Free breathing lung T1 mapping using image registration in patients with idiopathic pulmonary fibrosis

Purpose To assess the use of image registration for correcting respiratory motion in free breathing lung T1 mapping acquisition in patients with idiopathic pulmonary fibrosis (IPF). Theory and Methods The method presented used image registration to synthetic images during postprocessing to remove respiratory motion. Synthetic images were generated from a model of the inversion recovery signal of the acquired images that incorporated a periodic lung motion model. Ten healthy volunteers and 19 patients with IPF underwent 2D Look‐Locker T1 mapping acquisition at 1.5T during inspiratory breath‐hold and free breathing. Eight healthy volunteers and seven patients with IPF underwent T1 mapping acquisition during expiratory breath‐hold. Fourteen patients had follow‐up scanning at 6 months. Dice similarity coefficient (DSC) was used to evaluate registration efficacy. Results Image registration increased image DSC (P < .001) in the free breathing inversion recovery images. Lung T1 measured during a free breathing acquisition was lower in patients with IPF when compared with healthy controls (inspiration: P = .238; expiration: P = .261; free breathing: P = .021). Measured lung T1 was higher in expiration breath‐hold than inspiration breath‐hold in healthy volunteers (P < .001) but not in patients with IPF (P = .645). There were no other significant differences between lung T1 values within subject groups. Conclusions The registration technique significantly reduced motion in the Look‐Locker images acquired during free breathing and may improve the robustness of lung T1 mapping in patients who struggle to hold their breath. Lung T1 measured during a free breathing acquisition was significantly lower in patients with IPF when compared with healthy controls

Experimental and quantitative imaging techniques in interstitial lung disease.

Interstitial lung diseases (ILDs) are a heterogeneous group of conditions, with a wide and complex variety of imaging features. Difficulty in monitoring, treating and exploring novel therapies for these conditions is in part due to the lack of robust, readily available biomarkers. Radiological studies are vital in the assessment and follow-up of ILD, but currently CT analysis in clinical practice is qualitative and therefore somewhat subjective. In this article, we report on the role of novel and quantitative imaging techniques across a range of imaging modalities in ILD and consider how they may be applied in the assessment and understanding of ILD. We critically appraised evidence found from searches of Ovid online, PubMed and the TRIP database for novel and quantitative imaging studies in ILD. Recent studies have explored the capability of texture-based lung parenchymal analysis in accurately quantifying several ILD features. Newer techniques are helping to overcome the challenges inherent to such approaches, in particular distinguishing peripheral reticulation of lung parenchyma from pleura and accurately identifying the complex density patterns that accompany honeycombing. Robust and validated texture-based analysis may remove the subjectivity that is inherent to qualitative reporting and allow greater objective measurements of change over time. In addition to lung parenchymal feature quantification, pulmonary vessel volume analysis on CT has demonstrated prognostic value in two retrospective analyses and may be a sign of vascular changes in ILD which, to date, have been difficult to quantify in the absence of overt pulmonary hypertension. Novel applications of existing imaging techniques, such as hyperpolarised gas MRI and positron emission tomography (PET), show promise in combining structural and functional information. Although structural imaging of lung tissue is inherently challenging in terms of conventional proton MRI techniques, inroads are being made with ultrashort echo time, and dynamic contrast-enhanced MRI may be used for lung perfusion assessment. In addition, inhaled hyperpolarised 129Xenon gas MRI may provide multifunctional imaging metrics, including assessment of ventilation, intra-acinar gas diffusion and alveolar-capillary diffusion. PET has demonstrated high standard uptake values (SUVs) of 18F-fluorodeoxyglucose in fibrosed lung tissue, challenging the assumption that these are 'burned out' and metabolically inactive regions. Regions that appear structurally normal also appear to have higher SUV, warranting further exploration with future longitudinal studies to assess if this precedes future regions of macroscopic structural change. Given the subtleties involved in diagnosing, assessing and predicting future deterioration in many forms of ILD, multimodal quantitative lung structure-function imaging may provide the means of identifying novel, sensitive and clinically applicable imaging markers of disease. Such imaging metrics may provide mechanistic and phenotypic information that can help direct appropriate personalised therapy, can be used to predict outcomes and could potentially be more sensitive and specific than global pulmonary function testing. Quantitative assessment may objectively assess subtle change in character or extent of disease that can assist in efficacy of antifibrotic therapy or detecting early changes of potentially pneumotoxic drugs involved in early intervention studies

