Category Archives: Hyperpolarization

[NMR] ABSTRACT DEADLINE EXTENDED for PERM 2020: the first Parahydrogen Enhanced Resonance Meeting

CALL FOR ABSTRACTS

(Virtual) Parahydrogen Enhanced Resonance Meeting 2020

1st annual PERM, Monday, July 27th- Wednesday, July 29th on Zoom

http://perm-conference.org/

We would like to invite you to submit an abstract to the first annual Parahydrogen Enhanced Resonance Meeting, PERM 2020. The first instance of this (PERManent) meeting will be online with the benefit of zero registration cost. Not only are we making hyperpolarization affordable, but also the scientific conferences that go along with it! The meeting will feature invited educational talks, promoted research talks, plus brief “power pitches” that may provide previews to virtual poster sessions organized in parallel zoom meetings. (Food and Drinks will have to be provided privately.) All recorded materials will be made publicly available on a PERM YouTube channel within 2 weeks after the conference. Students (and those new to parahydrogen-enhanced NMR/MRI) are especially encouraged to participate!

Please submit an abstract (pdf format) with a maximum of 300 words in 12pt font along with 1 Figure (plus title and author list) to the PERM Organization Committee by Monday, June 1st 2020 – detailed abstract instructions will be posted on the conference web-site soon. Please indicate whether you are willing to have your lecture/power pitch recorded. If yes, your recorded lecture will be featured on the conference’s YouTube channel (PERManently).

Important dates:

Abstract Deadline (extended): Monday, June 8th

Invitations for Presentations: Monday, June 22nd

Acceptance Deadline: Wednesday, July 1st

Registration Closes: Monday, July 20th

Conference Dates Monday, July 27th-Weds July 29th 

Notice that exact presentation times will take into account presenters time zones. Relax, we will not make you give a talk in your nighttime! It’s a jet-lag free conference. Welcome to the future! Submit your abstracts at http://perm-conference.org/. Finally, we encourage you to forward this message to any other scientists and students who may be interested.

Sincerely, your PERM Organization Committee.

Thomas Theis (North Carolina State University)

Patrick TomHon (North Carolina State University)

Sören Lehmkuhl, (North Carolina State University)

Premila Jayaratne (North Carolina State University)

Eduard Chekmenev (Wayne State University, USA & Russian Academy of Science)

Boyd Goodson (Southern Illinois University Carbondale)

Matthew Rosen (Massachusetts General Hospital)

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A calibration-based approach to real-time in-vivo monitoring of pyruvate C1 and C2 polarization using the J_CC spectral asymmetry #DNPNMR

To measure the degree of polarization induced by the DNP process, one possibility is to calculate the ratio of the microwave OFF signal to microwave ON signal (neglecting depolarization under MAS conditions). While the ON signal is easy to measure since it typically a much better signal-to-noise ratio, measuring the OFF signal can often be challenging and the quality of the OFF signal will determine the error.

Measuring the NMR signal intensities of strongly coupled spin systems is a direct measure that does not require measuring the off signal. And a very elegant way is described in this paper from 2013:

Lau, Justin Y. C., Albert P. Chen, Yi-Ping Gu, and Charles H. Cunningham. “A Calibration-Based Approach to Real-Time in-Vivo Monitoring of Pyruvate C1 and C2 Polarization Using the J_CC Spectral Asymmetry #DNPNMR.” NMR in Biomedicine 26, no. 10 (October 2013): 1233–41. 

https://doi.org/10.1002/nbm.2942

A calibration-based technique for real-time measurement of pyruvate polarization by partial integral analysis of the doublet from the neighbouring J-coupled carbon is presented. In vitro calibration data relating the C2 and C1 asymmetries to the instantaneous C1 and C2 polarizations, respectively, were acquired in blood. The feasibility of using the in vitro calibration data to determine the instantaneous in vivo C1 and C2 polarizations was demonstrated in the analysis of rat kidney and pig heart spectral data. An approach for incorporating this technique into in vivo protocols is proposed.

A similar approach was used later by Vuichoud et al. analyzing the asymmetry of signal intensities of 2H Pake patterns. The same technique has been used in the Polarized Target Community to measure absolute target polarizations as initially described by Hamada et al.

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.

Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1 #DNPNMR

Granlund, Kristin L., Sui-Seng Tee, Hebert A. Vargas, Serge K. Lyashchenko, Ed Reznik, Samson Fine, Vincent Laudone, et al. “Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1.” Cell Metabolism 31, no. 1 (January 2020): 105-114.e3.

https://doi.org/10.1016/j.cmet.2019.08.024

Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. Targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI.

