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Purpose: Hypoxia plays a vital role in tumor development, angiogenesis, growth, and resistance to treatment with radiotherapy, chemotherapy, and even surgery. In the current study, we present the advanced non-invasive, robust and reliable tissue oxygenation approaches used for tumor oxygenation and hypoxia assessment.
Methods: 1H MRI-based OXygen Imaging (MOXI) is based on a multi-parametric matrix combination of proton T1, T2, and intravoxel incoherent motion (IVIM) perfusion measurements. Followed by multi-parametric acquisition, pO2 are estimated from the dependence of blood R2 relaxation rate on the inter-echo spacing and weak-field diffusion theory. MOXI can be applied to any routine clinical MRI scanner and it does not require complicated equipment for gas delivery setup. Preclinical and volunteer studies were performed to enhance and validate robust MOXI as a measure of tissue/tumor baseline oxygenation (normal air-breathing) at 3.0 T, 4.7 T, and 7.0 T.
Results: Our preliminary studies indicate that the MOXI technique can non-invasively measure tumor pO2 with validations by 19F MRI and immunohistochemical studies. We found that heterogeneity of perfusion fraction assessed by MRI coincided with the distribution of Hoechst 33342 observed in the excised tumors. We had successfully investigated the feasibility of the non-invasive tissue blood T2-based MOXI technique in the measurement of brain tissue pO2 at 7T and assessed the sensitivity of pO2 measurements in orthotopic U87 gliomas. Tumor hypoxic regions (HF10) measured by pimonidazole staining were in good agreement with the HF10 measured with the MOXI.
Conclusion: This study indicates that the MOXI method appears particularly pertinent and has shown promising in the assessment of oxygen metabolism since it provides quantitative maps of pO2 distributions in tumors non-invasively and avoids the need for any exogenous reporter molecule. MOXI strategy provides a useful tool for assessing tumor microenvironment and its response to various therapies