In vivo methods and applications of xenon-129 magnetic resonance

Abstract

Hyperpolarised gas lung MRI using xenon-129 can provide detailed 3D images of the ventilated lung airspaces, and can be applied to quantify lung microstructure and detailed aspects of lung function such as gas exchange. It is sensitive to functional and structural changes in early lung disease and can be used in longitudinal studies of disease progression and therapy response. The ability of ¹²⁹Xe to dissolve into the blood stream and its chemical shift sensitivity to its local environment allow monitoring of gas exchange in the lungs, perfusion of the brain and kidneys, and blood oxygenation. This article reviews the methods and applications of in vivo¹²⁹Xe MR in humans, with a focus on the physics of polarisation by optical pumping, radiofrequency coil and pulse sequence design, and the in vivo applications of ¹²⁹Xe MRI and MRS to examine lung ventilation, microstructure and gas exchange, blood oxygenation, and perfusion of the brain and kidneys.

Keywords: Brain; Hyperpolarised (129)Xe; Kidneys; Lungs; Magnetic resonance imaging/spectroscopy.

Graphical abstract

Fig. 1

Optical pumping. (a) Simplified conceptual picture of Rb-¹²⁹Xe spin-exchange optical pumping (SEOP). SEOP is a two-step process involving (i) the spin polarisation of Rb valence electrons through optical pumping of Rb vapour with circularly polarised light resonant with the Rb D₁ transition and (ii) transfer of the Rb electron polarisation to the nuclei of ¹²⁹Xe via spin-exchange collisions. The black arrows depict the polarisation of the Rb electron and ¹²⁹Xe nuclear spin states. OP and SE represent optical pumping and spin-exchange interactions, respectively. (b) Schematic of the key functional components of a continuous-flow Rb-¹²⁹Xe polariser, adapted with permission from . A stopped-flow set-up is essentially the same without the need for a cryostat and magnet (see bottom right). (c) Photo of ¹²⁹Xe spin-exchange optical pumping polariser located at the POLARIS laboratory, University of Sheffield. (d) Ceramic oven containing V = 3530 mL SEOP (7.5 cm diameter, 80 cm length) cell without the lid. The pool of rubidium is visible at the cell gas entrance (bottom of photo). Incident laser light P = 150 W (BrightLock 200 W, QPC, CA, USA), 794.77 nm wavelength. Gas mixture throughout: 3% Xe, 87% He, 10% N₂.

Fig. 2

Ventilation imaging. (a) ³He and ¹²⁹Xe ventilation images of a healthy non-smoker and a patient with COPD, adapted with permission from . (b) ¹²⁹Xe ventilation images of a healthy 6-year-old (HV, FEV₁ = 95%) and an 11-year-old with CF (CF, FEV₁ = 102%), adapted with permission from . (c) ¹²⁹Xe ventilation images (top) and coefficient of variation maps (bottom; blue = low COV, red = high COV) of a patient with asthma pre- and post-bronchodilator inhalation, adapted with permission from . (d) ¹²⁹Xe ventilation image (left) and binning map (right; red = defect, yellow = low intensity, green = medium intensity, blue = high intensity) from an older patient with asthma (FEV₁ = 53%), adapted with permission from . (In this case, ventilation defect percentage (VDP) is defined as the ratio of the number of red pixels to the total number of pixels in the whole lung × 100).

Fig. 3

Diffusion imaging. (a) Examples of histological slides from a healthy lung (top) and COPD lung with emphysema (bottom) that are used to calculate mean linear intercept (Lm) measurements, adapted with permission from . (b) ¹²⁹Xe ADC maps and whole lung ADC histograms for a healthy volunteer (23-year-old female, top) and COPD patient (68-year-old male, bottom). (c) (Left) Schematic drawing of the cylindrical model of acinar airway geometry based upon the Haefeli-Bleuer and Weibel acinar geometry , adapted with permission from . (c) (Right) Cylinder model ¹²⁹Xe lung morphometry maps of acinar airway radius (R) and mean linear intercept (Lm) in the same healthy volunteer and COPD patient as in (b). (d) (Left) Probability distributions of diffusive length scale derived from the stretched exponential model for the same healthy volunteer and COPD patient. (d) (Right) Stretched exponential model ¹²⁹Xe lung morphometry maps of mean diffusive length scale (Lm_D) for the same healthy volunteer and COPD patient.

