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BACKGROUND: Airway mucus plugs in asthma are associated with exacerbation frequency, increased eosinophilia, and reduced lung function. The relationship between mucus plugs and spatially overlapping ventilation abnormalities observed at hyperpolarized gas MRI has not been assessed quantitatively. PURPOSE: To assess regional associations between CT mucus plugs scored by individual bronchopulmonary segment and corresponding measurements of segmental ventilation defect percentage (VDP) at hyperpolarized helium 3 ((3)He) MRI. MATERIALS AND METHODS: In this secondary analysis of a Health Insurance Portability and Accountability Act–compliant prospective observational cohort, participants in the Severe Asthma Research Program (SARP) III (NCT01760915) between December 2012 and August 2015 underwent hyperpolarized (3)He MRI to determine segmental VDP. Segmental mucus plugs at CT were scored by two readers, with segments scored as plugged only if both readers agreed independently. A linear mixed-effects model controlling for interpatient variability was then used to assess differences in VDP in plugged versus plug-free segments. RESULTS: Forty-four participants with asthma were assessed (mean age ± standard deviation, 47 years ± 15; 29 women): 19 with mild-to-moderate asthma and 25 with severe asthma. Mucus plugs were observed in 49 total bronchopulmonary segments across eight of 44 patients. Segments containing mucus plugs had a median segmental VDP of 25.9% (25th–75th percentile, 7.3%–38.3%) versus 1.4% (25th–75th percentile, 0.1%–5.2%; P < .001) in plug-free segments. Similarly, the model estimated a segmental VDP of 18.9% (95% CI: 15.7, 22.2) for mucus-plugged segments versus 5.1% (95% CI: 3.3, 7.0) for plug-free segments (P < .001). Participants with one or more mucus plugs had a median whole-lung VDP of 11.1% (25th–75th percentile, 7.1%–18.9%) versus 3.1% (25th–75th percentile, 1.1%–4.4%) in those without plugs (P < .001). CONCLUSION: Airway mucus plugging at CT was associated with reduced ventilation in the same bronchopulmonary segment at hyperpolarized helium 3 MRI, suggesting that mucus plugging may be an important cause of ventilation defects in asthma. © RSNA, 2021 Online supplemental material is available for this article.

Ferumoxytol, an intravenous iron supplement, is commonly used to treat anemia in pregnancy. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a viable off-label alternative to gadolinium-enhanced MRA for assessment of pulmonary embolism (PE) in pregnancy.To describe our clinical experience with Fe-MRA in pregnant women with suspected PE.Retrospective, observational, cohort.A total of 98 Fe-MRA exams (consecutive sample) performed in 94 pregnant women.A 1.5 T and 3.0 T, 3D T1-weighted MRA.After IRB approval including a waiver of informed consent, electronic health records were reviewed retrospectively for all Fe-MRA exams performed at our institution in pregnant between January, 2017 and March, 2022. The Fe-MRA protocol included 3D-MRA for assessment of pulmonary arteries, and T1-weighted imaging for ancillary findings. Fe-MRA exam duration was measured from image time stamps. Fe-MRA exams were reviewed by three cardiovascular imagers using a 4-point Likert scale for image quality and confidence for PE diagnosis (score 4 = best, 1 = worst), and tabulation of ancillary findings.Continuous data are presented as mean ± standard deviation. The overall image quality and confidence score is given as the mean of three readers.The 98 Fe-MRA exams were performed in 94 pregnant women (age 30 ± 6, range 19-48 years, gestational week 23 ± 10, range 3-38 weeks), with four undergoing two Fe-MRA exams during their pregnancy. Median Fe-MRA exam durration was 8 minutes (interquantile range 6 minutes). Overall image quality score was 3.3 ± 0.9. Confidence score for diagnosing PE was 3.5 ± 0.8. One subject was positive for PE (1/94, 1%); 42 of the 94 (45%) subjects Fe-MRA had ancillary findings including hydronephrosis or pneumonia.Ferumoxytol enhanced MRA is a radiation- and gadolinium-free alternative for diagnosis of PE during pregancy.4 TECHNICAL EFFICACY: Stage 5.

Numerous issues must be addressed when developing standard operating procedures for clinical research studies involving chest computed tomography of lung disease in patients with cystic fibrosis (CF). Study success depends on the provision of adequate funding and the identification of personnel with the necessary expertise to conduct the study, along with clear guidelines that detail the CT operating procedure at each site, including breathing maneuvers, and image reconstruction. Close coordination of the quality assurance process between sites and the central review organization is required to maintain protocol adherence. The data transfer process must ensure the integrity and security of the data to comply with patient privacy regulations, and study outcome measures are best assessed with a scoring system or other structured method of imaging data analysis. The recommendations provided are designed to serve as a valuable reference guide for planning clinical research studies of patients with CF involving chest CT.

The purpose of this review is to acquaint the reader with recent advances in ultra-short echo time (UTE) magnetic resonance imaging (MRI) of the lung and its implications for pulmonary MRI when used in conjunction with functional MRI techniques. UTE MRI has three critical advantages for lung applications: 1) high resolution, whole-lung morphological images without the use of ionizing radiation; 2) mitigation of the short transverse relaxation time constant (T2*) caused by magnetic susceptibility effects prominent at air-tissue interfaces; and 3) in conjunction with a radial acquisition and hard respiratory gating, mitigation of cardiac and respiratory motion artifacts, enabling free breathing exams. UTE MRI clearly shows the lung parenchymal changes due to idiopathic pulmonary fibrosis (IPF) and cystic fibrosis (CF). The use of UTE MRI, in conjunction with established functional lung MRI in chronic lung diseases, will serve to mitigate the need for computed tomography (CT) in children. Current limitations of UTE MRI include long scan times, poor delineation of thin walled structures (e.g. cysts and reticulation) due to limited spatial resolution, low signal to noise (SNR), and imperfect motion compensation. Despite these limitations, UTE MRI can now be considered as an alternative to multi-detector CT for the longitudinal follow up of the morphological changes from lung diseases in neonates, children and young adults, particularly as a complement to the unique functional capabilities of MRI.

Purpose To compare the performance of three-dimensional radial ultrashort echo time (UTE) oxygen-enhanced (OE) MRI with that of hyperpolarized helium 3 (3He) MRI with respect to quantitative ventilation measurements in patients with cystic fibrosis (CF). Materials and Methods In this prospective study conducted from June 2013 to May 2015, 25 participants with CF aged 10-55 years (14 male; age range, 13-55 years; 11 female; age range, 10-37 years) successfully underwent pulmonary function tests, hyperpolarized 3He MRI, and OE MRI. OE MRI used two sequential 3.5-minute normoxic and hyperoxic steady-state free-breathing UTE acquisitions. Seven participants underwent imaging at two separate examinations 1-2 weeks apart to assess repeatability. Regional ventilation was quantified as ventilation defect percentage (VDP) individually from OE MRI and hyperpolarized 3He MRI by using the same automated quantification tool. Bland-Altman analysis, intraclass correlation coefficient (ICC), Spearman correlation coefficient, and Wilcoxon signed-rank test were used to evaluate repeatability. Results In all 24 participants, the global VDP measurements from either OE MRI (ρ = -0.66, P < .001) or hyperpolarized 3He MRI (ρ = -0.75, P < .001) were significantly correlated with the percentage predicted forced expiratory volume in 1 second. VDP reported at OE MRI was 5.0% smaller than (P = .014) but highly correlated with (ρ = 0.78, P < .001) VDP reported at hyperpolarized 3He MRI. Both OE MRI-based VDP and hyperpolarized 3He MRI-based VDP demonstrated good repeatability (ICC = 0.91 and 0.95, respectively; P ≤ .001). Conclusion In lungs with cystic fibrosis, ultrashort echo time oxygen-enhanced MRI showed similar performance compared with hyperpolarized 3He MRI for quantitative measures of ventilation defects and their repeatability. © RSNA, 2018 Online supplemental material is available for this article.

