MEMRI-based imaging pipeline for guiding preclinical studies in mouse models of sporadic medulloblastoma Journal Article

Authors: Rallapalli, H.; Tan, I. L.; Volkova, E.; Wojcinski, A.; Darwin, B. C.; Lerch, J. P.; Joyner, A. L.; Turnbull, D. H.
Article Title: MEMRI-based imaging pipeline for guiding preclinical studies in mouse models of sporadic medulloblastoma
Abstract: Purpose: Genetically engineered mouse models of sporadic cancers are critical for studying tumor biology and for preclinical testing of therapeutics. We present an MRI-based pipeline designed to produce high resolution, quantitative information about tumor progression and response to novel therapies in mouse models of medulloblastoma (MB). Methods: Sporadic MB was modeled in mice by inducing expression of an activated form of the Smoothened gene (aSmo) in a small number of cerebellar granule cell precursors. aSmo mice were imaged and analyzed at defined time-points using a 3D manganese-enhanced MRI-based pipeline optimized for high-throughput. Results: A semi-automated segmentation protocol was established that estimates tumor volume in a time-frame compatible with a high-throughput pipeline. Both an empirical, volume-based classifier and a linear discriminant analysis-based classifier were tested to distinguish progressing from nonprogressing lesions at early stages of tumorigenesis. Tumor centroids measured at early stages revealed that there is a very specific location of the probable origin of the aSmo MB tumors. The efficacy of the manganese-enhanced MRI pipeline was demonstrated with a small-scale experimental drug trial designed to reduce the number of tumor associated macrophages and microglia. Conclusion: Our results revealed a high level of heterogeneity between tumors within and between aSmo MB models, indicating that meaningful studies of sporadic tumor progression and response to therapy could not be conducted without an imaging-based pipeline approach. © 2019 International Society for Magnetic Resonance in Medicine
Keywords: controlled study; gene mutation; cancer localization; cancer growth; nonhuman; cancer staging; nuclear magnetic resonance imaging; cancer diagnosis; tumor associated leukocyte; mouse; gene; image analysis; tumor volume; animal experiment; animal model; high throughput screening; automation; carcinogenesis; gene expression regulation; gene activation; quantitative analysis; medulloblastoma; cell count; segmentation; mri; mouse model; image segmentation; microglia; process development; process optimization; article; cerebellum granular layer; linear discriminant analysis (lda); sonic hedgehog (shh); tumor associated macrophages and microglia (tams); smoothened gene; t1 weighted manganese enhanced magnetic resonance imaging
Journal Title: Magnetic Resonance in Medicine
Volume: 83
Issue: 1
ISSN: 0740-3194
Publisher: John Wiley & Sons  
Date Published: 2020-01-01
Start Page: 214
End Page: 227
Language: English
DOI: 10.1002/mrm.27904
PUBMED: 31403226
PROVIDER: scopus
PMCID: PMC6778701
Notes: Article -- Export Date: 1 November 2019 -- Source: Scopus
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MSK Authors
  1. Alexandra L Joyner
    73 Joyner
  2. I-Li Tan
    4 Tan