NMR shutter-speed elucidates apparent population inversion of 1 H 2 O signals due to active transmembrane water cycling

Xin Li, Silvia Mangia, Jing Huei Lee, Ruiliang Bai, Charles S. Springer

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Purpose: The desire to quantitatively discriminate the extra- and intracellular tissue 1H2O MR signals has gone hand-in-hand with the continual, historic increase in MRI instrument magnetic field strength [B0]. However, recent studies have indicated extremely valuable, novel metabolic information can be readily accessible at ultra–low B0. The two signals can be distinguished, and the homeostatic activity of the cell membrane sodium/potassium pump (Na+,K+,ATPase) detected. The mechanism allowing 1H2O MRI to do this is the newly discovered active transmembrane water cycling (AWC) phenomenon, which we found using paramagnetic extracellular contrast agents at clinical B0 values. AWC is important because Na+,K+,ATPase can be considered biology’s most vital enzyme, and its in vivo steady-state activity has not before been measurable, let alone amenable to mapping with high spatial resolution. Recent reports indicate AWC correlates with neuronal firing rate, with malignant tumor metastatic potential, and inversely with cellular reducing equivalent fraction. We wish to systematize the ways AWC can be precisely measured. Methods: We present a theoretical longitudinal relaxation analysis of considerable scope: it spans the low- and high–field situations. Results: We show the NMR shutter-speed organizing principle is pivotal in understanding how trans–membrane steady–state water exchange kinetics are manifest throughout the range. Our findings illuminate an aspect, apparent population inversion, which is crucial in understanding ultra-low field results. Conclusions: Without an appreciation of apparent population inversion, significant misinterpretations of future data are likely. These could have unfortunate diagnostic consequences.

Original languageEnglish (US)
Pages (from-to)411-424
Number of pages14
JournalMagnetic resonance in medicine
Volume82
Issue number1
DOIs
StatePublished - Jul 2019

Bibliographical note

Funding Information:
We thank Eric Baker, Thomas Barbara, Peter Basser, Michael Garwood, Erin Gilbert, Wei Huang, Shalom Michaeli, Martin Pike, William Rooney, Christopher Sotak, Lawrence Wald, Gregory Wilson, and Mark Woods for stimulating discussions, as well as Gangxu Han for Figure 3. X.L. and C.S.S. were supported in part by the Brenden–Colson Center for Pancreatic Care and the OHSU Advanced Imaging Research Center.

Funding Information:
information Brenden-Colsen Center for Pancreatic Care; Advanced Imaging Research CenterWe thank Eric Baker, Thomas Barbara, Peter Basser, Michael Garwood, Erin Gilbert, Wei Huang, Shalom Michaeli, Martin Pike, William Rooney, Christopher Sotak, Lawrence Wald, Gregory Wilson, and Mark Woods for stimulating discussions, as well as Gangxu Han for Figure. X.L. and C.S.S. were supported in part by the Brenden?Colson Center for Pancreatic Care and the OHSU Advanced Imaging Research Center.

Publisher Copyright:
© 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • active water cycling
  • apparent population-inversion
  • shutter-speed

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