Hyperpolarized Gas MR Imaging: Technique and Applications

Abstract

Functional imaging offers information more sensitive to changes in lung structure and function. Hyperpolarized helium ((3)He) and xenon ((129)Xe) MR imaging of the lungs provides sensitive contrast mechanisms to probe changes in pulmonary ventilation, microstructure, and gas exchange. Gas imaging has shifted to the use of (129)Xe. Xenon is well-tolerated. (129)Xe is soluble in pulmonary tissue, which allows exploring specific lung function characteristics involved in gas exchange and alveolar oxygenation. Hyperpolarized gases and (129)Xe in particular stand to be an excellent probe of pulmonary structure and function, and provide sensitive and noninvasive biomarkers for pulmonary diseases.

Keywords: Hyperpolarized gas; Lung imaging; MR imaging; Pulmonary gas exchange; Pulmonary ventilation; Xenon ((129)Xe).

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1

Anatomical relationship between the purely air conducting zone and the transitional/respiratory zones. Pulmonary function test (PFTs) lack the ability to detect early changes at the level of the small airways, the so-called ‘silent zone’ for PFTs. Adapted from Weibel E.R. Morphometry of the Human Lung. Heidelberg Springer, 1963; 111, with permission.

Figure 2

Coronal mid lung proton MR image without (a) and with (b) hyperpolarized 129 Xe Gas contrast (green overlay). It is obvious that proton MR imaging and the lungs are not really close friends: Conventional MR imaging excites and detects hydrogen nuclei (protons) in water. The lungs have a very low proton density and those that are present are difficult to image given their unfavorable relaxation characteristics. However, beyond the challenge of imaging parenchymal structure by MRI, there is an enormous need to image its function. This led to the development of contrast techniques using noble gases such as 3He or 129 Xe, which nicely demonstrate the lack of ventilation in a large right upper lobe bullae (arrow) in this patient.

Figure 2

Coronal mid lung proton MR image without (a) and with (b) hyperpolarized 129 Xe Gas contrast (green overlay). It is obvious that proton MR imaging and the lungs are not really close friends: Conventional MR imaging excites and detects hydrogen nuclei (protons) in water. The lungs have a very low proton density and those that are present are difficult to image given their unfavorable relaxation characteristics. However, beyond the challenge of imaging parenchymal structure by MRI, there is an enormous need to image its function. This led to the development of contrast techniques using noble gases such as 3He or 129 Xe, which nicely demonstrate the lack of ventilation in a large right upper lobe bullae (arrow) in this patient.

Figure 3

Schematics explain sequence involved in gas polarization. Under normal conditions, half of the nuclear spins within the gas volume are pointed up, along the magnetic field direction, and half are pointed down. This leads to zero polarization. If we put this sample in a large magnetic field (1.5 – 3.0 Tesla), it is slightly more favorable for spins to be up, but this leads to polarization of only a few parts per million. In hyperpolarization, we seek to have nearly all nuclei spins polarized in one direction. As shown in panel (a), from a physics perspective, all that is needed to transform this unpolarized sample of 3 down and 3 up spins, is to add 3 quanta of angular momentum (a) to flip the down spins to up, and polarize the sample. (b) We cannot directly flip nuclear, but we can flip electron spins in an alkali metal atom rubidium, which by absorbing angular momentum from laser photons, allows its outer-shell valence electron to become spin polarized. This process is known as optical pumping (Fig 3b). (c) Mother Nature takes care of the rest when 129 Xe or 3He nuclei collide with Rb and transfer polarization from its valence electron to the nuclear spin of the noble gas atom. This process is known as spin exchange.

Figure 3

Schematics explain sequence involved in gas polarization. Under normal conditions, half of the nuclear spins within the gas volume are pointed up, along the magnetic field direction, and half are pointed down. This leads to zero polarization. If we put this sample in a large magnetic field (1.5 – 3.0 Tesla), it is slightly more favorable for spins to be up, but this leads to polarization of only a few parts per million. In hyperpolarization, we seek to have nearly all nuclei spins polarized in one direction. As shown in panel (a), from a physics perspective, all that is needed to transform this unpolarized sample of 3 down and 3 up spins, is to add 3 quanta of angular momentum (a) to flip the down spins to up, and polarize the sample. (b) We cannot directly flip nuclear, but we can flip electron spins in an alkali metal atom rubidium, which by absorbing angular momentum from laser photons, allows its outer-shell valence electron to become spin polarized. This process is known as optical pumping (Fig 3b). (c) Mother Nature takes care of the rest when 129 Xe or 3He nuclei collide with Rb and transfer polarization from its valence electron to the nuclear spin of the noble gas atom. This process is known as spin exchange.

