Image Phenotyping of Preterm-Born Children Using Hyperpolarized 129Xe Lung Magnetic Resonance Imaging and Multiple-Breath Washout.

Rationale: Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood. Objectives: We assessed the differential associations between the historical diagnosis of bronchopulmonary dysplasia (BPD) and current lung function phenotypes on lung ventilation and microstructure in preterm-born children using hyperpolarized 129Xe ventilation and diffusion-weighted magnetic resonance imaging (MRI) and multiple-breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 yr), including 44 born preterm (⩽34 weeks' gestation) and 19 term-born control subjects (⩾37 weeks' gestation). Preterm-born children were classified, using spirometry, as prematurity-associated obstructive lung disease (POLD; FEV1 < lower limit of normal [LLN] and FEV1/FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (FEV1 < LLN and FEV1/FVC ⩾ LLN), preterm-(FEV1 ⩾ LLN) and term-born control subjects, and those with and without BPD. Ventilation heterogeneity metrics were derived from 129Xe ventilation MRI and SF6 MBW. Alveolar microstructural dimensions were derived from 129Xe diffusion-weighted MRI. Measurements and Main Results: 129Xe ventilation defect percentage and ventilation heterogeneity index were significantly increased in preterm-born children with POLD. In contrast, mean 129Xe apparent diffusion coefficient, 129Xe apparent diffusion coefficient interquartile range, and 129Xe mean alveolar dimension interquartile range were significantly increased in preterm-born children with BPD, suggesting changes of alveolar dimensions. MBW metrics were all significantly increased in the POLD group compared with preterm- and term-born control subjects. Linear regression confirmed the differential effects of obstructive disease on ventilation defects and BPD on lung microstructure. Conclusion: We show that ventilation abnormalities are associated with POLD, and BPD in infancy is associated with abnormal lung microstructure.

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BACKGROUND: Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton (1 H)-MRI lung segmentation.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 1 H-MRI, robust to pathology, acquisition protocol, vendor, and center. STUDY TYPE: Retrospective. POPULATION: A total of 809 1 H-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 1 H-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 <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 1 H-MRI lung segmentations on a heterogenous dataset, demonstrating robustness to disease pathology, sequence, vendor, and center. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 1.

Finite element simulations of hyperpolarized gas DWI in micro-CT meshes of acinar airways: validating the cylinder and stretched exponential models of lung microstructural length scales.

PURPOSE: This work assesses the accuracy of the stretched exponential (SEM) and cylinder models of lung microstructural length scales that can be derived from hyperpolarized gas DWI. This was achieved by simulating 3 He and 129 Xe DWI signals within two micro-CT-derived realistic acinar airspace meshes that represent healthy and idiopathic pulmonary fibrosis lungs. METHODS: The healthy and idiopathic pulmonary fibrosis acinar airway meshes were derived from segmentations of 3D micro-CT images of excised human lungs and meshed for finite element simulations of the Bloch-Torrey equations. 3 He and 129 Xe multiple b value DWI experiments across a range of diffusion times (3 He Δ = 1.6 ms; 129 Xe Δ = 5 to 20 ms) were simulated in each mesh. Global SEM mean diffusive length scale and cylinder model mean chord length value was derived from each finite element simulation and compared against each mesh's mean linear intercept length, calculated from intercept length measurements within micro-CT segmentation masks. RESULTS: The SEM-derived mean diffusive length scale was within ±10% of the mean linear intercept length for simulations with both 3 He (Δ = 1.6 ms) and 129 Xe (Δ = 7 to 13 ms) in the healthy mesh, and with 129 Xe (Δ = 13 to 20 ms) for the idiopathic pulmonary fibrosis mesh, whereas for the cylinder model-derived mean chord length the closest agreement with mean linear intercept length (11.7% and 22.6% difference) was at 129 Xe Δ = 20 ms for both healthy and IPF meshes, respectively. CONCLUSION: This work validates the use of the SEM for accurate estimation of acinar dimensions and indicates that the SEM is relatively robust across a range of experimental conditions and acinar length scales.

MR properties of 19 F C3 F8 gas in the lungs of healthy volunteers: T 2 ∗ and apparent diffusion coefficient at 1.5T and T 2 ∗ at 3T.

