Pulmonary MRI with hyperpolarized xenon-129 demonstrates novel alterations in gas transfer across the air-blood barrier in asthma.

BACKGROUND: Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. Hyperpolarized xenon-129 (Xe129) MRI is a novel imaging method to provide 3-D mapping of both ventilation and gas exchange in the human lung. PURPOSE: To evaluate the functional changes in adults with asthma as compared to healthy controls using Xe129 MRI. METHODS: All subjects (20 controls and 20 asthmatics) underwent lung function measurements and Xe129 MRI on the same day. Outcome measures included the pulmonary ventilation defect and transfer of inspired Xe129 into two soluble compartments: tissue and blood. Ten asthmatics underwent Xe129 MRI before and after bronchodilator to test whether gas transfer measures change with bronchodilator effects. RESULTS: Initial analysis of the results revealed striking differences in gas transfer measures based on age, hence we compared outcomes in younger (n = 24, ≤ 35 years) versus older (n = 16, > 45 years) asthmatics and controls. The younger asthmatics exhibited significantly lower Xe129 gas uptake by lung tissue (Asthmatic: 0.98% ± 0.24%, Control: 1.17% ± 0.12%, P = 0.035), and higher Xe129 gas transfer from tissue to the blood (Asthmatic: 0.40 ± 0.10, Control: 0.31% ± 0.03%, P = 0.035) than the younger controls. No significant difference in Xe129 gas transfer was observed in the older group between asthmatics and controls (P > 0.05). No significant change in Xe129 transfer was observed before and after bronchodilator treatment. CONCLUSIONS: By using Xe129 MRI, we discovered heterogeneous alterations of gas transfer that have associations with age. This finding suggests a heretofore unrecognized physiological derangement in the gas/tissue/blood interface in young adults with asthma that deserves further study.

Lung Volume Dependence and Repeatability of Hyperpolarized 129Xe MRI Gas Uptake Metrics in Healthy Volunteers and Participants with COPD.

Purpose: To assess the effect of lung volume on measured values and repeatability of xenon 129 (129Xe) gas uptake metrics in healthy volunteers and participants with chronic obstructive pulmonary disease (COPD). Materials and Methods: This Health Insurance Portability and Accountability Act-compliant prospective study included data (March 2014-December 2015) from 49 participants (19 with COPD [mean age, 67 years ± 9 (SD)]; nine women]; 25 older healthy volunteers [mean age, 59 years ± 10; 20 women]; and five young healthy women [mean age, 23 years ± 3]). Thirty-two participants underwent repeated 129Xe and same-breath-hold proton MRI at residual volume plus one-third forced vital capacity (RV+FVC/3), with 29 also undergoing one examination at total lung capacity (TLC). The remaining 17 participants underwent imaging at TLC, RV+FVC/3, and residual volume (RV). Signal ratios between membrane, red blood cell (RBC), and gas-phase compartments were calculated using hierarchical iterative decomposition of water and fat with echo asymmetry and least-squares estimation (ie, IDEAL). Repeatability was assessed using coefficient of variation and intraclass correlation coefficient, and volume relationships were assessed using Spearman correlation and Wilcoxon rank sum tests. Results: Gas uptake metrics were repeatable at RV+FVC/3 (intraclass correlation coefficient = 0.88 for membrane/gas; 0.71 for RBC/gas, and 0.88 for RBC/membrane). Relative ratio changes were highly correlated with relative volume changes for membrane/gas (r = -0.97) and RBC/gas (r = -0.93). Membrane/gas and RBC/gas measured at RV+FVC/3 were significantly lower in the COPD group than the corresponding healthy group (P ≤ .001). However, these differences lessened upon correction for individual volume differences (P = .23 for membrane/gas; P = .09 for RBC/gas). Conclusion: Dissolved-phase 129Xe MRI-derived gas uptake metrics were repeatable but highly dependent on lung volume during measurement.Keywords: Blood-Air Barrier, MRI, Chronic Obstructive Pulmonary Disease, Pulmonary Gas Exchange, Xenon Supplemental material is available for this article © RSNA, 2023.

