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Main Authors: Marchant, Joshua K., Lee, Hong-Hsi, Gerstner, Elizabeth R., Huang, Susie Y., Rosen, Bruce R.
Format: Preprint
Published: 2026
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Online Access:https://arxiv.org/abs/2605.02615
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author Marchant, Joshua K.
Lee, Hong-Hsi
Gerstner, Elizabeth R.
Huang, Susie Y.
Rosen, Bruce R.
author_facet Marchant, Joshua K.
Lee, Hong-Hsi
Gerstner, Elizabeth R.
Huang, Susie Y.
Rosen, Bruce R.
contents The lack of analytical models describing diffusion time dependence at intermediate time scales in complex tissue microstructure limits the accurate quantification of extracellular diffusivity and tissue microstructure. We introduce TRACED, a biophysical model that incorporates diffusion time dependence in cell distributions to quantify pathologically-relevant properties in solid tumors. Neural networks were trained on Monte Carlo diffusion simulations using sphere distribution-based geometries to enable the rapid computation of time-dependent diffusion MRI signals in cell populations of variable cell size. Model sensitivity and fit performance were assessed via simulation. Diffusion data from eight mixed-grade glioma patients was fitted using the TRACED model. Data fitting was performed using a novel physics-informed transfer learning pipeline, Sim2PINN. In two patients, cell size measurements were compared directly with image-localized histology. Simulation results indicate improved parameter estimation compared to the simple two-compartment model. TRACED enabled the simultaneous in vivo quantification of intracellular volume fraction, cell size distribution, extracellular intrinsic diffusivity, and tortuosity in glioma patients. Neural network implementations of diffusion time-dependence and tortuosity showed behavior consistent with coarse-graining and effective medium theory, respectively. Future work will explore the clinical utility of TRACED parameters in additional patients.
format Preprint
id arxiv_https___arxiv_org_abs_2605_02615
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle TRACED: In vivo imaging of extracellular intrinsic diffusivity, tortuosity, cell size distribution and cell density in human glioma patients
Marchant, Joshua K.
Lee, Hong-Hsi
Gerstner, Elizabeth R.
Huang, Susie Y.
Rosen, Bruce R.
Medical Physics
Machine Learning
Image and Video Processing
The lack of analytical models describing diffusion time dependence at intermediate time scales in complex tissue microstructure limits the accurate quantification of extracellular diffusivity and tissue microstructure. We introduce TRACED, a biophysical model that incorporates diffusion time dependence in cell distributions to quantify pathologically-relevant properties in solid tumors. Neural networks were trained on Monte Carlo diffusion simulations using sphere distribution-based geometries to enable the rapid computation of time-dependent diffusion MRI signals in cell populations of variable cell size. Model sensitivity and fit performance were assessed via simulation. Diffusion data from eight mixed-grade glioma patients was fitted using the TRACED model. Data fitting was performed using a novel physics-informed transfer learning pipeline, Sim2PINN. In two patients, cell size measurements were compared directly with image-localized histology. Simulation results indicate improved parameter estimation compared to the simple two-compartment model. TRACED enabled the simultaneous in vivo quantification of intracellular volume fraction, cell size distribution, extracellular intrinsic diffusivity, and tortuosity in glioma patients. Neural network implementations of diffusion time-dependence and tortuosity showed behavior consistent with coarse-graining and effective medium theory, respectively. Future work will explore the clinical utility of TRACED parameters in additional patients.
title TRACED: In vivo imaging of extracellular intrinsic diffusivity, tortuosity, cell size distribution and cell density in human glioma patients
topic Medical Physics
Machine Learning
Image and Video Processing
url https://arxiv.org/abs/2605.02615