Hyperpolarised xenon magnetic resonance spectroscopy for the longitudinal assessment of changes in gas diffusion in IPF

Abstract

Prognosticating idiopathic pulmonary fibrosis (IPF) is challenging, in part due to a lack of sensitive biomarkers. A recent article in Thorax described how hyperpolarised xenon magnetic resonance spectroscopy may quantify regional gas exchange in IPF lungs. In a population of patients with IPF, we find that the xenon signal from red blood cells diminishes relative to the tissue/plasma signal over a 12-month time period, even when the diffusion factor for carbon monoxide is static over the same time period. We conclude that hyperpolarised 129Xe MR spectroscopy may be sensitive to short-term changes in interstitial gas diffusion in IPF.

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

“…No indication of any such events was indicated by pulmonary function tests, specifically FEV1 and FVC, which were extremely repeatable, with CR = AE4.6 %p and CR = AE6.1 %p over the two visits, respectively. DL CO and RBC:Barrier have been shown to be highly correlated in disease populations, 12,14 and the CV for these two measurements were, in fact, comparable. Interestingly, the change in intervisit RBC:Barrier were strongly correlated with the corresponding change in DL CO , which points to longitudinal intrasubject changes in RBC:Barrier as a potential regional biomarker for monitoring individual progression or response to interventions.…”

“…Interestingly, the change in intervisit RBC:Barrier were strongly correlated with the corresponding change in DL CO , which points to longitudinal intrasubject changes in RBC:Barrier as a potential regional biomarker for monitoring individual progression or response to interventions. 14 Correlations between Barrier:Gas and RBC:Gas metrics and pulmonary function tests were generally low, which was somewhat surprising, given the strong associations reported in prior studies. Previous work has shown moderate-to-strong correlations between all these 129 Xe gas-exchange metrics (measured with whole-lung spectroscopy) and both FVC and DL CO .…”

“…Moreover, few studies to date have systematically assessed the dependence of the repeatability of these ratios on lung inflation volume. In a handful of prior studies, repeatability was reported for global lung HP 129 Xe MR spectroscopy measures of gas‐exchange or microstructural tissue properties, including both septal thickness and alveolar surface‐to‐volume measurements with chemical shift saturation recovery (CSSR) and repeatability of whole‐lung RBC:Barrier ratios . The dependence of global HP 129 Xe MR spectroscopy measures on lung inflation volume has also been investigated for Barrier:Gas and RBC:Gas ratios, but not for spectroscopic imaging.…”

“…In a handful of prior studies, repeatability was reported for global lung HP 129 Xe MR spectroscopy measures of gas‐exchange or microstructural tissue properties, including both septal thickness and alveolar surface‐to‐volume measurements with chemical shift saturation recovery (CSSR) and repeatability of whole‐lung RBC:Barrier ratios . The dependence of global HP 129 Xe MR spectroscopy measures on lung inflation volume has also been investigated for Barrier:Gas and RBC:Gas ratios, but not for spectroscopic imaging. A recent work investigated the repeatability of regional CSSR‐based measures, and compared these with 129 Xe dissolved‐phase 3D spectroscopic imaging measures, although dependence on lung inflation volume was not assessed.…”

Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography

“…Moreover, these invasive read-outs, such as hydroxyproline lung tissue content, histo-morphometric quantification of collagen deposition and fibrotic masses accumulation in the parenchyma surrounding the airways, require the animal sacrifice at designed time points, precluding longitudinal studies. In humans, longitudinal characterization of lung fibrotic diseases extent and progression by noninvasive imaging techniques, such as high-resolution computed tomography (HRCT) ( Lynch et al., 2018 ; Raghu et al., 2018 ; Sverzellati et al., 2018 ; Wu et al., 2018 ), magnetic resonance imaging (MRI) ( Weatherley et al., 2018 ; Wild, 2018 ), and positron emission tomography (PET) ( Justet et al., 2017 ; Win et al., 2018 ), is now well established. Recently, these techniques with the prefix of “Micro” (CT, PET and MRI) have been optimized and validated to assess lung fibrosis at different time points in living animals and so that each subject can act as their own control ( Egger et al., 2013 ; Egger et al., 2014 ; Withana et al., 2016 ; Désogère et al., 2017 ; Ruscitti et al., 2017 ; Ruscitti et al., 2018 ).…”