Brain active transmembrane water cycling measured by MR is associated with neuronal activity

Ruiliang Bai, Charles Jr Springer, Dietmar Plenz, Peter J. Basser

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: fMRI is widely used to study brain activity. Unfortunately, conventional fMRI methods assess neuronal activity only indirectly, through hemodynamic coupling. Here, we show that active, steady-state transmembrane water cycling (AWC) could serve as a basis for a potential fMRI mechanism for direct neuronal activity detection. Methods: AWC and neuronal actitivity in rat organotypic cortical cultures were simultaneously measured with a hybrid MR-fluorescence system. Perfusion with a paramagnetic MRI contrast agent, Gadoteridol, allows NMR determination of the kinetics of transcytolemmal water exchange. Changes in intracellular calcium concentration, [Cai 2+] were used as a proxy of neuronal activity and were monitored by fluorescence imaging. Results: When we alter neuronal activity by titrating with extracellular [K+] near the normal value, we see an AWC response resembling Na+-K+-ATPase (NKA) Michaelis-Menten behavior. When we treat with the voltage-gated sodium channel inhibitor, or with an excitatory postsynaptic inhibitor cocktail, we see AWC decrease by up to 71%. AWC was found also to be positively correlated with the basal level of spontaneous activity, which varies in different cultures. Conclusions: These results suggest that AWC is associated with neuronal activity and NKA activity is a major contributor in coupling AWC to neuronal activity. Although AWC comprises steady-state, homeostatic transmembrane water exchange, our analysis also yields a simultaneous measure of the average cell volume, which reports any slower net transmembrane water transport.

Original languageEnglish (US)
JournalMagnetic Resonance in Medicine
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Water
Magnetic Resonance Imaging
Brain
Sodium Channel Blockers
Optical Imaging
Proxy
Cell Size
Contrast Media
Perfusion
Fluorescence
Hemodynamics
Calcium
sodium-translocating ATPase
gadoteridol

Keywords

  • active
  • fMRI
  • functional MRI
  • membrane
  • Na/K ATPase
  • neuronal activity
  • pump
  • transcytolemmal
  • water exchange

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Brain active transmembrane water cycling measured by MR is associated with neuronal activity. / Bai, Ruiliang; Springer, Charles Jr; Plenz, Dietmar; Basser, Peter J.

In: Magnetic Resonance in Medicine, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "Purpose: fMRI is widely used to study brain activity. Unfortunately, conventional fMRI methods assess neuronal activity only indirectly, through hemodynamic coupling. Here, we show that active, steady-state transmembrane water cycling (AWC) could serve as a basis for a potential fMRI mechanism for direct neuronal activity detection. Methods: AWC and neuronal actitivity in rat organotypic cortical cultures were simultaneously measured with a hybrid MR-fluorescence system. Perfusion with a paramagnetic MRI contrast agent, Gadoteridol, allows NMR determination of the kinetics of transcytolemmal water exchange. Changes in intracellular calcium concentration, [Cai 2+] were used as a proxy of neuronal activity and were monitored by fluorescence imaging. Results: When we alter neuronal activity by titrating with extracellular [K+] near the normal value, we see an AWC response resembling Na+-K+-ATPase (NKA) Michaelis-Menten behavior. When we treat with the voltage-gated sodium channel inhibitor, or with an excitatory postsynaptic inhibitor cocktail, we see AWC decrease by up to 71{\%}. AWC was found also to be positively correlated with the basal level of spontaneous activity, which varies in different cultures. Conclusions: These results suggest that AWC is associated with neuronal activity and NKA activity is a major contributor in coupling AWC to neuronal activity. Although AWC comprises steady-state, homeostatic transmembrane water exchange, our analysis also yields a simultaneous measure of the average cell volume, which reports any slower net transmembrane water transport.",
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N2 - Purpose: fMRI is widely used to study brain activity. Unfortunately, conventional fMRI methods assess neuronal activity only indirectly, through hemodynamic coupling. Here, we show that active, steady-state transmembrane water cycling (AWC) could serve as a basis for a potential fMRI mechanism for direct neuronal activity detection. Methods: AWC and neuronal actitivity in rat organotypic cortical cultures were simultaneously measured with a hybrid MR-fluorescence system. Perfusion with a paramagnetic MRI contrast agent, Gadoteridol, allows NMR determination of the kinetics of transcytolemmal water exchange. Changes in intracellular calcium concentration, [Cai 2+] were used as a proxy of neuronal activity and were monitored by fluorescence imaging. Results: When we alter neuronal activity by titrating with extracellular [K+] near the normal value, we see an AWC response resembling Na+-K+-ATPase (NKA) Michaelis-Menten behavior. When we treat with the voltage-gated sodium channel inhibitor, or with an excitatory postsynaptic inhibitor cocktail, we see AWC decrease by up to 71%. AWC was found also to be positively correlated with the basal level of spontaneous activity, which varies in different cultures. Conclusions: These results suggest that AWC is associated with neuronal activity and NKA activity is a major contributor in coupling AWC to neuronal activity. Although AWC comprises steady-state, homeostatic transmembrane water exchange, our analysis also yields a simultaneous measure of the average cell volume, which reports any slower net transmembrane water transport.

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