Pompowanie optyczne z wymianą metastabilności (MEOP) helu-3 in situ

Polarized helium-3 is used as a contrast agent for lungs magnetic resonance imaging that has recently reached the pre-clinical applications. The main method to hyperpolarize 3He is the metastability exchange optical pumping (MEOP). Optical pumping is performed in standard conditions at low pressure (≈ 1 mbar) and low magnetic field (≈ 1 Gauss). In this work, the complete update of a low field polarizer dedicated to small animal lungs imaging is presented. The implementation of a new 10 W laser, new peristaltic compressor and others components resulted in a production of 3-4 scc/min for a polarization between 30 to 40%. Images of rat lungs made with better resolution and a new dynamic radial sequence are presented as a validation of the system. Since few years, MEOP has also been studied at higher pressures and higher magnetic fields in small sealed cells. It showed that, thanks to hyperfine decoupling effect induced by high magnetic field, it was also possible to efficiently polarize at higher pressure (67 mbar). Experiments done at 4.7 and 1.5 T are reported in this work. The first ones show a benefic (higher polarization values) and a negative effect (lower production rates) of the magnetic field. The seconds highlight the advantage of using an annular beam shape of the laser that matches the distribution of 23S state atoms at higher pressure. Nuclear polarization values of 66.4% at 32 mbar and 31% at 267 mbar were obtained in 20 mL sealed cells and a 10 times increase in the production rate compare to best standard conditions. These promising results were the first motivation for building a high-field polarizer working inside MRI scanner in hospital. The design and construction of such a polarizer is described in detail in the last part of the dissertation. The polarizer produces hyperpolarize 3He at 30-40% with a 4 times higher flow than the low field polarizer (10-15 scc/min). The first good quality human lungs images made in Poland with healthy volunteers are the main result of this work

Assessment of the influence of lung inflation state on the quantitative parameters derived from hyperpolarized gas lung ventilation MRI in healthy volunteers.

In this study, the effect of lung volume on quantitative measures of lung ventilation was investigated using MRI with hyperpolarized 3He and 129Xe. Six volunteers were imaged with hyperpolarized 3He at five different lung volumes (residual volume (RV), RV+1L, functional residual capacity (FRC), FRC+1L and total lung capacity (TLC)), and three were also imaged with hyperpolarized 129Xe. Imaging at each of the lung volumes was repeated twice on the same day with corresponding 1H lung anatomical images. Percentage lung ventilated volume (%VV) and variation of signal intensity (heterogeneity score, Hscore) were evaluated. Increased ventilation heterogeneity, quantified by reduced %VV and increased Hscore, was observed at lower lung volumes with the least ventilation heterogeneity observed at TLC. For 3He MRI data, the coefficient of variation of %VV was less than 1.5% and less than 5.5% for Hscore at all lung volumes, whilst for 129Xe data the values were 4% and 10% respectively. Generally, %VV generated from 129Xe images was lower than that seen from 3He images. The good repeatability of 3He %VV found here supports prior publications showing that percentage lung ventilated volume is a robust method for assessing global lung ventilation. The greater ventilation heterogeneity observed at lower lung volumes indicates that there may be partial airway closure in healthy lungs and that lung volume should be carefully considered for reliable longitudinal measurements of %VV and Hscore. The results suggest that imaging patients at different lung volumes may help to elucidate obstructive disease pathophysiology and progression

Airway microstructure in idiopathic pulmonary fibrosis: assessment at hyperpolarized 3He diffusion-weighted MRI

Background MRI with inhaled hyperpolarized helium 3 (3He) allows for functional and structural imaging of the lungs. Hyperpolarized gas diffusion-weighted (DW) MRI provides noninvasive and quantitative assessment of microstructural acinar changes in the lungs. Purpose To investigate whether microstructural imaging metrics from in-vivo hyperpolarized 3He DW MRI are sensitive to longitudinal changes in a cohort of participants with idiopathic pulmonary fibrosis (IPF) and to evaluate the reproducibility of these metrics and their correlation with existing clinical measures of IPF disease severity. Materials and Methods In this prospective study, 18 participants with IPF underwent 3He DW MRI at 1.5 T and 11 participants underwent an identical same-day examination for reproducibility assessment. Thirteen participants returned for 6- and 12-month follow-up examinations. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide and forced vital capacity, were performed at each examination. The apparent diffusion coefficient (ADC) and stretched exponential model–derived mean diffusive length scale (LmD) from DW MRI was compared with baseline CT fibrosis scores and pulmonary function tests by using Spearman rank correlation coefficient. Longitudinal changes in DW MRI and pulmonary function test measurements were assessed with Friedman tests and post hoc Dunn test. Results 3He ADC and LmD were reproducible (mean Bland-Altman analysis bias, 0.002 cm2 · sec-1 and −1.5 μm, respectively). Elevated ADC and LmD regions qualitatively corresponded to fibrotic regions at CT. ADC and LmD correlated with diffusing capacity of the lungs for carbon monoxide (respectively: r = −0.56, P = .017; and r = −0.54, P = .02) and CT fibrosis score (respectively: r = 0.71, P = .001; and r = 0.65, P = .003). LmD increased by 12 μm after 12 months (P = .001) whereas mean ADC (P = .17), forced vital capacity (P = .12), and diffusing capacity of the lungs for carbon monoxide (P > .99) were not statistically different between examinations. Conclusion Helium 3 diffusion-weighted MRI-derived mean diffusive length scale demonstrates longitudinal changes in lungs affected by idiopathic pulmonary fibrosis