Fig. 4

Probing gas exchange. (a) Cartoon of diffusive exchange of xenon gas from alveolus to capillary, via the parenchymal tissue barrier. The tissue wall thickness (air-blood barrier thickness) is represented by δ, and the total septal wall thickness separating neighbouring alveoli is represented by d. (b) ¹²⁹Xe MR spectra obtained from a healthy subject (black line) and a patient with IPF (blue line). (c) IDEAL CSI of dissolved ¹²⁹Xe in the lungs of a patient with moderate COPD, illustrated in the form of ratio maps (reproduced with permission from [104]). (d) Representative binning maps and histograms derived from Dixon-based dissolved-phase ¹²⁹Xe MRI acquired from a patient with IPF, highlighting the characteristic high TP (barrier) signal and low RBC signal compared with healthy normal subjects (dashed histogram), adapted with permission from . (The notation barrier: gas is equivalent to TP/Gas.)

Fig. 5

¹²⁹Xe dissolved in human blood. (a) Decaying spectra from ¹²⁹Xe dissolved in blood acquired with inter-pulse delay = 0.5 s. The inset shows a fit performed on the decreasing ¹²⁹Xe NMR signal (integrals of ¹²⁹Xe-red-blood-cell (RBC) and ¹²⁹Xe-plasma absorption peaks) in order to establish ¹²⁹Xe-RBC (red triangles) and ¹²⁹Xe-plasma T₁ values (blue squares). Here 0 ppm refers to the ¹²⁹Xe gas-phase resonance frequency. The decaying spectra are from a blood sample with sO₂ = 0.98. The data in (b) are the measured ¹²⁹Xe relaxation rates (1/T₁) in RBCs as a function of RBC oxygenation from (open blue circles) and (solid black triangles). In (c) it can be seen that with increasing oxygenation, the peak associated with ¹²⁹Xe dissolved in RBCs is seen to shift measurably towards higher resonance frequency. Here 0 ppm is in reference to the ¹²⁹Xe-plasma resonance frequency. Shown in (d) is a plot of the change in ¹²⁹Xe-RBC chemical shift as a function of RBC oxygenation from Refs. (open blue circles) and (solid black triangles).

Fig. 6

¹²⁹Xe beyond the lungs. (a) Spectrum of HP ¹²⁹Xe dissolved in the human head. Spectral peaks: 189 ppm: soft muscular tissue, 193 ppm: white matter, 196 ppm: grey matter, 200 ppm: interstitial and cerebrospinal fluids, and 217 ppm red blood cells. Brain perfusion images of (b) a healthy volunteer (adapted with permission from [60]) and (c) a volunteer with established stroke (adapted with permission from [281]), using inhaled hyperpolarised ¹²⁹Xe. (d) Kidney perfusion images of a healthy volunteer using inhaled hyperpolarized ¹²⁹Xe, adapted with permission from .

Fig. 7

¹²⁹Xe MRI in acute COVID-19. (a) ¹H anatomical SPGR image, (b) ¹²⁹Xe ventilation image and (c) ¹²⁹Xe RBC/TP map acquired with an IDEAL sequence of a coronal mid-posterior slice in a patient with acute COVID-19. For this slice, ventilated volume percentage = 99.6% and RBC/TP = 0.188 (mean RBC/TP in healthy volunteers = 0.47 [318]). RBC/TP = red blood cells to tissue and blood plasma ratio.