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Histology-informed microstructural diffusion simulations for MRI cancer characterisation—the Histo-μSim framework

Grigoriou, Athanasios, Macarro, Carlos, Palombo, Marco ORCID: https://orcid.org/0000-0003-4892-7967, Navarro-Garcia, Daniel, Voronova, Anna Kira, Bernatowicz, Kinga, Barba, Ignasi, Escriche, Alba, Greco, Emanuela, Abad, María, Simonetti, Sara, Serna, Garazi, Mast, Richard, Merino, Xavier, Roson, Núria, Escobar, Manuel, Vieito, Maria, Nuciforo, Paolo, Toledo, Rodrigo, Garralda, Elena, Sala-Llonch, Roser, Fieremans, Els, Novikov, Dmitry S., Perez-Lopez, Raquel and Grussu, Francesco 2025. Histology-informed microstructural diffusion simulations for MRI cancer characterisation—the Histo-μSim framework. Communications Biology 8 , 1695. 10.1038/s42003-025-09096-3

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Abstract

Diffusion Magnetic Resonance Imaging (dMRI) simulations in geometries mimicking the microscopic complexity of human tissues enable the development of innovative biomarkers with unprecedented fidelity to histology. Simulation-informed dMRI has traditionally focussed on brain imaging, and it has neglected other applications, as for example body cancer imaging, where new non-invasive biomarkers are still sought. This article fills this gap by introducing a Monte Carlo diffusion simulation framework informed by histology, for enhanced body dMR microstructural imaging: the Histo-μSim approach. We generate dictionaries of synthetic dMRI signals with coupled tissue properties from virtual cancer environments, reconstructed from hematoxylin-eosin stains of human liver biopsies. These enable the data-driven estimation of properties such as the intrinsic extra-cellular diffusivity, cell size or cell membrane permeability. We compare Histo-μSim to metrics from well-established analytical multi-compartment models in silico, on fixed mouse tissues scanned ex vivo (kidneys, spleens, and breast tumours) and in cancer patients in vivo. Results suggest that Histo-μSim is feasible in clinical settings, and that it delivers metrics that more accurately reflect histology as compared to analytical models. In conclusion, Histo-μSim offers histologically-meaningful tissue descriptors that may increase the specificity of dMRI towards cancer, and thus play a crucial role in precision oncology.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Schools > Computer Science & Informatics
Schools > Psychology
Research Institutes & Centres > Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Nature Research
Date of First Compliant Deposit: 11 November 2025
Date of Acceptance: 18 October 2025
Last Modified: 02 Dec 2025 12:29
URI: https://orca.cardiff.ac.uk/id/eprint/182344

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