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).