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Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation.
- Source :
-
Tissue engineering. Part C, Methods [Tissue Eng Part C Methods] 2016 Nov; Vol. 22 (11), pp. 1009-1017. - Publication Year :
- 2016
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Abstract
- Techniques to monitor the oxygen partial pressure (pO <subscript>2</subscript> ) 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 pO <subscript>2</subscript> utilizing proton ( <superscript>1</superscript> H) or fluorine ( <superscript>19</superscript> F) magnetic resonance spectroscopy (MRS) relaxometry. The value of the spin-lattice relaxation rate constant (R <subscript>1</subscript> ) 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 pO <subscript>2</subscript> of implanted TEGs. We evaluated six potential MRS pO <subscript>2</subscript> probes and measured their oxygen and temperature sensitivities and their intrinsic R <subscript>1</subscript> values 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 R <subscript>1</subscript> , pO <subscript>2</subscript> , 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. R <subscript>1</subscript> measurements from the TEGs were converted to pO <subscript>2</subscript> values using the established calibration equation and these in vivo pO <subscript>2</subscript> measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO <subscript>2</subscript> within 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 with <superscript>19</superscript> F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO <subscript>2</subscript> in vitro and in vivo.<br />Competing Interests: Statement No competing financial interests exist.
Details
- Language :
- English
- ISSN :
- 1937-3392
- Volume :
- 22
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Tissue engineering. Part C, Methods
- Publication Type :
- Academic Journal
- Accession number :
- 27758135
- Full Text :
- https://doi.org/10.1089/ten.TEC.2016.0106