Domain-Randomized Deep Learning for Neuroimage Analysis: Selecting Training Strategies, Navigating Challenges, and Maximizing Benefits
Deep learning has revolutionized neuroimage analysis by delivering unprecedented speed and accuracy. However, the narrow scope of many training datasets constrains model robustness and generalizability. This challenge is particularly acute in magnetic resonance imaging (MRI), where image appearance varies widely across pulse sequences and scanner hardware. A recent domain-randomization strategy addresses the generalization problem by training deep neural networks on synthetic images with randomized intensities and anatomical content. By generating diverse data from anatomical segmentation maps, the approach enables models to accurately process image types unseen during training, without retraining or fine-tuning. It has demonstrated effectiveness across modalities including MRI, computed tomography, positron emission tomography, and optical coherence tomography, as well as beyond neuroimaging in ultrasound, electron and fluorescence microscopy, and X-ray microtomography. This tutorial paper reviews the principles, implementation, and potential of the synthesis-driven training paradigm. It highlights key benefits, such as improved generalization and resistance to overfitting, while discussing trade-offs such as increased computational demands. Finally, the article explores practical considerations for adopting the technique, aiming to accelerate the development of generalizable tools that make deep learning more accessible to domain experts without extensive computational resources or machine learning knowledge.
Emerging Brain-to-Content Technologies from Generative AI and Deep Representation Learning
Rapid advances in generative artificial intelligence (AI) and deep representation learning have revolutionized numerous engineering applications in signal processing, computer vision, speech recognition and translation, and natural language processing due to amazingly powerful representation power (e.g., [1,2]). Generative AI-empowered tools, such as ChatGPT and Sora, have fundamentally changed the landscape of human-computer communications research. One emerging application along this line is to link the brain to the computer (i.e., brain-computer interface or BCI) and to develop paradigm-shift brain-to-content technologies. This BCI system upgrade (i.e., BCI 2.0) is empowered by generative AI and deep learning ("new engine") and large amounts of data ("gas"). In this article, we will revisit the old song sung in a new tune, highlight some state-of-the-art progresses, and briefly discuss the future outlook.
High-Dimensional MR Spatiospectral Imaging by Integrating Physics-Based Modeling and Data-Driven Machine Learning: Current progress and future directions
Magnetic resonance spectroscopic imaging (MRSI) offers a unique molecular window into the physiological and pathological processes in the human body. However, the applications of MRSI have been limited by a number of long-standing technical challenges due to high dimensionality and low signal-to-noise ratio (SNR). Recent technological developments integrating physics-based modeling and data-driven machine learning that exploit unique physical and mathematical properties of MRSI signals have demonstrated impressive performance in addressing these challenges for rapid, high-resolution, quantitative MRSI. This paper provides a systematic review of these progresses in the context of MRSI physics and offers perspectives on promising future directions.
Physics-/Model-Based and Data-Driven Methods for Low-Dose Computed Tomography: A survey
Since 2016, deep learning (DL) has advanced tomographic imaging with remarkable successes, especially in low-dose computed tomography (LDCT) imaging. Despite being driven by big data, the LDCT denoising and pure end-to-end reconstruction networks often suffer from the black box nature and major issues such as instabilities, which is a major barrier to apply deep learning methods in low-dose CT applications. An emerging trend is to integrate imaging physics and model into deep networks, enabling a hybridization of physics/model-based and data-driven elements. In this paper, we systematically review the physics/model-based data-driven methods for LDCT, summarize the loss functions and training strategies, evaluate the performance of different methods, and discuss relevant issues and future directions.
Physics-Driven Deep Learning for Computational Magnetic Resonance Imaging: Combining physics and machine learning for improved medical imaging
Physics-driven deep learning methods have emerged as a powerful tool for computational magnetic resonance imaging (MRI) problems, pushing reconstruction performance to new limits. This article provides an overview of the recent developments in incorporating physics information into learning-based MRI reconstruction. We consider inverse problems with both linear and non-linear forward models for computational MRI, and review the classical approaches for solving these. We then focus on physics-driven deep learning approaches, covering physics-driven loss functions, plug-and-play methods, generative models, and unrolled networks. We highlight domain-specific challenges such as real- and complex-valued building blocks of neural networks, and translational applications in MRI with linear and non-linear forward models. Finally, we discuss common issues and open challenges, and draw connections to the importance of physics-driven learning when combined with other downstream tasks in the medical imaging pipeline.