Hyperpolarized Xenon-129: A New Tool to Assess Pulmonary Physiology in Patients with Pulmonary Fibrosis.

PURPOSE: The existing tools to quantify lung function in interstitial lung diseases have significant limitations. Lung MRI imaging using inhaled hyperpolarized xenon-129 gas (129Xe) as a contrast agent is a new technology for measuring regional lung physiology. We sought to assess the utility of the 129Xe MRI in detecting impaired lung physiology in usual interstitial pneumonia (UIP). MATERIALS AND METHODS: After institutional review board approval and informed consent and in compliance with HIPAA regulations, we performed chest CT, pulmonary function tests (PFTs), and 129Xe MRI in 10 UIP subjects and 10 healthy controls. RESULTS: The 129Xe MRI detected highly heterogeneous abnormalities within individual UIP subjects as compared to controls. Subjects with UIP had markedly impaired ventilation (ventilation defect fraction: UIP: 30 ± 9%; healthy: 21 ± 9%; p = 0.026), a greater amount of 129Xe dissolved in the lung interstitium (tissue-to-gas ratio: UIP: 1.45 ± 0.35%; healthy: 1.10 ± 0.17%; p = 0.014), and impaired 129Xe diffusion into the blood (RBC-to-tissue ratio: UIP: 0.20 ± 0.06; healthy: 0.28 ± 0.05; p = 0.004). Most MRI variables had no correlation with the CT and PFT measurements. The elevated level of 129Xe dissolved in the lung interstitium, in particular, was detectable even in subjects with normal or mildly impaired PFTs, suggesting that this measurement may represent a new method for detecting early fibrosis. CONCLUSION: The hyperpolarized 129Xe MRI was highly sensitive to regional functional changes in subjects with UIP and may represent a new tool for understanding the pathophysiology, monitoring the progression, and assessing the effectiveness of treatment in UIP.

Image- versus histogram-based considerations in semantic segmentation of pulmonary hyperpolarized gas images.

PURPOSE: To characterize the differences between histogram-based and image-based algorithms for segmentation of hyperpolarized gas lung images. METHODS: Four previously published histogram-based segmentation algorithms (ie, linear binning, hierarchical k-means, fuzzy spatial c-means, and a Gaussian mixture model with a Markov random field prior) and an image-based convolutional neural network were used to segment 2 simulated data sets derived from a public (n = 29 subjects) and a retrospective collection (n = 51 subjects) of hyperpolarized 129Xe gas lung images transformed by common MRI artifacts (noise and nonlinear intensity distortion). The resulting ventilation-based segmentations were used to assess algorithmic performance and characterize optimization domain differences in terms of measurement bias and precision. RESULTS: Although facilitating computational processing and providing discriminating clinically relevant measures of interest, histogram-based segmentation methods discard important contextual spatial information and are consequently less robust in terms of measurement precision in the presence of common MRI artifacts relative to the image-based convolutional neural network. CONCLUSIONS: Direct optimization within the image domain using convolutional neural networks leverages spatial information, which mitigates problematic issues associated with histogram-based approaches and suggests a preferred future research direction. Further, the entire processing and evaluation framework, including the newly reported deep learning functionality, is available as open source through the well-known Advanced Normalization Tools ecosystem.

Measures of ventilation heterogeneity mapped with hyperpolarized helium-3 MRI demonstrate a T2-high phenotype in asthma.

