Quantitative Measure of Lung Structure and Function Obtained from Hyperpolarized Xenon Spectroscopy

Summary

The manuscript presents a detailed protocol for using hyperpolarized Xenon-129 chemical shift saturation recovery (CSSR) to trace pulmonary gas exchange, assess the apparent alveolar septal wall thickness, and measure the surface-to-volume ratio. The method has the potential to diagnose and monitor lung diseases.

Abstract

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI) provides tools for obtaining 2- or 3-dimensional maps of lung ventilation patterns, gas diffusion, Xenon uptake by lung parenchyma, and other lung function metrics. However, by trading spatial for temporal resolution, it also enables tracing of pulmonary Xenon gas exchange on a ms timescale. This article describes one such technique, chemical shift saturation recovery (CSSR) MR spectroscopy. It illustrates how it can be used to assess capillary blood volume, septal wall thickness, and the surface-to-volume ratio in the alveoli. The flip angle of the applied radiofrequency pulses (RF) was carefully calibrated. Single-dose breath-hold and multi-dose free-breathing protocols were employed for administering the gas to the subject. Once the inhaled Xenon gas reached the alveoli, a series of 90° RF pulses was applied to ensure maximum saturation of the accumulated Xenon magnetization in the lung parenchyma. Following a variable delay time, spectra were acquired to quantify the regrowth of the Xenon signal due to gas exchange between the alveolar gas volume and the tissue compartments of the lung. These spectra were then analyzed by fitting complex pseudo-Voigt functions to the three dominant peaks. Finally, the delay time-dependent peak amplitudes were fitted to a one-dimensional analytical gas-exchange model to extract physiological parameters.

Introduction

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI)¹ is a technique that offers unique insights into lung structure, function, and gas exchange processes. By dramatically amplifying the magnetization of Xenon gas through spin-exchange optical pumping, HXe MRI achieves an order-of-magnitude improvement in signal-to-noise ratio compared to thermally polarized Xenon MRI^2,3,4,5,6. This hyperpolarization enables the direct visualization and quantification....

Protocol

NOTE: While the hyperpolarized Xenon-129 CSSR MR spectroscopy technique described here is commonly used for animal and human imaging, the protocol below refers to human studies only. All imaging protocols adhered to FDA specific absorption rate (SAR) limitations (4 W/kg) and were approved by the Institutional Review Board at the University of Pennsylvania. Informed consent was obtained from each subject.

1. Pulse sequence design

1. Decide whether to perform a breath h.......

Discussion

HXe CSSR MR spectroscopy is a powerful technique for assessing several pulmonary function metrics that would be difficult or impossible to quantify in vivo using any other existing diagnostic modality²⁴. Nevertheless, the acquisition and subsequent data analysis are based on certain assumptions about physiological conditions and technical parameters that are never entirely achievable in living subjects. These limitations and their impact on the interpretation of the extracted metrics will.......

Materials

Name	Company	Catalog Number	Comments
Bi-directional Pneumotach	B&B Medical AccutachTM
Chest Vest Coil	Clinical MR Solutions		Adult Size
Face Mask	Hans Rudolph	7450
Matlab	Mathworks	Release 2018a	Optimization Toolbox required
Physiological Monitoring System	BIOPAC Systems Inc
Tedlar Bag	Jensen Inert Products		250-mL and 500-mL; specialised PVF bag
Xenon Polarizer	Xemed LLC	X-box E10
Whole-body MRI Scanner	Siemens	1.5 T Avanto