Abstract
Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however, in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1–13C]pyruvate. Biocompatible formulations of hyperpolarized [1–13C]pyruvate in, both, methanol-water, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as a minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe and scalable molecular imaging.
| Original language | English |
|---|---|
| Article number | 100129 |
| Journal | Journal of Magnetic Resonance Open |
| Volume | 16-17 |
| DOIs | |
| State | Published - Dec 2023 |
Funding
This work was supported by the NSF under grants CHE-1904780 and CHE-1905341 , and the National Institutes of Health (NIH) under R01EB029829 , S10OD021768 , and R21GM137227 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. TT also acknowledges funding from the Goodnight foundation . MSR acknowledges the gracious support of the Kiyomi and Ed Baird MGH Research Scholar Award. We also would like to acknowledge the support from NCSU's METRIC providing access to NMR instrumentation. This material is based upon work supported by the U.S. Department of Energy , Office of Biological and Environmental Research (BER) under Award Number(s) DE-SC0023334. Disclaimer: "This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, appa-ratus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency. This work was supported by the NSF under grants CHE-1904780 and CHE-1905341, and the National Institutes of Health (NIH) under R01EB029829, S10OD021768, and R21GM137227. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. TT also acknowledges funding from the Goodnight foundation. MSR acknowledges the gracious support of the Kiyomi and Ed Baird MGH Research Scholar Award. We also would like to acknowledge the support from NCSU's METRIC providing access to NMR instrumentation. This material is based upon work supported by the U.S. Department of Energy, Office of Biological and Environmental Research (BER) under Award Number(s) DE-SC0023334. Disclaimer: "This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, appa-ratus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency.
Keywords
- Hyperpolarized MRI
- Metabolic imaging
- Parahydrogen
- SABRE