Objective To compare the proportion of emergency department (ED) patients who undergo subsequent chest CT or MR within 1 year of an initially negative scan for pulmonary embolism (PE). Methods This single-center, retrospective, observational study examined the use of chest CT or MR for ED patients with MR angiography (MRA) negative for PE during April 2008 to March 2013. We compared the 1-year scan utilization for these cases to an age- and sex-matched cohort of patients who underwent CT angiography (CTA). We also calculated time to first follow-up scan and mean radiation dose in each arm. Trained data abstractors used a standardized protocol and electronic case report form to gather all outcomes of interest. Results are reported as means or proportions with their associated confidence intervals (CIs). Results In all, 717 ED patients (430 MRAs and 287 CTAs) were included. At 1 year, the proportion undergoing subsequent imaging (MRA 16.7%, CTA 15.3%; difference = 1.4%, 95% CI 4.05%-6.86%) and time to first follow-up scan (difference = 13 days, 95% CI −22.69-48.7) did not differ between arms. Mean radiation dose per patient at 1 year was significantly higher in the CTA arm (9.82 mSv; 95% CI 9.12-10.53) compared with 2.92 mSv (95% CI 1.86-3.98) with MRA. Those with an index MRA were more likely to undergo subsequent MRAs (odds ratio 3.68; 95% CI 1.22-11.12) than those with an index CTA. However, in both arms, the majority (85%) of subsequent scans were CTAs. Conclusions When comparing patients initially undergoing MRA versus CTA for the evaluation of PE, there was no difference in downstream chest CT or MR use at 1 year.

PURPOSE: To compare patient outcomes following magnetic resonance angiography (MRA) versus computed tomographic angiography (CTA) ordered for suspected pulmonary embolism (PE). METHODS: In this IRB-approved, single-center, retrospective, case-control study, we reviewed the medical records of all patients evaluated for PE with MRA during a 5-year period along with age- and sex-matched controls evaluated with CTA. Only the first instance of PE evaluation during the study period was included. After application of our exclusion criteria to both study arms, the analysis included 1173 subjects. The primary endpoint was major adverse PE-related event (MAPE), which we defined as major bleeding, venous thromboembolism, or death during the 6 months following the index imaging test (MRA or CTA), obtained through medical record review. Logistic regression, Chi-square test for independence, and Fisher’s exact test were used with a p

BACKGROUND. The link between mucus plugs and airflow obstruction has not been established in chronic severe asthma, and the role of eosinophils and their products in mucus plug formation is unknown. METHODS. In clinical studies, we developed and applied a bronchopulmonary segment–based scoring system to quantify mucus plugs on multidetector computed tomography (MDCT) lung scans from 146 subjects with asthma and 22 controls, and analyzed relationships among mucus plug scores, forced expiratory volume in 1 second (FEV1), and airway eosinophils. Additionally, we used airway mucus gel models to explore whether oxidants generated by eosinophil peroxidase (EPO) oxidize cysteine thiol groups to promote mucus plug formation. RESULTS. Mucus plugs occurred in at least 1 of 20 lung segments in 58% of subjects with asthma and in only 4.5% of controls, and the plugs in subjects with asthma persisted in the same segment for years. A high mucus score (plugs in ≥ 4 segments) occurred in 67% of subjects with asthma with FEV1 of less than 60% of predicted volume, 19% with FEV1 of 60%–80%, and 6% with FEV1 greater than 80% (P < 0.001) and was associated with marked increases in sputum eosinophils and EPO. EPO catalyzed oxidation of thiocyanate and bromide by H2O2 to generate oxidants that crosslink cysteine thiol groups and stiffen thiolated hydrogels. CONCLUSION. Mucus plugs are a plausible mechanism of chronic airflow obstruction in severe asthma, and EPO-generated oxidants may mediate mucus plug formation. We propose an approach for quantifying airway mucus plugging using MDCT lung scans and suggest that treating mucus plugs may improve airflow in chronic severe asthma. TRIAL REGISTRATION. Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01718197","term_id":"NCT01718197"}}NCT01718197, {"type":"clinical-trial","attrs":{"text":"NCT01606826","term_id":"NCT01606826"}}NCT01606826, {"type":"clinical-trial","attrs":{"text":"NCT01750411","term_id":"NCT01750411"}}NCT01750411, {"type":"clinical-trial","attrs":{"text":"NCT01761058","term_id":"NCT01761058"}}NCT01761058, {"type":"clinical-trial","attrs":{"text":"NCT01761630","term_id":"NCT01761630"}}NCT01761630, {"type":"clinical-trial","attrs":{"text":"NCT01759186","term_id":"NCT01759186"}}NCT01759186, {"type":"clinical-trial","attrs":{"text":"NCT01716494","term_id":"NCT01716494"}}NCT01716494, and {"type":"clinical-trial","attrs":{"text":"NCT01760915","term_id":"NCT01760915"}}NCT01760915. FUNDING. NIH grants P01 HL107201, R01 HL080414, U10 {"type":"entrez-nucleotide","attrs":{"text":"HL109146","term_id":"1051682664"}}HL109146, U10 {"type":"entrez-nucleotide","attrs":{"text":"HL109164","term_id":"1051682685"}}HL109164, U10 {"type":"entrez-nucleotide","attrs":{"text":"HL109172","term_id":"1051682699"}}HL109172, U10 {"type":"entrez-nucleotide","attrs":{"text":"HL109086","term_id":"1051682577"}}HL109086, U10 {"type":"entrez-nucleotide","attrs":{"text":"HL109250","term_id":"1051682815"}}HL109250, U10 {"type":"entrez-nucleotide","attrs":{"text":"HL109168","term_id":"1051682692"}}HL109168, U10 {"type":"entrez-nucleotide","attrs":{"text":"HL109257","term_id":"1051682826"}}HL109257, U10 {"type":"entrez-nucleotide","attrs":{"text":"HL109152","term_id":"1051682671"}}HL109152, and P01 HL107202 and National Center for Advancing Translational Sciences grants UL1TR0000427, UL1TR000448, and KL2TR000428.

Rationale and Objectives To determine lobar ventilation patterns in asthmatic lungs with hyperpolarized 3He magnetic resonance imaging (HP 3He MRI). Materials and Methods Eighty-two subjects (14 normal, 48 mild-to-moderate asthma, and 20 severe asthma) underwent HP 3He MRI, computed tomography (CT), and pulmonary function testing. After registering proton to 3He images, we segmented the lungs from proton MRI and further segmented the five lung lobes (right upper lobe [RUL], right middle lobe [RML], and right lower lobe [RLL]; left upper lobe and left lower lobe [LLL]) by referring to the lobar segmentation from CT. We classified the gas volume into four signal intensity levels as follows: ventilation defect percent (VDP), low ventilation percent, medium ventilation percent, and high ventilation percent. The local signal intensity variations in the ventilated volume were estimated using heterogeneity score (Hs). We compared each ventilation level and Hs measured in the whole lung and lobar regions across the three subject groups. Results In mild-to-moderate asthma, the RML and RUL showed significantly greater VDP than the two lower lobes (RLL and LLL) (P ≤ .047). In severe asthma, the pattern was more variable with the VDP in the RUL significantly greater than in the RLL (P = .026). In both asthma groups, the lower lobes (RLL and LLL) showed significantly higher high ventilation percent and Hs compared to the three upper lobes (all P ≤ .015). Conclusions In asthma, the RML and RUL showed greater ventilation abnormalities, and the RLL and LLL were more highly ventilated with greater local heterogeneity. These findings may facilitate guided bronchoscopic sampling and localized airway treatment in future studies.

Background A previous study demonstrated the feasibility of using 3D radial ultrashort echo time (UTE) oxygen-enhanced MRI (UTE OE-MRI) for functional imaging of healthy human lungs. The repeatability of quantitative measures from UTE OE-MRI needs to be established prior to its application in clinical research. Purpose To evaluate repeatability of obstructive patterns in asthma and cystic fibrosis (CF) with UTE OE-MRI with isotropic spatial resolution and full chest coverage. Study Type Volunteer and patient repeatability. Population Eighteen human subjects (five asthma, six CF, and seven normal subjects). Field Strength/Sequence Respiratory-gated free-breathing 3D radial UTE (80 μs) sequence at 1.5T. Assessment Two 3D radial UTE volumes were acquired sequentially under normoxic and hyperoxic conditions. A subset of subjects underwent repeat acquisitions on either the same day or ≤15 days apart. Asthma and CF subjects also underwent spirometry. A workflow including deformable registration and retrospective lung density correction was used to compute 3D isotropic percent signal enhancement (PSE) maps. Median PSE (MPSE) and ventilation defect percent (VDP) of the lung were measured from the PSE map. Statistical Tests The relations between MPSE, VDP, and spirometric measures were assessed using Spearman correlations. The test–retest repeatability was evaluated using Bland–Altman analysis and intraclass correlation coefficients (ICC). Results Ventilation measures in normal subjects (MPSE = 8.0%, VDP = 3.3%) were significantly different from those in asthma (MPSE = 6.0%, P = 0.042; VDP = 21.7%, P = 0.018) and CF group (MPSE = 4.5%, P = 0.0006; VDP = 27.2%, P = 0.002). MPSE correlated significantly with forced expiratory lung volume in 1 second percent predicted (ρ = 0.72, P = 0.017). The ICC of the test–retest VDP and MPSE were both ≥0.90. In all subject groups, an anterior/posterior gradient was observed with higher MPSE and lower VDP in the posterior compared to anterior regions (P ≤ 0.0021 for all comparisons). Data Conclusion 3D radial UTE OE-MRI supports quantitative differentiation of diseased vs. healthy lungs using either whole lung VDP or MPSE with excellent test–retest repeatability. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

