Multiparameter Uncertainty Mapping in Quantitative Molecular MRI using a Physics-Structured Variational Autoencoder (PS-VAE)

Quantitative imaging methods, such as magnetic resonance fingerprinting (MRF), aim to extract interpretable pathology biomarkers by estimating biophysical tissue parameters from signal evolutions. However, the pattern-matching algorithms or neural networks used in such inverse problems often lack principled uncertainty quantification, which limits the trustworthiness and transparency, required for clinical acceptance. Here, we describe a physics-structured variational autoencoder (PS-VAE) designed for rapid extraction of voxelwise multi-parameter posterior distributions. Our approach integrates a differentiable spin physics simulator with self-supervised learning, and provides a full covariance that captures the inter-parameter correlations of the latent biophysical space. The method was validated in a multi-proton pool chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) molecular MRF study, across in-vitro phantoms, tumor-bearing mice, healthy human volunteers, and a subject with glioblastoma. The resulting multi-parametric posteriors are in good agreement with those calculated using a brute-force Bayesian analysis, while providing an orders-of-magnitude acceleration in whole brain quantification. In addition, we demonstrate how monitoring the multi-parameter posterior dynamics across progressively acquired signals provides practical insights for protocol optimization and may facilitate real-time adaptive acquisition.

Fully 3D Unrolled Magnetic Resonance Fingerprinting Reconstruction via Staged Pretraining and Implicit Gridding

Magnetic Resonance Fingerprinting (MRF) enables fast quantitative imaging, yet reconstructing high-resolution 3D data remains computationally demanding. Non-Cartesian reconstructions require repeated non-uniform FFTs, and the commonly used Locally Low Rank (LLR) prior adds computational overhead and becomes insufficient at high accelerations. Learned 3D priors could address these limitations, but training them at scale is challenging due to memory and runtime demands. We propose SPUR-iG, a fully 3D deep unrolled subspace reconstruction framework that integrates efficient data consistency with a progressive training strategy. Data consistency leverages implicit GROG, which grids non-Cartesian data onto a Cartesian grid with an implicitly learned kernel, enabling FFT-based updates with minimal artifacts. Training proceeds in three stages: (1) pretraining a denoiser with extensive data augmentation, (2) greedy per-iteration unrolled training, and (3) final fine-tuning with gradient checkpointing. Together, these stages make large-scale 3D unrolled learning feasible within a reasonable compute budget. On a large in vivo dataset with retrospective undersampling, SPUR-iG improves subspace coefficient maps quality and quantitative accuracy at 1-mm isotropic resolution compared with LLR and a hybrid 2D/3D unrolled baseline. Whole-brain reconstructions complete in under 15-seconds, with up to $\times$111 speedup for 2-minute acquisitions. Notably, $T_1$ maps with our method from 30-second scans achieve accuracy on par with or exceeding LLR reconstructions from 2-minute scans. Overall, the framework improves both accuracy and speed in large-scale 3D MRF reconstruction, enabling efficient and reliable accelerated quantitative imaging.

MR Fingerprinting for Imaging Brain Hemodynamics and Oxygenation

Over the past decade, several studies have explored the potential of magnetic resonance fingerprinting (MRF) for the quantification of brain hemodynamics, oxygenation, and perfusion. Recent advances in simulation models and reconstruction frameworks have also significantly enhanced the accuracy of vascular parameter estimation. This review provides an overview of key vascular MRF studies, emphasizing advancements in geometrical models for vascular simulations, novel sequences, and state-of-the-art reconstruction techniques incorporating machine learning and deep learning algorithms. Both pre-clinical and clinical applications are discussed. Based on these findings, we outline future directions and development areas that need to be addressed to facilitate their clinical translation. Evidence Level N/A. Technical Efficacy Stage 1.

