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Updated: Nov 10, 2025
Tumor Hypoxia Assessment: In Vivo 3D Oxygen Imaging Through Electron Paramagnetic Resonance
Published on: February 14, 2025
Improving Tumor Hypoxia Location in 18F-Misonidazole PET with Dynamic Contrast-enhanced MRI Using Quantitative
Inna Gertsenshteyn1, Boris Epel1, Eugene Barth1
1Department of Radiology (I.G., X.F., H.K., R.F., M.B., A.K., G.K., C.M.K., C.T.C.), National Institutes of Health Center for Electron Paramagnetic Resonance Imaging in Vivo Physiology (I.G., B.E., E.B., D.B., S.S., H.H.), Department of Radiation and Cellular Oncology (I.G., B.E., E.B., D.B., H.H.), Integrated Small Animal Imaging Research Resource (L.L., E.M., H.M.T., X.F., D.B., M.Z., C.M.K., C.T.C.), and Department of Public Health Sciences (M.G.), University of Chicago, 5841 S Maryland Ave, MC-2026, Chicago, IL 60637.
Purpose:
To enhance the spatial accuracy of fluorine 18 (18F) misonidazole (MISO) PET imaging of hypoxia by using dynamic contrast-enhanced (DCE) MR images as a basis for modifying PET images and by using electron paramagnetic resonance (EPR) partial oxygen pressure (pO2) as the reference standard.
Materials And Methods:
Mice (n = 10) with leg-borne MCa4 mammary carcinomas underwent EPR imaging, T2-weighted and DCE MRI, and 18F-MISO PET/CT. Images were registered to the same space for analysis. The thresholds of hypoxia for PET and EPR images were tumor-to-muscle ratios greater than or equal to 2.2 mm Hg and less than or equal to 14 mm Hg, respectively. The Dice similarity coefficient (DSC) and Hausdorff distance (d ) were used to quantify the three-dimensional overlap of hypoxia between pO2 EPR and 18F-MISO PET images. A training subset (n = 6) was used to calculate optimal DCE MRI weighting coefficients to relate EPR to the PET signal; the group average weights were then applied to all tumors (from six training mice and four test mice). The DSC and d were calculated before and after DCE MRI-corrected PET images were obtained to quantify the improvement in overlap with EPR pO2 images for measuring tumor hypoxia.
Results:
The means and standard deviations of the DSC and d between hypoxic regions in original PET and EPR images were 0.35 mm ± 0.23 and 5.70 mm ± 1.7, respectively, for images of all 10 mice. After implementing a preliminary DCE MRI correction to PET data, the DSC increased to 0.86 mm ± 0.18 and the d decreased to 2.29 mm ± 0.70, showing significant improvement (P < .001) for images of all 10 mice. Specifically, for images of the four independent test mice, the DSC improved with correction from 0.19 ± 0.28 to 0.80 ± 0.29 (P = .02), and the d improved from 6.40 mm ± 2.5 to 1.95 mm ± 0.63 (P = .01).
Conclusion:
Using EPR information as a reference standard, DCE MRI information can be used to correct 18F-MISO PET information to more accurately reflect areas of hypoxia.Keywords: Animal Studies, Molecular Imaging, Molecular Imaging-Cancer, PET/CT, MR-Dynamic Contrast Enhanced, MR-Imaging, PET/MR, Breast, Oncology, Tumor Mircoenvironment, Electron Paramagnetic ResonanceSupplemental material is available for this article.© RSNA, 2021.
Insights
Dynamic contrast-enhanced MRI corrects fluorine-18 MISO PET imaging for more accurate hypoxia detection. This improves spatial accuracy in tumor microenvironment analysis, aiding cancer research.
Area of Science:
- Molecular imaging
- Oncology
- Tumor microenvironment
Background:
- Hypoxia is crucial in cancer, impacting treatment response and prognosis.
- Accurate spatial mapping of tumor hypoxia is essential for effective cancer therapy.
Purpose of the Study:
- To improve the spatial accuracy of fluorine-18 (18F) misonidazole (MISO) PET imaging for hypoxia detection.
- To utilize dynamic contrast-enhanced (DCE) MRI to correct PET images, using electron paramagnetic resonance (EPR) pO2 as the reference standard.
Main Methods:
- Mice with mammary carcinomas underwent EPR imaging, DCE MRI, and 18F-MISO PET/CT.
- Image registration and analysis quantified hypoxia overlap using Dice Similarity Coefficient (DSC) and Hausdorff distance (d).
- DCE MRI weighting coefficients were calculated to correct PET data.
Main Results:
- Initial PET and EPR hypoxia overlap showed a Dice Similarity Coefficient (DSC) of 0.35 ± 0.23.
- After DCE MRI correction, DSC significantly improved to 0.86 ± 0.18 (P < .001).
- Hausdorff distance significantly decreased from 5.70 ± 1.7 mm to 2.29 ± 0.70 mm post-correction.
Conclusions:
- DCE MRI can effectively correct 18F-MISO PET imaging for enhanced spatial accuracy of hypoxia.
- This combined approach provides a more precise method for assessing tumor hypoxia.
- The findings support improved molecular imaging for oncology and tumor microenvironment studies.
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