Highly accelerated dynamic acquisition of 3D grid-tagged hyperpolarized-gas lung images using compressed sensing.

PURPOSE: To develop and test compressed sensing-based multiframe 3D MRI of grid-tagged hyperpolarized gas in the lung. THEORY AND METHODS: Applying grid-tagging RF pulses to inhaled hyperpolarized gas results in images in which signal intensity is predictably and sparsely distributed. In the present work, this phenomenon was used to produce a sampling pattern in which k-space is undersampled by a factor of approximately seven, yet regions of high k-space energy remain densely sampled. Three healthy subjects received multiframe 3D 3 He tagging MRI using this undersampling method. Images were collected during a single exhalation at eight timepoints spanning the breathing cycle from end-of-inhalation to end-of-exhalation. Grid-tagged images were used to generate 3D displacement maps of the lung during exhalation, and time-resolved maps of principal strains and fractional volume change were generated from these displacement maps using finite-element analysis. RESULTS: Tags remained clearly resolvable for 4-6 timepoints (5-8 s) in each subject. Displacement maps revealed noteworthy temporal and spatial nonlinearities in lung motion during exhalation. Compressive normal strains occurred along all three principal directions but were primarily oriented in the head-foot direction. Fractional volume changes displayed clear bilateral symmetry, but with the lower lobes displaying slightly higher change than the upper lobes in 2 of the 3 subjects. CONCLUSION: We developed a compressed sensing-based method for multiframe 3D MRI of grid-tagged hyperpolarized gas in the lung during exhalation. This method successfully overcomes previous challenges for 3D dynamic grid-tagging, allowing time-resolved biomechanical readouts of lung function to be generated.

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).

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.

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.

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.

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.

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.

Hyperpolarized Gas Magnetic Resonance Lung Imaging in Children and Young Adults.

The assessment of early pulmonary disease and its severity can be difficult in young children, as procedures such as spirometry cannot be performed on them. Computed tomography provides detailed structural images of the pulmonary parenchyma, but its major drawback is that the patient is exposed to ionizing radiation. In this context, magnetic resonance imaging (MRI) is a promising technique for the evaluation of pediatric lung disease, especially when serial imaging is needed. Traditionally, MRI played a small role in evaluating the pulmonary parenchyma. Because of its low proton density, the lungs display low signal intensity on conventional proton-based MRI. Hyperpolarized (HP) gases are inhaled contrast agents with an excellent safety profile and provide high signal within the lung, allowing for high temporal and spatial resolution imaging of the lung airspaces. Besides morphologic information, HP MR images also offer valuable information about pulmonary physiology. HP gas MRI has already made new contributions to the understanding of pediatric lung diseases and may become a clinically useful tool. In this article, we discuss the HP gas MRI technique, special considerations that need to be made when imaging children, and the role of MRI in 2 of the most common chronic pediatric lung diseases, asthma and cystic fibrosis. We also will discuss how HP gas MRI may be used to evaluate normal lung growth and development and the alterations occurring in chronic lung disease of prematurity and in patients with a congenital diaphragmatic hernia.

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.

Fluoroscopy-guided jejunal extension tube placement through existing gastrostomy tubes: analysis of 391 procedures.

PURPOSE: We aimed to evaluate the safety and efficacy of fluoroscopically placed jejunal extension tubes (J-arm) in patients with existing gastrostomy tubes. METHODS: We conducted a retrospective review of 391 J-arm placements performed in 174 patients. Indications for jejunal nutrition were aspiration risk (35%), pancreatitis (17%), gastroparesis (13%), gastric outlet obstruction (12%), and other (23%). Technical success, complications, malfunctions, and patency were assessed. Percutaneous gastrostomy (PEG) tube location, J-arm course, and fluoroscopy time were correlated with success/failure. Failure was defined as inability to exit the stomach. Procedure-related complications were defined as adverse events related to tube placement occurring within seven days. Tube malfunctions and aspiration events were recorded and assessed. RESULTS: Technical success was achieved in 91.9% (95% CI, 86.7%-95.2%) of new tubes versus 94.2% (95% CI, 86.7%-95.2%) of replacements (P = 0.373). Periprocedural complications occurred in three patients (0.8%). Malfunctions occurred in 197 patients (50%). Median tube patency was 103 days (95% CI, 71-134 days). No association was found between successful J-arm placement and gastric PEG tube position (P = 0.677), indication for jejunal nutrition (P = 0.349), J-arm trajectory in the stomach and incidence of malfunction (P = 0.365), risk of tube migration and PEG tube position (P = 0.173), or J-arm length (P = 0.987). A fluoroscopy time of 21.3 min was identified as a threshold for failure. Malfunctions occurred more often in tubes replaced after 90 days than in tubes replaced before 90 days (P < 0.001). A total of 42 aspiration events occurred (OR 6.4, P < 0.001, compared with nonmalfunctioning tubes). CONCLUSION: Fluoroscopy-guided J-arm placement is safe for patients requiring jejunal nutrition. Tubes indwelling for longer than 90 days have higher rates of malfunction and aspiration.

IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma.

IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

Regional anisotropy of airspace orientation in the lung as assessed with hyperpolarized helium-3 diffusion MRI.

PURPOSE: To evaluate regional anisotropy of lung-airspace orientation by assessing the dependence of helium-3 ((3) He) apparent diffusion coefficient (ADC) values on the direction of diffusion sensitization at two field strengths. MATERIALS AND METHODS: Hyperpolarized (3) He diffusion-weighted magnetic resonance imaging (MRI) of the lung was performed at 0.43T and 1.5T in 12 healthy volunteers. A gradient-echo pulse sequence was used with a bipolar diffusion-sensitization gradient applied separately along three orthogonal directions. ADC maps, median ADC values, and signal-to-noise ratios were calculated from the diffusion-weighted images. Two readers scored the ADC maps for increased values at lung margins, major fissures, or within focal central regions. RESULTS: ADC values were found to depend on the direction of diffusion sensitization (P < 0.01, except for craniocaudal vs. anteroposterior directions at 1.5T) and were increased at the lateral and medial surfaces for left-right diffusion sensitization (12 of 12 subjects); at the apex and base (9 of 12), and along the major fissure (8 of 12), for craniocaudal diffusion sensitization; and at the most anterior and posterior lung (10 of 12) for anteroposterior diffusion sensitization. Median ADC values at 0.43T (0.201 ± 0.017, left-right; 0.193 ± 0.019, craniocaudal; and 0.187 ± 0.017 cm(2) /s, anteroposterior) were slightly lower than those at 1.5T (0.205 ± 0.017, 0.197 ± 0.017 and 0.194 ± 0.016 cm(2) /s, respectively; P < 0.05). CONCLUSION: These findings indicate that diffusion-weighted hyperpolarized (3) He MRI can detect regional anisotropy of lung-airspace orientation, including that associated with preferential orientation of terminal airways near pleural surfaces.

Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.

BACKGROUND & AIMS: This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). METHODS: Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. RESULTS: N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. CONCLUSION: N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.

Rapid acquisition of helium-3 and proton three-dimensional image sets of the human lung in a single breath-hold using compressed sensing.

PURPOSE: To develop and validate a method for acquiring helium-3 ((3) He) and proton ((1) H) three-dimensional (3D) image sets of the human lung with isotropic spatial resolution within a 10-s breath-hold by using compressed sensing (CS) acceleration, and to assess the fidelity of undersampled images compared with fully sampled images. METHODS: The undersampling scheme for CS acceleration was optimized and tested using (3) He ventilation data. Rapid 3D acquisition of both (3) He and (1) H data during one breath-hold was then implemented, based on a balanced steady-state free-precession pulse sequence, by random undersampling of k-space with reconstruction by means of minimizing the L1 norm and total variance. CS-reconstruction fidelity was evaluated quantitatively by comparing fully sampled and retrospectively undersampled image sets. RESULTS: Helium-3 and (1) H 3D image sets of the lung with isotropic 3.9-mm resolution were acquired during a single breath-hold in 12 s and 8 s using acceleration factors of 2 and 3, respectively. Comparison of fully sampled and retrospectively undersampled (3) He and (1) H images yielded mean absolute errors <10% and structural similarity indices >0.9. CONCLUSION: By randomly undersampling k-space and using CS reconstruction, high-quality (3) He and (1) H 3D image sets with isotropic 3.9-mm resolution can be acquired within an 8-s breath-hold.

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.