Improved Patch Denoising Diffusion Probabilistic Models for Magnetic Resonance Fingerprinting

Magnetic Resonance Fingerprinting (MRF) is a time-efficient approach to quantitative MRI, enabling the mapping of multiple tissue properties from a single, accelerated scan. However, achieving accurate reconstructions remains challenging, particularly in highly accelerated and undersampled acquisitions, which are crucial for reducing scan times. While deep learning techniques have advanced image reconstruction, the recent introduction of diffusion models offers new possibilities for imaging tasks, though their application in the medical field is still emerging. Notably, diffusion models have not yet been explored for the MRF problem. In this work, we propose for the first time a conditional diffusion probabilistic model for MRF image reconstruction. Qualitative and quantitative comparisons on in-vivo brain scan data demonstrate that the proposed approach can outperform established deep learning and compressed sensing algorithms for MRF reconstruction. Extensive ablation studies also explore strategies to improve computational efficiency of our approach.

Optimized Magnetic Resonance Fingerprinting Using Ziv-Zakai Bound

Magnetic Resonance Fingerprinting (MRF) has emerged as a promising quantitative imaging technique within the field of Magnetic Resonance Imaging (MRI), offers comprehensive insights into tissue properties by simultaneously acquiring multiple tissue parameter maps in a single acquisition. Sequence optimization is crucial for improving the accuracy and efficiency of MRF. In this work, a novel framework for MRF sequence optimization is proposed based on the Ziv-Zakai bound (ZZB). Unlike the Cram\'er-Rao bound (CRB), which aims to enhance the quality of a single fingerprint signal with deterministic parameters, ZZB provides insights into evaluating the minimum mismatch probability for pairs of fingerprint signals within the specified parameter range in MRF. Specifically, the explicit ZZB is derived to establish a lower bound for the discrimination error in the fingerprint signal matching process within MRF. This bound illuminates the intrinsic limitations of MRF sequences, thereby fostering a deeper understanding of existing sequence performance. Subsequently, an optimal experiment design problem based on ZZB was formulated to ascertain the optimal scheme of acquisition parameters, maximizing discrimination power of MRF between different tissue types. Preliminary numerical experiments show that the optimized ZZB scheme outperforms both the conventional and CRB schemes in terms of the reconstruction accuracy of multiple parameter maps.

Broadening Discovery through Structural Models: Multimodal Combination of Local and Structural Properties for Predicting Chemical Features

In recent years, machine learning has profoundly reshaped the field of chemistry, facilitating significant advancements across various applications, including the prediction of molecular properties and the generation of molecular structures. Language models and graph-based models are extensively utilized within this domain, consistently achieving state-of-the-art results across an array of tasks. However, the prevailing practice of representing chemical compounds in the SMILES format -- used by most datasets and many language models -- presents notable limitations as a training data format. In contrast, chemical fingerprints offer a more physically informed representation of compounds, thereby enhancing their suitability for model training. This study aims to develop a language model that is specifically trained on fingerprints. Furthermore, we introduce a bimodal architecture that integrates this language model with a graph model. Our proposed methodology synthesizes these approaches, utilizing RoBERTa as the language model and employing Graph Isomorphism Networks (GIN), Graph Convolutional Networks (GCN) and Graphormer as graph models. This integration results in a significant improvement in predictive performance compared to conventional strategies for tasks such as Quantitative Structure-Activity Relationship (QSAR) and the prediction of nuclear magnetic resonance (NMR) spectra, among others.

Upper-body free-breathing Magnetic Resonance Fingerprinting applied to the quantification of water T1 and fat fraction

Over the past decade, Magnetic Resonance Fingerprinting (MRF) has emerged as an efficient paradigm for the rapid and simultaneous quantification of multiple MRI parameters, including fat fraction (FF), water T1 ($T1_{H2O}$), water T2 ($T2_{H2O}$), and fat T1 ($T1_{fat}$). These parameters serve as promising imaging biomarkers in various anatomical targets such as the heart, liver, and skeletal muscles. However, measuring these parameters in the upper body poses challenges due to physiological motion, particularly respiratory motion. In this work, we propose a novel approach, motion-corrected (MoCo) MRF T1-FF, which estimates the motion field using an optimized preliminary motion scan and uses it to correct the MRF acquisition data before dictionary search for reconstructing motion-corrected FF and $T1_{H2O}$ parametric maps of the upper-body region. We validated this framework using an $\textit{in vivo}$ dataset comprising ten healthy volunteers and a 10-year-old boy with Duchenne muscular dystrophy. At the ROI level, in regions minimally affected by motion, no significant bias was observed between the uncorrected and MoCo reconstructions for FF (mean difference of -0.7%) and $T1_{H2O}$ (-4.9 ms) values. Moreover, MoCo MRF T1-FF significantly reduced the standard deviations of distributions assessed in these regions, indicating improved precision. Notably, in regions heavily affected by motion, such as respiratory muscles, liver, and kidneys, the MRF parametric maps exhibited a marked reduction in motion blurring and streaking artifacts after motion correction. Furthermore, the diaphragm was consistently discernible on parametric maps after motion correction. This approach lays the groundwork for the joint 3D quantification of FF and $T1_{H2O}$ in regions that are rarely studied, such as the respiratory muscles, particularly the intercostal muscles and diaphragm.

