Dissolved hyperpolarized xenon‐129 MRI in human kidneys

Abstract

Purpose To assess the feasibility of using dissolved hyperpolarized xenon‐129 (129Xe) MRI to study renal physiology in humans at 3 T. Methods Using a flexible transceiver RF coil, dynamic and spatially resolved 129Xe spectroscopy was performed in the abdomen after inhalation of hyperpolarized 129Xe gas with 3 healthy male volunteers. A transmit‐only receive‐only RF coil array was purpose‐built to focus RF excitation and enhance sensitivity for dynamic imaging of 129Xe uptake in the kidneys using spoiled gradient echo and balanced steady‐state sequences. Results Using spatially resolved spectroscopy, different magnitudes of signal from 129Xe dissolved in red blood cells and tissue/plasma could be identified in the kidneys and the aorta. The spectra from both kidneys showed peaks with similar amplitudes and chemical shift values. Imaging with the purpose‐built coil array was shown to provide more than a 3‐fold higher SNR in the kidneys when compared with surrounding tissues, while further physiological information from the dissolved 129Xe in the lungs and in transit to the kidneys was provided with the transceiver coil. The signal of dissolved hyperpolarized 129Xe could be imaged with both tested sequences for about 40 seconds after inhalation. Conclusion The uptake of 129Xe dissolved in the human kidneys was measured with spectroscopic and imaging experiments, demonstrating the potential of hyperpolarized 129Xe MR as a novel, noninvasive technique to image human kidney tissue perfusion.

Functionalized Lipopeptide Micelles as Highly Efficient NMR Depolarization Seed Points for Targeted Cell Labelling in Xenon MRI

“…Hyper‐CEST enables a switchable Xe MRI contrast through radiofrequency (RF)‐activated saturation transfer, i.e., a controlled depolarization that propagates rapidly into the bulk magnetization pool. MRI of well perfused organs with dissolved Xe from inhalation has made important progress that demonstrates the potential for such a targeted vascular reporter 23–25. The self‐assembling micelle approach with a core of multiple hosts that are accessible for Xe but shielded from other interactions is very promising compared to the administration of individual, bare Xe hosts that have several shortcomings: examples such as cucurbit[6]uril (CB6) are problematic since they are accessible for competitive guests and are difficult to functionalize.…”

“…We consider P‐CrA‐A2 micelles highly promising as future potential MRI reporters for the monitoring of highly vascularized brain regions such as tumors. Clinical lung imaging with Xe is already quite established and has recently been expanded by novel applications for mapping the Xe distribution in other organs like the human brain23,24,53 as well as the kidneys 25. It has benefitted from technical improvements found in modern polarizers,54 optimized RF antenna systems,55,56 and adapted readout protocols that will ultimately also enable (pre)clinical Hyper‐CEST studies.…”

“…MRI of well perfused organs with dissolved Xe from inhalation has made important progress that demonstrates the potential for such a targeted vascular reporter. [23][24][25] The self-assembling micelle approach with a core of multiple hosts that are accessible for Xe but shielded from other interactions is very promising compared to the administration of individual, bare Xe hosts that have several shortcomings: examples such as cucurbit [6]uril (CB6) are problematic since they are accessible for competitive guests and are difficult to functionalize. Thus, they currently require unrealistic high (mM) concentrations for in vivo applications.…”

“…Clinical lung imaging with Xe is already quite established and has recently been expanded by novel applications for mapping the Xe distribution in other organs like the human brain [23,24,53] as well as the kidneys. [25] It has benefitted from technical improvements found in modern polarizers, [54] optimized RF antenna systems, [55,56] and adapted readout protocols that will ultimately also enable (pre)clinical Hyper-CEST studies. Given such further advancements in MRI of 129 Xe dissolved in tissue, this type of reporter would enable a first meaningful in vivo application of Hyper-CEST with the potential for novel insights beyond targets detectable with existing contrast agents.…”

Probing Reversible Guest Binding with Hyperpolarized 129Xe-NMR: Characteristics and Applications for Cucurbit[n]urils

“…The feasibility for such conditions, including macromolecular Xe hosts with relatively fast exchange, has been demonstrated with a pharmacokinetic model for brain tissue [221]. Further translation of these concepts also benefits from recent advancements regarding Xe MRI beyond the gas phase: Detection in other organs like the human brain [222][223][224] as well as the kidneys [225] has become achievable. The potential of such supramolecular systems for diagnostic purposes is evident and together with the drug delivery strategies that are pursued for CB[n]s and related compounds, Xe NMR/MRI could make an important contribution to comprehensive therapeutic and diagnostic approaches.…”