Hyperpolarized 13C,15N2‐<scp>U</scp>rea <scp>MRI</scp> for assessment of the urea gradient in the porcine kidney

Hansen, Esben Søvsø Szocska; Stewart, Neil J.; Wild, Jim M.; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

doi:10.1002/mrm.26483

Cited by 29 publications

(38 citation statements)

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“…Nevertheless, both sets of results demonstrate the feasibility of obtaining approximately 1 mm isotropic resolution for hyperpolarized 13 C compounds, especially on 3T clinical scanners, as was recently demonstrated in [45]. Recent work on [ 13 C, 15 N 2 ]urea imaging on pigs at 3T [79] shows feasibility of imaging larger animals, although at a considerably coarser spatial resolution.…”

Section: Discussionsupporting

confidence: 61%

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques

Milshteyn

Morze

Reed

et al. 2017

Magnetic Resonance Imaging

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The goal of this project was to develop and apply techniques for T2 mapping and 3D high resolution (1.5 mm isotropic; 0.003 cm3) 13C imaging of hyperpolarized (HP) probes [1-13C]lactate, [1-13C]pyruvate, [2-13C]pyruvate, and [13C,15N2]urea in vivo. A specialized 2D bSSFP sequence was implemented on a clinical 3T scanner and used to obtain the first high resolution T2 maps of these different hyperpolarized compounds in both rats and tumor-bearing mice. These maps were first used to optimize timings for highest SNR for single time-point 3D bSSFP acquisitions with a 1.5 mm isotropic spatial resolution of normal rats. This 3D acquisition approach was extended to serial dynamic imaging with 2-fold compressed sensing acceleration without changing spatial resolution. The T2 mapping experiments yielded measurements of T2 values of greater than 1 s for all compounds within rat kidneys/vasculature and TRAMP tumors, except for [2-13C]pyruvate which was ~730 ms and ~320 ms, respectively. The high resolution 3D imaging enabled visualization the biodistribution of [1-13C]lactate, [1-13C]pyruvate, and [2-13C]pyruvate within different kidney compartments as well as in the vasculature. While the mouse anatomy is smaller, the resolution was also sufficient to image the distribution of all compounds within kidney, vasculature, and tumor. The development of the specialized 3D sequence with compressed sensing provided improved structural and functional assessments at a high (0.003 cm3) spatial and 2 s temporal resolution in vivo utilizing HP 13C substrates by exploiting their long T2 values. This 1.5 mm isotropic resolution is comparable to 1H imaging and application of this approach could be extended to future studies of uptake, metabolism, and perfusion in cancer and other disease models and may ultimately be of value for clinical imaging.

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Section: Discussionsupporting

confidence: 61%

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques

Milshteyn

Morze

Reed

et al. 2017

Magnetic Resonance Imaging

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“…In 2012, von Morze et al followed the fate of carbon‐13 labeled urea in the rat kidney, visualizing the intrarenal distribution of urea in concert with the urine concentration mechanism. These results have since then been confirmed by others in various renal disease models and been translated to the multi‐papillary kidney in pigs . In this study, we investigate the effect of glucagon on urea permeability in vivo in the rat kidney with hyperpolarized [ 13 C, 15 N]urea.…”

Section: Introductionsupporting

confidence: 60%

Glucagon infusion alters the hyperpolarized ¹³C‐urea renal hemodynamic signature

Mariager

Nielsen

et al. 2018

NMR in Biomedicine

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Renal urea handling is central to the urine concentrating mechanism, and as such the ability to image urea transport in the kidney is an important potential imaging biomarker for renal functional assessment. Glucagon levels associated with changes in dietary protein intake have been shown to influence renal urea handling; however, the exact mechanism has still to be fully understood. Here we investigate renal function and osmolite distribution using [13C,15N] urea dynamics and 23Na distribution before and 60 min after glucagon infusion in six female rats. Glucagon infusion increased the renal [13C,15N] urea mean transit time by 14%, while no change was seen in the sodium distribution, glomerular filtration rate or oxygen consumption. This change is related to the well‐known effect of increased urea excretion associated with glucagon infusion, independent of renal functional effects. This study demonstrates for the first time that hyperpolarized 13C‐urea enables monitoring of renal urinary excretion effects in vivo.

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“…CINE‐LVF was quantified with the freely available research tool Segment version 1.9 R3697 (http://segment.heiberg.se). No RF compensation was used in this study, as B 1 has been shown previously to be adequate to image the whole abdomen with sufficient signal . Statistics were performed with one‐way analysis of variance (ANOVA), with post hoc Holm–Sidak's multiple comparisons test in Prism (GraphPad Software, Inc., La Jolla, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1‐¹³C]pyruvate study

et al. 2017

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Cardiac metabolism has received considerable attention in terms of both diagnostics and prognostics, as well as a novel target for treatment. As human trials involving hyperpolarized magnetic resonance in the heart are imminent, we sought to evaluate the general feasibility of detection of an imposed shift in metabolic substrate utilization during metabolic modulation with glucose-insulin-potassium (GIK) infusion, and thus the limitations associated with this strategy, in a large animal model resembling human physiology. Four [1- C]pyruvate injections did not alter the blood pressure or ejection fraction over 180 min. Hyperpolarized [1- C]pyruvate conversion showed a generally high reproducibility, with intraclass correlation coefficients between the baseline measurements at 0 and 30 min as follows: lactate to pyruvate, 0.85; alanine to pyruvate, 1.00; bicarbonate to pyruvate, 0.83. This study demonstrates that hyperpolarized [1- C]pyruvate imaging is a feasible technique for cardiac studies and shows a generally high reproducibility in fasted large animals. GIK infusion increases the metabolic conversion of pyruvate to its metabolic derivatives lactate, alanine and bicarbonate, but with increased variability.

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Hyperpolarized ¹³C,¹⁵N₂‐Urea MRI for assessment of the urea gradient in the porcine kidney

Cited by 29 publications

References 29 publications

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques

Glucagon infusion alters the hyperpolarized ¹³C‐urea renal hemodynamic signature

Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1‐¹³C]pyruvate study

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Hyperpolarized 13C,15N2‐Urea MRI for assessment of the urea gradient in the porcine kidney

Cited by 29 publications

References 29 publications

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques

Glucagon infusion alters the hyperpolarized 13C‐urea renal hemodynamic signature

Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1‐13C]pyruvate study

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Product

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Hyperpolarized ¹³C,¹⁵N₂‐Urea MRI for assessment of the urea gradient in the porcine kidney

Glucagon infusion alters the hyperpolarized ¹³C‐urea renal hemodynamic signature

Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1‐¹³C]pyruvate study