Eruptions of Magnetic Ropes in Two Homologous Solar Events on 2002 June 1 and 2: a Key to Understanding of an Enigmatic Flare

The goal of this paper is to understand the drivers, configurations, and scenarios of two similar eruptive events, which occurred in the same solar active region 9973 on 2002 June 1 and 2. The June 2 event was previously studied by Sui, Holman, and Dennis (2006, 2008), who concluded that it was challenging for popular flare models. Using multi-spectral data, we analyze a combination of the two events. Each of the events exhibited an evolving cusp-like feature. We have revealed that these apparent ``cusps'' were most likely mimicked by twisted magnetic flux ropes, but unlikely to be related to the inverted Y-like magnetic configuration in the standard flare model. The ropes originated inside a funnel-like magnetic domain whose base was bounded by an EUV ring structure, and the top was associated with a coronal null point. The ropes appear to be the major drivers for the events, but their rise was not triggered by reconnection in the coronal null point. We propose a scenario and a three-dimensional scheme for these events in which the filament eruptions and flares were caused by interaction of the ropes.Comment: 22 pages, 11 figure

Voxel-wise comparison of co-registered quantitative CT and hyperpolarised gas diffusion-weighted MRI measurements in IPF

The patterns of idiopathic pulmonary fibrosis (IPF) lung disease that directly correspond to elevated hyperpolarised gas diffusion-weighted (DW) MRI metrics are currently unknown. This study aims to develop a spatial co-registration framework for a voxel-wise comparison of hyperpolarised gas DW-MRI and CALIPER quantitative CT patterns. Sixteen IPF patients underwent 3He DW-MRI and CT at baseline, and eleven patients had a 1-year follow-up DW-MRI. Six healthy volunteers underwent 129Xe DW-MRI at baseline only. Moreover, 3He DW-MRI was indirectly co-registered to CT via spatially aligned 3He ventilation and structural 1H MRI. A voxel-wise comparison of the overlapping 3He apparent diffusion coefficient (ADC) and mean acinar dimension (LmD) maps with CALIPER CT patterns was performed at baseline and after 1 year. The abnormal lung percentage classified with the LmD value, based on a healthy volunteer 129Xe LmD, and CALIPER was compared with a Bland–Altman analysis. The largest DW-MRI metrics were found in the regions classified as honeycombing, and longitudinal DW-MRI changes were observed in the baseline-classified reticular changes and ground-glass opacities regions. A mean bias of −15.3% (95% interval −56.8% to 26.2%) towards CALIPER was observed for the abnormal lung percentage. This suggests DW-MRI may detect microstructural changes in areas of the lung that are determined visibly and quantitatively normal by CT

Quantification of pulmonary perfusion in idiopathic pulmonary fibrosis with first pass dynamic contrast-enhanced perfusion MRI

Introduction Idiopathic pulmonary fibrosis (IPF) is a fatal disease of lung scarring. Many patients later develop raised pulmonary vascular pressures, sometimes disproportionate to the interstitial disease. Previous therapeutic approaches that have targeted pulmonary vascular changes have not demonstrated clinical efficacy, and quantitative assessment of regional pulmonary vascular involvement using perfusion imaging may provide a biomarker for further therapeutic insights. Methods We studied 23 participants with IPF, using dynamic contrast-enhanced MRI (DCE-MRI) and pulmonary function tests, including forced vital capacity (FVC), transfer factor (TLCO) and coefficient (KCO) of the lungs for carbon monoxide. DCE-MRI parametric maps were generated including the full width at half maximum (FWHM) of the bolus transit time through the lungs. Key metrics used were mean (FWHMmean) and heterogeneity (FWHMIQR). Nineteen participants returned at 6 months for repeat assessment. Results Spearman correlation coefficients were identified between TLCO and FWHMIQR (r=−0.46; p=0.026), KCO and FWHMmean (r=−0.42; p=0.047) and KCO and FWHMIQR (r=−0.51; p=0.013) at baseline. No statistically significant correlations were seen between FVC and DCE-MRI metrics. Follow-up at 6 months demonstrated statistically significant decline in FVC (p=0.040) and KCO (p=0.014), with an increase in FWHMmean (p=0.040), but no significant changes in TLCO (p=0.090) nor FWHMIQR (p=0.821). Conclusions DCE-MRI first pass perfusion demonstrates correlations with existing physiological gas exchange metrics, suggesting that capillary perfusion deficit (as well as impaired interstitial diffusion) may contribute to gas exchange limitation in IPF. FWHMmean showed a significant increase over a 6-month period and has potential as a quantitative biomarker of pulmonary vascular disease progression in IPF

