Gertsenshteyn I, Epel B, Barth E, Leoni L, Markiewicz E, Tsai HM, Fan X, Giurcanu M, Bodero D, Zamora M, Sundramoorthy S, Kim H, Freifelder R, Bhuiyan M, Kucharski A, Karczmar G, Kao CM, Halpern H, and Chen CT
Purpose: To enhance the spatial accuracy of fluorine 18 ( 18 F) 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 (pO 2 ) 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 18 F-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 pO 2 EPR and 18 F-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 pO 2 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 18 F-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 Resonance Supplemental material is available for this article. © RSNA, 2021., Competing Interests: Disclosures of Conflicts of Interest: I.G. disclosed no relevant relationships. B.E. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: co-owner of O2M Technologies, a company that fabricates EPR imaging instruments. No O2M instruments, IP, or technology was used in the present work. E.B. disclosed no relevant relationships. L.L. disclosed no relevant relationships. E.M. disclosed no relevant relationships. H.M.T. disclosed no relevant relationships. X.F. disclosed no relevant relationships. M.G. disclosed no relevant relationships. D.B. Activities related to the present article: National Cancer Institute grant R01CA236385 was used to partially fund the author’s salary for this project. Activities not related to the present article: money from O2M Technologies paid was part of the author’s transition to employment with O2M. These funds were not a part of the relevant work. Other relationships: disclosed no relevant relationships. M.Z. disclosed no relevant relationships. S.S. disclosed no relevant relationships. H.K. disclosed no relevant relationships. R.F. disclosed no relevant relationships. M.B. disclosed no relevant relationships. A.K. disclosed no relevant relationships. G.K. disclosed no relevant relationships. C.M.K. disclosed no relevant relationships. H.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: Inventor of several patents, including Magnetic Resonance Analysis of Substances in Samples that Include Dissipative Material (inventor: Howard Halpern; patent no.: 4,714,886); Selective Isotopic Labelling of Spin Labels for Electron Resonance Spectroscopy (inventors: Howard Halpern, Beverly A. Teicher; patent no.: 5,431,901) Imaging system performing substantially exact reconstruction and using non-traditional trajectories (inventors: Pan X, Zou, Yu, Yu L, Kao; C-M, King M, Giger M, Xia D, Halpern H, Pelizzari C, Sidky E, Cho S; patent no: 7,444,011); High isolation transmit/receive surface coils and method for EPRI (inventor: Halpern H; patent no. 8,644,955); T1-Senstivie inversion recovery-imaging method and apparatus for EPRI (inventors: Halpern H, Epel B; patent no.: 9,392,957); Method and apparatus for resonator signal production and measurement (inventors: Halpern H, Sundramoorthy S, Epel B; patent no.:10,551,450B2); Method and high isolation transmit/receive surface coils for EPRI (inventor: Howard J. Halpern; patent no.: 10,568,537); and Alderman-Grant/Loop-Gap High Isolation Crossed Field Bimodal Resonator (inventors: Halpern H, Epel B, Sundramoorthy S; submitted: 4/12/2011). C.T.C. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: royalties and stock options from RefleXion Medical, which is licensed from the University of Chicago for the author’s patent on PET or SPECT-guided radiation therapy. Other relationships: disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)