Parameterization of hyperpolarized 13C-bicarbonate-dissolution dynamic nuclear polarization

Scholz, David; Otto, Angela M.; Hintermair, J.; Schilling, Franz; Frank, Alexander; Köllisch, Ulrich; Janich, Martin A.; Schulte, Rolf F.; Schwaiger, Markus; Haase, Axel; Menzel, Marion I.

doi:10.1007/s10334-015-0500-9

Cited by 11 publications

(15 citation statements)

References 16 publications

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“…Hyperpolarized bicarbonate ( 2 ) was the first and so far only ratiometric sensor applied both in vitro and in vivo . A main drawback of the molecule is its short T 1 ( in vivo ∼10 s at both 3 T and 9.4 T,) and a small SNR of 13 CO 2 at physiological pH due to the low p K a , …”

Section: Hyperpolarized Ph Sensor Moleculesmentioning

confidence: 99%

Imaging of Extracellular pH Using Hyperpolarized Molecules

Hundshammer

Düwel

Schilling

2017

Israel Journal of Chemistry

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Many diseases can overrule natural pH regulatory mechanisms and alter the extracellular pH (pHe). A non‐invasive method that resolves pHe in vivo with high spatial and temporal resolution could therefore improve diagnosis and monitoring of diseases, contributing to the concept of precision medicine. During the last decades, several techniques have been proposed to image pHe non‐invasively. The majority of these methods rely on magnetic resonance because of its good spatial resolution, high penetration depth, non‐ionizing radiation and excellent complimentary soft tissue contrast. Dissolution dynamic nuclear polarization (DNP) is an emerging concept to enhance nuclear magnetic resonance (NMR) signals by more than four orders of magnitude, making it possible to observe in vivo metabolic processes in real‐time. Here, we summarize and review recent developments in pHe imaging techniques based on hyperpolarization methods and give an overview of recently discovered hyperpolarized pH sensor molecules that have been applied in vitro and in vivo.

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Section: Hyperpolarized Ph Sensor Moleculesmentioning

confidence: 99%

Imaging of Extracellular pH Using Hyperpolarized Molecules

Hundshammer

Düwel

Schilling

2017

Israel Journal of Chemistry

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“…Nevertheless, these concerns can likely be managed without serious detriment to the gains in SNR attainable with a multi‐excitation approach. One final consideration regarding clinical implementation of pH imaging is that the short BiC–CO 2 T 1 in vivo, measured as ~10 s within various mouse and/or rat tissues at field strengths ranging from 3–14T, may be prohibitive for future translation into patients. It has been suggested that this may be because of fast macromolecular binding–unbinding kinetics, in which case a short interstitial T 1 would be an insurmountable problem.…”

Section: Discussionmentioning

confidence: 99%

“…One final consideration regarding clinical implementation of pH imaging is that the short BiC–CO 2 T 1 in vivo, measured as ~10 s within various mouse and/or rat tissues at field strengths ranging from 3–14T, may be prohibitive for future translation into patients. It has been suggested that this may be because of fast macromolecular binding–unbinding kinetics, in which case a short interstitial T 1 would be an insurmountable problem. However, in humans there may be greater preservation of vascular HP BiC–CO 2 signal before tissue delivery, owing to a slower cardio‐respiratory cycle compared with rodents.…”

Section: Discussionmentioning

confidence: 99%

“…The mainstay molecule for HP pH imaging is HP [ 13 C]bicarbonate (BiC), which calculates pH on a per‐voxel basis by measuring the signal ratio between BiC and CO 2 using a modified Henderson‐Hasselbalch equation . Although some studies have measured intracellular pH in the heart using [ 13 C]bicarbonate and 13 CO 2 liberated from [1‐ 13 C]pyruvate decarboxylation, most studies have injected HP BiC itself to image interstitial pH in tumors, perfused lungs, and other tissues . However, HP BiC has several limitations for pH imaging, including low apparent in vivo T 1 and its sensitivity to field strength and local chemical environment .…”

Section: Introductionmentioning

confidence: 99%

“…Although some studies have measured intracellular pH in the heart using [ 13 C]bicarbonate and 13 CO 2 liberated from [1‐ 13 C]pyruvate decarboxylation, most studies have injected HP BiC itself to image interstitial pH in tumors, perfused lungs, and other tissues . However, HP BiC has several limitations for pH imaging, including low apparent in vivo T 1 and its sensitivity to field strength and local chemical environment . To address these limitations, we and others have sought to enhance signal through the polarization of bicarbonate precursor molecules, or to use alternative HP 13 C imaging agents, including ACES, DEMA, zymonic acid, and amino acid derivatives .…”

