a) a) Novel Pulse sequences for human applications: The EPR imaging system developed in our lab is in routine use for pre-clinical imaging of tumor oxygen status in mouse models of cancer, both as xenografts and orthotopic models. Scaling up of resonant structures to enable imaging larger objects for pO2. For implementation in human studies, it is necessary to develop a signal formation method using low RF levels to comply with FDA regulations. An RF excitation scheme called Frank Pulse Sequence was developed whereby signals can be generated with RF power levels of milliwatt compared to the conventional power of 50 Watts. This was possible by the development of an RF module which delivers pulses of excitation with pseudo-random ordering of the phase and a resonant structure which isolates the excitation and signal reception. We are now in the process of integrating the system for Wireless implantable RF coil/oxygen sensing probe assembly for long term oxygen assessment. A miniature wireless RF coil (4 mm dia) with an embedded paramagnetic solid in a biocompatible polymer has been developed which can be implanted in vivo to test the feasibility of monitoring tissue oxygen at the point of implantation. The implanted RF wireless coil has no leads but can be probed with an external coil which can excite the wireless coil and the paramagnetic probe. Thus this assembly can be implanted chronically at desired sites and oxygen changes can be monitored over periods of weeks/months. Preliminary studies show that a 5-7 fold enhanced sensitivity of detection has been realized. In vivo studies are underway. b) With the improvements in imaging of tumor oxygen dynamics, it was possible to use EPR imaging to: a) monitor the post radiation tumor reoxygenation and b: relationship between tumor oxygenation and glycolysis in tumor xenografts.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010476-14
Application #
9343625
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Matsumoto, Ken-Ichiro; Kishimoto, Shun; Devasahayam, Nallathamby et al. (2018) EPR-based oximetric imaging: a combination of single point-based spatial encoding and T1 weighting. Magn Reson Med 80:2275-2287
Matsumoto, Ken-Ichiro; Hyodo, Fuminori; Mitchell, James B et al. (2018) Effect of body temperature on the pharmacokinetics of a triarylmethyl-type paramagnetic contrast agent used in EPR oximetry. Magn Reson Med 79:1212-1218
Kishimoto, Shun; Krishna, Murali C; Khramtsov, Valery V et al. (2018) In Vivo Application of Proton-Electron Double-Resonance Imaging. Antioxid Redox Signal 28:1345-1364
Scroggins, Bradley T; Matsuo, Masayuki; White, Ayla O et al. (2018) Hyperpolarized [1-13C]-Pyruvate Magnetic Resonance Spectroscopic Imaging of Prostate Cancer In Vivo Predicts Efficacy of Targeting the Warburg Effect. Clin Cancer Res 24:3137-3148
Matsumoto, Ken-Ichiro; Mitchell, James B; Krishna, Murali C (2018) Comparative studies with EPR and MRI on the in vivo tissue redox status estimation using redox-sensitive nitroxyl probes: influence of the choice of the region of interest. Free Radic Res 52:248-255
Matsumoto, Shingo; Kishimoto, Shun; Saito, Keita et al. (2018) Metabolic and Physiologic Imaging Biomarkers of the Tumor Microenvironment Predict Treatment Outcome with Radiation or a Hypoxia-Activated Prodrug in Mice. Cancer Res 78:3783-3792
Matsuo, Masayuki; Kawai, Tatsuya; Kishimoto, Shun et al. (2018) Co-imaging of the tumor oxygenation and metabolism using electron paramagnetic resonance imaging and 13-C hyperpolarized magnetic resonance imaging before and after irradiation. Oncotarget 9:25089-25100
Kishimoto, Shun; Matsumoto, Ken-Ichiro; Saito, Keita et al. (2018) Pulsed Electron Paramagnetic Resonance Imaging: Applications in the Studies of Tumor Physiology. Antioxid Redox Signal 28:1378-1393
Takakusagi, Yoichi; Kishimoto, Shun; Naz, Sarwat et al. (2018) Radiotherapy Synergizes with the Hypoxia-Activated Prodrug Evofosfamide: In Vitro and In Vivo Studies. Antioxid Redox Signal 28:131-140
Yasui, Hironobu; Kawai, Tatsuya; Matsumoto, Shingo et al. (2017) Quantitative imaging of pO2 in orthotopic murine gliomas: hypoxia correlates with resistance to radiation. Free Radic Res 51:861-871

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