TY - JOUR
T1 - Simultaneous spatiotemporal tracking and oxygen sensing of transient implants in vivo using hot-spot MRI and machine learning
AU - Spanoudaki, Virginia
AU - Doloff, Joshua C.
AU - Huang, Wei
AU - Norcross, Samuel R.
AU - Farah, Shady
AU - Langer, Robert
AU - Anderson, Daniel G.
N1 - Funding Information:
ACKNOWLEDGMENTS. All animal imaging studies were performed at the Animal Imaging and Preclinical Testing (AIPT) core at the Swanson Biotechnology Center of the Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology (MIT). The authors thank Prof. Nicolas Bertrand from Quebec University for his assistance with the development of the PFCE emulsion protocol, Dr. Scott Malstrom from AIPT at MIT for his assistance with MRI instrumentation and initial measurements, and Prof. Alan Jasanoff from MIT for the useful discussions on fluorine MRI imaging. This work has been supported by the Juvenile Diabetes Research Foundation (JDRF) (Grant 17-2007-1063), by the Leona M. and Harry B. Helmsley Charitable Trust Foundation (Grants 09PG-T1D027 and 2017PG-T1D027), by the Parviz Tayebati Research Fund, and in part by the Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute. J.C.D. was supported by a JDRF postdoctoral fellowship (Grant 3-PDF-2015-91-A-N).
Publisher Copyright:
© 2019 National Academy of Sciences. All Rights Reserved.
PY - 2019
Y1 - 2019
N2 - A varying oxygen environment is known to affect cellular function in disease as well as activity of various therapeutics. For transient structures, whether they are unconstrained therapeutic transplants, migrating cells during tumor metastasis, or cell populations induced by an immunological response, the role of oxygen in their fate and function is known to be pivotal albeit not well understood in vivo. To address such a challenge in the case of generation of a bioartificial pancreas, we have combined fluorine magnetic resonance imaging and unsupervised machine learning to monitor over time the spatial arrangement and the oxygen content of implants encapsulating pancreatic islets that are unconstrained in the intraperitoneal (IP) space of healthy and diabetic mice. Statistically significant trends in the postimplantation temporal dependence of oxygen content between aggregates of 0.5-mm or 1.5-mm alginate microcapsules were identified in vivo by looking at their dispersity as well as arrangement in clusters of different size and estimating oxygen content on a pixelby- pixel basis from thousands of 2D images. Ultimately, we found that this dependence is stronger for decreased implant capsule size consistent with their tendency to also induce a larger immunological response. Beyond the bioartificial pancreas, this work provides a framework for the simultaneous spatiotemporal tracking and oxygen sensing of other cell populations and biomaterials that change over time to better understand and improve therapeutic design across diverse applications such as cellular transplant therapy, treatments preventing metastatic formation, and modulators for improving immunologic response, for all of which oxygen is a major mechanistic component.
AB - A varying oxygen environment is known to affect cellular function in disease as well as activity of various therapeutics. For transient structures, whether they are unconstrained therapeutic transplants, migrating cells during tumor metastasis, or cell populations induced by an immunological response, the role of oxygen in their fate and function is known to be pivotal albeit not well understood in vivo. To address such a challenge in the case of generation of a bioartificial pancreas, we have combined fluorine magnetic resonance imaging and unsupervised machine learning to monitor over time the spatial arrangement and the oxygen content of implants encapsulating pancreatic islets that are unconstrained in the intraperitoneal (IP) space of healthy and diabetic mice. Statistically significant trends in the postimplantation temporal dependence of oxygen content between aggregates of 0.5-mm or 1.5-mm alginate microcapsules were identified in vivo by looking at their dispersity as well as arrangement in clusters of different size and estimating oxygen content on a pixelby- pixel basis from thousands of 2D images. Ultimately, we found that this dependence is stronger for decreased implant capsule size consistent with their tendency to also induce a larger immunological response. Beyond the bioartificial pancreas, this work provides a framework for the simultaneous spatiotemporal tracking and oxygen sensing of other cell populations and biomaterials that change over time to better understand and improve therapeutic design across diverse applications such as cellular transplant therapy, treatments preventing metastatic formation, and modulators for improving immunologic response, for all of which oxygen is a major mechanistic component.
KW - Cellular therapy
KW - Diabetes
KW - Implants
KW - Magnetic resonance imaging
KW - Oxygen sensing
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U2 - 10.1073/pnas.1815909116
DO - 10.1073/pnas.1815909116
M3 - Article
C2 - 30808810
AN - SCOPUS:85062851695
SN - 0027-8424
VL - 116
SP - 4861
EP - 4870
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 11
ER -