Near-unity nuclear polarization with an open-source ¹²⁹ Xe hyperpolarizer for NMR and MRI

Abstract

The exquisite NMR spectral sensitivity and negligible reactivity of hyperpolarized xenon-129 (HP 129 Xe) make it attractive for a number of magnetic resonance applications; moreover, HP 129 Xe embodies an alternative to rare and nonrenewable 3 He. However, the ability to reliably and inexpensively produce large quantities of HP 129 Xe with sufficiently high 129 Xe nuclear spin polarization (P Xe ) remains a significant challenge-particularly at high Xe densities. We present results from our "open-source" large-scale (∼1 L/h) 129Xe polarizer for clinical, preclinical, and materials NMR and MRI research. Automated and composed mostly of off-the-shelf components, this "hyperpolarizer" is designed to be readily implementable in other laboratories. The device runs with high resonant photon flux (up to 200 W at the Rb D 1 line) in the xenon-rich regime (up to 1,800 torr Xe in 500 cc) in either single-batch or stopped-flow mode, negating in part the usual requirement of Xe cryocollection. Excellent agreement is observed among four independent methods used to measure spin polarization. In-cell P Xe values of ∼90%, ∼57%, ∼50%, and ∼30% have been measured for Xe loadings of ∼300, ∼500, ∼760, and ∼1,570 torr, respectively. P Xe values of ∼41% and ∼28% (with ∼760 and ∼1,545 torr Xe loadings) have been measured after transfer to Tedlar bags and transport to a clinical 3 T scanner for MR imaging, including demonstration of lung MRI with a healthy human subject. Long "in-bag"129 Xe polarization decay times have been measured (T 1 ∼38 min and ∼5.9 h at ∼1.5 mT and 3 T, respectively)-more than sufficient for a variety of applications.hyperpolarization | laser-polarized xenon | lung imaging | optical pumping O wing to the detection sensitivity provided by their high, nonequilibrium nuclear spin polarization, hyperpolarized (HP) noble gases (e.g., Xe is of particular interest. Moreover, xenon is soluble in blood (6), other tissues (7, 8), and many biologically compatible liquids (9), and its proclivity for interacting with other substances and its wide chemical shift range make HP 129 Xe a sensitive NMR probe of molecular and material surfaces (1,(10)(11)(12) Xe is usually created via spin-exchange optical pumping (SEOP) (23), whereby the unpaired electronic spins of an alkali metal vapor (e.g., Rb) are polarized via optical pumping with circularly polarized light, and the polarization is transferred to noble gas nuclear spins during collisions. It is generally anticipated that high P Xe is achievable only in the low xenon-density regime (18, 24), because (i) higher Xe densities increase the destruction of Rb polarization from nonspin-conserving collisions at a rate that is orders of magnitude worse than those of other gases like N 2 and He (25-27); and (ii) higher total pressures tend to quench the threebody van der Waals contribution to Rb-Xe spin exchange-leaving the less-efficient two-body term (18,23). Most large-scale polarizers, in particular all that are available commercially, operate in this low-Xe density ...

Delivering strong 1 H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

“…Both the effective T 1 relaxation times and polarization levels increased with the best-performing catalyst, [IrCl(COD)(d 22 -IMes)], giving average polarization levels of ca. 22.0% under 3 bar p-H 2 in both methanol-d 4 and ethanol-d 6 , which reflects a 250% improvement in the latter case.…”

“…In methanol-d 4 solution we see an increase in H-2 polarization to 26.4% and 28.5% at 4.0 and 5.5 bar, respectively. A more significant effect is observed in ethanol-d 6 solution, where a 55% increase in enhancement is observed at 5.5 bar of p-H 2 compared with 3.0 bar. This results in a 41.7% polarization being measured on the H-2 site of 2b under these conditions.…”

“…This process has been exemplified by studies on pyruvate that harness dissolution dynamic nuclear polarization (DNP) (4) to produce the signal strength necessary to track its metabolism (5). Additionally, the related method of optical pumping noble gases, such as 129 Xe (6), has provided the sensitivity needed to produce lung MR images that probe pulmonary disease (5,7). A recent report using γ-rays in conjunction with hyperpolarized 131 Xe has been used to image the distribution of a radioactive tracer at high sensitivity (8).…”

Development of an antibody-based, modular biosensor for129Xe NMR molecular imaging of cells at nanomolar concentrations

“…spin hyperpolarization | targeted imaging W hen referring to xenon magnetic resonance imaging (MRI), the best-known application is the use of the isotope 129 Xe for facilitating the direct visualization of the airspaces and function of the lung (1)(2)(3)(4). However, in the past few years, the scope for using 129 Xe for targeted biosensor imaging has notably increased (5).…”

Remote detection of hyperpolarized 129Xe resonances via multiple distant dipolar field interactions with 1H

“…This was achieved by multiplying each nth FID by a factor of 1 exp{ 30×n T 1×60 } , using a T 1 relaxation time of 38 min for xenon gas outside of the magnetic field. 27 The left, central left, central right, and right columns in Figure 6 show, respectively, 2D spectra without T 1 relaxation correction, indirectly detected spectrum without T 1 relaxation correction, 2D spectra with T 1 relaxation correction, and the indirectly detected spectrum with T 1 relaxation correction. All the figures are normalized to the strongest peak in each figure.…”