Improving Tumor Hypoxia Location in 18 F-Misonidazole PET with Dynamic Contrast-enhanced MRI Using Quantitative Electron Paramagnetic Resonance Partial Oxygen Pressure Images

Radiol Imaging Cancer. 2021 Mar 26;3(2):e200104. doi: 10.1148/rycan.2021200104. eCollection 2021 Mar.


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 H ) 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 H 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 H 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 H 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 H 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.

Keywords: Animal Studies; Breast; Electron Paramagnetic Resonance; MR-Dynamic Contrast Enhanced; MR-Imaging; Molecular Imaging; Molecular Imaging-Cancer; Oncology; PET/CT; PET/MR; Tumor Mircoenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electron Spin Resonance Spectroscopy
  • Hypoxia / diagnostic imaging
  • Magnetic Resonance Imaging
  • Mice
  • Misonidazole*
  • Oxygen
  • Positron Emission Tomography Computed Tomography
  • Positron-Emission Tomography
  • Tumor Hypoxia*


  • Misonidazole
  • Oxygen