PURPOSE: To measure the transverse relaxation time ( T 2 ∗ ) and apparent diffusion coefficient (ADC) of 19 F-C3 F8 gas in vivo in human lungs at 1.5T and 3T, and to determine the representative distribution of values of these parameters in a cohort of healthy volunteers. METHODS: Mapping of ADC at lung inflation levels of functional residual capacity (FRC) and total lung capacity (TLC) was performed with inhaled 19 F-C3 F8 (eight subjects) and 129 Xe (six subjects) at 1.5T. T 2 ∗ mapping with 19 F-C3 F8 was performed at 1.5T (at FRC and TLC) for 8 subjects and at 3T (at TLC for seven subjects). RESULTS: At both FRC and TLC, the 19 F-C3 F8 ADC was smaller than the free diffusion coefficient demonstrating airway microstructural diffusion restriction. From FRC to TLC, the mean ADC significantly increased from 1.56 mm2 /s to 1.83 mm2 /s (P = .0017) for 19 F-C3 F8, and from 2.49 mm2 /s to 3.38 mm2 /s (P = .0015) for 129 Xe. The posterior-to-anterior gradient in ADC for FRC versus TLC in the superior half of the lungs was measured as 0.0308 mm2 /s per cm versus 0.0168 mm2 /s per cm for 19 F-C3 F8 and 0.0871 mm2 /s per cm versus 0.0326 mm2 /s per cm for 129 Xe. A consistent distribution of 19 F-C3 F8 T 2 ∗ values was observed in the lungs, with low values observed near the diaphragm and large pulmonary vessels. The mean T 2 ∗ across volunteers was 4.48 ms at FRC and 5.33 ms at TLC for 1.5T, and 3.78 ms at TLC for 3T. CONCLUSION: In this feasibility study, values of physiologically relevant parameters of lung microstructure measurable by MRI ( T 2 ∗ , and ADC) were established for C3 F8 in vivo lung imaging in healthy volunteers.

An asymmetrical whole-body birdcage RF coil without RF shield for hyperpolarized 129 Xe lung MR imaging at 1.5 T.

PURPOSE: This study describes the development and testing of an asymmetrical xenon-129 (129 Xe) birdcage radiofrequency (RF) coil for 129 Xe lung ventilation imaging at 1.5 Tesla, which allows proton (1 H) system body coil transmit-receive functionality. METHODS: The 129 Xe RF coil is a whole-body asymmetrical elliptical birdcage constructed without an outer RF shield to enable 1 H imaging. B1+ field homogeneity and flip angle mapping of the 129 Xe birdcage RF coil and 1 H system body RF coil with the 129 Xe RF coil in situ were evaluated in the MR scanner. The functionality of the 129 Xe birdcage RF coil was demonstrated through hyperpolarized 129 Xe lung ventilation imaging with the birdcage in both transceiver configuration and transmit-only configuration when combined with an 8-channel 129 Xe receive-only RF coil array. The functionality of 1 H system body coil with the 129 Xe RF coil in situ was demonstrated by acquiring coregistered 1 H lung anatomical MR images. RESULTS: The asymmetrical birdcage produced a homogeneous B1+ field (±10%) in agreement with electromagnetic simulations. Simulations indicated an optimal detuning configuration with 4 diodes. The obtained g-factor of 1.4 for acceleration factor of R = 2 indicates optimal array configuration. Coregistered 1 H anatomical images from the system body coil along with 129 Xe lung images demonstrated concurrent and compatible arrangement of the RF coils. CONCLUSION: A large asymmetrical birdcage for homogenous B1+ transmission with high sensitivity reception for 129 Xe lung MRI at 1.5 Tesla has been demonstrated. The unshielded asymmetrical birdcage design enables 1 H structural lung MR imaging in the same exam.

Protocols for multi-site trials using hyperpolarized 129 Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the 129 Xe MRI clinical trials consortium.

Hyperpolarized (HP) 129 Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129 Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129 Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129 Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129 Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129 Xe MRI. Recommendations are described for the most common HP gas MRI techniques-calibration, ventilation, alveolar-airspace size, and gas exchange-across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129 Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129 Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129 Xe MRI for multi-site pulmonary research.

