Ex Vivo MR Histology and Cytometric Feature Mapping Connect Three-dimensional in Vivo MR Images to Two-dimensional Histopathologic Images of Murine Sarcomas.
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Purpose To establish a platform for quantitative tissue-based interpretation of cytoarchitecture features from tumor MRI measurements. Materials and Methods In a pilot preclinical study, multicontrast in vivo MRI of murine soft-tissue sarcomas in 10 mice, followed by ex vivo MRI of fixed tissues (termed MR histology), was performed. Paraffin-embedded limb cross-sections were stained with hematoxylin-eosin, digitized, and registered with MRI. Registration was assessed by using binarized tumor maps and Dice similarity coefficients (DSCs). Quantitative cytometric feature maps from histologic slides were derived by using nuclear segmentation and compared with registered MRI, including apparent diffusion coefficients and transverse relaxation times as affected by magnetic field heterogeneity (T2* maps). Cytometric features were compared with each MR image individually by using simple linear regression analysis to identify the features of interest, and the goodness of fit was assessed on the basis of R2 values. Results Registration of MR images to histopathologic slide images resulted in mean DSCs of 0.912 for ex vivo MR histology and 0.881 for in vivo MRI. Triplicate repeats showed high registration repeatability (mean DSC, >0.9). Whole-slide nuclear segmentations were automated to detect nuclei on histopathologic slides (DSC = 0.8), and feature maps were generated for correlative analysis with MR images. Notable trends were observed between cell density and in vivo apparent diffusion coefficients (best line fit: R2 = 0.96, P < .001). Multiple cytoarchitectural features exhibited linear relationships with in vivo T2* maps, including nuclear circularity (best line fit: <i>R</i>2 = 0.99, P < .001) and variance in nuclear circularity (best line fit: <i>R</i>2 = 0.98, P < .001). Conclusion An infrastructure for registering and quantitatively comparing in vivo tumor MRI with traditional histologic analysis was successfully implemented in a preclinical pilot study of soft-tissue sarcomas. <b>Keywords:</b> MRI, Pathology, Animal Studies, Tissue Characterization Supplemental material is available for this article. © RSNA, 2021.
Published Version (Please cite this version)10.1148/rycan.2021200103
Publication InfoBlocker, Stephanie J; Cook, James; Mowery, Yvonne M; Everitt, Jeffrey I; Qi, Yi; Hornburg, Kathryn J; ... Johnson, G Allan (2021). Ex Vivo MR Histology and Cytometric Feature Mapping Connect Three-dimensional in Vivo MR Images to Two-dimensional Histopathologic Images of Murine Sarcomas. Radiology. Imaging cancer, 3(3). pp. e200103. 10.1148/rycan.2021200103. Retrieved from https://hdl.handle.net/10161/23389.
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Cristian Tudorel Badea
Professor in Radiology
Our lab's research focus lies primarily in developing novel quantitative imaging systems, reconstruction algorithms and analysis methods. My major expertise is in preclinical CT. Currently, we are particularly interested in developing novel strategies for spectral CT imaging using nanoparticle-based contrast agents for theranostics (i.e. therapy and diagnostics). We are also engaged in developin
Assistant Professor in Radiology
Jeffrey Ira Everitt
Professor in Pathology
Data Administration Analyst
G. Allan Johnson
Charles E. Putman University Distinguished Professor of Radiology
Dr. Johnson is the Charles E. Putman University Professor of Radiology, Professor of Physics, and Biomedical Engineering, and Director of the Duke Center for In Vivo Microscopy (CIVM). The CIVM is an NIH/NIBIB national Biomedical Technology Resource Center with a mission to develop novel technologies for preclinical imaging (basic sciences) and apply the technologies to critical biomedical questions. Dr. Johnson was one of the first researchers to bring Paul Lauterbur's vision of magnetic resona
David Guy Kirsch
Barbara Levine University Distinguished Professor
My clinical interests are the multi-modality care of patients with bone and soft tissue sarcomas and developing new sarcoma therapies. My laboratory interests include utilizing mouse models of cancer to study cancer and radiation biology in order to develop new cancer therapies in the pre-clinical setting.
Yvonne Marie Mowery
Butler Harris Assistant Professor in Radiation Oncology
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