Clinical-Scale, Stopped-flow 129Xe Hyperpolarizer Development
Aaron M. Coffey1, Panayiotis Nikolaou1, Kaili Ranta2, Iga Muradyan3, Matthew S. Rosen4, Samuel Patz3, Michael J. Barlow5, Boyd M. Goodson2, and Eduard Y. Chekmenev1

1Radiology, Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, 2Southern Illinois University, Carbondale, IL, United States, 3Brigham & Women's Hospital, Boston, MA, United States, 4Harvard University, Cambridge, MA, United States, 5University of Nottingham, Nottingham, United Kingdom

Synopsis

We report on the development of a first and second generation 129Xe hyperpolarizers, capable of producing high (~25-90%) 129Xe hyperpolarization at high Xe densities (up to 2000 Torr partial pressure), suitable for clinical and materials MRS/MRI applications.

Overview

Owing to the detection sensitivity provided by their high, non-equilibrium nuclear spin polarizations, hyperpolarized (HP) noble gases (e.g. 129Xe and 3He) are utilized in a growing number of MRS/MRI applications—ranging from biomedical imaging and spectroscopy to probing molecular and materials surfaces. Lung imaging with HP 129Xe is of particular interest. Although 3He has a nearly 3-fold greater gyromagnetic ratio, 129Xe has 26% natural abundance and higher solubility in blood and tissues. Moreover, 129Xe’s proclivity for interacting with substances and its wide chemical shift range make it a more sensitive MR probe of biological environments.

HP 129Xe is usually created by spin-exchange optical pumping (SEOP). It is traditionally expected that high 129Xe polarizations (PXe) can only be obtained with low in-cell Xe densities because (i) higher Xe densities increase the destruction of the alkali metal polarization from non-spin-conserving collisions and (ii) higher total pressures tend to quench the more efficient van der Waals contribution to Rb-Xe spin exchange. Indeed, many polarizer designs tend to go to great lengths to produce large amounts of HP 129Xe while still satisfying this condition within the cell. Such polarizers also tend to be complex, expensive, and strictly regulated by their controlling entities—factors that hinder large-scale HP 129Xe generation for many unaffiliated laboratories.

Building upon our previous work exploring batch-mode or “stopped-flow” Rb/Xe SEOP under conditions of high resonant laser flux, we constructed a first-generation large-scale (>1 L/hr) “open-source” xenon polarizer for clinical, pre-clinical, and materials NMR/MRI applications comprised mostly of off-the-shelf components (including a 200 W VHG-narrowed LDA laser) [1–2]. This hyperpolarizer was cleared for preclinical work and approved by the FDA (IND #116,662) for operation at Brigham & Women’s Hospital. Unlike most clinical-scale 129Xe polarizers, this first-generation device runs with Xe-rich gas mixtures in single-batch mode. In-cell PXe values during SEOP of up to ~90%, ~57%, ~50%, and ~28% have been measured for Xe partial pressures of ~300, ~500, ~760, and ~1570 Torr, respectively [1–2].

Experience gained in building this first-generation 129Xe polarizer lead to construction of our second-generation 129Xe polarizer (dubbed “XeUS”) [3–5]. The new design encompasses a variety of improvements and new technologies. For example, the water-cooled 200 W VHG-narrowed LDA laser possesses a novel integrated air-cooled optical train assembly. Implementation of a thermoelectric cooler (TEC) and incorporation of a quiet air compressor eliminates the need for external gas or liquid-N2 supplies for heating/cooling of the OP cell oven or for pneumatic valve operation. The polycarbonate oven for the OP cell is manufactured via 3D printing and houses the TEC module. Further integration of the requisite instrumentation and optics into this 3D-printed oven in conjunction with the laser telescope greatly simplified system construction and laser alignment with the optical pumping cell. A high-pressure gas manifold using premixed gases also greatly simplifies the first-generation gas manifold design. Taken together, these various improvements have lead to the second-generation hyperpolarizer achieving higher performance, with PXe of ~74% at 1,000 Torr [3] and PXe of ~90% at 500 Torr [5] as well as the improvements in the production rate [3-5].

Acknowledgements

Laura Walkup, Brogan Gust, Hayley Newton, and Scott Barcus contributed to this work. Work at SIUC and Vanderbilt is supported by a DoD CDMRP Era of Hope Award W81XWH-12-1-0159/BC112431, W81XWH-15-1-0271 and W81XWH-15-1-0272. M.J.B is supported by the School of Medical & Surgical Sciences, U. of Nottingham.

References

[1] Nikolaou, et al., PNAS 110, 14150-14155 (2013). [2] Nikolaou, et al., Magn. Reson. Imaging 32, 541-550 (2014). [3] Nikolaou, et al., JACS 136, 1636-1642 (2014). [4] Nikolaou, et al., J Phys Chem B 118, 4809-4816 (2014). [5] Nikolaou, et al. Anal. Chem., 86, 8206-8212 (2014).

Figures

Figure 1. First-generation 129Xe hyperpolarizer schematic (left) and quality assurance NMR spectroscopy measurements (right).

Figure 2. False-color 2D slices from a 3D 129Xe gradient echo chest image from a healthy subject following inhalation of HP 129Xe prepared using the XeNA polarizer (anterior to posterior, reading left to right, top to bottom).

Figure 3. a) Design of XeUS polarizer; b) 1H in situ reference NMR signal from water (100,000 scans), b) 129Xe in situ NMR signal from natural abundance 129Xe PXe = 74% (1 scan) at 1000 Torr Xe pressure, d) IR spectroscopy reporting on PRb in situ.

Figure 4. Temperature-ramped SEOP. (a) Exponential fit buildup (72 °C) and decay curves of OP cell cool down to 42 and 55 °C, respectively, of 500 Torr 129Xe. (b) T1 decay of hyperpolarized 129Xe (500 Torr partial pressure) at room temperature with laser off.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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