Hyperpolarized Xenon for NMR and MRI Applications

Summary

The production of hyperpolarized xenon by means of spin exchange optical pumping (SEOP) is described. This method yields a ~10000-fold enhancement of the nuclear spin polarization of Xe-129 and has applications in nuclear magnetic resonance spectroscopy and imaging. Examples of gas phase and solution state experiments are given.

Abstract

Nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) suffer from intrinsic low sensitivity because even strong external magnetic fields of ~10 T generate only a small detectable net-magnetization of the sample at room temperature ¹. Hence, most NMR and MRI applications rely on the detection of molecules at relative high concentration (e.g., water for imaging of biological tissue) or require excessive acquisition times. This limits our ability to exploit the very useful molecular specificity of NMR signals for many biochemical and medical applications. However, novel approaches have emerged in the past few years: Manipulation of the detected spin species prior to detection inside the NMR/MRI magnet can dramatically increase the magnetization and therefore allows detection of molecules at much lower concentration ².

Here, we present a method for polarization of a xenon gas mixture (2-5% Xe, 10% N₂, He balance) in a compact setup with a ca. 16000-fold signal enhancement. Modern line-narrowed diode lasers allow efficient polarization ⁷ and immediate use of gas mixture even if the noble gas is not separated from the other components. The SEOP apparatus is explained and determination of the achieved spin polarization is demonstrated for performance control of the method.

The hyperpolarized gas can be used for void space imaging, including gas flow imaging or diffusion studies at the interfaces with other materials ^8,9. Moreover, the Xe NMR signal is extremely sensitive to its molecular environment ⁶. This enables the option to use it as an NMR/MRI contrast agent when dissolved in aqueous solution with functionalized molecular hosts that temporarily trap the gas ^10,11. Direct detection and high-sensitivity indirect detection of such constructs is demonstrated in both spectroscopic and imaging mode.

Introduction

Hyperpolarized agents are gaining increasing attention for NMR/MRI applications since they can solve the sensitivity problem under certain circumstances ². Three major approaches are currently used (dynamic nuclear polarization, DNP; para-hydrogen induced polarization, PHIP; and spin exchange optical pumping, SEOP) that all prepare an artificially increased spin population difference outside an NMR magnet prior to the actual spectroscopy or imaging experiment. Here we describe the function and operation of a SEOP setup that has been optimized for production of hyperpolarized¹²⁹Xe used in solution state experiments.

An ....

Protocol

1. Preparation of the SEOP Setup

Rubidium must be brought into the optical pumping cell, to facilitate the transfer of polarization from the laser light to xenon. Due to its high reactivity this process must occur without the Rb coming into contact with oxygen or water, otherwise it will become oxidized and won't polarize Xe. Extra caution should be taken as Rb reacts violently with water.

1. If the optical cell has previously been used it will be coated with a layer of Rb and Rb oxide, as can be seen in Figure 4b. The cell must first be clean before use. Close the inlet and outlet tubes of the optical cell. While ....

Discussion

Critical aspects in the preparation of hyperpolarized xenon are oxygen impurities in the gas manifold including the pumping cell and sufficient illumination of the cell with circularly polarized light. The above mentioned light bulb test is a simple way to detect deleterious oxygen concentrations while transferring rubidium. The alkali metal might loose its shiny surface by the time the cell is installed in the polarizer. However, sufficient vaporization of non-oxidized Rb can be monitored by reduced laser transmission (.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Rb ingot	Sigma-Aldrich	276332-1G
P4O10	Sigma-Aldrich	79610-500G
Ar	Praxair
Xe	Sigma-Aldrich	00472-1EA
O2	Sigma-Aldrich	00476-1EA
Laser system	QPC Lasers/Laser Operations	Brightlock 50
Vacuum system	Pfeiffer	HiCube
Thermocouples	Newport Omega	SA2F-KI-3M
Silicon heater	Newport Omega	FMA5514
Pressure transducer	Newport Omega	PR 33X-V-10
Process meter	Newport Omega	INFCP-100B
Mass flow controllers	Newport Omega	MFC
PID regulators	Newport Omega	CN7800
Control Software	Newport Omega	DasyLab
Data acquisition	Newport Omega	Daqboard 3000
Vacuum sensor	Oerlikon	TTR91
Vacuum controller	Vacom	MVC-3
Beam collimator	Thorlabs	F810SMA-780
Polarizing beam splitter cube	Thorlabs	GL15-B
λ/4 wave plate	Thorlabs	WPQ10M-780
Beam expansion lenses	Thorlabs
Optical spectrometer	Ocean Optics	HR4000
Optical fiber	Ocean Optics
Low pressure NMR tube	Wilmad	513-7LPV-7
5mm NMR tube	Sigma-Aldrich	HX58.1
Helmholtz coils	Phywe	06960-00
Fused silica capillaries	Polymicro	TSG 250350