Renal ischemia and reperfusion assessment with three‐dimensional hyperpolarized <sup>13</sup>C,<sup>15</sup>N2‐urea

Nielsen, Per Mose; Hansen, Esben Søvsø Szocska; Nørlinger, Thomas Stokholm; Nørregaard, Rikke; Bertelsen, Lotte Bonde; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

doi:10.1002/mrm.26377

Cited by 41 publications

(51 citation statements)

References 37 publications

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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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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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“…Several complementary MRI techniques have previously demonstrated promising results for AKI monitoring. Conventional perfusion imaging using either arterial spin labeling or contrast agents, have demonstrated reduced perfusion in the post-ischemic kidney4041, similarly recently found with hyperpolarized 13 C-urea42. Diffusion weighted imaging (DWI), a well-suited imaging marker of renal complications have shown diffusion restrictions already at onset of AKI and this restriction is associate with the severity of AKI, inflammatory cell infiltration and interstitial renal fibrosis43.…”

Section: Discussionmentioning

confidence: 86%

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

Nielsen

Eldirdiri

Bertelsen

et al. 2017

Sci Rep

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Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), and at present, there is a lack of reliable biomarkers that can diagnose AKI and measure early progression because the commonly used methods cannot evaluate single-kidney IRI. Hyperpolarized [1,4-13C2]fumarate conversion to [1,4-13C2]malate by fumarase has been proposed as a measure of necrosis in rat tumor models and in chemically induced AKI rats. Here we show that the degradation of cell membranes in connection with necrosis leads to elevated fumarase activity in plasma and urine and secondly that hyperpolarized [1,4-13C2]malate production 24 h after reperfusion correlates with renal necrosis in a 40-min unilateral ischemic rat model. Fumarase activity screening on bio-fluids can detect injury severity, in bilateral as well as unilateral AKI models, differentiating moderate and severe AKI as well as short- and long-term AKI. Furthermore after verification of renal injury by bio-fluid analysis the precise injury location can be monitored by in vivo measurements of the fumarase activity non-invasively by hyperpolarized [1,4-13C]fumarate MR imaging. The combined in vitro and in vivo biomarker of AKI responds to the essential requirements for a new reliable biomarker of AKI.

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“…Furthermore, 3D isotropic imaging is most desirable due to the ability to limit patient scanning, while simultaneously acquiring all the desired information in all three planes [76]. Recently, work by Nielsen et al [77] and Bertelsen et al [78] demonstrated 1.25 mm isotropic resolution imaging of [ 13 C, 15 N 2 ]urea with a 3D bSSFP sequence in rat kidneys on a 9.4T preclinical scanner with higher performance gradients enabling shorter achievable TRs. This allowed high spatial resolutions to be achieved.…”

Section: Discussionmentioning

confidence: 99%

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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Renal ischemia and reperfusion assessment with three‐dimensional hyperpolarized ¹³C,¹⁵N2‐urea

Cited by 41 publications

References 37 publications

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

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

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

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

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Renal ischemia and reperfusion assessment with three‐dimensional hyperpolarized 13C,15N2‐urea

Cited by 41 publications

References 37 publications

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

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

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

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

Contact Info

Product

Resources

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Renal ischemia and reperfusion assessment with three‐dimensional hyperpolarized ¹³C,¹⁵N2‐urea

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

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