BACKGROUND: Hyperpolarized gas with helium (HHe-3) MR (magnetic resonance) is a noninvasive imaging method which maps and quantifies regions of ventilation heterogeneity (VH) in the lung. VH is an important feature of asthma, but little is known as to how VH informs patient phenotypes. PURPOSE: To determine if VH indicators quantified by HHe-3 MR imaging (MRI) predict phenotypic characteristics and map to regions of inflammation in children with problematic wheeze or asthma. METHODS: Sixty children with poorly-controlled wheeze or asthma underwent HHe-3 MRI, including 22 with bronchoalveolar lavage (BAL). The HHe-3 signal intensity defined four ventilation compartments. The non-ventilated and hypoventilated compartments divided by the total lung volume defined a VH index (VHI %). RESULTS: Children with VHI % in the upper quartile had significantly greater airflow limitation, bronchodilator responsiveness, blood eosinophils, expired nitric oxide (FeNO), and BAL eosinophilic or neutrophilic granulocyte patterns compared to children with VHI % in the lower quartile. Lavage return from hypoventilated bronchial segments had greater eosinophil % than from ventilated segments. CONCLUSION: In children with asthma, greater VHI % as measured by HHe-3 MRI identifies a severe phenotype with higher type 2 inflammatory markers, and maps to regions of lung eosinophilia. Listed on ClinicalTrials. gov (NCT02577497).

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders: Fleischner Society Position Paper.

Pulmonary MRI provides structural and quantitative functional images of the lungs without ionizing radiation, but it has had limited clinical use due to low signal intensity from the lung parenchyma. The lack of radiation makes pulmonary MRI an ideal modality for pediatric examinations, pregnant women, and patients requiring serial and longitudinal follow-up. Fortunately, recent MRI techniques, including ultrashort echo time and zero echo time, are expanding clinical opportunities for pulmonary MRI. With the use of multicoil parallel acquisitions and acceleration methods, these techniques make pulmonary MRI practical for evaluating lung parenchymal and pulmonary vascular diseases. The purpose of this Fleischner Society position paper is to familiarize radiologists and other interested clinicians with these advances in pulmonary MRI and to stratify the Society recommendations for the clinical use of pulmonary MRI into three categories: (a) suggested for current clinical use, (b) promising but requiring further validation or regulatory approval, and (c) appropriate for research investigations. This position paper also provides recommendations for vendors and infrastructure, identifies methods for hypothesis-driven research, and suggests opportunities for prospective, randomized multicenter trials to investigate and validate lung MRI methods.

Emphysema Index Based on Hyperpolarized 3He or 129Xe Diffusion MRI: Performance and Comparison with Quantitative CT and Pulmonary Function Tests.

Background Apparent diffusion coefficient (ADC) maps of inhaled hyperpolarized gases have shown promise in the characterization of emphysema in patients with chronic obstructive pulmonary disease (COPD), yet an easily interpreted quantitative metric beyond mean and standard deviation has not been established. Purpose To introduce a quantitative framework with which to characterize emphysema burden based on hyperpolarized helium 3 (3He) and xenon 129 (129Xe) ADC maps and compare its diagnostic performance with CT-based emphysema metrics and pulmonary function tests (PFTs). Materials and Methods Twenty-seven patients with mild, moderate, or severe COPD and 13 age-matched healthy control subjects participated in this retrospective study. Participants underwent CT and multiple b value diffusion-weighted 3He and 129Xe MRI examinations and standard PFTs between August 2014 and November 2017. ADC-based emphysema index was computed separately for each gas and b value as the fraction of lung voxels with ADC values greater than in the healthy group 99th percentile. The resulting values were compared with quantitative CT results (relative lung area <-950 HU) as the reference standard. Diagnostic performance metrics included area under the receiver operating characteristic curve (AUC). Spearman rank correlations and Wilcoxon rank sum tests were performed between ADC-, CT-, and PFT-based metrics, and intraclass correlation was performed between repeated measurements. Results Thirty-six participants were evaluated (mean age, 60 years ± 6 [standard deviation]; 20 women). ADC-based emphysema index was highly repeatable (intraclass correlation coefficient > 0.99) and strongly correlated with quantitative CT (r = 0.86, P < .001 for 3He; r = 0.85, P < .001 for 129Xe) with high AUC (≥0.93; 95% confidence interval [CI]: 0.85, 1.00). ADC emphysema indices were also correlated with percentage of predicted diffusing capacity of lung for carbon monoxide (r = -0.81, P < .001 for 3He; r = -0.80, P < .001 for 129Xe) and percentage of predicted residual lung volume divided by total lung capacity (r = 0.65, P < .001 for 3He; r = 0.61, P < .001 for 129Xe). Conclusion Emphysema index based on hyperpolarized helium 3 or xenon 129 diffusion MRI provides a repeatable measure of emphysema burden, independent of gas or b value, with similar diagnostic performance as quantitative CT or pulmonary function metrics. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Schiebler and Fain in this issue.

