@article{5b8690d5e42245b39a512c937a2b960c,
title = "Longitudinal preclinical magnetic resonance imaging of diffuse tumor burden in intramedullary myeloma following bortezomib therapy",
abstract = "Multiple myeloma (MM) is a largely incurable, debilitating hematologic malignancy of terminally differentiated plasma cells in the bone marrow (BM). Identification of therapeutic response is critical for improving outcomes and minimizing costs and off-target toxicities. To assess changes in BM environmental factors and therapy efficacy, there is a need for noninvasive, nonionizing, longitudinal, preclinical methods. Here, we demonstrate the feasibility of preclinical magnetic resonance imaging (MRI) for longitudinal imaging of diffuse tumor burden in a syngeneic, immunocompetent model of intramedullary MM. C57Bl/KaLwRij mice were implanted intravenously with 5TGM1-GFP tumors and treated with a proteasome inhibitor, bortezomib, or vehicle control. MRI was performed weekly with a Helmholtz radiofrequency coil placed on the hind leg. Mean normalized T1-weighted signal intensities and T2 relaxation times were quantified for each animal following manual delineation of BM regions in the femur and tibia. Finally, tumor burden was quantified for each tissue using hematoxylin and eosin staining. Changes in T2 relaxation times correlated strongly to cell density and overall tumor burden in the BM. Median T2 relaxation times and regional T1-weighted contrast uptake were shown to be most relevant in identifying posttherapy disease stage in this model of intramedullary MM. In summary, our results highlighted potential preclinical MRI markers for assessing tumor burden and BM heterogeneity following bortezomib therapy, and demonstrated the application of longitudinal imaging with preclinical MRI in an immunocompetent, intramedullary setting.",
keywords = "bortezomib treatment response, diffuse tumor burden, intramedullary multiple myeloma, longitudinal imaging, preclinical MRI",
author = "Hathi, {Deep K.} and Engelbach, {John A.} and Jens Hillengass and Deborah Veis and Samuel Achilefu and Garbow, {Joel R.} and Monica Shokeen",
note = "Funding Information: Informative discussions with Dr Joseph J. H. Ackerman regarding MRI aspects of this study are gratefully acknowledged. Ms Gail Sudlow assisted in intravenous injections and tumor implantations. Ms Crystal Idleburg assisted in tissue sectioning and H&E staining. Dr Scott Beeman and Dr James Quirk assisted with sequence optimization and coil development. Dr Francesca Fontana and Dr Katherine Weilbaecher provided valuable insights and preliminary data collection assistance. This work was supported by the Alafi Neuroimaging Laboratory, the Hope Center for Neurological Disorders, and NIH Shared Instrumentation Grant (S10 RR0227552) to Washington University. This work was also supported by the Small-Animal Cancer Imaging Shared Resource of the Alvin J. Siteman Cancer Center, an NCI-designated Comprehensive Cancer Center (P30 CA091842). This research was primarily funded by NIH grants R01 CA176221 and U54 CA199092 (NCI funded Center for Multiple Myeloma Nanotherapy). We acknowledge additional support from NIH P50 CA094056, DE-SC0012737, K08CA154790, and pilot imaging funds from the Mallinckrodt Institute of Radiology at the Washington University School of Medicine. Funding Information: Informative discussions with Dr Joseph J. H. Ackerman regarding MRI aspects of this study are gratefully acknowledged. Ms Gail Sudlow assisted in intravenous injections and tumor implantations. Ms Crystal Idleburg assisted in tissue sectioning and H&E staining. Dr Scott Beeman and Dr James Quirk assisted with sequence optimization and coil development. Dr Francesca Fontana and Dr Katherine Weilbaecher provided valuable insights and preliminary data collection assistance. This work was supported by the Alafi Neuroimaging Laboratory, the Hope Center for Neurological Disorders, and NIH Shared Instrumentation Grant (S10 RR0227552) to Washington University. This work was also supported by the Small‐ Animal Cancer Imaging Shared Resource of the Alvin J. Siteman Cancer Center, an NCI‐designated Comprehensive Cancer Center (P30 CA091842). This research was primarily funded by NIH grants R01 CA176221 and U54 CA199092 (NCI funded Center for Multiple Myeloma Nanotherapy). We acknowledge additional support from NIH P50 CA094056, DE‐SC0012737, K08CA154790, and pilot imaging funds from the Mallinckrodt Institute of Radiology at the Washington University School of Medicine. Funding Information: NIH grants R01 CA176221 and U54 CA199092 (NCI‐funded Center for Multiple Myeloma Nanotherapy). Additional support from NIH P50 CA094056, DE‐SC0012737, K08CA154790, and pilot imaging funds from the Mallinckrodt Institute of Radiology at the Washington University School of Medicine. Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons, Ltd.",
year = "2019",
month = sep,
doi = "10.1002/nbm.4122",
language = "English (US)",
volume = "32",
journal = "NMR in Biomedicine",
issn = "0952-3480",
publisher = "John Wiley and Sons Ltd",
number = "9",
}