Hyperpolarized 129Xe MR Spectroscopy in the Lung Shows 1-year Reduced Function in Idiopathic Pulmonary Fibrosis.

Background Idiopathic pulmonary fibrosis (IPF) is a temporally and spatially heterogeneous lung disease. Identifying whether IPF in a patient is progressive or stable is crucial for treatment regimens. Purpose To assess the role of hyperpolarized (HP) xenon 129 (129Xe) MRI measures of ventilation and gas transfer in IPF generally and as an early signature of future IPF progression. Materials and Methods In a prospective study, healthy volunteers and participants with IPF were consecutively recruited between December 2015 and August 2019 and underwent baseline HP 129Xe MRI and chest CT. Participants with IPF were followed up with forced vital capacity percent predicted (FVC%p), diffusing capacity of the lungs for carbon monoxide percent predicted (DLco%p), and clinical outcome at 1 year. IPF progression was defined as reduction in FVC%p by at least 10%, reduction in DLco%p by at least 15%, or admission to hospice care. CT and MRI were spatially coregistered and a measure of pulmonary gas transfer (red blood cell [RBC]-to-barrier ratio) and high-ventilation percentage of lung volume were compared across groups and across fibrotic versus normal-appearing regions at CT by using Wilcoxon signed rank tests. Results Sixteen healthy volunteers (mean age, 57 years ± 14 [SD]; 10 women) and 22 participants with IPF (mean age, 71 years ± 9; 15 men) were evaluated, as follows: nine IPF progressors (mean age, 72 years ± 7; five women) and 13 nonprogressors (mean age, 70 years ± 10; 11 men). Reduction of high-ventilation percent (13% ± 6.1 vs 8.2% ± 5.9; P = .03) and RBC-to-barrier ratio (0.26 ± 0.06 vs 0.20 ± 0.06; P = .03) at baseline were associated with progression of IPF. Participants with progressive disease had reduced RBC-to-barrier ratio in structurally normal-appearing lung at CT (0.21 ± 0.07 vs 0.28 ± 0.05; P = .01) but not in fibrotic regions of the lung (0.15 ± 0.09 vs 0.14 ± 0.04; P = .62) relative to the nonprogressive group. Conclusion In this preliminary study, functional measures of gas transfer and ventilation measured with xenon 129 MRI and the extent of fibrotic structure at CT were associated with idiopathic pulmonary fibrosis disease progression. Differences in gas transfer were found in regions of nonfibrotic lung. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gleeson and Fraser in this issue.

Transverse relaxation rates of pulmonary dissolved-phase Hyperpolarized 129 Xe as a biomarker of lung injury in idiopathic pulmonary fibrosis.

PURPOSE: The MR properties (chemical shifts and R2∗ decay rates) of dissolved-phase hyperpolarized (HP) 129 Xe are confounded by the large magnetic field inhomogeneity present in the lung. This work improves measurements of these properties using a model-based image reconstruction to characterize the R2∗ decay rates of dissolved-phase HP 129 Xe in healthy subjects and patients with idiopathic pulmonary fibrosis (IPF). METHODS: Whole-lung MRS and 3D radial MRI with four gradient echoes were performed after inhalation of HP 129 Xe in healthy subjects and patients with IPF. A model-based image reconstruction formulated as a regularized optimization problem was solved iteratively to measure regional signal intensity in the gas, barrier, and red blood cell (RBC) compartments, while simultaneously measuring their chemical shifts and R2∗ decay rates. RESULTS: The estimation of spectral properties reduced artifacts in images of HP 129 Xe in the gas, barrier, and RBC compartments and improved image SNR by over 20%. R2∗ decay rates of the RBC and barrier compartments were lower in patients with IPF compared to healthy subjects (P < 0.001 and P = 0.005, respectively) and correlated to DLCO (R = 0.71 and 0.64, respectively). Chemical shift of the RBC component measured with whole-lung spectroscopy was significantly different between IPF and normal subjects (P = 0.022). CONCLUSION: Estimates for R2∗ in both barrier and RBC dissolved-phase HP 129 Xe compartments using a regional signal model improved image quality for dissolved-phase images and provided additional biomarkers of lung injury in IPF.

Repeatability of regional pulmonary functional metrics of Hyperpolarized 129 Xe dissolved-phase MRI.