Current state of the art MRI for the longitudinal assessment of cystic fibrosis.

Pulmonary MRI can now provide high-resolution images that are sensitive to early disease and specific to inflammation in cystic fibrosis (CF) lung disease. With specificity and function limited via computed tomography (CT), there are significant advantages to MRI. Many of the modern MRI techniques can be performed throughout life, and can be employed to understand changes over time, in addition to quantification of treatment response. Proton density and T1 /T2 contrast images can be obtained within a single breath-hold, providing depiction of structural abnormalities and active inflammation. Modern radial and/or spiral ultrashort echo-time (UTE) techniques rival CT in resolution for depiction and quantification of structure, for both airway and parenchymal abnormalities. Contrast perfusion MRI techniques are now utilized routinely to visualize changes in pulmonary and bronchial circulation that routinely occur in CF lung disease, and noncontrast techniques are moving closer to clinical translation. Functional information can be obtained from noncontrast proton images alone, using techniques such as Fourier decomposition. Hyperpolarized-gas MRI, increasingly using 129 Xe, is now becoming more widespread and has been demonstrated to have high sensitivity to early airway obstruction in CF via ventilation MRI. The sensitivity of 129 Xe MRI promises future use in personalized medicine, management of early CF lung disease, and in future clinical trials. By combining structural and functional techniques, with or without hyperpolarized gases, regional structure-function relationships can be obtained, giving insight into the pathophysiology of disease and improved clinical management. This article reviews the modern MRI techniques that can routinely be employed for CF lung disease in nearly any large medical center. Level of Evidence: 4 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019.

A hybrid proton and hyperpolarized gas tagging MRI technique for lung respiratory motion imaging: a feasibility study.

The aim of this work was to develop a novel hybrid 3D hyperpolarized (HP) gas tagging MRI (t-MRI) technique and to evaluate it for lung respiratory motion measurement with comparison to deformable image registrations (DIR) methods. Three healthy subjects underwent a hybrid MRI which combines 3D HP gas t-MRI with a low resolution (Low-R, 4.5 mm isotropic voxels) 3D proton MRI (p-MRI), plus a high resolution (High-R, 2.5 mm isotropic voxels) 3D p-MRI, during breath-holds at the end-of-inhalation (EOI) and the end-of-exhalation (EOE). Displacement vector field (DVF) of the lung motion was determined from the t-MRI images by tracking tagging grids and from the High-R p-MRI using three DIR methods (B-spline based method implemented by Velocity, Free Form Deformation by MIM, and B-spline by an open source software Elastix: denoted as A, B, and C, respectively), labeled as tDVF and dDVF, respectively. The tDVF from the HP gas t-MRI was used as ground-truth reference to evaluate performance of the three DIR methods. Differences in both magnitude and angle between the tDVF and dDVFs were analyzed. The mean lung motion of the three subjects was 37.3 mm, 8.9 mm and 12.9 mm, respectively. Relatively large discrepancies were observed between the tDVF and the dDVFs as compared to previously reported DIR errors. The mean ± standard deviation (SD) DVF magnitude difference was 8.3 ± 5.6 mm, 9.2 ± 4.5 mm, and 9.3 ± 6.1 mm, and the mean ± SD DVF angular difference was 29.1 ± 12.1°, 50.1 ± 28.6°, and 39.0 ± 6.3°, for the DIR Methods A, B, and C, respectively. These preliminary results showed that the hybrid HP gas t-MRI technique revealed different lung motion patterns as compared to the DIR methods. It may provide unique perspectives in developing and evaluating DIR of the lungs. Novelty and Significance We designed a MRI protocol that includes a novel hybrid MRI technique (3D HP gas t-MRI with a low resolution 3D p-MRI) plus a high resolution 3D p-MRI. We tested the novel hybrid MRI technique on three healthy subjects for measuring regional lung respiratory motion with comparison to deformable image registrations (DIR) methods, and observed relatively large discrepancies in lung motion between HP gas t-MRI and DIR methods.

