AUTHOR=Blocker Stephanie J. , Mowery Yvonne M. , Everitt Jeffrey I. , Cook James , Cofer Gary Price , Qi Yi , Bassil Alex M. , Xu Eric S. , Kirsch David G. , Badea Cristian T. , Johnson G. Allan TITLE=MR histology reveals tissue features beneath heterogeneous MRI signal in genetically engineered mouse models of sarcoma JOURNAL=Frontiers in Oncology VOLUME=14 YEAR=2024 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1287479 DOI=10.3389/fonc.2024.1287479 ISSN=2234-943X ABSTRACT=Purpose

To identify significant relationships between quantitative cytometric tissue features and quantitative MR (qMRI) intratumorally in preclinical undifferentiated pleomorphic sarcomas (UPS).

Materials and methods

In a prospective study of genetically engineered mouse models of UPS, we registered imaging libraries consisting of matched multi-contrast in vivo MRI, three-dimensional (3D) multi-contrast high-resolution ex vivo MR histology (MRH), and two-dimensional (2D) tissue slides. From digitized histology we generated quantitative cytometric feature maps from whole-slide automated nuclear segmentation. We automatically segmented intratumoral regions of distinct qMRI values and measured corresponding cytometric features. Linear regression analysis was performed to compare intratumoral qMRI and tissue cytometric features, and results were corrected for multiple comparisons. Linear correlations between qMRI and cytometric features with p values of <0.05 after correction for multiple comparisons were considered significant.

Results

Three features correlated with ex vivo apparent diffusion coefficient (ADC), and no features correlated with in vivo ADC. Six features demonstrated significant linear relationships with ex vivo T2*, and fifteen features correlated significantly with in vivo T2*. In both cases, nuclear Haralick texture features were the most prevalent type of feature correlated with T2*. A small group of nuclear topology features also correlated with one or both T2* contrasts, and positive trends were seen between T2* and nuclear size metrics.

Conclusion

Registered multi-parametric imaging datasets can identify quantitative tissue features which contribute to UPS MR signal. T2* may provide quantitative information about nuclear morphology and pleomorphism, adding histological insights to radiological interpretation of UPS.