Figure 3

Schematics explain sequence involved in gas polarization. Under normal conditions, half of the nuclear spins within the gas volume are pointed up, along the magnetic field direction, and half are pointed down. This leads to zero polarization. If we put this sample in a large magnetic field (1.5 – 3.0 Tesla), it is slightly more favorable for spins to be up, but this leads to polarization of only a few parts per million. In hyperpolarization, we seek to have nearly all nuclei spins polarized in one direction. As shown in panel (a), from a physics perspective, all that is needed to transform this unpolarized sample of 3 down and 3 up spins, is to add 3 quanta of angular momentum (a) to flip the down spins to up, and polarize the sample. (b) We cannot directly flip nuclear, but we can flip electron spins in an alkali metal atom rubidium, which by absorbing angular momentum from laser photons, allows its outer-shell valence electron to become spin polarized. This process is known as optical pumping (Fig 3b). (c) Mother Nature takes care of the rest when 129 Xe or 3He nuclei collide with Rb and transfer polarization from its valence electron to the nuclear spin of the noble gas atom. This process is known as spin exchange.

Figure 4

Schematic of the device used to hyperpolarize 129 Xe. The optical pumping and spin-exchange process occurs in the optical cell in a flowing mixture of 1% hyperpolarized 129 Xe, 89% 4He and 10% N2. Once the mixture flows out of the optical cell, 129 Xe can be separated from the 4He N2 buffer gases by exploiting the fact that xenon freezes readily at the 77 K temperature of liquid nitrogen, while the other gases remain gaseous. Once a sufficient quantity of HP 129 Xe has been frozen and accumulated, it is thawed and evacuated into a perfluoropolymer bag for delivery to the patient and subsequent imaging. In these bags, the hyperpolarized state has about a 1 hour half life, allowing ample time for delivery.

Figure 5

Quantified ventilation defects using a 4 color ventilation mask with color red representing the most impaired ventilation in a asthma patient Pre (a) and Post (b) bronchodilator therapy. From these images, the ventilation defect percentage (VDP) can be calculated. In this patient with FEV1=31%, the pre-bronchodilator VDP = 30%; post-bronchodilator, the FEV1 remained at 31%, while VDP reduced significantly to 19%. Based on ATS criteria patient would represent a non-responder to bronchodilatation by PFT criteria, while quantified HP gas ventilation confirms a significant and positive effect to bronchodilator therapy.

Figure 5

Quantified ventilation defects using a 4 color ventilation mask with color red representing the most impaired ventilation in a asthma patient Pre (a) and Post (b) bronchodilator therapy. From these images, the ventilation defect percentage (VDP) can be calculated. In this patient with FEV1=31%, the pre-bronchodilator VDP = 30%; post-bronchodilator, the FEV1 remained at 31%, while VDP reduced significantly to 19%. Based on ATS criteria patient would represent a non-responder to bronchodilatation by PFT criteria, while quantified HP gas ventilation confirms a significant and positive effect to bronchodilator therapy.

Figure 6

Hyperpolarized 3He 129 Xe images of healthy volunteer, old but otherwise healthy individual, smoker without COPD, COPD, asthma and IPF patients. Hyperpolarized 129 Xe images accurately depict different ventilation patterns related to underlying pulmonary disease.

Figure 7

Diffusion-weighted imaging of hyperpolarized 129 Xe can reveal airspace enlargement. The schematics compares diffusion of gas atoms in normal lung airspaces (a) versus enlarged airspaces (b). In normal airspaces the diffusion of 129Xe is constrained by the normal alveolar architecture. However, when alveolar spaces become enlarged such as occurs in emphysema, 129Xe diffusion is no longer constrained, and measured apparent diffusion coefficients (ADC) become higher.

Figure 8

Apparent diffusion coefficient (ADC) MRI using HP 129 Xe gas. The color scale shows escalating enlargement of airspaces from normal lung tissue (blue) to severe bullous emphysematous parenchymal destruction (red). Note parenchymal destruction depicted by CT paralleling the change of ADC values.

Figure 9

Hyperpolarized 129Xe can be separately detected in airspaces, interstitial tissues, and red blood cells (RBCs). A small fraction of the inhaled 129Xe dissolves in pulmonary tissues and blood plasma (referred to as the barrier tissues), and changes its MR frequency dramatically compared to 129Xe left in the airspaces. When 129Xe diffuses further into the RBCs it changes its detection frequency again. Because 129Xe follows essentially the same pathway as oxygen, these spectroscopic properties of 129Xe present an enormously powerful means to directly assess pulmonary gas exchange.

Figure 10

Dissolved Hyperpolarized 129Xe MR imaging in healthy individual and patient with idiopathic pulmonary fibrosis (IPF). (a) Recent improvements in 3D radially acquired, breath-hold images of inhaled 129Xe now enable simultaneous depiction of 129Xe in airspaces as well as 129Xe transfered to the barrier and RBC compartments. (b) Note that in the patient with IPF, numerous focal defects are visible in the Xe-RBC transfer images. These defects nicely correspond to fibrotic changes seen on CT (yellow arrows).