Hyperpolarised 129-xenon diffusion-weighted MRI for assessing lung microstructure in IPF

Background Hyperpolarised 129-xenon (129Xe) magnetic resonance imaging (MRI) shows promise in monitoring the progression of idiopathic pulmonary fibrosis (IPF) due to the lack of ionising radiation and the ability to quantify functional impairment. Diffusion-weighted (DW)-MRI with hyperpolarised gases can provide information about lung microstructure. The aims were to compare 129Xe DW-MRI measurements with pulmonary function tests (PFTs), and to assess whether they can detect early signs of disease progression in patients with newly diagnosed IPF. Methods This is a prospective, single-centre, observational imaging study of patients presenting with IPF to Northern General Hospital (Sheffield, UK). Hyperpolarised 129Xe DW-MRI was performed at 1.5 T on a whole-body General Electric HDx scanner and PFTs were performed on the same day as the MRI scan. Results There was an increase in global 129Xe apparent diffusion coefficient (ADC) between the baseline and 12-month visits (mean 0.043 cm2·s−1, 95% CI 0.040–0.047 cm2·s−1 versus mean 0.045 cm2·s−1, 95% CI 0.040–0.049 cm2·s−1; p=0.044; n=20), with no significant change in PFTs over the same time period. There was also an increase in 129Xe ADC in the lower zone (p=0.027), and an increase in 129Xe mean acinar dimension in the lower zone (p=0.033) between the baseline and 12-month visits. 129Xe DW-MRI measurements correlated strongly with diffusing capacity of the lung for carbon monoxide (% predicted), transfer coefficient of the lung for carbon monoxide (KCO) and KCO (% predicted). Conclusions 129Xe DW-MRI measurements appear to be sensitive to early changes of microstructural disease that are consistent with progression in IPF at 12 months. As new drug treatments are developed, the ability to quantify subtle changes using 129Xe DW-MRI could be particularly valuable

Stability analysis of agegraphic dark energy in Brans-Dicke cosmology

Stability analysis of agegraphic dark energy in Brans-Dicke theory is presented in this paper. We constrain the model parameters with the observational data and thus the results become broadly consistent with those expected from experiment. Stability analysis of the model without best fitting shows that universe may begin from an unstable state passing a saddle point and finally become stable in future. However, with the best fitted model, There is no saddle intermediate state. The agegraphic dark energy in the model by itself exhibits a phantom behavior. However, contribution of cold dark matter on the effective energy density modifies the state of teh universe from phantom phase to quintessence one. The statefinder diagnosis also indicates that the universe leaves an unstable state in the past, passes the LCDM state and finally approaches the sable state in future.Comment: 15 pages, 12 figure

Josephson Coupling and Fiske Dynamics in Ferromagnetic Tunnel Junctions

We report on the fabrication of Nb/AlO_x/Pd_{0.82}Ni_{0.18}/Nb superconductor/insulator/ferromagnetic metal/superconductor (SIFS) Josephson junctions with high critical current densities, large normal resistance times area products, high quality factors, and very good spatial uniformity. For these junctions a transition from 0- to \pi-coupling is observed for a thickness d_F ~ 6 nm of the ferromagnetic Pd_{0.82}Ni_{0.18} interlayer. The magnetic field dependence of the \pi-coupled junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd_{0.82}Ni_{0.18} has an out-of-plane anisotropy and large saturation magnetization, indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes provides information on the junction quality factor and the relevant damping mechanisms up to about 400 GHz. Whereas losses due to quasiparticle tunneling dominate at low frequencies, the damping is dominated by the finite surface resistance of the junction electrodes at high frequencies. High quality factors of up to 30 around 200 GHz have been achieved. Our analysis shows that the fabricated junctions are promising for applications in superconducting quantum circuits or quantum tunneling experiments.Comment: 15 pages, 9 figure

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

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