Probing Changes in Lung Physiology in COPD Using CT, Perfusion MRI, and Hyperpolarized Xenon-129 MRI.

RATIONALE AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is highly heterogeneous and not well understood. Hyperpolarized xenon-129 (Xe129) magnetic resonance imaging (MRI) provides a unique way to assess important lung functions such as gas uptake. In this pilot study, we exploited multiple imaging modalities, including computed tomography (CT), gadolinium-enhanced perfusion MRI, and Xe129 MRI, to perform a detailed investigation of changes in lung morphology and functions in COPD. Utility and strengths of Xe129 MRI in assessing COPD were also evaluated against the other imaging modalities. MATERIALS AND METHODS: Four COPD patients and four age-matched normal subjects participated in this study. Lung tissue density measured by CT, perfusion measures from gadolinium-enhanced MRI, and ventilation and gas uptake measures from Xe129 MRI were calculated for individual lung lobes to assess regional changes in lung morphology and function, and to investigate correlations among the different imaging modalities. RESULTS: No significant differences were found for all measures among the five lobes in either the COPD or age-matched normal group. Strong correlations (R > 0.5 or < -0.5, p < 0.001) were found between ventilation and perfusion measures. Also gas uptake by blood as measured by Xe129 MRI showed strong correlations with CT tissue density and ventilation measures (R > 0.5 or < -0.5, p < 0.001) and moderate to strong correlations with perfusion measures (R > 0.4 or < -0.5, p < 0.01). Four distinctive patterns of functional abnormalities were found in patients with COPD. CONCLUSION: Xe129 MRI has high potential to uniquely identify multiple changes in lung physiology in COPD using a single breath-hold acquisition.

Using Hyperpolarized Xenon-129 MRI to Quantify Early-Stage Lung Disease in Smokers.

RATIONALE AND OBJECTIVES: Hyperpolarized xenon-129 magnetic resonance (MR) provides sensitive tools that may detect early stages of lung disease in smokers before it has progressed to chronic obstructive pulmonary disease (COPD) apparent to conventional spirometric measures. We hypothesized that the functional alveolar wall thickness as assessed by hyperpolarized xenon-129 MR spectroscopy would be elevated in clinically healthy smokers before xenon MR diffusion measurements would indicate emphysematous tissue destruction. MATERIALS AND METHODS: Using hyperpolarized xenon-129 MR we measured the functional septal wall thickness and apparent diffusion coefficient of the gas phase in 16 subjects with smoking-related COPD, 9 clinically healthy current or former smokers, and 10 healthy never smokers. All subjects were age-matched and characterized by conventional pulmonary function tests. A total of 11 data sets from younger healthy never smokers were added to determine the age dependence of the septal wall thickness measurements. RESULTS: In healthy never smokers the septal wall thickness increased by 0.04 µm per year of age. The healthy smoker cohort exhibited normal pulmonary function test measures that did not significantly differ from the never-smoker cohort. The age-corrected septal wall thickness correlated well with diffusion capacity for carbon monoxide (R2 = 0.56) and showed a highly significant difference between healthy subjects and COPD patients (8.8 µm vs 12.3 µm; p < 0.001), but was the only measure that actually discriminated healthy subjects from healthy smokers (8.8 µm vs 10.6 µm; p < 0.006). CONCLUSION: Functional alveolar wall thickness assessed by hyperpolarized xenon-129 MR allows discrimination between healthy subjects and healthy smokers and could become a powerful new measure of early-stage lung disease.

Convolutional Neural Networks with Template-Based Data Augmentation for Functional Lung Image Quantification.

