Pilot Quality-Assurance Study of a Third-Generation Batch-Mode Clinical-Scale Automated Xenon-129 Hyperpolarizer.

Jonathan R Birchall,Michael J Barlow,Md Raduanul H Chowdhury,Panayiotis Nikolaou,Eduard Y Chekmenev,Yuri A Chekmenev,Boyd M Goodson,Anton Shcherbakov

doi:10.3390/molecules27041327

Abstract

We present a pilot quality assurance (QA) study of a clinical-scale, automated, third-generation (GEN-3) 129Xe hyperpolarizer employing batch-mode spin-exchange optical pumping (SEOP) with high-Xe densities (50% natural abundance Xe and 50% N2 in ~2.6 atm total pressure sourced from Nova Gas Technologies) and rapid temperature ramping enabled by an aluminum heating jacket surrounding the 0.5 L SEOP cell. 129Xe hyperpolarization was performed over the course of 700 gas loading cycles of the SEOP cell, simulating long-term hyperpolarized contrast agent production in a clinical lung imaging setting. High levels of 129Xe polarization (avg. %PXe = 51.0% with standard deviation σPXe = 3.0%) were recorded with fast 129Xe polarization build-up time constants (avg. Tb = 25.1 min with standard deviation σTb = 3.1 min) across the first 500 SEOP cell refills, using moderate temperatures of 75 °C. These results demonstrate a more than 2-fold increase in build-up rate relative to previously demonstrated results in a comparable QA study on a second-generation (GEN-2) 129Xe hyperpolarizer device, with only a minor reduction in maximum achievable %PXe and with greater consistency over a larger number of SEOP cell refill processes at a similar polarization lifetime duration (avg. T1 = 82.4 min, standard deviation σT1 = 10.8 min). Additionally, the effects of varying SEOP jacket temperatures, distribution of Rb metal, and preparation and operation of the fluid path are quantified in the context of device installation, performance optimization and maintenance to consistently produce high 129Xe polarization values, build-up rates (Tb as low as 6 min) and lifetimes over the course of a typical high-throughput 129Xe polarization SEOP cell life cycle. The results presented further demonstrate the significant potential for hyperpolarized 129Xe contrast agent in imaging and bio-sensing applications on a clinical scale.

Highlights

Nuclear magnetic resonance (NMR) has seen widespread application in the fields of anatomical and physiological clinical imaging
In addition to comparing 129Xe hyperpolarization build-up efficiency as a function of spin-exchange optical pumping (SEOP) cell temperature, we describe how variation in other polarizer-specific parameters, such as the time interval between NMR acquisitions and the amount of cooling power supplied to external fans on the device impact operation of the hyperpolarizer performance
Production of good %PXe levels of ~50% has been demonstrated with high reproducibility of hyperpolarizer performance in a clinical-scale 129Xe contrast agent production setting, using high-Xe densities (50% Xe fraction in ~2.6 atm total pressure) and rapid temperature ramping enabled by an aluminum heating jacket surrounding the SEOP cell. 129Xe hyperpolarization was performed over the course of 700 gas-loading cycles, simulating long-term HP contrast agent production

Summary

Introduction

Nuclear magnetic resonance (NMR) has seen widespread application in the fields of anatomical and physiological clinical imaging. Hyperpolarization techniques are capable of boosting P to the order of unity, resulting in five or more orders of magnitude increase in the detection sensitivity of MR spectroscopic and imaging techniques [1,2,3,4] Such gains in sensitivity facilitate detection of these hyperpolarized (HP) nuclear species in the form of inhalable MR contrast agents [5,6,7,8,9,10,11,12,13,14,15,16], as well as other applications related to molecular sensing [8,9,17,18,19,20]. Their relative safety and suitability for this task are underpinned by both the inert nature and the low natural abundance of 3He and 129Xe, minimizing background signal from non-HP nuclei

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