Reproducibility in Matrix and Tensor Decompositions: Focus on Model Match, Interpretability, and Uniqueness
Interpreting Brain Biomarkers: Challenges and solutions in interpreting machine learning-based predictive neuroimaging
Predictive modeling of neuroimaging data (predictive neuroimaging) for evaluating individual differences in various behavioral phenotypes and clinical outcomes is of growing interest. However, the field is experiencing challenges regarding the interpretability of the results. Approaches to defining the specific contribution of functional connections, regions, or networks in prediction models are urgently needed, which may help explore the underlying mechanisms. In this article, we systematically review the methods and applications for interpreting brain signatures derived from predictive neuroimaging based on a survey of 326 research articles. Strengths, limitations, and the suitable conditions for major interpretation strategies are also deliberated. In-depth discussion of common issues in existing literature and the corresponding recommendations to address these pitfalls are provided. We highly recommend exhaustive validation on the reliability and interpretability of the biomarkers across multiple datasets and contexts, which thereby could translate technical advances in neuroimaging into concrete improvements in precision medicine.
Light-Field Microscopy for Optical Imaging of Neuronal Activity: When Model-Based Methods Meet Data-Driven Approaches
Understanding how networks of neurons process information is one of the key challenges in modern neuroscience. A necessary step to achieve this goal is to be able to observe the dynamics of large populations of neurons over a large area of the brain. Light-field microscopy (LFM), a type of scanless microscope, is a particularly attractive candidate for high-speed three-dimensional (3D) imaging. It captures volumetric information in a single snapshot, allowing volumetric imaging at video frame-rates. Specific features of imaging neuronal activity using LFM call for the development of novel machine learning approaches that fully exploit priors embedded in physics and optics models. Signal processing theory and wave-optics theory could play a key role in filling this gap, and contribute to novel computational methods with enhanced interpretability and generalization by integrating model-driven and data-driven approaches. This paper is devoted to a comprehensive survey to state-of-the-art of computational methods for LFM, with a focus on model-based and data-driven approaches.
Unsupervised Deep Learning Methods for Biological Image Reconstruction and Enhancement: An overview from a signal processing perspective
Recently, deep learning approaches have become the main research frontier for biological image reconstruction and enhancement problems thanks to their high performance, along with their ultra-fast inference times. However, due to the difficulty of obtaining matched reference data for supervised learning, there has been increasing interest in unsupervised learning approaches that do not need paired reference data. In particular, self-supervised learning and generative models have been successfully used for various biological imaging applications. In this paper, we overview these approaches from a coherent perspective in the context of classical inverse problems, and discuss their applications to biological imaging, including electron, fluorescence and deconvolution microscopy, optical diffraction tomography and functional neuroimaging.
Multiway Graph Signal Processing on Tensors: Integrative analysis of irregular geometries
Graph signal processing (GSP) is an important methodology for studying data residing on irregular structures. As acquired data is increasingly taking the form of multi-way tensors, new signal processing tools are needed to maximally utilize the multi-way structure within the data. In this paper, we review modern signal processing frameworks generalizing GSP to multi-way data, starting from graph signals coupled to familiar regular axes such as time in sensor networks, and then extending to general graphs across all tensor modes. This widely applicable paradigm motivates reformulating and improving upon classical problems and approaches to creatively address the challenges in tensor-based data. We synthesize common themes arising from current efforts to combine GSP with tensor analysis and highlight future directions in extending GSP to the multi-way paradigm.
Neural Networks, Hypersurfaces, and the Generalized Radon Transform
Asymptotic Network Independence in Distributed Stochastic Optimization for Machine Learning
We provide a discussion of several recent results which, in certain scenarios, are able to overcome a barrier in distributed stochastic optimization for machine learning. Our focus is the so-called asymptotic network independence property, which is achieved whenever a distributed method executed over a network of nodes asymptotically converges to the optimal solution at a comparable rate to a centralized method with the same computational power as the entire network. We explain this property through an example involving the training of ML models and sketch a short mathematical analysis for comparing the performance of distributed stochastic gradient descent (DSGD) with centralized stochastic gradient decent (SGD).