RATIONALE AND OBJECTIVES: We propose an automated segmentation pipeline based on deep learning for proton lung MRI segmentation and ventilation-based quantification which improves on our previously reported methodologies in terms of computational efficiency while demonstrating accuracy and robustness. The large data requirement for the proposed framework is made possible by a novel template-based data augmentation strategy. Supporting this work is the open-source ANTsRNet-a growing repository of well-known deep learning architectures first introduced here. MATERIALS AND METHODS: Deep convolutional neural network (CNN) models were constructed and trained using a custom multilabel Dice metric loss function and a novel template-based data augmentation strategy. Training (including template generation and data augmentation) employed 205 proton MR images and 73 functional lung MRI. Evaluation was performed using data sets of size 63 and 40 images, respectively. RESULTS: Accuracy for CNN-based proton lung MRI segmentation (in terms of Dice overlap) was left lung: 0.93 ± 0.03, right lung: 0.94 ± 0.02, and whole lung: 0.94 ± 0.02. Although slightly less accurate than our previously reported joint label fusion approach (left lung: 0.95 ± 0.02, right lung: 0.96 ± 0.01, and whole lung: 0.96 ± 0.01), processing time is <1 second per subject for the proposed approach versus ∼30 minutes per subject using joint label fusion. Accuracy for quantifying ventilation defects was determined based on a consensus labeling where average accuracy (Dice multilabel overlap of ventilation defect regions plus normal region) was 0.94 for the CNN method; 0.92 for our previously reported method; and 0.90, 0.92, and 0.94 for expert readers. CONCLUSION: The proposed framework yields accurate automated quantification in near real time. CNNs drastically reduce processing time after offline model construction and demonstrate significant future potential for facilitating quantitative analysis of functional lung MRI.

An initial investigation of hyperpolarized gas tagging magnetic resonance imaging in evaluating deformable image registration-based lung ventilation.

BACKGROUND: Deformable image registration (DIR)-based lung ventilation mapping is attractive due to its simplicity, and also challenging due to its susceptibility to errors and uncertainties. In this study, we explored the use of 3D Hyperpolarized (HP) gas tagging MRI to evaluate DIR-based lung ventilation. METHOD AND MATERIAL: Three healthy volunteers included in this study underwent both 3D HP gas tagging MRI (t-MRI) and 3D proton MRI (p-MRI) using balanced steady-state free precession pulse sequence at end of inhalation and end of exhalation. We first obtained the reference displacement vector fields (DVFs) from the t-MRIs by tracking the motion of each tagging grid between the exhalation and the inhalation phases. Then, we determined DIR-based DVFs from the p-MRIs by registering the images at the two phases with two commercial DIR algorithms. Lung ventilations were calculated from both the reference DVFs and the DIR-based DVFs using the Jacobian method and then compared using cross correlation and mutual information. RESULTS: The DIR-based lung ventilations calculated using p-MRI varied considerably from the reference lung ventilations based on t-MRI among all three subjects. The lung ventilations generated using Velocity AI were preferable for the better spatial homogeneity and accuracy compared to the ones using MIM, with higher average cross correlation (0.328 vs 0.262) and larger average mutual information (0.528 vs 0.323). CONCLUSION: We demonstrated that different DIR algorithms resulted in different lung ventilation maps due to underlining differences in the DVFs. HP gas tagging MRI provides a unique platform for evaluating DIR-based lung ventilation.

Unenhanced MRI as an Alternative to 99mTc-Labeled Dimercaptosuccinic Acid Scintigraphy in the Detection of Pediatric Renal Scarring.

