title: Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation.
abstract: Techniques to monitor the oxygen partial pressure (pO2) within implanted tissue-engineered grafts (TEGs) are critically necessary for TEG development, but current methods are invasive and inaccurate. In this study, we developed an accurate and noninvasive technique to monitor TEG pO2utilizing proton (1H) or fluorine (19F) magnetic resonance spectroscopy (MRS) relaxometry. The value of the spin-lattice relaxation rate constant (R1) of some biocompatible compounds is sensitive to dissolved oxygen (and temperature), while insensitive to other external factors. Through this physical mechanism, MRS can measure the pO2of implanted TEGs. We evaluated six potential MRS pO2probes and measured their oxygen and temperature sensitivities and their intrinsic R1values at 16.4 T. Acellular TEGs were constructed by emulsifying porcine plasma with perfluoro-15-crown-5-ether, injecting the emulsion into a macroencapsulation device, and cross-linking the plasma with a thrombin solution. A multiparametric calibration equation containing R1, pO2, and temperature was empirically generated from MRS data and validated with fiber optic (FO) probes in vitro. TEGs were then implanted in a dorsal subcutaneous pocket in a murine model and evaluated with MRS up to 29 days postimplantation. R1measurements from the TEGs were converted to pO2values using the established calibration equation and these in vivo pO2measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO2within implanted TEGs that received supplemental oxygen delivery. Finally, based on a comparison of our MRS data with previously reported data, ultra-high-field (16.4 T) is shown to have an advantage for measuring hypoxia with19F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO2in vitro and in vivo.
authors.affiliation: 1 Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Einstein
authors.affiliation: 1 Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Weegman
authors.affiliation: 2 Department of Medicine, Stem Cell Institute, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Meri T
authors.initials: MT
authors.lastname: Firpo
authors.affiliation: 3 Department of Surgery, University of Arizona , Tucson, Arizona.
authors.forename: Klearchos K
authors.initials: KK
authors.lastname: Papas
authors.affiliation: 1 Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Michael
authors.initials: M
authors.lastname: Garwood
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D006085:Graft Survival; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D023822:Tissue Engineering
chemical_list: D010100:Oxygen
keywords: 19F-MRS; islet transplantation; oximetry; oxygen measurement; relaxometry; tissue-engineered graft