Single-particle cryo-electron microscopy: Mathematical theory, computational challenges, and opportunities
In recent years, an abundance of new molecular structures have been elucidated using cryo-electron microscopy (cryo-EM), largely due to advances in hardware technology and data processing techniques. Owing to these new exciting developments, cryo-EM was selected by Nature Methods as Method of the Year 2015, and the Nobel Prize in Chemistry 2017 was awarded to three pioneers in the field. The main goal of this article is to introduce the challenging and exciting computational tasks involved in reconstructing 3-D molecular structures by cryo-EM. Determining molecular structures requires a wide range of computational tools in a variety of fields, including signal processing, estimation and detection theory, high-dimensional statistics, convex and non-convex optimization, spectral algorithms, dimensionality reduction, and machine learning. The tools from these fields must be adapted to work under exceptionally challenging conditions, including extreme noise levels, the presence of missing data, and massively large datasets as large as several Terabytes. In addition, we present two statistical models: multi-reference alignment and multi-target detection, that abstract away much of the intricacies of cryo-EM, while retaining some of its essential features. Based on these abstractions, we discuss some recent intriguing results in the mathematical theory of cryo-EM, and delineate relations with group theory, invariant theory, and information theory.
Deep-Learning Methods for Parallel Magnetic Resonance Imaging Reconstruction: A Survey of the Current Approaches, Trends, and Issues
Following the success of deep learning in a wide range of applications, neural network-based machine learning techniques have received interest as a means of accelerating magnetic resonance imaging (MRI). A number of ideas inspired by deep learning techniques from computer vision and image processing have been successfully applied to non-linear image reconstruction in the spirit of compressed sensing for both low dose computed tomography and accelerated MRI. The additional integration of multi-coil information to recover missing k-space lines in the MRI reconstruction process, is still studied less frequently, even though it is the de-facto standard for currently used accelerated MR acquisitions. This manuscript provides an overview of the recent machine learning approaches that have been proposed specifically for improving parallel imaging. A general background introduction to parallel MRI is given that is structured around the classical view of image space and k-space based methods. Both linear and non-linear methods are covered, followed by a discussion of recent efforts to further improve parallel imaging using machine learning, and specifically using artificial neural networks. Image-domain based techniques that introduce improved regularizers are covered as well as k-space based methods, where the focus is on better interpolation strategies using neural networks. Issues and open problems are discussed as well as recent efforts for producing open datasets and benchmarks for the community.
Plug-and-Play Methods for Magnetic Resonance Imaging: Using Denoisers for Image Recovery
Magnetic Resonance Imaging (MRI) is a non-invasive diagnostic tool that provides excellent soft-tissue contrast without the use of ionizing radiation. Compared to other clinical imaging modalities (e.g., CT or ultrasound), however, the data acquisition process for MRI is inherently slow, which motivates undersampling and thus drives the need for accurate, efficient reconstruction methods from undersampled datasets. In this article, we describe the use of "plug-and-play" (PnP) algorithms for MRI image recovery. We first describe the linearly approximated inverse problem encountered in MRI. Then we review several PnP methods, where the unifying commonality is to iteratively call a denoising subroutine as one step of a larger optimization-inspired algorithm. Next, we describe how the result of the PnP method can be interpreted as a solution to an equilibrium equation, allowing convergence analysis from the equilibrium perspective. Finally, we present illustrative examples of PnP methods applied to MRI image recovery.
Structured Low-Rank Algorithms: Theory, Magnetic Resonance Applications, and Links to Machine Learning
In this survey, we provide a detailed review of recent advances in the recovery of continuous domain multidimensional signals from their few non-uniform (multichannel) measurements using structured low-rank matrix completion formulation. This framework is centered on the fundamental duality between the compactness (e.g., sparsity) of the continuous signal and the rank of a structured matrix, whose entries are functions of the signal. This property enables the reformulation of the signal recovery as a low-rank structured matrix completion, which comes with performance guarantees. We will also review fast algorithms that are comparable in complexity to current compressed sensing methods, which enables the application of the framework to large-scale magnetic resonance (MR) recovery problems. The remarkable flexibility of the formulation can be used to exploit signal properties that are difficult to capture by current sparse and low-rank optimization strategies. We demonstrate the utility of the framework in a wide range of MR imaging (MRI) applications, including highly accelerated imaging, calibration-free acquisition, MR artifact correction, and ungated dynamic MRI.