New insights into the nature of short-lived paramagnetic intermediates of ketoprofen. Photo-CIDNP study

Babenko, Simon V., Polina S. Kuznetsova, Nikolay E. Polyakov, Aleksandr I. Kruppa, and Tatyana V. Leshina. “New Insights into the Nature of Short-Lived Paramagnetic Intermediates of Ketoprofen. Photo-CIDNP Study.” Journal of Photochemistry and Photobiology A: Chemistry 392 (April 2020): 112383.

https://doi.org/10.1016/j.jphotochem.2020.112383

The short-lived paramagnetic particles formed during the UV irradiation of nonsteroidal antiinflammatory drug – ketoprofen (KP) have been investigated using chemically induced dynamic nuclear polarization (CIDNP). This study answers the questions about the nature of paramagnetic particles which can be responsible for KP phototoxic effects. Phototoxic side effects of NSAIDs, according modern point of view, are associated with the action of free radicals, however, there is insufficient information regarding the nature of the radical species. In contrast, most ketoprofen photodegradation schemes include carbanion as a precursor of products. CIDNP effects analysis has shown that all the major products of KP photodegradation can form via radical pairs (RPs) involving benzyl (2’), ketyl (3’) and CO2H● or CO2-● free radicals and solvated electron. Radical ways of KP photodegradation include: decarboxylation via RP with benzyl radical formation (I) in nonaqueous solution and both, (I) and photoreduction with formation of ketyl radicals in the presence of water. Moreover, it was found that the photoinduced radical decarboxylation of KP represents a reversible process.

Conformational control of nonplanar free base porphyrins: towards bifunctional catalysts of tunable basicity #DNPNMR

Roucan, M., M. Kielmann, S. J. Connon, S. S. R. Bernhard, and M. O. Senge. “Conformational Control of Nonplanar Free Base Porphyrins: Towards Bifunctional Catalysts of Tunable Basicity.” Chemical Communications 54, no. 1 (2018): 26–29.

https://doi.org/10.1039/C7CC08099A

For the first time, free base and N-methylated porphyrins have been utilized as bifunctional organocatalysts in Michael additions and it was found that distortion of the macrocycle is a vital prerequisite for their catalytic activity. Conformational design has been used to tailor the properties of nonplanar porphyrins with regards to availability of the N–H units for hydrogen bonding (distortion-dependent hydrogen bonding) and the basicity of the heterocyclic groups. NMR spectroscopic- and catalyst screening studies provided insight into the likely mode of catalyst action. This unprecedented use of free base and N-substituted porphyrins as organocatalysts opens a new functional role for porphyrins.

Room temperature optical nanodiamond hyperpolarizer: Physics, design, and operation #DNPNMR

Ajoy, A., R. Nazaryan, E. Druga, K. Liu, A. Aguilar, B. Han, M. Gierth, et al. “Room Temperature Optical Nanodiamond Hyperpolarizer: Physics, Design, and Operation.” Review of Scientific Instruments 91, no. 2 (February 1, 2020): 023106.

https://doi.org/10.1063/1.5131655

Dynamic Nuclear Polarization (DNP) is a powerful suite of techniques that deliver multifold signal enhancements in nuclear magnetic resonance (NMR) and MRI. The generated athermal spin states can also be exploited for quantum sensing and as probes for many-body physics. Typical DNP methods require the use of cryogens, large magnetic fields, and high power microwave excitation, which are expensive and unwieldy. Nanodiamond particles, rich in Nitrogen-Vacancy (NV) centers, have attracted attention as alternative DNP agents because they can potentially be optically hyperpolarized at room temperature. Here, unraveling new physics underlying an optical DNP mechanism first introduced by Ajoy et al. [Sci. Adv. 4, eaar5492 (2018)], we report the realization of a miniature “optical nanodiamond hyperpolarizer,” where 13C nuclei within the diamond particles are hyperpolarized via the NV centers. The device occupies a compact footprint and operates at room temperature. Instrumental requirements are very modest: low polarizing fields, low optical and microwave irradiation powers, and convenient frequency ranges that enable miniaturization. We obtain the best reported optical 13C hyperpolarization in diamond particles exceeding 720 times of the thermal 7 T value (0.86% bulk polarization), corresponding to a ten-million-fold gain in averaging time to detect them by NMR. In addition, the hyperpolarization signal can be background-suppressed by over two-orders of magnitude, retained for multiple-minute long periods at low fields, and deployed efficiently even to 13C enriched particles. Besides applications in quantum sensing and bright-contrast MRI imaging, this work opens possibilities for low-cost room-temperature DNP platforms that relay the 13C polarization to liquids in contact with the high surface-area particles.