Section: Introductionmentioning

confidence: 99%

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Using bidirectional chemical exchange for improved hyperpolarized [¹³C]bicarbonate pH imaging

Korenchan

Gordon

Sukumar

et al. 2019

Magnetic Resonance in Med

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Purpose: Rapid chemical exchange can affect SNR and pH measurement accuracy for hyperpolarized pH imaging with [ 13 C]bicarbonate. The purpose of this work was to investigate chemical exchange effects on hyperpolarized imaging sequences to identify optimal sequence parameters for high SNR and pH accuracy. Methods: Simulations were performed under varying rates of bicarbonate-CO 2 chemical exchange to analyze exchange effects on pH quantification accuracy and SNR under different sampling schemes. Four pulse sequences, including 1 new technique, a multiple-excitation 2D EPI (multi-EPI) sequence, were compared in phantoms using hyperpolarized [ 13 C]bicarbonate, varying parameters such as tip angles, repetition time, order of metabolite excitation, and refocusing pulse design. In vivo hyperpolarized bicarbonate-CO 2 exchange measurements were made in transgenic murine prostate tumors to select in vivo imaging parameters. Results: Modeling of bicarbonate-CO 2 exchange identified a multiple-excitation scheme for increasing CO 2 SNR by up to a factor of 2.7. When implemented in phantom imaging experiments, these sampling schemes were confirmed to yield high pH accuracy and SNR gains. Based on measured bicarbonate-CO 2 exchange in vivo, a 47% CO 2 SNR gain is predicted. Conclusion: The novel multi-EPI pulse sequence can boost CO 2 imaging signal in hyperpolarized 13 C bicarbonate imaging while introducing minimal pH bias, helping to surmount a major hurdle in hyperpolarized pH imaging. K E Y W O R D S bicarbonate, chemical exchange, hyperpolarized 13 C, MRI, NMR spectroscopy pH imaging 960 | KORENCHAN Et Al. | 961 KORENCHAN Et Al.

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Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1‐13C]pyruvate

Lau

Miller

Tyler

2016

Magnetic Resonance in Med

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PurposeTo demonstrate the feasibility of mapping intracellular pH within the in vivo rodent heart. Alterations in cardiac acid‐base balance can lead to acute contractile depression and alterations in Ca2+ signaling. The transient reduction in adenosine triphosphate (ATP) consumption and cardiac contractility may be initially beneficial; however, sustained pH changes can be maladaptive, leading to myocardial damage and electrical arrhythmias.MethodsSpectrally selective radiofrequency (RF) pulses were used to excite the HCO3− and CO2 resonances individually while preserving signal from the injected hyperpolarized [1‐13C]pyruvate. The large flip angle pulses were placed within a three‐dimensional (3D) imaging acquisition, which exploited CA‐mediated label exchange between HCO3− and CO2. Images at 4.5 × 4.5 × 5 mm3 resolution were obtained in the in vivo rodent heart. The technique was evaluated in healthy rodents scanned at baseline and during high cardiac workload induced by dobutamine infusion.ResultsThe intracellular pH was measured to be 7.15 ± 0.04 at baseline, and decreased to 6.90 ± 0.06 following 15 min of continuous β‐adrenergic stimulation.ConclusionsVolumetric maps of intracellular pH can be obtained following an injection of hyperpolarized [1‐13C]pyruvate. The new method is anticipated to enable assessment of stress‐inducible ischemia and potential ventricular arrythmogenic substrates within the ischemic heart. Magn Reson Med 77:1810–1817, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Parameterization of hyperpolarized 13C-bicarbonate-dissolution dynamic nuclear polarization

Abstract: An optimized bicarbonate preparation and experimental procedure provided improved T1 and SNR values, allowing in vitro and in vivo applications.

Cited by 11 publications

References 16 publications

Imaging of Extracellular pH Using Hyperpolarized Molecules

Imaging of Extracellular pH Using Hyperpolarized Molecules

Using bidirectional chemical exchange for improved hyperpolarized [¹³C]bicarbonate pH imaging

Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1‐13C]pyruvate

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Parameterization of hyperpolarized 13C-bicarbonate-dissolution dynamic nuclear polarization

Abstract: An optimized bicarbonate preparation and experimental procedure provided improved T1 and SNR values, allowing in vitro and in vivo applications.

Cited by 11 publications

References 16 publications

Imaging of Extracellular pH Using Hyperpolarized Molecules

Imaging of Extracellular pH Using Hyperpolarized Molecules

Using bidirectional chemical exchange for improved hyperpolarized [13C]bicarbonate pH imaging

Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1‐13C]pyruvate

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Using bidirectional chemical exchange for improved hyperpolarized [¹³C]bicarbonate pH imaging