Category Archives: MRS

In Vivo Hyperpolarized 13C MRS and MRI Applications #DNPNMR

Marco-Rius, Irene, and Arnaud Comment. “In Vivo Hyperpolarized 13C MRS and MRI Applications,” 7:12, 2018.

https://doi.org/10.1002/9780470034590.emrstm1592

The tremendous polarization enhancement afforded by dissolution dynamic nuclear polarization (DNP) can be taken advantage of to perform molecular and metabolic imaging. Following the injection of molecules that are hyperpolarized via dissolution DNP, real-time measurements of their biodistribution and metabolic conversion can be recorded. This technology therefore provides a unique and invaluable tool for probing cellular metabolism in vivo in a noninvasive manner. It gives the opportunity to follow and evaluate disease progression and treatment response without requiring ex vivo destructive tissue assays. Seven sites across the globe are currently performing human studies using hyperpolarized 13C-pyruvate, and several other institutions are on the brink of being ready to inject their first patients. The most promising fields of application of this technology are in oncology and cardiology, and the aim of this article is to provide an overview of some of the current in vivo preclinical and clinical applications of hyperpolarized 13C magnetic resonance spectroscopy and imaging. Some new approaches and potential future developments to improve the hyperpolarized 13C technology are also presented and discussed.

The use of dynamic nuclear polarization 13C-pyruvate MRS in cancer

Gutte, H., et al., The use of dynamic nuclear polarization 13C-pyruvate MRS in cancer. Am J Nucl Med Mol Imaging 2015. 5(5): p. 548-560.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620180/pdf/ajnmmi0005-0548.pdf

In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is 13C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized 13C-pyruvate results in appearance of 13C-lactate, 13C-alanine and 13C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced 13C-pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized 13C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated 13C-lactate/13C-pyruvate ratio in regions of biopsy-proven prostate cancer compared to noncancerous tissue. However, more studies are needed in order to establish use of hyperpolarized 13C MRS imaging of cancer.

Feasibility of multianimal hyperpolarized (13) C MRS

Ramirez, M.S., et al., Feasibility of multianimal hyperpolarized (13) C MRS. Magn Reson Med, 2015. 73(5): p. 1726-32.

http://www.ncbi.nlm.nih.gov/pubmed/24903532

PURPOSE: There is great potential for real-time investigation of metabolism with MRS and hyperpolarized (HP) (13) C agents. Unfortunately, HP technology has high associated costs and efficiency limitations that may constrain in vivo studies involving many animals. To improve the throughput of preclinical investigations, we evaluate the feasibility of performing HP MRS on multiple animals simultaneously. METHODS: Simulations helped assess the viability of a dual-coil strategy for spatially localized multivolume MRS. A dual-mouse system was assembled and characterized with bench- and scanner-based experiments. Enzyme phantoms mixed with HP [1-(13) C] pyruvate emulated real-time metabolism and offered a controlled mechanism for evaluating system performance. Finally, a normal mouse and a mouse bearing a subcutaneous xenograft of colon cancer were simultaneously scanned in vivo using an agent containing HP [1-(13) C] pyruvate. RESULTS: Geometric separation/rotation, active decoupling, and use of low input impedance preamplifiers permitted an encode-by-channel approach for spatially localized MRS. A precalibrated shim allowed straightforward metabolite differentiation in enzyme phantom and in vivo experiments at 7 Tesla, with performance similar to conventional acquisitions. CONCLUSION: The initial feasibility of multi-animal HP (13) C MRS was established. Throughput scales with the number of simultaneously scanned animals, demonstrating the potential for significant improvements in study efficiency.

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