# Characterization of the microstructural complexity of tumor tissue using timedependent diffusion in the 60 -240 Hz range

Philippe Garteiser, Stéphanie Depinay, Amira Sebouai, Selena Prantner, Gwenaël Pagé, Sabrina Doblas, Bernard van Beers

► To cite this version:

Philippe Garteiser, Stéphanie Depinay, Amira Sebouai, Selena Prantner, Gwenaël Pagé, et al.. Characterization of the microstructural complexity of tumor tissue using timedependent diffusion in the 60 -240 Hz range. 2025 SFRMBM conference, SFRMBM, Mar 2025, Saint-Malo, France. hal-05016574

HAL Id: hal-05016574

https://hal.science/hal-05016574v1

Submitted on 24 Apr 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# Characterization of the microstructural complexity of tumor tissue using time-dependent diffusion in the 60 - 240 Hz range

Philippe Garteiser<fnref n="1" /> (philippe.garteiser@inserm.fr), Stéphanie Depinay<fnref n="1" />, Amira Sebouai<fnref n="1" />, Selena

Prantner<fnref n="1" />,², Gwenaël Pagé<fnref n="3" />, Sabrina Doblas<fnref n="1" />, Bernard Van Beers<fnref n="1" />,⁴

**Objectives:** Among numerous perturbations, tumor tissue is characterized by spatially heterogeneous alterations in cellular<fnref n="1" />, stromal² and vascular features<fnref n="3" />. These microstructural features may be studied with oscillating gradient spin echo (OGSE) diffusion MRI⁴, ⁵. In OGSE, imaging markers are sensitized to microstructure, giving rise to different frequency response regimes for the diffusion coefficient. In the long-time regime (LTR), the diffusion length is larger than the scale of the restrictions, while the opposite is true in the short-time regime (STR)⁶. The objective of the present work was to interrogate the diffusion regime in the 60 - 240 Hz frequency range using phantoms and a murine model of breast tumor.

**Methods:** A spin echo EPI sequence with trapezoidal diffusion encoding gradients at 60, 120, 170 and 240 Hz was used with b-values up to 500 s/mm². Centrifugally packed polystyrene bead phantoms of 3, 15, 30, 75 or 100 µm in diameter were used. Murine model experiments were carried out on subcutaneous 4T1 breast tumors. Dispersion curves were analyzed with

$(D^{LTR} = D_{\infty}^{LTR} + k^{LTR} \cdot \omega^\gamma \text{ and } D^{STR} = D_{0}^{STR} \left( 1 - (k^{STR}/r) \sqrt{D_{0}^{STR}/\omega} \right)$ as reviewed in Reynaud⁶.

**Results:** The error terms from the packed beads indicate that bead sizes 3 and 15 µm were associated with LTR, and higher sizes (≥ 30 µm) with STR (fig. top row). In murine tumors (n = 21, figs. A: MRI and histology, B: diffusion maps at individual frequencies), the LTR regime was mainly represented (92 ± 3 % of pixels, root mean squared error $rmse_{LTR} = 2.5 \times 10^{-8} \text{ mm}^2/\text{s}$, $rmse_{STR} = 7.1 \times 10^{-8} \text{ mm}^2/\text{s}$, paired t-test $p < 0.0001$, fig. C), indicating predominantly small barrier sizes (< 30 µm). Based on observed LTR frequency dispersion values (1.300 ± 0.002), tumor tissue behaved

similarly to beads of 22.3 ± 0.8 µm in size. The low frequency limit of diffusion $D_{\infty}^{LTR}$ (0.83 ± 0.04 × 10⁻<fnref n="3" /> mm²/s) was 1.38 ± 0.03 times smaller than the high frequency limit of diffusion $D_{0}^{STR}$ (1.16 ± 0.03 × 10⁻<fnref n="3" /> mm²/s) (fig. D). The STR-estimated barrier distance of 46.2 ± 0.9 µm was negatively correlated ($r_{Pearson} = -0.92, p < 0.0001$) to the $D_{0}^{STR} / D_{\infty}^{LTR}$ ratio.

**Conclusion:** OGSE MRI was successfully performed in vivo in the 60 - 240 Hz range in a breast tumor model. Cancerous tissue was found to display LTR-like dispersion regime with an effective barrier size of 22 µm. Tissue effective size was negatively correlated to the ratio between asymptotic diffusion values of the STR and LTR regimes. We plan investigating the relationship between OGSE-derived metrics and histological features in future studies.

**References:** [1] Lafaro et al. Am J Path 2019. [2] Cox. Nat Rev Cancer 2021. [3] Nia et al. Science 2020. [4] Gore et al. NMR Biomed 2010. [5] Wagner et al. JMRI 2020. [6] Reynaud O. Front Phys 2017.

**Funding & thanks:** StediNASH (ANR-20-CE19-0005), MistraXL (PCSI-2024-C24036HS), France Life Imaging (ANR-11-INBS-0006), FRIM platform (Inserm UMS34)

<figure><img src="image_2.png" /><figcaption>Figure: bead results (top row), representative image (Panes A-D)</figcaption></figure>

<footnote n="1">¹Centre de Recherche sur l'Inflammation, Inserm U1149, Université Paris Cité, Paris. ²University of Vienna, Wien.</footnote>

<footnote n="3">³Biomaps, CEA, Université Paris Saclay, Saclay. ⁴Hopital Beaujon, AP-HP, Clichy</footnote>