Human whole-blood 1H2O longitudinal relaxation with normal and high-relaxivity contrast reagents: Influence of trans-cell-membrane water exchange

Gregory J. Wilson, Mark Woods, Charles Jr Springer, Sarah Bastawrous, Puneet Bhargava, Jeffrey H. Maki

Research output: Contribution to journalArticle

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Abstract

Purpose: Accurate characterization of contrast reagent (CR) longitudinal relaxivity in whole blood is required to predict arterial signal intensity in contrast-enhanced MR angiography (CE-MRA). This study measured the longitudinal relaxation rate constants (R1) over a concentration range for non-protein-binding and protein-binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0 Tesla (T) under physiologic arterial conditions.

Methods: Relaxivities of gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from 0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be expected in CE-MRA.

Results: In plasma, the 1H2O R2 [CR]-dependence was nonlinear for gadobenate and gadofosveset secondary to CR interactions with the serum macromolecule albumin, and was well described by an analytical expression for effective 1:1 binding stoichiometry. In whole blood, the 1H2O R2 [CR]-dependence was markedly non-linear for all CRs, and was well-predicted by an expression for equilibrium exchange of water molecules between plasma and intracellular spaces using a priori parameter values only.

Conclusion: In whole blood, 2H2O R1 exhibits a nonlinear relationship with [CR] over 0 to 18 mM CR. The nonlinearity is well described by exchange of water between erythrocyte and plasma compartments, and is particularly evident for high relaxivity CRs.

Original languageEnglish (US)
Pages (from-to)1746-1754
Number of pages9
JournalMagnetic Resonance in Medicine
Volume72
Issue number6
DOIs
StatePublished - Dec 1 2014

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Cell Membrane
Water
Angiography
Intracellular Space
Protein Binding
Serum Albumin
Longitudinal Studies
Carrier Proteins
Erythrocytes

Keywords

  • Contrast agents
  • MR angiography
  • MRI
  • Relaxation rate constant
  • Relaxation time constant

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Human whole-blood 1H2O longitudinal relaxation with normal and high-relaxivity contrast reagents : Influence of trans-cell-membrane water exchange. / Wilson, Gregory J.; Woods, Mark; Springer, Charles Jr; Bastawrous, Sarah; Bhargava, Puneet; Maki, Jeffrey H.

In: Magnetic Resonance in Medicine, Vol. 72, No. 6, 01.12.2014, p. 1746-1754.

Research output: Contribution to journalArticle

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AU - Maki, Jeffrey H.

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N2 - Purpose: Accurate characterization of contrast reagent (CR) longitudinal relaxivity in whole blood is required to predict arterial signal intensity in contrast-enhanced MR angiography (CE-MRA). This study measured the longitudinal relaxation rate constants (R1) over a concentration range for non-protein-binding and protein-binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0 Tesla (T) under physiologic arterial conditions.Methods: Relaxivities of gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from 0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be expected in CE-MRA.Results: In plasma, the 1H2O R2 [CR]-dependence was nonlinear for gadobenate and gadofosveset secondary to CR interactions with the serum macromolecule albumin, and was well described by an analytical expression for effective 1:1 binding stoichiometry. In whole blood, the 1H2O R2 [CR]-dependence was markedly non-linear for all CRs, and was well-predicted by an expression for equilibrium exchange of water molecules between plasma and intracellular spaces using a priori parameter values only.Conclusion: In whole blood, 2H2O R1 exhibits a nonlinear relationship with [CR] over 0 to 18 mM CR. The nonlinearity is well described by exchange of water between erythrocyte and plasma compartments, and is particularly evident for high relaxivity CRs.

AB - Purpose: Accurate characterization of contrast reagent (CR) longitudinal relaxivity in whole blood is required to predict arterial signal intensity in contrast-enhanced MR angiography (CE-MRA). This study measured the longitudinal relaxation rate constants (R1) over a concentration range for non-protein-binding and protein-binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0 Tesla (T) under physiologic arterial conditions.Methods: Relaxivities of gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from 0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be expected in CE-MRA.Results: In plasma, the 1H2O R2 [CR]-dependence was nonlinear for gadobenate and gadofosveset secondary to CR interactions with the serum macromolecule albumin, and was well described by an analytical expression for effective 1:1 binding stoichiometry. In whole blood, the 1H2O R2 [CR]-dependence was markedly non-linear for all CRs, and was well-predicted by an expression for equilibrium exchange of water molecules between plasma and intracellular spaces using a priori parameter values only.Conclusion: In whole blood, 2H2O R1 exhibits a nonlinear relationship with [CR] over 0 to 18 mM CR. The nonlinearity is well described by exchange of water between erythrocyte and plasma compartments, and is particularly evident for high relaxivity CRs.

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