$ is insufficient. We show that for a 2D transformation, four unique finite difference approximations of $|J|$'s must be positive to ensure the entire domain is invertible and free of folding at the pixel level. We also show that in 3D, ten unique finite differences approximations of $|J|$'s are required to be positive. Our proposed digital diffeomorphism criteria solves several errors inherent in the central difference approximation of $|J|$ and accurately detects non-diffeomorphic digital transformations.