Ex Vivo MR Histology and Cytometric Feature Mapping Connect Three-dimensional in Vivo MR Images to Two-dimensional Histopathologic Images of Murine Sarcomas.
Abstract
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.
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https://hdl.handle.net/10161/23389Published Version (Please cite this version)
10.1148/rycan.2021200103Publication Info
Blocker, 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
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
Stephanie Blocker
Assistant Professor in Radiology
Jeffrey Ira Everitt
Professor in Pathology
Kathryn Hornburg
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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