Purpose To achieve motion robust high resolution 3D free-breathing pulmonary MRI utilizing a novel dynamic 3D image navigator derived directly from imaging data. Methods Five-minute free-breathing scans were acquired with a 3D ultrashort echo time (UTE) sequence with 1.25 mm isotropic resolution. From this data, dynamic 3D self-navigating images were reconstructed under locally low rank (LLR) constraints and used for motion compensation with one of two methods: a soft-gating technique to penalize the respiratory motion induced data inconsistency, and a respiratory motion-resolved technique to provide images of all respiratory motion states. Results Respiratory motion estimation derived from the proposed dynamic 3D self-navigator of 7.5 mm isotropic reconstruction resolution and a temporal resolution of 300 ms was successful for estimating complex respiratory motion patterns. This estimation improved image quality compared to respiratory belt and DC-based navigators. Respiratory motion compensation with soft-gating and respiratory motion-resolved techniques provided good image quality from highly undersampled data in volunteers and clinical patients. Conclusion An optimized 3D UTE sequence combined with the proposed reconstruction methods can provide high-resolution motion robust pulmonary MRI. Feasibility was shown in patients who had irregular breathing patterns in which our approach could depict clinically relevant pulmonary pathologies. Magn Reson Med 79:2954-2967, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Pulmonary embolism (PE) is a leading cause of acute cardiovascular death throughout the world. Although computed tomography angiography (CTA) is the primary imaging study used to diagnose acute PE, pulmonary magnetic resonance angiography (MRA) is increasingly being used in patients with contraindications for CTA. This manuscript reviews the MRA techniques used for the diagnosis of PE and discuss how these techniques can be implemented in routine clinical practice. In addition, the efficacy and effectiveness of these techniques will be compared to other modalities.

BACKGROUND Ultrashort echo time (UTE) proton MRI has gained popularity for assessing lung structure and function in pulmonary imaging; however, the development of rapid biomarker extraction and regional quantification has lagged behind due to labor-intensive lung segmentation. PURPOSE To evaluate a deep learning (DL) approach for automated lung segmentation to extract image-based biomarkers from functional lung imaging using 3D radial UTE oxygen-enhanced (OE) MRI. STUDY TYPE Retrospective study aimed to evaluate a technical development. POPULATION Forty-five human subjects, including 16 healthy volunteers, 5 asthma, and 24 patients with cystic fibrosis. FIELD STRENGTH/SEQUENCE 1.5T MRI, 3D radial UTE (TE = 0.08 msec) sequence. ASSESSMENT Two 3D radial UTE volumes were acquired sequentially under normoxic (21% O2 ) and hyperoxic (100% O2 ) conditions. Automated segmentation of the lungs using 2D convolutional encoder-decoder based DL method, and the subsequent functional quantification via adaptive K-means were compared with the results obtained from the reference method, supervised region growing. STATISTICAL TESTS Relative to the reference method, the performance of DL on volumetric quantification was assessed using Dice coefficient with 95% confidence interval (CI) for accuracy, two-sided Wilcoxon signed-rank test for computation time, and Bland-Altman analysis on the functional measure derived from the OE images. RESULTS The DL method produced strong agreement with supervised region growing for the right (Dice: 0.97; 95% CI = [0.96, 0.97]; P < 0.001) and left lungs (Dice: 0.96; 95% CI = [0.96, 0.97]; P < 0.001). The DL method averaged 46 seconds to generate the automatic segmentations in contrast to 1.93 hours using the reference method (P < 0.001). Bland-Altman analysis showed nonsignificant intermethod differences of volumetric (P ≥ 0.12) and functional measurements (P ≥ 0.34) in the left and right lungs. DATA CONCLUSION DL provides rapid, automated, and robust lung segmentation for quantification of regional lung function using UTE proton MRI. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1169-1181.

Objective Our aim was to validate the previously published claim of a positive relationship between low blood hemoglobin level (anemia) and pulmonary embolism (PE). Methods This was a retrospective study of patients undergoing cross-sectional imaging to evaluate for PE at an academic medical center. Patients were identified using billing records for charges attributed to either magnetic resonance angiography or computed tomography angiography of the chest from 2008 to 2013. The main outcome measure was mean hemoglobin levels among those with and without PE. Our reference standard for PE status included index imaging results and a 6-month clinical follow-up for the presence of interval venous thromboembolism, conducted via review of the electronic medical record. Secondarily, we performed a subgroup analysis of only those patients who were seen in the emergency department. Finally, we again compared mean hemoglobin levels when limiting our control population to an age- and sex-matched cohort of the included cases. Results There were 1294 potentially eligible patients identified, of whom 121 were excluded. Of the remaining 1173 patients, 921 had hemoglobin levels analyzed within 24 hours of their index scan and thus were included in the main analysis. Of those 921 patients, 107 (11.6%; 107/921) were positive for PE. We found no significant difference in mean hemoglobin level between those with and without PE regardless of the control group used (12.4 ± 2.1 g/dL and 12.3 ± 2.0 g/dL [ P = .85], respectively). Conclusions Our data demonstrated no relationship between anemia and PE.

Rationale and Objectives This study aimed to compare the performance of a semiautomated ventilation defect segmentation approach, adaptive K -means, with manual segmentation of hyperpolarized helium-3 magnetic resonance imaging in subjects with exercise-induced bronchoconstriction (EIB). Materials and Methods Six subjects with EIB underwent hyperpolarized helium-3 magnetic resonance imaging and spirometry tests at baseline, post exercise, and recovery over two separate visits. Ventilation defects were analyzed by two methods. First, two independent readers manually segmented ventilation defects. Second, defects were quantified by an adaptive K -means method that corrected for coil sensitivity, applied a vesselness filter to estimate pulmonary vasculature, and segmented defects adaptively based on the overall low-intensity signals in the lungs. These two methods were then compared in four aspects: (1) ventilation defect percent (VDP) measurements, (2) correlation between spirometric measures and measured VDP, (3) regional VDP variations pre- and post exercise challenge, and (4) Dice coefficient for spatial agreement. Results The adaptive K -means method was ~5 times faster, and the measured VDP bias was under 2%. The correlation between predicted forced expiratory volume in 1 second over forced vital capacity and VDP measured by adaptive K -means ( ρ = −0.64, P 0.0001) and by the manual method ( ρ = −0.63, P 0.0001) yielded almost identical 95% confidence intervals. Neither method of measuring VDP indicated apical/basal or anterior dependence in this small study cohort. Conclusions Compared to the manual method, the adaptive K -means method provided faster, reproducible, comparable measures of VDP in EIB and may be applied to a variety of lung diseases.