Detection of early sub-clinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarized gas MRI

Hyperpolarised 3He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6–16 years) with clinically stable mild cystic fibrosis (CF) (FEV1>−1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure–function relationships

Implementable Deep Learning for Multi-sequence Proton MRI Lung Segmentation:A Multi-center, Multi-vendor, and Multi-disease Study

Background: Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton (1H)-MRI lung segmentation. However, previous deep learning studies have utilized single-center data and limited acquisition parameters.Purpose: Develop a generalizable CNN for lung segmentation in 1H-MRI, robust to pathology, acquisition protocol, vendor, and center.Study type: Retrospective.Population: A total of 809 1H-MRI scans from 258 participants with various pulmonary pathologies (median age (range): 57 (6–85); 42% females) and 31 healthy participants (median age (range): 34 (23–76); 34% females) that were split into training (593 scans (74%); 157 participants (55%)), testing (50 scans (6%); 50 participants (17%)) and external validation (164 scans (20%); 82 participants (28%)) sets.Field Strength/Sequence: 1.5-T and 3-T/3D spoiled-gradient recalled and ultrashort echo-time 1H-MRI.Assessment: 2D and 3D CNNs, trained on single-center, multi-sequence data, and the conventional spatial fuzzy c-means (SFCM) method were compared to manually delineated expert segmentations. Each method was validated on external data originating from several centers. Dice similarity coefficient (DSC), average boundary Hausdorff distance (Average HD), and relative error (XOR) metrics to assess segmentation performance.Statistical Tests: Kruskal–Wallis tests assessed significances of differences between acquisitions in the testing set. Friedman tests with post hoc multiple comparisons assessed differences between the 2D CNN, 3D CNN, and SFCM. Bland–Altman analyses assessed agreement with manually derived lung volumes. A P value of &lt;0.05 was considered statistically significant.Results: The 3D CNN significantly outperformed its 2D analog and SFCM, yielding a median (range) DSC of 0.961 (0.880–0.987), Average HD of 1.63 mm (0.65–5.45) and XOR of 0.079 (0.025–0.240) on the testing set and a DSC of 0.973 (0.866–0.987), Average HD of 1.11 mm (0.47–8.13) and XOR of 0.054 (0.026–0.255) on external validation data.Data Conclusion: The 3D CNN generated accurate 1H-MRI lung segmentations on a heterogenous dataset, demonstrating robustness to disease pathology, sequence, vendor, and center.Evidence Level: 4.Technical Efficacy: Stage 1.</p

Supine posture changes lung volumes and increases ventilation heterogeneity in cystic fibrosis

INTRODUCTION: Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. METHODS: 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. RESULTS: From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01). LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude of change with posture for both LCIalv and FRCalv in both groups, with a greater effect of change in lung volume in HC compared with children with CF. The % change in LCIalv for all subjects correlated significantly with lung volume % changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r = 0.54,p<0.001)). CONCLUSION: There is a significant increase in LCI from sitting to supine, which we believe to be in part due to changes in lung volume and also increasing ventilation heterogeneity related to posture. This may have implications in longitudinal measurements from infancy to older childhood and for studies comparing supine imaging methods to LCI

Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID)

Introduction The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD). Methods and analysis The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment. Ethics and dissemination All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals. Conclusion This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD

Metastability Exchange Optical Pumping (MEOP) of 3He in situ

2011Polarized helium-3 is used as a contrast agent for lungs magnetic resonance imaging that has recently reached the pre-clinical applications. One method to hyperpolarize 3He is the metastability exchange optical pumping (MEOP). Optical pumping is performed in standard conditions at low pressure (~ 1 mbar) and low magnetic field (~ 1 Gauss). In this work, the complete update of a low field polarizer dedicated to small animal lungs imaging is presented. The implementation of a new 10 W laser, new peristaltic compressor and others components resulted in a production of 3-4 scc/min for a polarization between 30 to 40%. Images of rat lungs made with better resolution and a new dynamic radial sequence are presented as a validation of the system. Since few years, MEOP has also been studied at higher pressures and higher magnetic fields in small sealed cells. It showed that, thanks to hyperfine decoupling effect induced by high magnetic field, it was also possible to efficiently polarize at higher pressure (67 mbar). Experiments done at 4.7 and 1.5 T are reported in this work. The first ones show a benefic (higher polarization values) and a negative effect (lower production rates) of the magnetic field. The seconds highlight the advantage of using an annular beam shape of the laser that matches the distribution of 23S state atoms at higher pressure. Nuclear polarization values of 66.4% at 32 mbar and 31% at 267 mbar were obtained in 20 mL sealed cells and a 10 times increase in the production rate compare to best standard conditions. These promising results were the first motivation for building a high-field polarizer working inside MRI scanner in hospital. The design and the construction of such a polarizer are described in detail in the last part of the dissertation. The polarizer produces hyperpolarize 3He at 30-40% with a 4 times higher flow than the low field polarizer (10-15 scc/min). The first good quality human lungs images made in Poland with healthy volunteers are the main result of this work