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.

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. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Altes and Flors in this issue.

Comparison of in vivo lung morphometry models from 3D multiple b-value 3 He and 129 Xe diffusion-weighted MRI.

PURPOSE: To compare in vivo lung morphometry parameters derived from theoretical gas diffusion models, the cylinder model and stretched exponential model, in a range of acinar microstructural length scales encountered in healthy and diseased lungs with 3 He and 129 Xe diffusion-weighted MRI. METHODS: Three-dimensional multiple b-value 3 He and 129 Xe diffusion-weighted MRI was acquired with compressed sensing at 1.5 T from 51 and 31 subjects, respectively, including healthy volunteers, ex-smokers, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease patients. For each subject, the stretched exponential model-derived mean diffusive length scale (LmD ) was calculated from the diffusion signal decay, and was compared with the cylinder model-derived mean chord length (Lm) and mean alveolar diameter (LAlv ) in order to determine the relationships among the different lung morphometry parameters. RESULTS: For both 3 He and 129 Xe diffusion-weighted MRI, the mean global LmD value was significantly related (P < .001) to Lm in a nonlinear power relationship, whereas the LAlv demonstrated excellent linear correlation (P < .001) with LmD . A mean bias of +1.0% and - 2.6% toward LmD was obtained for Bland-Altman analyses of 3 He and 129 Xe LmD and LAlv values, suggesting that the two morphometric parameters are equivalent measures of mean acinar dimensions. CONCLUSION: Within the experimental range of parameters considered here for both 3 He and 129 Xe, the stretched exponential model-derived LmD is related nonlinearly to cylinder model-derived Lm, and demonstrates excellent agreement with the cylinder model-derived LAlv .

Single breath-held acquisition of coregistered 3D 129 Xe lung ventilation and anatomical proton images of the human lung with compressed sensing.

PURPOSE: To develop and assess a method for acquiring coregistered proton anatomical and hyperpolarized 129 Xe ventilation MR images of the lungs with compressed sensing (CS) in a single breath hold. METHODS: Retrospective CS simulations were performed on fully sampled ventilation images acquired from one healthy smoker to optimize reconstruction parameters. Prospective same-breath anatomical and ventilation images were also acquired in five ex-smokers with an acceleration factor of 3 for hyperpolarized 129 Xe images, and were compared to fully sampled images acquired during the same session. The following metrics were used to assess data fidelity: mean absolute error (MAE), root mean square error, and linear regression of the signal intensity between fully sampled and undersampled images. The effect of CS reconstruction on two quantitative imaging metrics routinely reported [percentage ventilated volume (%VV) and heterogeneity score] was also investigated. RESULTS: Retrospective simulations showed good agreement between fully sampled and CS-reconstructed (acceleration factor of 3) images with MAE (root mean square error) of 3.9% (4.5%). The prospective same-breath images showed a good match in ventilation distribution with an average R2 of 0.76 from signal intensity linear regression and a negligible systematic bias of +0.1% in %VV calculation. A bias of -1.8% in the heterogeneity score was obtained. CONCLUSION: With CS, high-quality 3D images of hyperpolarized 129 Xe ventilation (resolution 4.2 × 4.2 × 7.5 mm3 ) can be acquired with coregistered 1 H anatomical MRI in a 15-s breath hold. The accelerated acquisition time dispenses with the need for registration between separate breath-hold 129 Xe and 1 H MRI, enabling more accurate %VV calculation.

3D diffusion-weighted 129 Xe MRI for whole lung morphometry.