The objective of this study was to increase the spatial and temporal resolution of dynamic 3-dimensional (3D) magnetic resonance imaging (MRI) of lung volumes and diaphragm motion. To achieve this goal, we evaluate the utility of the proposed blind compressed sensing (BCS) algorithm to recover data from highly undersampled measurements.We evaluated the performance of the BCS scheme to recover dynamic data sets from retrospectively and prospectively undersampled measurements. We also compared its performance against that of view-sharing, the nuclear norm minimization scheme, and the l1 Fourier sparsity regularization scheme. Quantitative experiments were performed on a healthy subject using a fully sampled 2D data set with uniform radial sampling, which was retrospectively undersampled with 16 radial spokes per frame to correspond to an undersampling factor of 8. The images obtained from the 4 reconstruction schemes were compared with the fully sampled data using mean square error and normalized high-frequency error metrics. The schemes were also compared using prospective 3D data acquired on a Siemens 3 T TIM TRIO MRI scanner on 8 healthy subjects during free breathing. Two expert cardiothoracic radiologists (R1 and R2) qualitatively evaluated the reconstructed 3D data sets using a 5-point scale (0-4) on the basis of spatial resolution, temporal resolution, and presence of aliasing artifacts.The BCS scheme gives better reconstructions (mean square error = 0.0232 and normalized high frequency = 0.133) than the other schemes in the 2D retrospective undersampling experiments, producing minimally distorted reconstructions up to an acceleration factor of 8 (16 radial spokes per frame). The prospective 3D experiments show that the BCS scheme provides visually improved reconstructions than the other schemes do. The BCS scheme provides improved qualitative scores over nuclear norm and l1 Fourier sparsity regularization schemes in the temporal blurring and spatial blurring categories. The qualitative scores for aliasing artifacts in the images reconstructed by nuclear norm scheme and BCS scheme are comparable.The comparisons of the tidal volume changes also show that the BCS scheme has less temporal blurring as compared with the nuclear norm minimization scheme and the l1 Fourier sparsity regularization scheme. The minute ventilation estimated by BCS for tidal breathing in supine position (4 L/min) and the measured supine inspiratory capacity (1.5 L) is in good correlation with the literature. The improved performance of BCS can be explained by its ability to efficiently adapt to the data, thus providing a richer representation of the signal.The feasibility of the BCS scheme was demonstrated for dynamic 3D free breathing MRI of lung volumes and diaphragm motion. A temporal resolution of ∼500 milliseconds, spatial resolution of 2.7 × 2.7 × 10 mm, with whole lung coverage (16 slices) was achieved using the BCS scheme.

The purpose of this work was to quantify the redistribution of ventilation-weighted signal in the lungs of asthmatic subjects during a breath-hold using high temporal-spatial resolution hyperpolarized (HP) He-3 MRI. HP He-3 MRI was used to obtain time-resolved, volumetric images of lung ventilation during breath-hold in 39 human subjects classified as either healthy/nondiseased ( n = 14), mild-to-moderate asthmatic ( n = 17), or severely asthmatic ( n = 8). Signals were normalized to a standard lung volume, so that voxels within the lung from all 39 subjects could be analyzed as a group to increase statistical power and enable semiautomated classification of voxels into 1 of 5 ventilation level categories (ranging from defect to hyperintense). End-inspiratory ventilation distribution and temporal rates of mean signal change for each of the five ventilation categories were compared using ANOVA. Time rates of signal change were hypothesized to represent underlying gas redistribution processes, potentially influenced by disease. We found that mild-to-moderate asthmatic subjects showed the greatest rate of signal change, even though those with severe asthma had the greatest end-inspiration ventilation heterogeneity. The observed results support the existence of local differences in airway resistances associated with the different obstructive patterns in the lungs for severe vs. mild-to-moderate asthmatic subjects.

PURPOSE: To compare the performance of three-dimensional radial ultrashort echo time (UTE) oxygen-enhanced (OE) MRI with that of hyperpolarized helium 3 ((3)He) MRI with respect to quantitative ventilation measurements in patients with cystic fibrosis (CF). MATERIALS AND METHODS: In this prospective study conducted from June 2013 to May 2015, 25 participants with CF aged 10–55 years (14 male; age range, 13–55 years; 11 female; age range, 10–37 years) successfully underwent pulmonary function tests, hyperpolarized (3)He MRI, and OE MRI. OE MRI used two sequential 3.5-minute normoxic and hyperoxic steady-state free-breathing UTE acquisitions. Seven participants underwent imaging at two separate examinations 1–2 weeks apart to assess repeatability. Regional ventilation was quantified as ventilation defect percentage (VDP) individually from OE MRI and hyperpolarized (3)He MRI by using the same automated quantification tool. Bland-Altman analysis, intraclass correlation coefficient (ICC), Spearman correlation coefficient, and Wilcoxon signed-rank test were used to evaluate repeatability. RESULTS: In all 24 participants, the global VDP measurements from either OE MRI (ρ = −0.66, P < .001) or hyperpolarized (3)He MRI (ρ = −0.75, P < .001) were significantly correlated with the percentage predicted forced expiratory volume in 1 second. VDP reported at OE MRI was 5.0% smaller than (P = .014) but highly correlated with (ρ = 0.78, P < .001) VDP reported at hyperpolarized (3)He MRI. Both OE MRI-based VDP and hyperpolarized (3)He MRI-based VDP demonstrated good repeatability (ICC = 0.91 and 0.95, respectively; P ≤ .001). CONCLUSION: In lungs with cystic fibrosis, ultrashort echo time oxygen-enhanced MRI showed similar performance compared with hyperpolarized (3)He MRI for quantitative measures of ventilation defects and their repeatability. © RSNA, 2018 Online supplemental material is available for this article.

OBJECTIVES: To investigate intra- and inter-observer repeatability of aortic annulus CT measurements for transcatheter aortic valve replacement (TAVR) by readers with different levels of experience and evaluate the impact of different multi-reader paradigms to improve prosthesis sizing. METHODS: 82 TAVR screening CTAs were evaluated twice by three raters with six (R1=radiologist), three (R2=3D-laboratory technician) or zero (R3=medical student) years of experience. Results were translated into hypothetical TAVR size recommendations. Intra- and inter-observer repeatability between single readers and three different multi-reader paradigms ([A]: two readers, [B]: three readers, or [C]: two readers + an optional third reader) were evaluated. RESULTS: Intra-observer variability did not differ significantly (range: 50.1-67.8mm(2)). However, we found significant differences in mean inter-observer variance (p=0.001). Multi-reader paradigms led to significantly increased precision (lower variability) for scenarios [B] and [C] (p=0.03, p

To demonstrate the feasibility of free-breathing three-dimensional (3D) radial ultrashort echo time (UTE) magnetic resonance (MR) imaging in the simultaneous detection of pulmonary embolism (PE) and high-quality evaluation of lung parenchyma.The institutional animal care committee approved this study. A total of 12 beagles underwent MR imaging and computed tomography (CT) before and after induction of PE with autologous clots. Breath-hold 3D MR angiography and free-breathing 3D radial UTE (1.0-mm isotropic spatial resolution; echo time, 0.08 msec) were performed at 3 T. Two blinded radiologists independently marked and graded all PEs on a four-point scale (1 = low confidence, 4 = absolutely certain) on MR angiographic and UTE images. Image quality of pulmonary arteries and lung parenchyma was scored on a four-point-scale (1 = poor, 4 = excellent). Locations and ratings of emboli were compared with reference standard CT images by using an alternative free-response receiver operating characteristic curve (AFROC) method. Areas under the curve and image quality ratings were compared by using the F test and the Wilcoxon signed-rank test.A total of 48 emboli were detected with CT. Both readers showed higher sensitivity for PE detection with UTE (83% and 79%) than with MR angiography (75% and 71%). The AFROC area under the curve was higher for UTE than for MR angiography (0.95 vs 0.89), with a significant difference in area under the curve of 0.06 (95% confidence interval: 0.01, 0.11; P = .018). UTE image quality exceeded that of MR angiography for subsegmental arteries (3.5 ± 0.7 vs 2.9 ± 0.5, P = .002) and lung parenchyma (3.8 ± 0.5 vs 2.2 ± 0.2, P.001). The apparent signal-to-noise ratio in pulmonary arteries and lung parenchyma was significantly higher for UTE than for MR angiography (41.0 ± 5.2 vs 24.5 ± 6.2 [P.001] and 10.2 ± 1.8 vs 3.5 ± 0.8 [P.001], respectively). The apparent contrast-to-noise ratio between arteries and PEs was higher for UTE than for MR angiography (20.3 ± 5.2 vs 15.4 ± 6.7, P = .055).In a canine model, free-breathing 3D radial UTE performs better than breath-hold 3D MR angiography in the detection of PE and yields better image quality for visualization of small vessels and lung parenchyma. Free-breathing 3D radial UTE for detection of PE is feasible and warrants evaluation in human subjects.

This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)—hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas—and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children. J. Magn. Reson. Imaging 2015.

