Diagnostic Utility of Spinal Ultrasounds in Neonates.

OBJECTIVE: Ultrasound (US) is a common imaging modality used to evaluate spinal anomalies in newborns. However, many indications for the use of spinal US are associated with low diagnostic yield. The purpose of this study is to evaluate the indications and the diagnostic utility of spinal USs performed in newborns at our institution. We also review patient presentations for caudal regression syndrome (CRS) that was identified from the USs performed. STUDY DESIGN: This study is a retrospective review of spinal USs performed between January 1, 2006, and December 31, 2021, in newborns at a single institution. Indications for each US and any associated abnormalities were noted. Infants with abnormal USs showing CRS are described with their long-term medical outcomes. RESULTS: A total of 592 USs were performed during the specified time period of which 72 (12%) were abnormal. The presence of a sacral dimple was the most common indication for performing a spinal US, although only 14 (4%) were identified as abnormal. Of these 14, 6 (43%) were further evaluated by spinal magnetic resonance imaging (MRI) at the recommendations of a pediatric radiologist and of these, only 2 (14%) had abnormal MRI findings. The two newborns with abnormal MRI findings had mothers with diabetes mellitus in their pregnancies. Of note, one additional newborn had abnormalities on spinal US that was never confirmed on MRI due to being lost to follow-up. Among the other indications, anorectal anomalies (odds ratio [OR], 7.55; 95% confidence interval [CI], 3.01-18.91), spinal mass (OR, 17.99; 95% CI, 7.86-41.2), and meningocele were most associated with abnormal findings. CONCLUSION: Overall, spinal US has a low diagnostic yield. Sacral dimple was the most common indication for performing a spinal US but had a low yield with few long-term sequelae. Anorectal anomalies had a strong association with abnormal US findings. KEY POINTS: · Sacral dimple is a common indication for spinal ultrasound.. · Spinal ultrasound has low diagnostic yield when performed for sacral dimple.. · Caudal regression syndrome is associated with maternal diabetes and numerous long-term comorbidities..

Unusually High Prevalence of Stroke and Cerebral Vasculopathy in Hemoglobin SC Disease: A Retrospective Single Institution Study.

INTRODUCTION: Unlike homozygous hemoglobin SS (HbSS) disease, stroke is a rare complication in hemoglobin SC (HbSC) disease. However, recent studies have demonstrated a high prevalence of silent stroke in HbSC disease. The factors associated with stroke and cerebral vasculopathy in the HbSC population are unknown. METHODS: We conducted a retrospective study of all patients with sickle cell disease treated at the University of Missouri, Columbia, over an 18-year period (2000-2018). The goal of the study was to characterize the silent, overt stroke, and cerebral vasculopathy in HbSC patients and compare them to patients with HbSS and HbS/ß thalassemia1 (thal) in this cohort. We also analyzed the laboratory and clinical factors associated with stroke and cerebral vasculopathy in the HbSC population. RESULTS: Of the 34 HbSC individuals, we found that the overall prevalence of stroke and cerebral vasculopathy was 17.7%. Only females had evidence of stroke or cerebral vasculopathy in our HbSC cohort (33.3%, p = 0.019). Time-averaged means of maximum velocities were lower in the HbSC group than the HbSS group and did not correlate with stroke outcome. Among HbSC individuals, those with stroke and cerebral vasculopathy had a marginally higher serum creatinine than those without these complications (0.77 mg/dL vs. 0.88 mg/dL, p = 0.08). Stroke outcome was associated with recurrent vaso-occlusive pain crises (Rec VOCs) (75 vs. 25%, p = 0.003) in HbSC patients. The predominant cerebrovascular lesions in HbSC included microhemorrhages and leukoencephalopathy. CONCLUSION: There is a distinct subset of individuals with HbSC who developed overt, silent stroke, and cerebral vasculopathy. A female predominance and association with Rec VOCs were identified in our cohort; however, larger clinical trials are needed to identify and confirm specific clinical and laboratory markers associated with stroke and vasculopathy in HbSC disease.

Characterisation of gas exchange in COPD with dissolved-phase hyperpolarised xenon-129 MRI.