PURPOSE: To obtain whole lung morphometry measurements from 129 Xe in a single breath-hold with 3D multiple b-value 129 Xe diffusion-weighted MRI (DW-MRI) with an empirically optimized diffusion time and compressed sensing for scan acceleration. METHODS: Prospective three-fold undersampled 3D multiple b-value hyperpolarized 129 Xe DW-MRI datasets were acquired, and the diffusion time (Δ) was iterated so as to provide diffusive length scale (LmD ) estimates from the stretched exponential model (SEM) that are comparable to those from 3 He. The empirically optimized 129 Xe diffusion time was then implemented with a four-fold undersampling scheme and was prospectively benchmarked against 3 He measurements in a cohort of five healthy volunteers, six ex-smokers, and two chronic obstructive pulmonary disease patients using both SEM-derived LmD and cylinder model (CM)-derived mean chord length (Lm). RESULTS: Good agreement between the mean 129 Xe and 3 He LmD (mean difference, 2.2%) and Lm (mean difference, 1.1%) values was obtained in all subjects at an empirically optimized 129 Xe Δ = 8.5 ms. CONCLUSION: Compressed sensing has facilitated single-breath 3D multiple b-value 129 Xe DW-MRI acquisitions, and results at 129 Xe Δ = 8.5 ms indicate that 129 Xe provides a viable alternative to 3 He for whole lung morphometry mapping with either the SEM or CM. Magn Reson Med 79:2986-2995, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Comparison of 3 He and 129 Xe MRI for evaluation of lung microstructure and ventilation at 1.5T.

BACKGROUND: To support translational lung MRI research with hyperpolarized 129 Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from 3 He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of 129 Xe functional metrics have not been reported. PURPOSE/HYPOTHESIS: To compare hyperpolarized 129 Xe and 3 He MRI-derived quantitative metrics of lung ventilation and microstructure, and their repeatability, at 1.5T. STUDY TYPE: Retrospective. POPULATION: Fourteen healthy nonsmokers (HN), five exsmokers (ES), five patients with chronic obstructive pulmonary disease (COPD), and 16 patients with nonsmall-cell lung cancer (NSCLC). FIELD STRENGTH/SEQUENCE: 1.5T. NSCLC, COPD patients and selected HN subjects underwent 3D balanced steady-state free-precession lung ventilation MRI using both 3 He and 129 Xe. Selected HN, all ES, and COPD patients underwent 2D multislice spoiled gradient-echo diffusion-weighted lung MRI using both hyperpolarized gas nuclei. ASSESSMENT: Ventilated volume percentages (VV%) and mean apparent diffusion coefficients (ADC) were derived from imaging. COPD patients performed the whole MR protocol in four separate scan sessions to assess repeatability. Same-day pulmonary function tests were performed. STATISTICAL TESTS: Intermetric correlations: Spearman's coefficient. Intergroup/internuclei differences: analysis of variance / Wilcoxon's signed rank. Repeatability: coefficient of variation (CV), intraclass correlation (ICC) coefficient. RESULTS: A significant positive correlation between 3 He and 129 Xe VV% was observed (r = 0.860, P < 0.001). VV% was larger for 3 He than 129 Xe (P = 0.001); average bias, 8.79%. A strong correlation between mean 3 He and 129 Xe ADC was obtained (r = 0.922, P < 0.001). MR parameters exhibited good correlations with pulmonary function tests. In COPD patients, mean CV of 3 He and 129 Xe VV% was 4.08% and 13.01%, respectively, with ICC coefficients of 0.541 (P = 0.061) and 0.458 (P = 0.095). Mean 3 He and 129 Xe ADC values were highly repeatable (mean CV: 2.98%, 2.77%, respectively; ICC: 0.995, P < 0.001; 0.936, P < 0.001). DATA CONCLUSION: 129 Xe lung MRI provides near-equivalent information to 3 He for quantitative lung ventilation and microstructural MRI at 1.5T. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018.

Whole lung morphometry with 3D multiple b-value hyperpolarized gas MRI and compressed sensing.