OBJECTIVES The objectives of this study were to compare pulmonary blood flow (PBF) measurements acquired with 3 previously published models (low-dose "single bolus," "dual bolus" and a "nonlinear correction" algorithm) for addressing the nonlinear relationship between contrast agent concentration and magnetic resonance signal in the arterial input function (AIF) and to compare both lung signal and PBF measurements obtained using gadopentetate dimeglumine (Gd-DTPA, Magnevist) with those obtained using the high-relaxivity agent gadobenate dimeglumine (Gd-BOPTA, Multihance). MATERIALS AND METHODS Ten of 12 healthy humans were successfully scanned on 2 consecutive days at 1.5 T. Contrast-enhanced pulmonary perfusion scans were acquired with a 3-dimensional spoiled gradient echo pulse sequence and interleaved variable density k-space sampling with a 1-second frame rate and 4 × 4 × 4-mm resolution. Each day, 2 perfusion scans were acquired with either Gd-DTPA or Gd-BOPTA; the order of the administered contrast agent was randomized. Region of interest analysis was used to determine PBF on the basis of the indicator dilution theory. Linear mixed-effects modeling was used to compare the AIF models and contrast agents. RESULTS With Gd-DTPA, no significant differences were observed between the mean PBF calculated for the single bolus (323 ± 110 mL/100mL/min), dual bolus (315 ± 177 mL/100mL/min), and nonlinear correction (298 ± 100 mL/100mL/min) approach. With Gd-BOPTA, the mean PBF using the dual bolus approach (245 ± 103 mL/100mL/min) was lower than with the single bolus (345 ± 130 mL/100mL/min P < 0.01) and nonlinear correction (321 ± 115 mL/100mL/min; P = 0.02). Peak lung enhancement was significantly higher in all regions with Gd-BOPTA than with Gd-DTPA (P << 0.01). CONCLUSIONS The dual bolus approach with Gd-BOPTA resulted in a significantly lower PBF than did the other combinations of contrast agent and AIF model. No other statistically significant differences were found. Given the much higher signal in the lung parenchyma using Gd-BOPTA, the use of Gd-BOPTA with either single bolus or the nonlinear correction method appears most promising for voxelwise perfusion quantification using 3-dimensional dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging.

Objective To evaluate the effects of lumacaftor/ivacaftor (LUM/IVA) combination therapy on lung morphology and physiology with computed tomography (CT) scanning in patients aged 6 to 11 years with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation. Methods Baseline CT scans were obtained in 19 patients (12 active treatment, 7 placebo) from the phase 3 LUM/IVA trial (NCT02514473), and 24 week CT scans were completed in 7 active treatment and 3 placebo patients. CT scans were obtained at total lung capacity and at residual volume (RV). CT scans were scored by 2 independent readers blinded to all patient and time point information using the Brody score, which evaluates the extent and severity of multiple aspects of CF lung disease, including bronchiectasis and air trapping. Scores are presented as mean (SD); no statistical testing was performed for this preliminary study. Results Mean total CT score (sum of the subcomponent scores) decreased from 20.6 to 12.5 (mean change [SD], 8.1 [13.6]) in the LUM/IVA group and increased from 32.8 to 41.4 (8.6 [14.6]) in the placebo group. The mean bronchiectasis score decreased from 3.2 to 2.5 (0.7 [1.3]) in the LUM/IVA group and increased from 6.4 to 8.1 (1.7 [2.1]) in the placebo group. Additionally, the diameter of ectatic bronchi decreased in several patients on active treatment. The mean air trapping score decreased from 7.8 to 5.9 (mean difference [SD], 1.9 [6.8]) in the active group and increased from 9.8 to 14.5 (4.7 [11.7]) in the placebo group, as shown for 1 patient (figure 1). Conclusion This is the first report to describe CT lung findings after CFTR corrector/potentiator therapy in patients aged 6 to 11 years homozygous for F508del. In this 24 week exploratory analysis, bronchiectasis and air trapping scores improved in patients treated with LUM/IVA and worsened in the placebo group. These data suggest that LUM/IVA treatment may reduce CF disease-related changes in lung morphology and/or physiology and support the need for further study. Please refer to page A257 for declarations of interest in relation to abstract S93.

Objective To evaluate ultrashort echo time (UTE) magnetic resonance imaging (MRI) as a feasible endpoint in a multicenter trial using a subset of patients aged 6 to 11 years with cystic fibrosis (CF) homozygous for the F508del mutation treated with lumacaftor/ivacaftor (LUM/IVA) combination therapy (NCT02514473). Methods UTE MRI scans were obtained at study baseline (n=10); a second scan was completed at week 24 in 9 subjects (4 active treatment, 5 placebo) at 3 institutions using MRI hardware from 2 vendors. One of the platforms was 3D radial UTE (Johnson et al. Magn Reson Med. 2013;70:1241–1250); the other was 3D “stack of stars” UTE (Lederlin et al. J Magn Reson Imaging. 2014;40:839–847). Scans were obtained during 5 min of tidal breathing without the use of intravenous contrast. MRI scans were scored by 2 independent readers using the Brody score after supervised training on UTE MRI scans. Readers were blinded to time point and treatment group. Scores are presented as mean (SD); no statistical testing was performed. Results Despite the lower image quality of MRI compared with computed tomography, potential treatment effects were seen on the UTE MRI images (figure 1A). Mean total Brody score decreased from 41.1 to 32.5 with treatment, a change from baseline (SD) of 8.4 (11.2) with active treatment, but increased from 31.3 to 34.6, a change from baseline of 3.3 (8.2) with placebo (figure 1B). Mucus plugging subscore decreased by 5.0 (5.1) from 8.5 to 3.5 with active treatment but increased by 1.4 (4.4) from 4.2 to 5.6 with placebo. There were no noticeable changes in other subscores (bronchiectasis, peribronchial thickening, parenchyma, or hyperinflation). Conclusion In this analysis from an exploratory substudy in patients with CF aged 6 to 11 years homozygous for F508del, UTE MRI was a feasible approach for detecting the effect of LUM/IVA, despite the small sample size, short duration of treatment, and limitations in image quality. As optimisation in UTE MRI technology improves image quality, monitoring disease course in patients with CF may improve. Please refer to page A259 for declarations of interest in relation to abstract P254.

Purpose To assess the feasibility of spatial–temporal constrained reconstruction for accelerated regional lung perfusion using highly undersampled dynamic contrast-enhanced (DCE) three-dimensional (3D) radial MRI with ultrashort echo time (UTE). Methods A combined strategy was used to accelerate DCE MRI for 3D pulmonary perfusion with whole lung coverage. A highly undersampled 3D radial UTE MRI acquisition was combined with an iterative constrained reconstruction exploiting principal component analysis and wavelet soft-thresholding for dimensionality reduction in space and time. The performance of the method was evaluated using a 3D fractal-based DCE digital lung phantom. Simulated perfusion maps and contrast enhancement curves were compared with ground truth using the structural similarity index (SSIM) to determine robust threshold and regularization levels. Feasibility studies were then performed in a canine and a human subject with 3D radial UTE (TE = 0.08 ms) acquisition to assess feasibility of mapping regional 3D perfusion. Results The method was able to accurately recover perfusion maps in the phantom with a nominal isotropic spatial resolution of 1.5 mm (SSIM of 0.949). The canine and human subject studies demonstrated feasibility for providing artifact-free perfusion maps in a simple 3D breath-held acquisition. Conclusion The proposed method is promising for fast and flexible 3D pulmonary perfusion imaging. Magn Reson Med 73:555–564, 2015. © 2014 Wiley Periodicals, Inc.

Pulmonary hypertension is a condition of varied etiology, commonly associated with poor clinical outcome. Patients are categorized on the basis of pathophysiological, clinical, radiologic, and therapeutic similarities. Pulmonary arterial hypertension (PAH) is often diagnosed late in its disease course, with outcome dependent on etiology, disease severity, and response to treatment. Recent advances in quantitative magnetic resonance imaging (MRI) allow for better initial characterization and measurement of the morphologic and flow-related changes that accompany the response of the heart-lung axis to prolonged elevation of pulmonary arterial pressure and resistance and provide a reproducible, comprehensive, and noninvasive means of assessing the course of the disease and response to treatment. Typical features of PAH occur primarily as a result of increased pulmonary vascular resistance and the resultant increased right ventricular (RV) afterload. Several MRI-derived diagnostic markers have emerged, such as ventricular mass index, interventricular septal configuration, and average pulmonary artery velocity, with diagnostic accuracy similar to that of Doppler echocardiography. Furthermore, prognostic markers have been identified with independent predictive value for identification of treatment failure. Such markers include large RV end-diastolic volume index, low left ventricular end-diastolic volume index, low RV ejection fraction, and relative area change of the pulmonary trunk. MRI is ideally suited for longitudinal follow-up of patients with PAH because of its noninvasive nature and high reproducibility and is advantageous over other biomarkers in the study of PAH because of its sensitivity to change in morphologic, functional, and flow-related parameters. Further study on the role of MRI image based biomarkers in the clinical environment is warranted.

