Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation

Summary

Hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI) is a method for studying regionally resolved aspects of pulmonary function. This work presents an end-to-end standardized workflow for hyperpolarized ¹²⁹Xe MRI of lung ventilation, with specific attention to pulse sequence design, ¹²⁹Xe dose preparation, scan workflow, and best practices for subject safety monitoring.

Abstract

Hyperpolarized ¹²⁹Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is increasingly important given the recent FDA approval of ¹²⁹Xe as an MR contrast agent and as interest in ¹²⁹Xe MRI increases among research and clinical institutions. Members of the ¹²⁹Xe MRI Clinical Trials Consortium (Xe MRI CTC) have agreed upon best practices for each of the key aspects of the ¹²⁹Xe MRI workflow, and these recommendations are summarized in a recent publication. This work provides practical information to develop an end-to-end workflow for collecting ¹²⁹Xe MR images of lung ventilation according to the Xe MRI CTC recommendations. Preparation and administration of ¹²⁹Xe for MR studies will be discussed and demonstrated, with specific topics including choice of appropriate gas volumes for entire studies and for individual MR scans, preparation and delivery of individual ¹²⁹Xe doses, and best practices for monitoring subject safety and ¹²⁹Xe tolerability during studies. Key MR technical considerations will also be covered, including pulse sequence types and optimized parameters, calibration of ¹²⁹Xe flip angle and center frequency, and ¹²⁹Xe MRI ventilation image analysis.

Introduction

Hyperpolarized ¹²⁹Xe MRI is an exciting tool for non-invasive, spatially-resolved characterization and quantification of specific aspects of pulmonary function^1,2,3. Acquisition and reconstruction approaches similar to those used in anatomical proton MRI yield images of inhaled ¹²⁹Xe in the lungs, permitting visualization of non-ventilated lung regions and region-resolved quantification of ventilation distribution^4,5,6,7,8. More advanced pulse sequence and analysis techniques yield further complementary information, including quantification of gas-exchange efficacy between alveoli and pulmonary capillaries via spectroscopic MRI^{9,10,11,12,13} and characterization of alveolar microstructure integrity via diffusion-weighted MRI^14,15,16.

Inhaled ¹²⁹Xe has been proven safe and tolerable in adult and pediatric subjects, including those with pulmonary disease^17,18. Measurements of lung function derived from ¹²⁹Xe MRI have shown sensitivity to structural and functional alterations in many pulmonary disease contexts, including chronic obstructive pulmonary disease^6,10,19, cystic fibrosis^20,21,22, idiopathic pulmonary fibrosis^23,24,25, and asthma^7,10,26. Given the high safety and tolerability of ¹²⁹Xe MRI, the lack of ionizing radiation in MRI compared with other common imaging approaches, and the high reproducibility of ¹²⁹Xe MRI results^27,28, ¹²⁹Xe MRI holds significant promise, in particular for precise serial monitoring of individuals receiving a time course of therapy for chronic pulmonary disease.

The safety and clinical promise of ¹²⁹Xe MRI have led to its FDA approval in December 2022 for lung ventilation imaging in persons aged 12 years and older²⁹. Given this, it is anticipated that the number of research and clinical sites capable of performing ¹²⁹Xe MRI (currently ~20 worldwide) will increase significantly over the coming years. As ¹²⁹Xe MRI spreads to new institutions, it is important that robust methodological resources exist to allow sites to build out clinically relevant ¹²⁹Xe MRI techniques quickly and to perform scans and generate results that are closely comparable with those of existing sites.

In this work, we will outline the current best practices for human hyperpolarized ¹²⁹Xe MRI of lung ventilation, as agreed upon by member institutions of the ¹²⁹Xe MRI Clinical Trials Consortium (Xe MRI CTC) and summarized in a recent position paper³⁰. Topics will include the preparation of tailored pulse sequences ideal for a complete ¹²⁹Xe MRI workflow, preparation, and administration of hyperpolarized ¹²⁹Xe gas, an optimized workflow for human ¹²⁹Xe MRI sessions, and best practices for monitoring subject safety and comfort during MRI sessions.

Protocol

All research involving human subjects must be approved by an institutional review board (IRB). IRB involvement is not necessary for regulatory-approved clinical use of 129Xe MRI. Before participating in a research study, prospective subjects must be provided with an approved informed consent document. The person obtaining consent must explain the contents of the document, including the purpose, procedures, benefits, and risks of the study, must answer any questions, and must obtain consent from the subject to …

Representative Results

Figure 1 shows representative ventilation and three-plane localizer images from a healthy individual. High 129Xe signal can be observed throughout the lungs in the ventilation images, and no ventilation impairment is evident in this individual. Figure 2, Figure 3, and Figure 4 show representative ventilation and anatomical images from diseased individuals. <strong …

Discussion

The ventilation and anatomical MRI approaches outlined above are designed to maximize image quality and SNR while maintaining simplicity of implementation – these sequence protocols can in general be adapted from vendor product pulse sequences, provided multinuclear operation is enabled, and images will automatically reconstruct on the scanner computer. One disadvantage of the 2D approaches described here is the use of slice-selective excitation RF pulses, which introduces signal differences between slices collected earl…

Materials

1.5T or 3T human MRI scanner	Siemens		MAGNETOM Symphony (1.5T) or Vida (3T); older models fine, as long as multinuclear option is/can be installed; scanners also available from GE and Philips
129Xe hyperpolarizer	Polarean	9820
129Xe MRI phantom
129Xe MRI vest coil	Clinical MR Solutions		Also available from other vendors
129Xe polarization measurement station	Polarean	2881
1H MRI phantom
Coil file for 129Xe MRI vest coil			Also available from other vendors for their respective coils
ECG machine
Helium buffer gas
Interface box from coil to scanner			May be built into coil, but needs to be included separately if not
Liquid nitrogen
MRI-safe pulse oximeter	Philips	Expression MR200
Nitrogen buffer gas
PFT machine
Programming/image analysis software	MATLAB	R2023a	Various other options available
Pulse sequence design software	Siemens		IDEA software package; also available from GE and Philips for their respective scanners
Scanner multinuclear option	Siemens		Scanner integrated hardware/software package; also available from GE and Philips for their respective scanners
Tedlar gas sampling bags (500, 750, 1000, 1250, 1500 mL)
Xenon gas (129Xe isotopically enriched)