To investigate whether hyperpolarised xenon-129 MRI (HXeMRI) enables regional and physiological resolution of diffusing capacity limitations in chronic obstructive pulmonary disease (COPD), we evaluated 34 COPD subjects and 11 healthy volunteers. We report significant correlations between airflow abnormality quantified by HXeMRI and per cent predicted forced expiratory volume in 1 s; HXeMRI gas transfer capacity to red blood cells and carbon monoxide diffusion capacity (%DLCO); and HXeMRI gas transfer capacity to interstitium and per cent emphysema quantified by multidetector chest CT. We further demonstrate the capability of HXeMRI to distinguish varying pathology underlying COPD in subjects with low %DLCO and minimal emphysema.

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.

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.

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.

The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society.

With more than 900 000 confirmed cases worldwide and nearly 50 000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.

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.

Volumetric characteristics of idiopathic pulmonary fibrosis lungs: computational analyses of high-resolution computed tomography images of lung lobes.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease involving progressive degeneration of lung capacity. Current diagnosis of IPF heavily relies on visual evaluation of fibrotic features in high-resolution computed tomography (HRCT) images of the lungs. Although the characteristics of this disease have been studied at the molecular and cellular levels, little is known about the mechanical characteristics of IPF lungs inferred from HRCT images. To this end, we performed a pilot study to investigate the radiographic and volumetric characteristics of lungs in subjects with IPF. METHODS: We collected HRCT images of healthy (N = 13) and IPF (N = 9) lungs acquired at breath-holds after full inspiration (expanded state) and full expiration (contracted state). We performed statistical analyses on Hounsfield unit (HU) histograms, lobar volumes (V: lobe volume normalized by the lung volume), and lobar flows (Q: the difference in lobe volume divided by the difference in lung volume between the expanded and contracted states). RESULTS: Parameters characterizing the HU histograms (i.e., mean, median, skewness, and kurtosis) significantly differed between healthy and IPF subjects, for all lobes in both expanded and contracted states. The distribution of V across lobes differed significantly between the groups in both states. The distribution of Q also differed significantly between the groups: Q values of the lower lobes for the IPF group were 33% (right) and 22% (left) smaller than those for the healthy group, consistent with the observation that radiographic scores were highest in the lower lung section in IPF. Notably, the root-mean-squared difference (RMSD) of Q, a measure of distance from the mean value of the healthy group, clearly distinguished the IPF subjects (RMSD of Q > 1.59) from the healthy group (RMSD of Q < 0.67). CONCLUSION: This study shows that lung volume and flow distribution change heterogeneously across the lung lobes of IPF subjects, with reduced capacity in the lower lobes. These volumetric changes may improve our understanding of the pathophysiology in IPF lungs.

Dynamics of the Tracheal Airway and Its Influences on Respiratory Airflows: An Exemplar Study.

Respiration is a dynamic process accompanied by morphological changes in the airways. Although deformation of large airways is expected to exacerbate pulmonary disease symptoms by obstructing airflow during increased minute ventilation, its quantitative effects on airflow characteristics remain unclear. Here, we used in vivo dynamic imaging and examined the effects of tracheal deformation on airflow characteristics under different conditions based on imaging data from a single healthy volunteer. First, we measured tracheal deformation profiles of a healthy lung using magnetic resonance imaging (MRI) during forced exhalation, which we simulated to characterize the subject-specific airflow patterns. Subsequently, for both inhalation and exhalation, we compared the airflows when the modeled deformation in tracheal cross-sectional area was 0% (rigid), 33% (mild), 50% (moderate), or 75% (severe). We quantified differences in airflow patterns between deformable and rigid airways by computing the correlation coefficients (R) and the root-mean-square of differences (Drms) between their velocity contours. For both inhalation and exhalation, airflow patterns were similar in all branches between the rigid and mild conditions (R > 0.9; Drms < 32%). However, airflow characteristics in the moderate and severe conditions differed markedly from those in the rigid and mild conditions in all lung branches, particularly for inhalation (moderate: R > 0.1, Drms < 76%; severe: R > 0.2, Drms < 96%). Our exemplar study supports the use of a rigid airway assumption to compute flows for mild deformation. For moderate or severe deformation, however, dynamic contraction should be considered, especially during inhalation, to accurately predict airflow and elucidate the underlying pulmonary pathology.

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.

Assessing Airflow Sensitivity to Healthy and Diseased Lung Conditions in a Computational Fluid Dynamics Model Validated In Vitro.