Optimization Methods for Magnetic Resonance Image Reconstruction: Key Models and Optimization Algorithms
The development of compressed sensing methods for magnetic resonance (MR) image reconstruction led to an explosion of research on models and optimization algorithms for MR imaging (MRI). Roughly 10 years after such methods first appeared in the MRI literature, the U.S. Food and Drug Administration (FDA) approved certain compressed sensing methods for commercial use, making compressed sensing a clinical success story for MRI. This review paper summarizes several key models and optimization algorithms for MR image reconstruction, including both the type of methods that have FDA approval for clinical use, as well as more recent methods being considered in the research community that use data-adaptive regularizers. Many algorithms have been devised that exploit the structure of the system model and regularizers used in MRI; this paper strives to collect such algorithms in a single survey.
Deep Magnetic Resonance Image Reconstruction: Inverse Problems Meet Neural Networks
Image reconstruction from undersampled k-space data has been playing an important role in fast MRI. Recently, deep learning has demonstrated tremendous success in various fields and has also shown potential in significantly accelerating MRI reconstruction with fewer measurements. This article provides an overview of the deep learning-based image reconstruction methods for MRI. Two types of deep learning-based approaches are reviewed: those based on unrolled algorithms and those which are not. The main structure of both approaches are explained, respectively. Several signal processing issues for maximizing the potential of deep reconstruction in fast MRI are discussed. The discussion may facilitate further development of the networks and the analysis of performance from a theoretical point of view.
Compressed Sensing: From Research to Clinical Practice with Deep Neural Networks
Compressed sensing (CS) reconstruction methods leverage sparse structure in underlying signals to recover high-resolution images from highly undersampled measurements. When applied to magnetic resonance imaging (MRI), CS has the potential to dramatically shorten MRI scan times, increase diagnostic value, and improve overall patient experience. However, CS has several shortcomings which limit its clinical translation such as: 1) artifacts arising from inaccurate sparse modelling assumptions, 2) extensive parameter tuning required for each clinical application, and 3) clinically infeasible reconstruction times. Recently, CS has been extended to incorporate deep neural networks as a way of learning complex image priors from historical exam data. Commonly referred to as unrolled neural networks, these techniques have proven to be a compelling and practical approach to address the challenges of sparse CS. In this tutorial, we will review the classical compressed sensing formulation and outline steps needed to transform this formulation into a deep learning-based reconstruction framework. Supplementary open source code in Python will be used to demonstrate this approach with open databases. Further, we will discuss considerations in applying unrolled neural networks in the clinical setting.
Computational MRI with Physics-based Constraints: Application to Multi-contrast and Quantitative Imaging
Compressed sensing takes advantage of low-dimensional signal structure to reduce sampling requirements far below the Nyquist rate. In magnetic resonance imaging (MRI), this often takes the form of sparsity through wavelet transform, finite differences, and low rank extensions. Though powerful, these image priors are phenomenological in nature and do not account for the mechanism behind the image formation. On the other hand, MRI signal dynamics are governed by physical laws, which can be explicitly modeled and used as priors for reconstruction. These explicit and implicit signal priors can be synergistically combined in an inverse problem framework to recover sharp, multi-contrast images from highly accelerated scans. Furthermore, the physics-based constraints provide a recipe for recovering quantitative, bio-physical parameters from the data. This article introduces physics-based modeling constraints in MRI and shows how they can be used in conjunction with compressed sensing for image reconstruction and quantitative imaging. We describe model-based quantitative MRI, as well as its linear subspace approximation. We also discuss approaches to selecting user-controllable scan parameters given knowledge of the physical model. We present several MRI applications that take advantage of this framework for the purpose of multi-contrast imaging and quantitative mapping.
Computational MRI: Compressive Sensing and Beyond
