Quantitative Mapping of Specific Ventilation in the Human Lung using Proton Magnetic Resonance Imaging and Oxygen as a Contrast Agent

Summary

Specific ventilation imaging is a functional magnetic resonance imaging technique that allows for quantification of regional specific ventilation in the human lung, using inhaled oxygen as a contrast agent. Here, we present a protocol to collect and analyze specific ventilation imaging data.

Abstract

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation ― the ratio of the fresh gas entering a lung region divided by the region’s end-expiratory volume ― in the human lung, using only inhaled oxygen as a contrast agent. Regional quantification of specific ventilation has the potential to help identify areas of pathologic lung function. Oxygen in solution in tissue shortens the tissue’s longitudinal relaxation time (T₁), and thus a change in tissue oxygenation can be detected as a change in T₁-weighted signal with an inversion recovery acquired image. Following an abrupt change between two concentrations of inspired oxygen, the rate at which lung tissue within a voxel equilibrates to a new steady-state reflects the rate at which resident gas is being replaced by inhaled gas. This rate is determined by specific ventilation. To elicit this sudden change in oxygenation, subjects alternately breathe 20-breath blocks of air (21% oxygen) and 100% oxygen while in the MRI scanner. A stepwise change in inspired oxygen fraction is achieved through use of a custom three-dimensional (3D)-printed flow bypass system with a manual switch during a short end-expiratory breath hold. To detect the corresponding change in T₁, a global inversion pulse followed by a single shot fast spin echo sequence was used to acquire two-dimensional T₁-weighted images in a 1.5 T MRI scanner, using an eight-element torso coil. Both single slice and multi-slice imaging are possible, with slightly different imaging parameters. Quantification of specific ventilation is achieved by correlating the time-course of signal intensity for each lung voxel with a library of simulated responses to the air/oxygen stimulus. SVI estimations of specific ventilation heterogeneity have been validated against multiple breath washout and proved to accurately determine the heterogeneity of the specific ventilation distribution.

Introduction

The overall goal of specific ventilation imaging (SVI) ― a proton magnetic resonance imaging (MRI) technique that uses oxygen as a contrast agent¹ ― is to quantitatively map specific ventilation in the human lung. Specific ventilation is the ratio of fresh gas delivered to a lung region in one breath divided by the end expiratory volume of the same lung region¹. In conjunction with measurements of local lung density, specific ventilation can be used to compute regional ventilation². Measurements of local ventilation and ventilation heterogeneity that are provided by SVI have the potent....

Protocol

The University of California, San Diego Human Research Protection Program has approved this protocol.

1. Subject Safety and Training

1. Obtain written, informed consent from the subject. Describe the potential risks presented by exposure to rapidly changing magnetic fields, and the potential discomfort of using facial mask and breathing dry gas.
2. Ensure that the subject can safely undergo MR scanning, utilizing the locally approved MRI safety screening questionnaire.
3. If the subject is a female of childbearing age, and uncertain of her pregnancy status, ask her to self-administer an over-the-counter pregnancy test....

Results

Single slice SVI in a healthy subject
Specific ventilation imaging produces quantitative maps of specific ventilation as shown in Figure 3A, which depicts a single slice in the right lung of a 39-year-old healthy female. Note the presence of the expected vertical gradient in specific ventilation; the dependent portion of the lung presents higher specific ventilation than the non-dependent portion of the lung. A histogram of the mapped specific vent.......

Discussion

Specific ventilation imaging allows quantitative mapping of the spatial distribution of specific ventilation in the human lung. Alternatives to SVI exist but are limited in some manner: Multiple breath washout provides a measure of heterogeneity but lacks spatial information²³. Alternative imaging methods expose patients to ionizing radiation (e.g., SPECT, PET, CT, gamma scintigraphy) or are not widely available (hyperpolarized gas imaging using MRI). Specific ventilation imaging provides spatial .......

Materials

Name	Company	Catalog Number	Comments
3D-printed flow bypass system
Face mask	Hans Rudolph		7400 series Oro-nasal mask, different sizes
Gas/oxygen regulator
Mask head set	Hans Rudolph		7400 compatible head set
Matlab	Mathworks		analysis software developed locally
Medical oxygen	Air Liquide/Linde		Oxygen to be delivered to the subject
MRI	GE healthcare		1.5 T GE HDx Excite twin-speed scanner
Plastic tubing			¼”, 3/8” and 1/2” tubing and connectors
Pulse oximeter	Nonin		7500 FO (MR compatible)
Switch valve
Torso coil	GE healthcare		High gain torso coil for GE scanner