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This research introduces a physics-structured variational autoencoder that integrates differentiable spin simulators with self-supervised learning to enable rapid, uncertainty-aware quantification in molecular MRI. By providing full covariance matrices for biophysical parameters, the method achieves Bayesian-level accuracy while offering orders-of-magnitude speedup over brute-force approaches, directly addressing critical needs for clinical transparency and protocol optimization.
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Multiparameter Uncertainty Mapping in Quantitative Molecular MRI using a Physics-Structured Variational Autoencoder (PS-VAE)

arXiv2 min read

arXiv:2602.03317v2 Announce Type: replace-cross Abstract: 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.

Abstract: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.

Accepted by IEEE Transactions on Medical Imaging. This project was funded by the European Union (ERC, BabyMagnet, project no. 101115639). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them

Machine Learning (stat.ML); Artificial Intelligence (cs.AI); Machine Learning (cs.LG); Medical Physics (physics.med-ph)

arXiv:2602.03317 [stat.ML]

(or arXiv:2602.03317v2 [stat.ML] for this version)

A. Finkelstein et al., "Multiparameter Uncertainty Mapping in Quantitative Molecular MRI using a Physics-Structured Variational Autoencoder (PS-VAE)", IEEE Transactions on Medical Imaging, 2026

https://doi.org/10.1109/TMI.2026.3740952 DOI(s) linking to related resources

Full text under the publisher's open licence · 287 words

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