PURPOSE: To demonstrate three-dimensional (3D) multiple b-value diffusion-weighted (DW) MRI of hyperpolarized 3 He gas for whole lung morphometry with compressed sensing (CS). METHODS: A fully-sampled, two b-value, 3D hyperpolarized 3 He DW-MRI dataset was acquired from the lungs of a healthy volunteer and retrospectively undersampled in the ky and kz phase-encoding directions for CS simulations. Optimal k-space undersampling patterns were determined by minimizing the mean absolute error between reconstructed and fully-sampled 3 He apparent diffusion coefficient (ADC) maps. Prospective three-fold, undersampled, 3D multiple b-value 3 He DW-MRI datasets were acquired from five healthy volunteers and one chronic obstructive pulmonary disease (COPD) patient, and the mean values of maps of ADC and mean alveolar dimension (LmD ) were validated against two-dimensional (2D) and 3D fully-sampled 3 He DW-MRI experiments. RESULTS: Reconstructed undersampled datasets showed no visual artifacts and good preservation of the main image features and quantitative information. A good agreement between fully-sampled and prospective undersampled datasets was found, with a mean difference of +3.4% and +5.1% observed in mean global ADC and LmD values, respectively. These differences were within the standard deviation range and consistent with values reported from healthy and COPD lungs. CONCLUSIONS: Accelerated CS acquisition has facilitated 3D multiple b-value 3 He DW-MRI scans in a single breath-hold, enabling whole lung morphometry mapping. Magn Reson Med 77:1916-1925, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Quantifying normal geometric variation in human pulmonary lobar geometry from high resolution computed tomography.

Previous studies of the ex vivo lung have suggested significant intersubject variability in lung lobe geometry. A quantitative description of normal lung lobe shape would therefore have value in improving the discrimination between normal population variability in shape and pathology. To quantify normal human lobe shape variability, a principal component analysis (PCA) was performed on high resolution computed tomography (HRCT) imaging of the lung at full inspiration. Volumetric imaging from 22 never-smoking subjects (10 female and 12 male) with normal lung function was included in the analysis. For each subject, an initial finite element mesh geometry was generated from a group of manually selected nodes that were placed at distinct anatomical locations on the lung surface. Each mesh used cubic shape functions to describe the surface curvilinearity, and the mesh was fitted to surface data for each lobe. A PCA was performed on the surface meshes for each lobe. Nine principal components (PCs) were sufficient to capture >90% of the normal variation in each of the five lobes. The analysis shows that lobe size can explain between 20% and 50% of intersubject variability, depending on the lobe considered. Diaphragm shape was the next most significant intersubject difference. When the influence of lung size difference is removed, the angle of the fissures becomes the most significant shape difference, and the variability in relative lobe size becomes important. We also show how a lobe from an independent subject can be projected onto the study population's PCs, demonstrating potential for abnormalities in lobar geometry to be defined in a quantitative manner.

Individualised Transcranial Magnetic Stimulation Targeting of the Left Dorsolateral Prefrontal Cortex for Enhancing Cognition: A Randomised Controlled Trial.

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex (L-DLPFC) for enhancing cognitive flexibility based on performance on a cognitive task. First, forty healthy participants had their single target site at the L-DLPFC determined based on each individual's performance on a random letter generation task. Participants then received, in a cross-over single-blinded experimental design, a single session of intermittent theta burst stimulation (iTBS) to their individualised DLPFC target site, an active control site and sham iTBS. Following each treatment condition, participants completed the Task Switching task and Colour-Word Stroop test. There was no significant main effect of treatment condition on the primary outcome measure of switch reaction times from the Task Switching task [F = 1.16 (2, 21.6), p = 0.33] or for any of the secondary cognitive outcome measures. The current results do not support the use of our novel individualised targeting methodology for enhancing cognitive flexibility in healthy participants. Research into alternative methodological targeting approaches is required to further improve rTMS's cognitive enhancing effects.

Prolonged intermittent theta burst stimulation targeting the left prefrontal cortex and cerebellum does not affect executive functions in healthy individuals.

Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.

Hyperpolarised xenon-129 diffusion-weighted magnetic resonance imaging for assessing lung microstructure in idiopathic pulmonary fibrosis.

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.

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.

Longitudinal Lung Function Assessment of Patients Hospitalized With COVID-19 Using 1H and 129Xe Lung MRI.

BACKGROUND: Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear. RESEARCH QUESTION: Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52 weeks following hospitalization? STUDY DESIGN AND METHODS: Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange. RESULTS: Nine patients were recruited (age 57 ± 14 [median ± interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n = 9), 12 (n = 9), 25 (n = 6), and 51 (n = 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6 weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6- to 25-week period. At 12 weeks, all patients with lung perfusion data (n = 6) showed an increase in both pulmonary blood volume and flow compared with 6 weeks, although this was not statistically significant. At 12 weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and 51. INTERPRETATION: 129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52 weeks.