Deep Image Priors for Magnetic Resonance Fingerprinting with pretrained Bloch-consistent denoising autoencoders

The estimation of multi-parametric quantitative maps from Magnetic Resonance Fingerprinting (MRF) compressed sampled acquisitions, albeit successful, remains a challenge due to the high underspampling rate and artifacts naturally occuring during image reconstruction. Whilst state-of-the-art DL methods can successfully address the task, to fully exploit their capabilities they often require training on a paired dataset, in an area where ground truth is seldom available. In this work, we propose a method that combines a deep image prior (DIP) module that, without ground truth and in conjunction with a Bloch consistency enforcing autoencoder, can tackle the problem, resulting in a method faster and of equivalent or better accuracy than DIP-MRF.

StoDIP: Efficient 3D MRF image reconstruction with deep image priors and stochastic iterations

Magnetic Resonance Fingerprinting (MRF) is a time-efficient approach to quantitative MRI for multiparametric tissue mapping. The reconstruction of quantitative maps requires tailored algorithms for removing aliasing artefacts from the compressed sampled MRF acquisitions. Within approaches found in the literature, many focus solely on two-dimensional (2D) image reconstruction, neglecting the extension to volumetric (3D) scans despite their higher relevance and clinical value. A reason for this is that transitioning to 3D imaging without appropriate mitigations presents significant challenges, including increased computational cost and storage requirements, and the need for large amount of ground-truth (artefact-free) data for training. To address these issues, we introduce StoDIP, a new algorithm that extends the ground-truth-free Deep Image Prior (DIP) reconstruction to 3D MRF imaging. StoDIP employs memory-efficient stochastic updates across the multicoil MRF data, a carefully selected neural network architecture, as well as faster nonuniform FFT (NUFFT) transformations. This enables a faster convergence compared against a conventional DIP implementation without these features. Tested on a dataset of whole-brain scans from healthy volunteers, StoDIP demonstrated superior performance over the ground-truth-free reconstruction baselines, both quantitatively and qualitatively.

MARVEL: MR Fingerprinting with Additional micRoVascular Estimates using bidirectional LSTMs

The Magnetic Resonance Fingerprinting (MRF) approach aims to estimate multiple MR or physiological parameters simultaneously with a single fast acquisition sequence. Most of the MRF studies proposed so far have used simple MR sequence types to measure relaxation times (T1, T2). In that case, deep learning algorithms have been successfully used to speed up the reconstruction process. In theory, the MRF concept could be used with a variety of other MR sequence types and should be able to provide more information about the tissue microstructures. Yet, increasing the complexity of the numerical models often leads to prohibited simulation times, and estimating multiple parameters from one sequence implies new dictionary dimensions whose sizes become too large for standard computers and DL architectures.In this paper, we propose to analyze the MRF signal coming from a complex balance Steady-state free precession (bSSFP) type sequence to simultaneously estimate relaxometry maps (T1, T2), Field maps (B1, B0) as well as microvascular properties such as the local Cerebral Blood Volume (CBV) or the averaged vessel Radius (R).To bypass the curse of dimensionality, we propose an efficient way to simulate the MR signal coming from numerical voxels containing realistic microvascular networks as well as a Bidirectional Long Short-Term Memory network used for the matching process.On top of standard MRF maps, our results on 3 human volunteers suggest that our approach can quickly produce high-quality quantitative maps of microvascular parameters that are otherwise obtained using longer dedicated sequences and intravenous injection of a contrast agent. This approach could be used for the management of multiple pathologies and could be tuned to provide other types of microstructural information.