Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation

Samuel A. Einstein, Bradley P. Weegman, Meri T. Firpo, Klearchos K Papas, Michael Garwood

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 pO2 utilizing 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 pO2 of implanted TEGs. We evaluated six potential MRS pO2 probes and measured their oxygen and temperature sensitivities and their intrinsic R1 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 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. R1 measurements from the TEGs were converted to pO2 values using the established calibration equation and these in vivo pO2 measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO2 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 19F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO2 in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)1009-1017
Number of pages9
JournalTissue Engineering - Part C: Methods
Volume22
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Magnetic resonance spectroscopy
Oxygenation
Magnetic resonance
Grafts
Magnetic Resonance Spectroscopy
Tissue
Transplants
Oxygen
Fiber optics
Calibration
Temperature
Plasmas
Spin-lattice relaxation
Fluorine
Partial Pressure
Dissolved oxygen
Emulsions
Thrombin
Partial pressure
Protons

Keywords

  • F-MRS
  • islet transplantation
  • oximetry
  • oxygen measurement
  • relaxometry
  • tissue-engineered graft

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Bioengineering
  • Biomedical Engineering

Cite this

Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation. / Einstein, Samuel A.; Weegman, Bradley P.; Firpo, Meri T.; Papas, Klearchos K; Garwood, Michael.

In: Tissue Engineering - Part C: Methods, Vol. 22, No. 11, 01.11.2016, p. 1009-1017.

Research output: Contribution to journalArticle

@article{d421030edc924829a1c064a398e8c846,
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 pO2 utilizing 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 pO2 of implanted TEGs. We evaluated six potential MRS pO2 probes and measured their oxygen and temperature sensitivities and their intrinsic R1 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 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. R1 measurements from the TEGs were converted to pO2 values using the established calibration equation and these in vivo pO2 measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO2 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 19F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO2 in vitro and in vivo.",
keywords = "F-MRS, islet transplantation, oximetry, oxygen measurement, relaxometry, tissue-engineered graft",
author = "Einstein, {Samuel A.} and Weegman, {Bradley P.} and Firpo, {Meri T.} and Papas, {Klearchos K} and Michael Garwood",
year = "2016",
month = "11",
day = "1",
doi = "10.1089/ten.tec.2016.0106",
language = "English (US)",
volume = "22",
pages = "1009--1017",
journal = "Tissue Engineering - Part C: Methods",
issn = "1937-3384",
publisher = "Mary Ann Liebert Inc.",
number = "11",

}

TY - JOUR

T1 - Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation

AU - Einstein, Samuel A.

AU - Weegman, Bradley P.

AU - Firpo, Meri T.

AU - Papas, Klearchos K

AU - Garwood, Michael

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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 pO2 utilizing 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 pO2 of implanted TEGs. We evaluated six potential MRS pO2 probes and measured their oxygen and temperature sensitivities and their intrinsic R1 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 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. R1 measurements from the TEGs were converted to pO2 values using the established calibration equation and these in vivo pO2 measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO2 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 19F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO2 in vitro and in vivo.

AB - 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 pO2 utilizing 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 pO2 of implanted TEGs. We evaluated six potential MRS pO2 probes and measured their oxygen and temperature sensitivities and their intrinsic R1 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 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. R1 measurements from the TEGs were converted to pO2 values using the established calibration equation and these in vivo pO2 measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO2 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 19F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO2 in vitro and in vivo.

KW - F-MRS

KW - islet transplantation

KW - oximetry

KW - oxygen measurement

KW - relaxometry

KW - tissue-engineered graft

UR - http://www.scopus.com/inward/record.url?scp=84996614627&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84996614627&partnerID=8YFLogxK

U2 - 10.1089/ten.tec.2016.0106

DO - 10.1089/ten.tec.2016.0106

M3 - Article

VL - 22

SP - 1009

EP - 1017

JO - Tissue Engineering - Part C: Methods

JF - Tissue Engineering - Part C: Methods

SN - 1937-3384

IS - 11

ER -