Purpose To develop and demonstrate a breathheld 3D radial ultrashort echo time (UTE) acquisition to visualize co-registered lung perfusion and vascular structure. Materials and Methods Nine healthy dogs were scanned twice at 3 Tesla (T). Contrast-enhanced pulmonary perfusion scans were acquired with a temporally interleaved three-dimensional (3D) radial UTE (TE = 0.08 ms) sequence in a breathhold (1 s time frames over a 33 s breathhold). The 3D breathheld volume was reconstructed into time-resolved perfusion datasets, and a composite vascular structure dataset. For structural comparison, a 5 min respiratory-gated 3D radial UTE scan was acquired. Data were analyzed by quantitative metrics and radiologist scoring. Results Appropriate time-course of contrast was seen in all subjects. Right ventricle to aorta transit times were 7.4 ± 2.0 s. Relative lung enhancement was a factor of 8.4 ± 1.5. Radiologist scoring showed similarly excellent visualization of the pulmonary arteries to the subsegmental level in breathheld (94% of cases) and respiratory-gated (100% of cases) acquisitions (P = 0.33) despite the aggressive under sampling in the breathheld scan. Similarly, differentiation of lung tissue and airways was achieved by both acquisition methods. Conclusion A time-resolved 3D radial UTE sequence for simultaneous imaging of pulmonary perfusion and co-registered vascular structure is feasible. J. Magn. Reson. Imaging 2015;41:52–59. © 2013 Wiley Periodicals, Inc.

Purpose To develop and evaluate a free-breathing chemical-shift-encoded (CSE) spoiled gradient-recalled echo (SPGR) technique for whole-heart water–fat imaging at 3 Tesla (T). Methods We developed a three-dimensional (3D) multi-echo SPGR pulse sequence with electrocardiographic gating and navigator echoes and evaluated its performance at 3T in healthy volunteers (N = 6) and patients (N = 20). CSE-SPGR, 3D SPGR, and 3D balanced-SSFP with chemical fat saturation were compared in six healthy subjects with images evaluated for overall image quality, level of residual artifacts, and quality of fat suppression. A similar scoring system was used for the patient datasets. Results Images of diagnostic quality were acquired in all but one subject. CSE-SPGR performed similarly to SPGR with fat saturation, although it provided a more uniform fat suppression over the whole field of view. Balanced-SSFP performed worse than SPGR-based methods. In patients, CSE-SPGR produced excellent fat suppression near metal. Overall image quality was either good (7/20) or excellent (12/20) in all but one patient. There were significant artifacts in 5/20 clinical cases. Conclusion CSE-SPGR is a promising technique for whole-heart water–fat imaging during free-breathing. The robust fat suppression in the water-only image could improve assessment of complex morphology at 3T and in the presence of off-resonance, with additional information contained in the fat-only image. Magn Reson Med 72:718–725, 2014. © 2013 Wiley Periodicals, Inc.

Purpose To investigate the utility of hyperpolarized He-3 MRI for detecting regional lung ventilated volume (VV) changes in response to exercise challenge and leukotriene inhibitor montelukast, human subjects were recruited with Exercise Induced Bronchoconstriction (EIB), a condition described by airway constriction following exercise leading to reduced Forced Expiratory Volume in 1 second (FEV1) coinciding with ventilation defects on hyperpolarized He-3 MRI.

Pulmonary Embolism (PE) is an important cause of death in the industrialized world (1,2). Ionizing radiation administered for medical imaging is of increasing clinical concern, particularly for younger patients and female patients (3,4). In a recent epidemiological study, medical radiation at the 50 mSv level was shown to have increased incidence of brain malignancy and leukemia above what could be expected in an unexposed population (5). Chest radiation for younger women is potentially problematic due to its cumulative effects and the radiation sensitivity of breast tissue (3,6). In symptomatic patients with a clinical suspicion for pulmonary embolus, the currently accepted reference standard is computed tomographic angiography (CTA-PE) (7–12). An alternative test that requires no ionizing radiation for the detection of pulmonary embolism would be highly beneficial, so long as it has sufficient effectiveness (4–12). There is recent evidence showing that the number of pulmonary embolism (PE) diagnoses has significantly increased in the United States without a corresponding significant drop in death rate (13–15). CTA-PE is a frequently ordered test that maybe over-used (16). This high degree of usage by clinicians likely reflects the excellent performance (efficacy) of CTA-PE and its ability to diagnose even tiny, subsegmental pulmonary emboli. Recently, some authors have challenged the necessity to treat all sub-segmental PE with anti-coagulation (13,14,17), noting the 4–8% incidence of serious bleeding complications from treatment of PE (1,14,18,19). For this reason, alternative exams such as pulmonary MR angiography (MRA-PE), which have a lower accuracy (efficacy) than CTA-PE for diagnosis of subsegmental PE, may be more than adequate for detection of clinically significant emboli that require anticoagulation. (17,20–24). Use of patient outcomes for the determination of test effectiveness is often employed when there is no available reference standard to determine the efficacy of a test. Recently, Douglas and colleagues have suggested that the determination of test effectiveness, as established by patient outcomes, is actually much more important for the evaluation of clinical utility than test efficacy (29). Lack of a measurable adverse clinical event over the follow-up period is a useful surrogate for utility of a test in this situation. In the clinical evaluation of heart disease, the patient outcome surrogate is a Major Adverse Cardiac Event (MACE) during the chosen follow-up interval (29). In the nuclear medicine literature, outcomes analysis have be used for many years in the determination of test negativity in the workup of suspected PE (30). Use of 1-year outcomes for the determination of CTA-PE effectiveness has been reported by the highly respected cardio-pulmonary radiology group in Lille, France (31). They studied 185 patients and found that CTA-PE had a negative predictive value of 98%, with three episodes of fatal PE (31). Early work on the efficacy of MRA-PE was published in 1999 by Gupta and colleagues has now been shown to be on target with current results (25). They found that larger PEs (lobar and segmental) are well seen with contrast enhanced MRA-PE, but that the sub-segmental PEs were frequently missed (25). There are many studies showing that MRA-PE is a test of lower efficacy than CTA-PE for the diagnosis of subsegmental pulmonary embolism (20,21,28,32–34). However, a conclusion from the PIOPED III study was that if the MRA-PE could be performed in a technically adequate manner, that MRA-PE is highly diagnostic for this condition (20). The purpose of our retrospective study was to determine the effectiveness of MRA-PE in symptomatic patients, using the clinical outcome measure of Venous ThromboEmbolism (VTE, deep venous thrombosis and/or PE) or death from PE as determined by review of the electronic medical record (EMR) for 3 months following the MRA-PE and a second review at 1 year.

The purpose of this study was to assess the ability of d-dimer testing to obviate the need for cross-sectional imaging for patients at “non-high risk” for pulmonary embolism (PE). This is a retrospective study of emergency department patients at an academic medical center who underwent cross-sectional imaging (MRA or CTA) to evaluate for PE from 2008 to 2013. The primary outcome was the NPV of d-dimer testing when used in conjunction with clinical decision instruments (CDIs = Wells’, Revised Geneva, and Simplified Revised Geneva Scores). The reference standard for PE status included image test results and a 6-month chart review follow-up for venous thromboembolism as a proxy for false negative imaging. Secondary analyses included ROC curves for each CDI and calculation of PE prevalence in each risk stratum. Of 459 patients, 41 (8.9%) had PE. None of the 76 patients (16.6%) with negative d-dimer results had PE. Thus, d-dimer testing had 100% sensitivity and NPV, and there were no differences in CDI performance. Similarly, when evaluated independently of d-dimer results, no CDI outperformed the others (areas under the ROC curves ranged 0.53–0.55). There was a significantly higher PE prevalence in the high versus “non-high risk” groups when stratified by the Wells’ Score (p = 0.03). Negative d-dimer testing excluded PE in our retrospective cohort. Each CDI had similar NPVs, whether analyzed in conjunction with or independently of d-dimer results. Our results confirm that PE can be safely excluded in patients with “non-high risk” CDI scores and a negative d-dimer.

