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.

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.

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.

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.

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.

Lung MRI with hyperpolarised gases: current & future clinical perspectives.

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique - hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe - a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.

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.

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.

Gallium-67 Scan with Single Photon Emission Computed Tomography for the Evaluation and Monitoring of Infected Abdominal Aortic Aneurysms: A 10-Year Case Series.

PURPOSE: This study aimed to evaluate the role of gallium-67 single photon emission computed tomography (SPECT) with contrast computed tomography (CT) in the evaluation and monitoring of infected abdominal aortic aneurysms (IAAA). MATERIALS AND METHODS: A retrospective cohort analysis was performed using prospectively collected data of consecutive patients with IAAA in Princess Margaret Hospital in Hong Kong between January 2010 and December 2020. The patients were identified using the Radiology Information System. RESULTS: All five patients had proven IAAA on CT and/or metabolic imaging. Among them, three were further supported by positive blood culture results. Gallium- 67 SPECT with contrast CT was useful in the detection of residual disease, monitoring, and detection of recurrence. CONCLUSION: Gallium-67 SPECT with contrast CT is helpful for evaluating IAAA. It serves an important role in guiding management, especially during long-term follow-up.

In vivo methods and applications of xenon-129 magnetic resonance.

Hyperpolarised gas lung MRI using xenon-129 can provide detailed 3D images of the ventilated lung airspaces, and can be applied to quantify lung microstructure and detailed aspects of lung function such as gas exchange. It is sensitive to functional and structural changes in early lung disease and can be used in longitudinal studies of disease progression and therapy response. The ability of 129Xe to dissolve into the blood stream and its chemical shift sensitivity to its local environment allow monitoring of gas exchange in the lungs, perfusion of the brain and kidneys, and blood oxygenation. This article reviews the methods and applications of in vivo129Xe MR in humans, with a focus on the physics of polarisation by optical pumping, radiofrequency coil and pulse sequence design, and the in vivo applications of 129Xe MRI and MRS to examine lung ventilation, microstructure and gas exchange, blood oxygenation, and perfusion of the brain and kidneys.

Airspace Dimension Assessment (AiDA) by inhaled nanoparticles: benchmarking with hyperpolarised 129Xe diffusion-weighted lung MRI.

Enlargements of distal airspaces can indicate pathological changes in the lung, but accessible and precise techniques able to measure these regions are lacking. Airspace Dimension Assessment with inhaled nanoparticles (AiDA) is a new method developed for in vivo measurement of distal airspace dimensions. The aim of this study was to benchmark the AiDA method against quantitative measurements of distal airspaces from hyperpolarised 129Xe diffusion-weighted (DW)-lung magnetic resonance imaging (MRI). AiDA and 129Xe DW-MRI measurements were performed in 23 healthy volunteers who spanned an age range of 23-70 years. The relationship between the 129Xe DW-MRI and AiDA metrics was tested using Spearman's rank correlation coefficient. Significant correlations were observed between AiDA distal airspace radius (rAiDA) and mean 129Xe apparent diffusion coefficient (ADC) (p < 0.005), distributed diffusivity coefficient (DDC) (p < 0.001) and distal airspace dimension (LmD) (p < 0.001). A mean bias of - 1.2 µm towards rAiDA was observed between 129Xe LmD and rAiDA, indicating that rAiDA is a measure of distal airspace dimension. The AiDA R0 intercept correlated with MRI 129Xe α (p = 0.02), a marker of distal airspace heterogeneity. This study demonstrates that AiDA has potential to characterize the distal airspace microstructures and may serve as an alternative method for clinical examination of the lungs.

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.

Tc-99m sulfur colloid SPECT-CT and assessment of functional liver reserve after Y90 radioembolization: A case report.

INTRODUCTION: Quantitative assessment is an essential tool in determining the proportion of liver to be reserved before lobectomy. Technetium-99 m sulfur colloid single-photon emission computed tomography (Tc-99 m SC SPECT-CT) can help in the quantitative assessment of functioning liver tissues and percentage of liver reserve before segmentectomy and lobectomy Matesan et al. (2017), Bowen et al. (2016) and Lam et al. (2013). PRESENTATION OF CASE: A 64-year-old man with alcoholic cirrhosis was admitted to our hospital with a 15 × 10 x 13 cm bilobar HCC. Y90 radioembolization was utilized to downstage the liver tumor. On follow-up CT scan of the liver after radiotherapy, the HCC was much reduced to 6.5 cm in size but still viable with elevated alpha fetoprotein ([AFP] from 225 to 381 to 959 ng/mL). Resection was considered. Constitutional indocyanine green retention at 15 min (ICG-R-15) was 22%. We introduced the Tc-99 m SC SPECT-CT scan in order to assess the percentage liver function of each lobe. It showed minimal uptake in the remaining functioning right lobe with a hypertrophic left lobe to whole liver uptake ratio of 87.1%. This finding gave us confidence to perform right hepatectomy. DISCUSSION: We used Tc-99 m SC SPECT-CT to estimate the normal functional liver reserve after Y90 radioembolization of a hepatocellular carcinoma (HCC). To our understanding, it is the first case report using Tc-99 m SC to predict the percentage of functional liver reserve after yttrium-90 (Y90) radioembolization. CONCLUSION: Tc-99 m SC SPECT-CT is a novel helper used to assess the differential liver function after Y90 radioembolization of HCC and before segmentectomy and lobectomy of the liver.

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.

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.

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 + 1 liter (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. Percent 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 <1.5% and <5.5% for Hscore at all lung volumes, while 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 percent 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. NEW & NOTEWORTHY We present repeatability data of quantitative metrics of lung function derived from hyperpolarized helium-3, xenon-129, and proton anatomical images acquired at five lung volumes in volunteers. Increased regional ventilation heterogeneity at lower lung inflation levels was observed in the lungs of healthy volunteers.

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.

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 .