Functional imaging of the lungs with gas agents

Abstract

This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)-hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas--and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children.

Keywords: 129Xe MRI; 3He MRI; COPD; asthma; cystic fibrosis; fluorinated gas MRI; hyperpolarized noble gas; oxygen-enhanced MRI; pulmonary MRI.

Figure 1

(a) Schematic of the tissue-capillary boundary. Gas phase is contained within the alveoli (AL). Septal wall comprises the liquid lining (LL), tissue epithelium (EP), interstitial space (IS), and tissue endothelium (EN). Blood volume comprises the PL = blood plasma, and RBC = red blood cells (Adapted from (72)). (b) ¹²⁹Xe MR spectrum from the human lung with peaks corresponding to the gas, plasma-tissue, and red blood cell (RBC) compartments. Note that the spectral peak for the ¹²⁹Xe gas in the airspaces is attenuated by a factor of ~100 by using a lower flip angle relative to the dissolved phases.

Figure 2

³He MRI lung images showing a strong VDP response to challenge pre (baseline) and post-exercise challenge in a subject with exercise-induced bronchoconstriction and treatment with Montelukast (visit 1 vs. visits 2 and 3). Defects (arrows) occur most prominently after exercise challenge and post-challenge decreases in FEV1 for this subject coincide with decreases in VDP as indicated. Recovery 45 minutes post-exercise shows residual VDP for visit 3. Overall, residual VDP after recovery was significantly higher on ³He MRI but not on FEV1. Plcb = “placebo visit”; Tx = “treatment visit.” Adapted from Ref. (144) with permission.

Figure 3

Timing and general protocol for oxygen-enhanced MRI as performed in (11). Typically, images are acquired at different concentrations of inhaled oxygen (usually 21% and 100%), with a 1–2 minute wash-out period to avoid transient effects. Similar approaches are used for other OE-MRI acquisition techniques.

Figure 4

ADC maps derived from coronal slices acquired using diffusion-weighted ³He MRI for (a) non smoker with (b) histogram for the typical slice shown, mean ADC = 0.166 cm²/s and (c) smoker with (d) histogram mean ADC = 0.268 cm²/s. Color bar units: mm²/s. Adapted from Ref. (134) with permission.

Figure 5

Axial reformation of 3D radial UTE FID MRI ventilation imaging with C₃F₈. This dataset was acquired in a 15-second breath hold. Good image quality and the expected homogeneity of gas distribution are observable in this healthy normal human subject.

Figure 6

SF₆ MRI as a surrogate for V/Q measurement in a rat model of ventilation obstruction (left upper lobe). Multiple slices of a 3D volume acquired with the hyperoxic 30% SF₆ / 70% O₂ mixture (numerator) (a), and normoxic 80% SF₆/20% O₂ mixture (denominator) (b), and resulting ratio images (c). The color bars of the corresponding V/Q scale are the width of the SD of the ratio values. This figure is republished from (215) with permission of the Journal of Magnetic Resonance in Medicine.

Figure 7

(a) ventilation image of a lung transplant recipient (coronal field of view 40 cm). Prior to this study, both lungs had developed BOS after transplant from a non-sibling donor. The right lung was then transplanted from a sibling donor. The high ¹⁹F signal intensity in the healthy right lung is clearly differentiable from the BOS left lung. (b) Matching CT slices (coronal field of view ~34 cm) to provide structural reference. This figure is republished from (49) with permission.

Figure 8

(a) Coronal IR-SSFSE image showing low-signal regions in the right lung corresponding to bullae. (b) OE MRI showing ventilation defects (arrows) in the bullous regions. This figure was originally published in (2), and is reprinted here with the permission of Nature Medicine.

Figure 9

Example from (11) showing a healthy normal subject with parametric color map. The isotropic 3D resolution is apparent in the axial, coronal, and sagittal reformations of the same dataset. The color bar is in units of percent signal enhancement (PSE).

Figure 10

Comparison of hyperpolarized (HP) ³He MRI images (top row) with OE-MRI images (bottom row) originally presented in (223). Arrows indicated regions of agreement in ventilation defect extent and location. The in-plane spatial resolution of the HP ³He images is greater than in the OE MRI images by a factor of 3.2. However, the resolution in the OE MRI images in this study was isotropic in all 3 dimensions, while the HP ³He images were thick axial images.