Computational models are useful for understanding respiratory physiology. Crucial to such models are the boundary conditions specifying the flow conditions at truncated airway branches (terminal flow rates). However, most studies make assumptions about these values, which are difficult to obtain in vivo. We developed a computational fluid dynamics (CFD) model of airflows for steady expiration to investigate how terminal flows affect airflow patterns in respiratory airways. First, we measured in vitro airflow patterns in a physical airway model, using particle image velocimetry (PIV). The measured and computed airflow patterns agreed well, validating our CFD model. Next, we used the lobar flow fractions from a healthy or chronic obstructive pulmonary disease (COPD) subject as constraints to derive different terminal flow rates (i.e., three healthy and one COPD) and computed the corresponding airflow patterns in the same geometry. To assess airflow sensitivity to the boundary conditions, we used the correlation coefficient of the shape similarity (R) and the root-mean-square of the velocity magnitude difference (Drms) between two velocity contours. Airflow patterns in the central airways were similar across healthy conditions (minimum R, 0.80) despite variations in terminal flow rates but markedly different for COPD (minimum R, 0.26; maximum Drms, ten times that of healthy cases). In contrast, those in the upper airway were similar for all cases. Our findings quantify how variability in terminal and lobar flows contributes to airflow patterns in respiratory airways. They highlight the importance of using lobar flow fractions to examine physiologically relevant airflow characteristics.

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.

Signal-to-noise ratio, T2 , and T2* for hyperpolarized helium-3 MRI of the human lung at three magnetic field strengths.

PURPOSE: To evaluate T2 , T2*, and signal-to-noise ratio (SNR) for hyperpolarized helium-3 (3 He) MRI of the human lung at three magnetic field strengths ranging from 0.43T to 1.5T. METHODS: Sixteen healthy volunteers were imaged using a commercial whole body scanner at 0.43T, 0.79T, and 1.5T. Whole-lung T2 values were calculated from a Carr-Purcell-Meiboom-Gill spin-echo-train acquisition. T2* maps and SNR were determined from dual-echo and single-echo gradient-echo images, respectively. Mean whole-lung SNR values were normalized by ventilated lung volume and administered 3 He dose. RESULTS: As expected, T2 and T2* values demonstrated a significant inverse relationship to field strength. Hyperpolarized 3 He images acquired at all three field strengths had comparable SNR values and thus appeared visually very similar. Nonetheless, the relatively small SNR differences among field strengths were statistically significant. CONCLUSIONS: Hyperpolarized 3 He images of the human lung with similar image quality were obtained at three field strengths ranging from 0.43T and 1.5T. The decrease in susceptibility effects at lower fields that are reflected in longer T2 and T2* values may be advantageous for optimizing pulse sequences inherently sensitive to such effects. The three-fold increase in T2* at lower field strength would allow lower receiver bandwidths, providing a concomitant decrease in noise and relative increase in SNR. Magn Reson Med 78:1458-1463, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

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.

Clinical correlates of lung ventilation defects in asthmatic children.

BACKGROUND: Lung ventilation defects identified by using hyperpolarized 3-helium gas ((3)He) lung magnetic resonance imaging (MRI) are prevalent in asthmatic patients, but the clinical importance of ventilation defects is poorly understood. OBJECTIVES: We sought to correlate the lung defect volume quantified by using (3)He MRI with clinical features in children with mild and severe asthma. METHODS: Thirty-one children with asthma (median age, 10 years; age range, 3-17 years) underwent detailed characterization and (3)He lung MRI. Quantification of the (3)He signal defined ventilation defect and hypoventilated, ventilated, and well-ventilated volumes. RESULTS: The ventilation defect to total lung volume fraction ranged from 0.1% to 11.6%. Children with ventilation defect percentages in the upper tercile were more likely to have severe asthma than children in the lower terciles (P = .005). The ventilation defect percentage correlated (P < .05 for all) positively with the inhaled corticosteroid dose, total number of controller medications, and total blood eosinophil counts and negatively with the Asthma Control Test score, FEV1 (percent predicted), FEV1/forced vital capacity ratio (percent predicted), and forced expiratory flow rate from 25% to 75% of expired volume (percent predicted). CONCLUSION: The lung defect volume percentage measured by using (3)He MRI correlates with several clinical features of asthma, including severity, symptom score, medication requirement, airway physiology, and atopic markers.

Atlas-based estimation of lung and lobar anatomy in proton MRI.