OBJECTIVE: The purpose of this study was to determine whether unenhanced MRI without sedation is a feasible substitute for dimercaptosuccinic acid (DMSA) scintigraphy in the detection of renal scars in pediatric patients. SUBJECTS AND METHODS: Patients scheduled for 99mTc-labeled DMSA scintigraphy for assessment of possible renal scars were recruited to undergo unenhanced MRI (free-breathing fat-suppressed T2-weighted single-shot turbo spin-echo and T1-weighted gradient-echo imaging, 13 minutes' total imaging time). Scintigraphic and MRI studies were evaluated by two independent blinded specialty-based radiologists. For each imaging examination, readers identified scars in upper, middle, and lower kidney zones and rated their diagnostic confidence and the quality of each study. The scintigraphic readers' consensus score opinion for the presence of scars was considered the reference standard. RESULTS: DMSA scintigraphy showed scarring in 19 of the 78 (24.4%) evaluated zones and MRI in 18 of the 78 (23.1%). The two MRI readers found mean sensitivities of 94.7% and 89.5%, identical specificities of 100%, and diagnostic accuracies of 98.7% and 97.4%. Interobserver agreement was 98.7% for MRI and 92.3% for DMSA scintigraphy. The MRI readers were significantly more confident in determining the absence rather than the presence of scars (p = 0.02). MRI readers were more likely to rate study quality as excellent (84.6%) than were the scintigraphic readers (57.7%) (p = 0.024). CONCLUSION: Unenhanced MRI has excellent sensitivity, specificity, diagnostic accuracy, and interobserver agreement for detecting renal scars in older children who do not need sedation. It may serve as a substitute modality, especially when DMSA is not available.

Hyperpolarized helium-3 magnetic resonance lung imaging of non-sedated infants and young children: a proof-of-concept study.

PURPOSE: To develop and evaluate a protocol for hyperpolarized helium-3 (HHe) ventilation magnetic resonance imaging (MRI) of the lungs of non-sedated infants and children. MATERIALS AND METHODS: HHe ventilation MRI was performed on seven children ≤4years old. Contiguous 2D-spiral helium-3 images were acquired sequentially with a scan time of ≤0.2s/slice. RESULTS: Motion-artifact-free, high signal-to-noise ratio (SNR) images of lung ventilation were obtained. Gas was homogeneously distributed in healthy individuals; focal ventilation defects were found in patients with respiratory diseases. CONCLUSION: HHe ventilation MRI can aid assessment of pediatric lung disease even at a young age.

Skeletal development of the hand and wrist: digital bone age companion-a suitable alternative to the Greulich and Pyle atlas for bone age assessment?

PURPOSE: To assess reader performance and subjective workflow experience when reporting bone age studies with a digital bone age reference as compared to the Greulich and Pyle atlas (G&P). We hypothesized that pediatric radiologists would achieve equivalent results with each method while digital workflow would improve speed, experience, and reporting quality. MATERIALS AND METHODS: IRB approval was obtained for this HIPAA-compliant study. Two pediatric radiologists performed research interpretations of bone age studies randomized to either the digital (Digital Bone Age Companion, Oxford University Press) or G&P method, generating reports to mimic clinical workflow. Bone age standard selection, interpretation-reporting time, and user preferences were recorded. Reports were reviewed for typographical or speech recognition errors. Comparisons of agreement were conducted by way of Fisher's exact tests. Interpretation-reporting times were analyzed on the natural logarithmic scale via a linear mixed model and transformed to the geometric mean. Subjective workflow experience was compared with an exact binomial test. Report errors were compared via a paired random permutation test. RESULTS: There was no difference in bone age determination between atlases (p = 0.495). The interpretation-reporting time (p < 0.001) was significantly faster with the digital method. The faculty indicated preference for the digital atlas (p < 0.001). Signed reports had fewer errors with the digital atlas (p < 0.001). CONCLUSIONS: Bone age study interpretations performed with the digital method were similar to those performed with the Greulich and Pyle atlas. The digital atlas saved time, improved workflow experience, and reduced reporting errors relative to the Greulich and Pyle atlas when integrated into electronic workflow.

Hyperpolarized Helium-3 Diffusion-weighted Magnetic Resonance Imaging Detects Abnormalities of Lung Structure in Children With Bronchopulmonary Dysplasia.

