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In Vivo Hypoxia Monitoring Via Magnetic Resonance Imaging for Mouse Models

N Virani1*, A Protti2, J Kwon3, R Berbeco1, (1) Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute & Harvard Medical School, Boston, MA, (2) Lurie Family Imaging Center, Department of Radiology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, (3) Hokkaido University, Sapporo, 01, JP

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose: The therapeutic efficacy of radiation therapy is challenged by hypoxic tumor microenvironments. Many chemotherapeutics and novel vascular directed treatments are similarly affected by hypoxia. To better understand the microenvironment, tools are needed to monitor long-term hypoxia changes in translational animal models. Currently, in vivo hypoxia monitoring in small animals is limited due to the need for either long circulating contrast agents or low signal to noise ratios (SNR). In this study we develop an MRI based technique for serial in vivo hypoxia monitoring in a mouse glioblastoma model.


Methods: Mice were inoculated with an orthotopic glioblastoma model (GL261-luc2). On day 22, a set of T2*-weighted Gradient Echo (GRE) images were taken with and without an oxygen challenge. Following imaging, mice were injected with pimonidazole, a hypoxia specific marker that is reduced when pO2 = 10 mmHg, and tissue was collected for immunohistochemistry. Images were analyzed by an in-house MATLAB program comparing changes in T2* maps during oxygen and air breathing.


Results: Blood Oxygen Level Dependent (BOLD) imaging has been previously used to highlight areas of hypoxia in rats or larger animals. We have developed a sequence to adapt the BOLD concept to mouse models. We identified regions within each tumor as hypoxic relative to normoxic tissue with high SNR. We show strong correlation between regions staining positive for pimonidazole and regions highlighted as highly hypoxic (low change < 5%) in the oxygen to air change T2* maps.


Conclusion: We have developed a technique to monitor long-term hypoxia in mouse models with validation from immunohistochemistry. This technique will open new avenues for studying the trajectory of tumor microenvironment response to therapy with implications for timing of repeat treatment administration.

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