Original Research

²³Na Triple-quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra- and extracellular signal

Corresponding Author

Michaela A.U. Hoesl MS

[email protected]

orcid.org/0000-0002-9177-1470

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Address reprint requests to: M.A.U.H., Computer Assisted Clinical Medicine, Heidelberg University, 68167 Mannheim, Germany. E-mail: [email protected]Search for more papers by this author

Dennis Kleimaier MS,

Dennis Kleimaier MS

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

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Ruomin Hu MS,

Ruomin Hu MS

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

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Matthias Malzacher MS,

Matthias Malzacher MS

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

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Cordula Nies,

Cordula Nies

Institute of Functional Interfaces, Karlsruhe Institute of Technology, Karlsruhe, Germany

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Eric Gottwald PhD,

Eric Gottwald PhD

Institute of Functional Interfaces, Karlsruhe Institute of Technology, Karlsruhe, Germany

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Lothar R. Schad PhD,

Lothar R. Schad PhD

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

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Michaela A.U. Hoesl MS,

Corresponding Author

Michaela A.U. Hoesl MS

[email protected]

orcid.org/0000-0002-9177-1470

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Address reprint requests to: M.A.U.H., Computer Assisted Clinical Medicine, Heidelberg University, 68167 Mannheim, Germany. E-mail: [email protected]Search for more papers by this author

Dennis Kleimaier MS,

Dennis Kleimaier MS

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Search for more papers by this author

Ruomin Hu MS,

Ruomin Hu MS

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Search for more papers by this author

Matthias Malzacher MS,

Matthias Malzacher MS

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Search for more papers by this author

Cordula Nies,

Cordula Nies

Institute of Functional Interfaces, Karlsruhe Institute of Technology, Karlsruhe, Germany

Search for more papers by this author

Eric Gottwald PhD,

Eric Gottwald PhD

Institute of Functional Interfaces, Karlsruhe Institute of Technology, Karlsruhe, Germany

Search for more papers by this author

Lothar R. Schad PhD,

Lothar R. Schad PhD

Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

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First published: 25 January 2019

https://doi.org/10.1002/jmri.26666

Citations: 12

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Abstract

Background

Triple-quantum (TQ) filtered sequences have become more popular in sodium MR due to the increased usage of scanners with field strengths exceeding 3T. Disagreement as to whether TQ signal can provide separation of intra- and extracellular compartments persists.

Purpose

To provide insight into TQ signal behavior on a cellular level.

Study Type

Prospective.

Phantom/Specimen

Cell-phantoms in the form of liposomes, encapsulated 0 mM, 145 mM, 154 mM Na+ in a double-lipid membrane similar to cells. Poly(lactic-co-glycolic acid) nanoparticles encapsulated 154 mM Na+ within a single-layer membrane structure. Two microcavity chips with each 6 × 10⁶ human HEP G2 liver cells were measured in an MR-compatible bioreactor.

Field Strength/Sequence

Spectroscopic TQ sequence with time proportional phase-increments at 9.4T.

Assessment

The TQ signal of viable, dead cells, and cell-phantoms was assessed by a fit in the time domain and by the amplitude in the frequency domain.

Statistical Tests

The noise variance (σ) was evaluated to express the deviation of the measured TQ signal amplitude from noise.

Results

TQ signal >20σ was found for liposomes encapsulating sodium ions. Liposomal encapsulation of 0 mM Na+ and 154 mM Na+ encapsulation in the nanoparticles resulted in <2σ TQ signal. Cells under normal perfusion resulted in >9σ TQ signal. Compared with TQ signal under normal perfusion, a 56% lower TQ signal of was observed (25σ) during perfusion stop. TQ signal returned to 92% of the initial signal after reperfusion.

Data Conclusion

Our measurements indicate that TQ signal in liposomes was observed due to the trapping of ions within the double-lipid membrane rather than from the intraliposomal space. Transfer to the cell results suggests that TQ signal was observed from motion restriction equivalent to trapping.

Level of Evidence: 1

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2019;50:435–444.

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Citing Literature

Volume50, Issue2

August 2019

Pages 435-444

²³Na Triple-quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra- and extracellular signal

Abstract

Background

Purpose

Study Type

Phantom/Specimen

Field Strength/Sequence

Assessment

Statistical Tests

Results

Data Conclusion

References

Citing Literature

References

Information

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23Na Triple-quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra- and extracellular signal

Abstract

Background

Purpose

Study Type

Phantom/Specimen

Field Strength/Sequence

Assessment

Statistical Tests

Results

Data Conclusion

References

Citing Literature

References

Related

Information

²³Na Triple-quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra- and extracellular signal