Proton MRI is able to depict the major changes in CF lung disease in a similar way to CT, albeit there will be shortcomings in the detection of more subtle or smaller abnormalities. Further studies are warranted to determine whether the additional structural detail provided by CT is necessary for the evaluation of the severity and progression of CF lung disease. At the same time, proton and hyperpolarized gas MRI provide a broad spectrum of additional functional information in CF lung diseases that is otherwise not available to patients and clinicians. The MRI techniques to be applied in CF lung disease are novel and further development and studies are required to fully implement and assess their potential impact in CF. It is currently unknown whether the combination of functional and structural information from MRI will be more useful than the mere structural information provided by CT in the clinical assessment of CF. It is conceivable that MRI and CT will be complementary as they have different advantages and disadvantages in elucidating the complex interrelation of lung structure and function.

Purpose To demonstrate the feasibility of direct virtual coil (DVC) in the setting of 4D dynamic imaging used in multiple clinical applications. Theory and Methods Three dynamic imaging applications were chosen: pulmonary perfusion, liver perfusion, and peripheral MR angiography (MRA), with 18, 11, and 10 subjects, respectively. After view-sharing, the k-space data were reconstructed twice: once with channel-by-channel (CBC) followed by sum-of-squares coil combination and once with DVC. Images reconstructed using CBC and DVC were compared and scored based on overall image quality by two experienced radiologists using a five-point scale. Results The CBC and DVC showed similar image quality in image domain. Time course measurements also showed good agreement in the temporal domain. CBC and DVC images were scored as equivalent for all pulmonary perfusion cases, all liver perfusion cases, and four of the 10 peripheral MRA cases. For the remaining six peripheral MRA cases, DVC were scored as slightly better (not clinically significant) than the CBC images by Radiologist A and as equivalent by Radiologist B. Conclusion For dynamic contrast-enhanced MR applications, it is clinically feasible to reduce image reconstruction time while maintaining image quality and time course measurement using the DVC technique. Magn Reson Med 71:783–789, 2014. © 2013 Wiley Periodicals, Inc.

To quantitatively evaluate interday, interreader, and intersite agreement of readers of hyperpolarized helium 3 (HPHe) MR images in patients with exercise-induced bronchoconstriction.This HIPAA-compliant, institutional review board approved study included 13 patients with exercise-induced bronchoconstriction. On two separate days, HPHe MR imaging of the lungs was performed at baseline, immediately after a 10-minute exercise challenge (postchallenge), and 45 minutes after exercise (recovery). Patients were imaged at two sites, six at site A and seven at site B. Images were analyzed independently by multiple readers at each site. Lung volume, ventilation defect volume, ventilated volume, and the number of defects were measured quantitatively, and the location of defects was evaluated qualitatively at site A. Interday and interreader agreement were evaluated by using the intraclass correlation coefficient (ICC), and intersite agreement was evaluated by using a modified Bland-Altman analysis.The ICC between days for ventilation defect volume, ventilated volume, and number of defects was at least 0.74 at both sites. The ICC for lung volume was greater at site B (0.83-0.86) than at site A (0.60-0.65). Defects seen in the same location in the lung on both days included 19.7% of those seen on baseline images and 29.2% and 18.6% of defects on postchallenge and recovery images, respectively. Interreader ICC for each measurement was at least 0.82 for each site. Analysis of intersite agreement showed biases of 612 mL for lung volume, -60.7 mL for ventilation defect volume, 2.91% for ventilated volume, and -6.56 for number of defects.The reported measures of reproducibility of HPHe MR imaging may help in the design and interpretation of single- and multicenter studies of patients with exercise-induced bronchoconstriction.

Purpose: To demonstrate the feasibility of performing single breathhold, noncardiac gated, ultrafast, high spatial-temporal resolution whole chest MR pulmonary perfusion imaging in humans. Materials and Methods: Eight subjects (five male, three female) were scanned with the proposed method on a 3 Tesla clinical scanner using a 32-channel phased-array coil. Seven (88%) were healthy volunteers, and one was a patient volunteer with sarcoidosis. The peak lung enhancement phase for each subject was scored for gravitational effect, peak parenchymal enhancement and severity of artifacts by three cardiothoracic radiologists independently. Results: All studies were successfully performed by MR technologists without any additional training. Mean parenchymal signal was very good, measuring 0.78 ± 0.13 (continuous scale, 0 = “none” 1 = “excellent”). Mean level of motion artifacts was low, measuring 0.13 ± 0.08 (continuous scale, 0 = “none” 1 = “severe”). Conclusion: It is feasible to perform single breathhold, noncardiac gated, ultrafast, high spatial-temporal resolution whole chest MR pulmonary perfusion imaging in humans. J. Magn. Reson. Imaging 2013;38:751–756. © 2013 Wiley Periodicals, Inc.

Purpose To optimize 3D radial ultrashort echo time MRI for high resolution whole-lung imaging. Methods 3D radial ultrashort echo time was implemented on a 3T scanner to investigate the effects of: (1) limited field-of-view excitation, (2) variable density readouts, and (3) radial oversampling. Improvements in noise performance and spatial resolution were assessed through simulation and phantom studies. Their effects on lung and airway visualization in five healthy male human subjects (mean age 32 years) were compared qualitatively through blinded ordinal scoring by two cardiothoracic radiologists using a nonparametric Friedman test (P < 0.05). Relative signal difference between endobronchial air and adjacent lung tissue, normalized to nearby vessel, was used as a surrogate for lung tissue signal. Quantitative measures were compared using the paired Student's t-test (P < 0.05). Finally, clinical feasibility was investigated in a patient with interstitial fibrosis. Results Simulation and phantom studies showed up to 67% improvement in SNR and reduced blurring for short T2* species using all three optimizations. In vivo images showed decreased artifacts and improved lung tissue and airway visualization both qualitatively and quantitatively. Conclusion The use of limited field-of-view excitation, variable readout gradients, and radial oversampling significantly improve the technical quality of 3D radial ultrashort echo time lung images. Magn Reson Med 70:1241–1250, 2013. © 2012 Wiley Periodicals, Inc.

Purpose: To determine optimal delay times and flip angles for T1-weighted hepatobiliary imaging at 1.5 Tesla (T) with gadoxetic acid and to demonstrate the feasibility of using a high-resolution navigated optimized T1-weighted pulse sequence to evaluate biliary disease. Materials and Methods: Eight healthy volunteers were scanned at 1.5T using a T1-weighted three-dimensional (3D)-SPGR pulse sequence following the administration of 0.05 mmol/kg of gadoxetic acid. Navigator-gating enabled acquisition of high spatial resolution (1.2 × 1.4 × 1.8 mm3, interpolated to 0.7 × 0.7 × 0.9 mm3) images in approximately 5 min of free-breathing. Multiple breath-held acquisitions were performed at flip angles between 15° and 45° to optimize T1 weighting. To evaluate the performance of this optimized sequence in the setting of biliary disease, the image quality and biliary excretion of 51 consecutive clinical scans performed to assess primary sclerosing cholangitis (PSC) were evaluated. Results: Optimal hepatobiliary imaging occurs at 15–25 min, using a 40° flip angle. The image quality and visualization of biliary excretion in the PSC scans were excellent, despite the decreased liver function in some patients. Visualization of reduced excretion often provided diagnostic information that was unavailable by conventional magnetic resonance cholangiopancreatography (MRCP). Conclusion: High-resolution navigated 3D-SPGR hepatobiliary imaging using gadoxetic acid and optimized scan parameters is technically feasible and can be clinically useful, even in patients with decreased hepatobiliary function. J. Magn. Reson. Imaging 2012;36:890–899. © 2012 Wiley Periodicals, Inc.

Purpose: To investigate the value of gadoxetic acid-enhanced three-dimensional T1-weighted MR cholangiography (T1w-MRC) in comparison to three-dimensional T2-weighted MR cholangiopancreaticography (T2w-MRCP) in patients with primary sclerosing cholangitis (PSC). Materials and Methods: Thirty-four MR exams in 29 patients (46.0 ± 16.1 years; 19 men, 10 women) scanned within a 14-month period were retrospectively included. Two abdominal radiologists independently evaluated image quality regarding image contrast, image quality degradation due to artifacts, and visualization quality of ducts. The order of biliary tree branches that were visualized and reader preference toward each method were recorded. Helpfulness of T1w-MRC was scored in consensus. Confirmatory endoscopic retrograde cholangiopancreaticography (ERCP) performed within 3 months of the MR examination was available in 8 patients. Results: Image quality of T1w-MRC and T2w-MRCP was graded good to excellent in all cases. There were advantages for both T1w-MRC (functional information, less degradation due to artifacts) and T2w-MRCP (higher order of visualized branches, better branch depiction). Both readers showed preference for T2w-MRCP; however, both readers found gadoxetic acid–enhanced T1w-MRC helpful in the majority of cases. Conclusion: Gadoxetic acid-enhanced T1w-MRC is complementary to, but should not replace, T2w-MRCP. T1w-MRC is a useful adjunct to T2w-MRCP for morphologic evaluation and provides additional diagnostic information. J. Magn. Reson. Imaging 2012;36:632–640. © 2012 Wiley Periodicals, Inc.