PURPOSE: To propose an accurate methodological framework for automatically segmenting pulmonary proton MRI based on an optimal consensus of a spatially normalized library of annotated lung atlases. METHODS: A library of 62 manually annotated lung atlases comprising 48 mixed healthy, chronic obstructive pulmonary disease, and asthmatic subjects of a large age range with multiple ventilation levels is used to produce an optimal segmentation in proton MRI, based on a consensus of the spatially normalized library. An extension of this methodology is used to provide best-guess estimates of lobar subdivisions in proton MRI from annotated computed tomography data. RESULTS: A leave-one-out evaluation strategy was used for evaluation. Jaccard overlap measures for the left and right lungs were used for performance comparisons relative to the current state-of-the-art (0.966 ± 0.018 and 0.970 ± 0.016, respectively). Best-guess estimates for the lobes exhibited comparable performance levels (left upper: 0.882 ± 0.059, left lower: 0.868 ± 0.06, right upper: 0.852 ± 0.067, right middle: 0.657 ± 0.130, right lower: 0.873 ± 0.063). CONCLUSION: An annotated atlas library approach can be used to provide good lung and lobe estimation in proton MRI. The proposed framework is useful for subsequent anatomically based analysis of structural and/or functional pulmonary image data. Magn Reson Med 76:315-320, 2016. © 2015 Wiley Periodicals, Inc.

Detecting pulmonary capillary blood pulsations using hyperpolarized xenon-129 chemical shift saturation recovery (CSSR) MR spectroscopy.

PURPOSE: To investigate whether chemical shift saturation recovery (CSSR) MR spectroscopy with hyperpolarized xenon-129 is sensitive to the pulsatile nature of pulmonary blood flow during the cardiac cycle. METHODS: A CSSR pulse sequence typically uses radiofrequency (RF) pulses to saturate the magnetization of xenon-129 dissolved in lung tissue followed, after a variable delay time, by an RF excitation and subsequent acquisition of a free-induction decay. Thereby it is possible to monitor the uptake of xenon-129 by lung tissue and extract physiological parameters of pulmonary gas exchange. In the current studies, the delay time was instead held at a constant value, which permitted observation of xenon-129 gas uptake as a function of breath-hold time. CSSR studies were performed in 13 subjects (10 healthy, 2 chronic obstructive pulmonary disease [COPD], 1 second-hand smoke exposure), holding their breath at total lung capacity. RESULTS: The areas of the tissue/plasma and the red-blood-cell peaks in healthy subjects varied by an average of 1.7±0.7% and 15.1±3.8%, respectively, during the cardiac cycle. In 2 subjects with COPD these peak pulsations were not detectable during at least part of the measurement period. CONCLUSION: CSSR spectroscopy is sufficiently sensitive to detect oscillations in the xenon-129 gas-uptake rate associated with the cardiac cycle.

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. METHODS: Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. RESULTS: A total of 110 subjects were enrolled (age 10.4 ±â€Š3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. CONCLUSIONS: LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.

Phenotype of asthmatics with increased airway S-nitrosoglutathione reductase activity.

S-Nitrosoglutathione is an endogenous airway smooth muscle relaxant. Increased airway S-nitrosoglutathione breakdown occurs in some asthma patients. We asked whether patients with increased airway catabolism of this molecule had clinical features that distinguished them from other asthma patients. We measured S-nitrosoglutathione reductase expression and activity in bronchoscopy samples taken from 66 subjects in the Severe Asthma Research Program. We also analysed phenotype and genotype data taken from the program as a whole. Airway S-nitrosoglutathione reductase activity was increased in asthma patients (p=0.032). However, only a subpopulation was affected and this subpopulation was not defined by a "severe asthma" diagnosis. Subjects with increased activity were younger, had higher IgE and an earlier onset of symptoms. Consistent with a link between S-nitrosoglutathione biochemistry and atopy: 1) interleukin 13 increased S-nitrosoglutathione reductase expression and 2) subjects with an S-nitrosoglutathione reductase single nucleotide polymorphism previously associated with asthma had higher IgE than those without this single nucleotide polymorphism. Expression was higher in airway epithelium than in smooth muscle and was increased in regions of the asthmatic lung with decreased airflow. An early-onset, allergic phenotype characterises the asthma population with increased S-nitrosoglutathione reductase activity.