Optically generated hyperpolarization for sensitivity enhancement in solution-state NMR spectroscopy #DNPNMR

Dale, Matthew W., and Christopher J. Wedge. “Optically Generated Hyperpolarization for Sensitivity Enhancement in Solution-State NMR Spectroscopy.” Chemical Communications 52, no. 90 (2016): 13221–24.

https://doi.org/10.1039/C6CC06651H.

We show that optical excitation of radical triplet pair systems can produce a fourfold NMR signal enhancement in solution, without the need for microwave pumping. Development of optical hyperpolarization methods will significantly impact all NMR user groups by boosting sensitivity and reducing signal averaging times.

Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology #DNPNMR

Kurhanewicz, John, Daniel B. Vigneron, Jan Henrik Ardenkjaer-Larsen, James A. Bankson, Kevin Brindle, Charles H. Cunningham, Ferdia A. Gallagher, et al. “Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology.” Neoplasia 21, no. 1 (January 2019): 1–16.

https://doi.org/10.1016/j.neo.2018.09.006

This white paper discusses prospects for advancing hyperpolarization technology to better understand cancer metabolism, identify current obstacles to HP (hyperpolarized) 13C magnetic resonance imaging’s (MRI’s) widespread clinical use, and provide recommendations for overcoming them. Since the publication of the first NIH white paper on hyperpolarized 13C MRI in 2011, preclinical studies involving [1-13C]pyruvate as well a number of other 13C labeled metabolic substrates have demonstrated this technology\’s capacity to provide unique metabolic information. A dose-ranging study of HP [1-13C]pyruvate in patients with prostate cancer established safety and feasibility of this technique. Additional studies are ongoing in prostate, brain, breast, liver, cervical, and ovarian cancer. Technology for generating and delivering hyperpolarized agents has evolved, and new MR data acquisition sequences and improved MRI hardware have been developed. It will be important to continue investigation and development of existing and new probes in animal models. Improved polarization technology, efficient radiofrequency coils, and reliable pulse sequences are all important objectives to enable exploration of the technology in healthy control subjects and patient populations. It will be critical to determine how HP 13C MRI might fill existing needs in current clinical research and practice, and complement existing metabolic imaging modalities. Financial sponsorship and integration of academia, industry, and government efforts will be important factors in translating the technology for clinical research in oncology. This white paper is intended to provide recommendations with this goal in mind.

[NMR] Research Assistant: Hyperpolarized Gas and Pulmonary MRI #DNPNMR

The Center for Pulmonary Imaging Research (CPIR) at Cincinnati Children’s Hospital Medical Center (CCHMC) is soliciting applications for a staff position at the level of Research Assistant II. Highly qualified applicants will be considered at the RA III level. The CPIR is a multidisciplinary center affiliated with the Radiology, Neonatology, and Pulmonary Medicine. CCHMC is currently ranked #4 in the U.S. in Pulmonary Medicine and ranked #3 overall in Pediatric Medicine. The CPIR focuses on hyperpolarized gas and proton NMR and MRI of the respiratory system, with the goal of understanding pulmonary and airway structure and function in children and adults with a wide range of chronic respiratory disorders, including cystic fibrosis, asthma, rare-lung diseases and lung-transplantation rejection. Team members have backgrounds that range from atomic physics and physical chemistry, to engineering, to pulmonary medicine and biology and collaborate to perform cutting-edge research in animal models and humans subjects of all ages. (Website:

http://cpir.cchmc.org)

Position Requirements and Responsibilities: The candidate must have at least B.S. or B.A. in a physical science (i.e., chemistry or physics), engineering, or related discipline. Recent graduates are encouraged to apply. Experience with magnetic resonance, electronics, high-pressures, glassware, or coding experience (MATLAB, C++, python) is desired. The accepted applicant will possess excellent communication skills, strong attention to detail, and the desire to promote a safe working environment. The abilities to synthesize information, learn new skills, and teach others in a dynamic, multidisciplinary environment are essential.

Job responsibilities will include producing hyperpolarized gas using commercial and homebuilt equipment, maintaining and developing specialized equipment, following and revising standard operating procedures (SOPs), and documenting compliance with FDA and institutional regulations. The applicant will also collect and analyze imaging data after appropriate training.

To Apply: Please submit a cover letter, a resume detailing research experience and technical expertise, and the names and contact information of three references by email to Carolyn Lipchik. (Carolyn.Lipchik@cchmc.org).

Cincinnati Children’s is an Equal Opportunity Employer. Qualified applicants receive consideration for employment without regard to race, color, religion, sex, national origin, age, genetic information, physical or mental disability, military or veteran status, sexual orientation, gender identity/expression, or other protected status in accordance with applicable federal, state, and local laws and regulations.

Cincinnati Children’s will not discriminate against applicants and employees for inquiring about, discussing or disclosing their pay or, in certain circumstances, the pay of their co-workers.

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