BACKGROUND: MRI of hyperpolarized 129 Xenon (HP 129 Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP 129 Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology. PURPOSE: To quantify global average and regional repeatability of Barrier:gas, RBC:gas, and RBC:Barrier ratios derived from dissolved-phase 129 Xe imaging and their dependence on intervisit changes in lung inflation volume. STUDY TYPE: Prospective. POPULATION: Fourteen healthy volunteers. One subject was unable to complete the study resulting in 13 subjects for analysis (eight female, five male, ages 24-69, 53.8 ± 13.9). FIELD STRENGTH: 1.5T. ASSESSMENT: Subjects were imaged using a 3D radial 1-point Dixon method to separate Barrier and RBC component signals, at two different timepoints, with ~1 month between visits. RBC:Gas, Barrier:Gas, and RBC:Barrier measures were compared across time and with pulmonary function tests (PFTs). STATISTICAL TESTS: Repeatablilty was quantified using Bland-Altman plots, coefficient of repeatability, coefficient of variation (CV), and intraclass correlation coefficients (ICCs). Dependence of imaging measures on PFTs and lung volume was evaluated using Spearman and Pearson correlation coefficients, respectively. Statistical significance was determined by F-test for intraclass correlations, and t-test for Spearman correlations and regression. RESULTS: Mean RBC:Gas, Barrier:Gas, and RBC:Barrier had CVs of 19.2%, 20.0%, and 11.5%, respectively, and had significant ICCs, equal to 0.78, 0.79, and 0.92, respectively. Intervisit differences in RBC:Barrier were significantly correlated with intervisit differences in DLCO (r = 0.93, P = 0.007). Significant correlations with intervisit lung volume differences and intervisit differences in mean RBC:Gas (r = -0.73, P = 0.005) and Barrier:Gas (r = -0.69, P = 0.009) were found. DATA CONCLUSION: Three commonly used 129 Xe MRI-based measures of gas-exchange show good repeatability, particularly the Barrier:RBC ratio, which did not depend on lung inflation volume and was strongly associated with intervisit changes in DLCO . LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1182-1190.

Removal of hyperpolarized 129 Xe gas-phase contamination in spectroscopic imaging of the lungs.

PURPOSE: A novel technique is presented for retrospective estimation and removal of gas-phase hyperpolarized Xenon-129 (HP 129 Xe) from images of HP 129 Xe dissolved in the barrier (comprised of parenchymal lung tissue and blood plasma) and red blood cell (RBC) phases. The primary aim is mitigating RF pulse performance limitations on measures of gas exchange (e.g., barrier-gas and RBC-gas ratios). Correction for gas contamination would simplify technical dissemination of HP 129 Xe applications across sites with varying hardware performance, scanner vendors, and models. METHODS: Digital lung phantom and human subject experiments (N = 8 healthy; N = 1 with idiopathic pulmonary fibrosis) were acquired with 3D radial trajectory and 1-point Dixon spectroscopic imaging to assess the correction method for mitigating barrier and RBC imaging artifacts. Dependence of performance on TE, image SNR, and gas contamination level were characterized. Inter- and intra-subject variation in the dissolved-phase ratios were quantified and compared to human subject experiments before and after correction. RESULTS: Gas contamination resulted in image artifacts similar to those in disease that were mitigated after correction in both simulated and human subject data; for simulation experiments performance varied with TE, but was independent of image SNR and the amount of gas contamination. Artifacts and variation of barrier and RBC components were reduced after correction in both simulation and healthy human lungs (barrier, P = 0.01; RBC, P = 0.045). CONCLUSION: The proposed technique significantly reduced regional variations in barrier and RBC ratios, separated using a 1-point Dixon approach, with improved accuracy of dissolved-phase HP 129 Xe images confirmed in simulation experiments.

Functional xenon-129 magnetic resonance imaging response to antifibrotic treatment in idiopathic pulmonary fibrosis.

A measure of regional gas exchange on HP 129Xe MRI was able to detect apparent improvements in IPF patients treated with antifibrotic medication after 1 year, while no such improvements were found in patients treated with conventional therapies https://bit.ly/3ZXipzD.

"Structure-Function Imaging of Lung Disease Using Ultrashort Echo Time MRI".

RATIONALE AND OBJECTIVES: The purpose of this review is to acquaint the reader with recent advances in ultrashort echo time (UTE) magnetic resonance imaging (MRI) of the lung and its implications for pulmonary MRI when used in conjunction with functional MRI technique. MATERIALS AND METHODS: We provide an overview of recent technical advances of UTE and explore the advantages of combined structure-function pulmonary imaging in the context of restrictive and obstructive pulmonary diseases such as idiopathic pulmonary fibrosis (IPF) and cystic fibrosis (CF). RESULTS: UTE MRI clearly shows the lung parenchymal changes due to IPF and CF. The use of UTE MRI, in conjunction with established functional lung MRI in chronic lung diseases, will serve to mitigate the need for computed tomography in children. CONCLUSION: Current limitations of UTE MRI include long scan times, poor delineation of thin-walled structures (e.g. cysts and reticulation) due to limited spatial resolution, low signal to noise ratio, and imperfect motion compensation. Despite these limitations, UTE MRI can now be considered as an alternative to multidetector computed tomography for the longitudinal follow-up of the morphological changes from lung diseases in neonates, children, and young adults, particularly as a complement to the unique functional capabilities of MRI.

The role of hyperpolarized 129xenon in MR imaging of pulmonary function.

In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium (3He) and xenon (129Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available 129Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP 129Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP 129Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP 129Xe MRI, and (4) propose clinical applications.