PURPOSE: The aim of the study was to determine whether hyperpolarized He diffusion-weighted magnetic resonance imaging detects abnormalities in the lungs in children with bronchopulmonary dysplasia (BPD) as compared with age-matched normal children. MATERIALS AND METHODS: All experiments were compliant with Health Insurance Portability and Accountability Act (HIPAA) and performed with Food and Drug Administration approval under an IND application. The protocol was approved by our Institutional Review Board, and written informed consent was obtained. Hyperpolarized He diffusion-weighted magnetic resonance imaging was performed in 16 subjects with a history of preterm birth complicated by BPD (age range, 6.8 to 13.5 y; mean, 9.0 y) and in 29 healthy term-birth subjects (age range, 4.5-14.7 y; mean, 9.2 y) using a gradient-echo sequence with bipolar diffusion gradients and with measurements at 2 b values (0 and 1.6 s/cm). Age-related comparison of the whole-lung mean apparent diffusion coefficient (ADC), 90th percentile ADC, and percentage of whole-lung volume with ADC>0.2 cm/s between the 2 groups was examined using ordinary least-squares multiple regression. RESULTS: The mean ADC was significantly greater in subjects with BPD (0.187 vs. 0.152 cm/s, P<0.001). The 90th percentile ADC and mean percentage lung volume with ADC>0.2 cm/s were also higher in the BPD group (0.258 vs. 0.215 cm/s, 30.3% vs. 11.9%, P<0.001 for both). The body surface area-adjusted ventilated lung volume was similar in the 2 groups (1.93 vs. 1.91 L, P=0.90). CONCLUSIONS: Children with BPD had higher ADCs and the same lung volumes when compared with age-matched healthy subjects, suggesting that children with BPD have enlarged alveoli that are reduced in number.

Use of hyperpolarized helium-3 MRI to assess response to ivacaftor treatment in patients with cystic fibrosis.

BACKGROUND: This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized 3He-magnetic resonance imaging (MRI)-defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation. METHODS: Part A (single-blind) comprised 4weeks of ivacaftor treatment; Part B (open-label) comprised 48weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio). RESULTS: Mean change in TVD ranged from -8.2% (p=0.0547) to -12.8% (p=0.0078) in Part A (n=8) and -6.3% (p=0.1953) to -9.0% (p=0.0547) in Part B (n=8) as assessed by human reader and computer algorithm, respectively. CONCLUSIONS: TVD responded to ivacaftor therapy. 3He-MRI provides an individual quantification of disease burden that may be able to detect aspects of the disease missed by population-based spirometry metrics. Assessments by human reader and computer algorithm exhibit similar trends, but the latter appears more sensitive. www.clinicaltrials.gov identifier: NCT01161537.

Direct comparison of 129 Xe diffusion measurements with quantitative histology in human lungs.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is an irreversible lung disease characterized by small-airway obstruction and alveolar-airspace destruction. Hyperpolarized 129 Xe diffusion MRI of lung is a promising biomarker for assessing airspace enlargement, but has yet to be validated by direct comparison to lung histology. Here we have compared diffusion measurements of hyperpolarized (HP) 129 Xe in explanted lungs to regionally matched morphological measures of airspace size. METHODS: Explanted lungs from five COPD patients and two idiopathic pulmonary fibrosis (IPF) patients were imaged using MRI with hyperpolarized 129 Xe using a two-b-value gradient-echo diffusion sequence, and 34 histological samples were taken from these lungs for quantitative histology. Mean-linear-intercept (Lm ) was compared with spatially matched measures of apparent diffusion coefficient (ADC) from 129 Xe MRI. RESULTS: The mean ADC from COPD lung samples was 0.071 ± 0.011 cm2 /s, and for IPF lungs was 0.033 ± 0.001 cm2 /s (P < 10-15 between groups). The mean Lm in COPD samples was 0.076 ± 0.027 cm and 0.041 ± 0.004 cm in IPF (P = 2.7 × 10-7 between groups). The Pearson-correlation between ADC and Lm measurements was r = 0.59. CONCLUSIONS: Diffusion MRI of HP 129 Xe quantifies regional airspace enlargement in COPD. 129 Xe ADC showed much less overlap between groups than quantitative histology, consistent with our past experience with 3 He diffusion MRI in COPD. Magn Reson Med 77:265-272, 2017. © 2016 Wiley Periodicals, Inc.