Purpose: To evaluate the signal to noise ratio (SNR) and contrast to noise ratio (CNR) performance of 0.05 mmol/kg gadoxetic acid and 0.1 mmol/kg gadobenate dimeglumine for dynamic and hepatobiliary phase imaging. In addition, flip angles (FA) that maximize relative contrast-to-noise performance for hepatobiliary phase imaging were determined. Materials and Methods: A cross-over study in 10 volunteers was performed using each agent. Imaging was performed at 3 Tesla (T) with a 32-channel phased-array coil using breathheld 3D spoiled gradient echo sequences for SNR and CNR analysis, and for FA optimization of hepatobiliary phase imaging. Results: Gadobenate dimeglumine (0.1 mmol/kg) had superior SNR performance during the dynamic phase, statistically significant for portal vein and hepatic vein in the portal venous and venous phase (for all, P < 0.05) despite twice the approved dose of gadoxetic acid (0.05 mmol/kg), while gadoxetic acid had superior SNR performance during the hepatobiliary phase. Optimal FAs for hepatobiliary phase imaging using gadoxetic acid and gadobenate dimeglumine were 25–30° and 20–30° for relative contrast liver versus muscle (surrogate for nonhepatocellular tissues), and 45° and 20° (relative contrast liver versus biliary structures), respectively. Conclusion: Gadobenate dimeglumine may be preferable for applications that require dynamic phase imaging only, while gadoxetic acid may be preferable when the hepatobiliary phase is clinically important. Hepatobiliary phase imaging with both agents benefits from flip angle optimization. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.

Purpose To determine the incidence of actionable findings on contrast-enhanced magnetic resonance angiography (MRA) scans performed for the primary diagnosis of pulmonary embolism (PE). Materials and methods This was a HIPAA-compliant and IRB-approved single center, retrospective study of consecutive series of patients evaluated with contrast-enhanced MRA for PE. The final radiology report of each MRA was reviewed. All technically adequate negative exams were included in the analysis. The findings were divided into three types: those requiring further action (actionable—Type 1) those not requiring follow-up (non-actionable—Type 2) and normal exams. We compared our results with the literature regarding the use of computed tomographic angiography (CTA) in this scenario using Fisher’s exact test. Results 580 MRA scans for PE were performed. There were 561/580 (97%) technically adequate exams. Of these, 514/580 (89%) were negative and 47/580 (8%) were positive for PE. In the PE negative group of 514 exams, Type 1 findings were identified in 85/514 (17%), 188/514 (36%) cases were Type 2 and 241/514 (47.0%) were Type 3. There was no significant difference between the incidence of Type 1 and the combination of Type 2 and Type 3 findings on MRA and the reported incidence of actionable findings derived from CTA negative exams for PE (p Conclusion MRA as a first-line test for PE can identify actionable findings in those patients without PE, with an incidence similar to that reported in the literature for CTA.

PurposeTo investigate the utility of a free-breathing ultrashort echo time (UTE) sequence for the evaluation of small pulmonary nodules in oncology patients by using a hybrid positron emission tomography (PET)/magnetic resonance (MR) imaging system and to compare the nodule detection rate between UTE and a conventional three-dimensional gradient-recalled-echo (GRE) technique.Materials and methodsIn this HIPAA-compliant, institutional review board-approved prospective study, 82 pulmonary nodules were identified in eight patients with extrathoracic malignancies. Patients underwent free-breathing UTE and dual-echo three-dimensional GRE imaging of the lungs in a hybrid PET/MR imaging unit immediately after clinical PET/computed tomography (CT). CT was considered the reference standard for nodule detection. Two reviewers identified nodules and obtained measurements on MR images. The McNemar test was used to evaluate differences in nodule detection rate between MR techniques, and interrater agreement was assessed by using Bland-Altman plots.ResultsMean nodule diameter ± standard deviation was 6.2 mm ± 2.7 (range, 3-17 mm). The detection rate was higher for UTE imaging than for dual-echo GRE imaging for nodules of at least 4 mm (82% vs 34%, respectively; P < .001), with the largest difference in detection noted in the 4-8-mm nodule group (79% vs 21%, P < .001). UTE imaging displayed a higher detection rate than dual-echo GRE imaging for nodules without fluorodeoxyglucose avidity (68% vs 22%, respectively; P < .001). Interrater reliability of nodule detection with MR imaging was high (κ = 0.90 for UTE imaging and κ = 0.92 for dual-echo GRE imaging).ConclusionA free-breathing UTE sequence has high sensitivity for the detection of small pulmonary nodules (4-8 mm) and outperformed a three-dimensional dual-echo GRE technique for the detection of small, non-fluorodeoxyglucose-avid nodules.

Geometric distortions and poor image resolution are well known shortcomings of single-shot echo-planar imaging (ss-EPI). Yet, due to the motion immunity of ss-EPI, it remains the most common sequence for diffusion-weighted imaging (DWI). Moreover, both navigated DW interleaved EPI (iEPI) and parallel imaging (PI) methods, such as sensitivity encoding (SENSE) and generalized autocalibrating parallel acquisitions (GRAPPA), can improve the image quality in EPI. In this work, DW-EPI accelerated by PI is proposed as a self-calibrated and unnavigated form of interleaved acquisition. The PI calibration is performed on the b = 0 s/mm2 data and applied to each shot in the rest of the DW data set, followed by magnitude averaging. Central in this study is the comparison of GRAPPA and SENSE in the presence of off-resonances and motion. The results show that GRAPPA is more robust than SENSE against both off-resonance and motion-related artifacts. The SNR efficiency was also investigated, and it is shown that the SNR/scan time ratio is equally high for one- to three-shot high-resolution diffusion scans due to the shortened EPI readout train length. The image quality improvements without SNR efficiency loss, together with motion tolerance, make the GRAPPA-driven DW-EPI sequence clinically attractive.

To compare gadoxetic acid alone and combined gadoxetic acid/gadofosveset trisodium-enhanced liver MRI for detection of metastases and differentiation of metastases from haemangiomas. Ninety-one patients underwent gadoxetic acid-enhanced liver MRI before and after additional injection of gadofosveset. First, two readers retrospectively identified metastases on gadoxetic acid alone enhanced delayed hepatobiliary phase T1-weighted images together with all other MR images (dynamic images, T2-weighted images, diffusion-weighted images). Second, readers assessed additional T1-weighted images obtained after administration of gadofosveset trisodium. For both interpretations, readers rated lesion conspicuity and confidence in differentiating metastases from haemangiomas. Results were compared using alternative free-response receiver-operating characteristic (AFROC) and conventional ROC methods. Histology and follow-up served as reference standard. There were 145 metastases and 16 haemangiomas. Both readers detected more metastases using combined gadoxetic acid/gadofosveset (reader 1 = 130; reader 2 = 124) compared to gadoxetic acid alone (reader 1 = 104; reader 2 = 103). Sensitivity of combined gadoxetic acid/gadofosveset (reader 1 = 90 %; reader 2 = 86 %) was higher than that of gadoxetic acid alone (reader 1 = 72 %; reader 2 = 71 %, both P

The performance of contrast enhanced pulmonary magnetic resonance angiography (MRA) for the diagnosis of pulmonary embolism (PE) is an effective non-ionizing alternative to contrast enhanced computed tomography and nuclear medicine ventilation/perfusion scanning. However, the technical success of these exams is very dependent on careful attention to the details of the MRA acquisition protocol and requires reader familiarity with MRI and its artifacts. Most practicing radiologists are very comfortable with the performance and interpretation of computed tomographic angiography (CTA) performed to detect pulmonary embolism but not all are as comfortable with the use of MRA in this setting. The purpose of this review is to provide the general radiologist with the tools necessary to build a successful pulmonary embolism MRA program. This review will cover in detail image acquisition, image interpretation, and some key elements of outreach that help to frame the role of MRA to consulting clinicians and hospital administrators. It is our aim that this resource will help build successful clinical pulmonary embolism MRA programs that are well received by patients and physicians, reduce the burden of medical imaging radiation, and maintain good patient outcomes.