Comparison of hyperpolarized 3He-MRI, CT based parametric response mapping, and mucus scores in asthmatics.

Purpose: The purpose of this study was to anatomically correlate ventilation defects with regions of air trapping by whole lung, lung lobe, and airway segment in the context of airway mucus plugging in asthma. Methods: A total of 34 asthmatics [13M:21F, 13 mild/moderate, median age (range) of 49.5 (36.8-53.3) years and 21 severe, 56.1 (47.1-62.6) years] and 4 healthy subjects [1M:3F, 38.5 (26.6-52.2) years] underwent HP 3He MRI and CT imaging. HP 3He MRI was assessed for ventilation defects using a semi-automated k-means clustering algorithm. Inspiratory and expiratory CTs were analyzed using parametric response mapping (PRM) to quantify markers of emphysema and functional small airways disease (fSAD). Segmental and lobar lung masks were obtained from CT and registered to HP 3He MRI in order to localize ventilation defect percent (VDP), at the lobar and segmental level, to regions of fSAD and mucus plugging. Spearman's correlation was utilized to compare biomarkers on a global and lobar level, and a multivariate analysis was conducted to predict segmental fSAD given segmental VDP (sVDP) and mucus score as variables in order to further understand the functional relationships between regional measures of obstruction. Results: On a global level, fSAD was correlated with whole lung VDP (r = 0.65, p < 0.001), mucus score (r = 0.55, p < 0.01), and moderately correlated (-0.60 ≤ r ≤ -0.56, p < 0.001) to percent predicted (%p) FEV1, FEF25-75 and FEV1/FVC, and more weakly correlated to FVC%p (-0.38 ≤ r ≤ -0.35, p < 0.001) as expected from previous work. On a regional level, lobar VDP, mucus scores, and fSAD were also moderately correlated (r from 0.45-0.66, p < 0.01). For segmental colocalization, the model of best fit was a piecewise quadratic model, which suggests that sVDP may be increasing due to local airway obstruction that does not manifest as fSAD until more extensive disease is present. sVDP was more sensitive to the presence of a mucus plugs overall, but the prediction of fSAD using multivariate regression showed an interaction in the presence of a mucus plugs when sVDP was between 4% and 10% (p < 0.001). Conclusion: This multi-modality study in asthma confirmed that areas of ventilation defects are spatially correlated with air trapping at the level of the airway segment and suggests VDP and fSAD are sensitive to specific sources of airway obstruction in asthma, including mucus plugs.

Imaging Regional Airway Involvement of Asthma: Heterogeneity in Ventilation, Mucus Plugs and Remodeling.

The imaging of asthma using chest computed tomography (CT) is well-established (Jarjour et al., Am J Respir Crit Care Med 185(4):356-62, 2012; Castro et al., J Allergy Clin Immunol 128:467-78, 2011). Moreover, recent advances in functional imaging of the lungs with advanced computer analysis of both CT and magnetic resonance images (MRI) of the lungs have begun to play a role in quantifying regional obstruction. Specifically, quantitative measurements of the airways for bronchial wall thickening, luminal narrowing and distortion, the amount of mucus plugging, parenchymal density, and ventilation defects that could contribute to the patient's disease course are instructive for the entire care team. In this chapter, we will review common imaging methods and findings that relate to the heterogeneity of asthma. This information can help to guide treatment decisions. We will discuss mucous plugging, quantitative assessment of bronchial wall thickening, delta lumen phenomenon, parenchymal low-density lung on CT, and ventilation defect percentage on MRI as metrics for assessing regional ventilatory dysfunction.

MR Angiography of Pulmonary Vasculature.

Pulmonary MR angiography (MRA) is a useful alternative to computed tomographic angiography (CTA) for the study of the pulmonary vasculature. For pulmonary hypertension and partial anomalous pulmonary venous return, a cardiac MR imaging and the pulmonary MRA are useful for flow quantification and planning treatment. For the diagnosis of pulmonary embolism (PE), MRA-PE has been shown to have non-inferior outcomes at 6 months when compared with CTA-PE. Over the last 15 years, pulmonary MRA has become a routine and reliable examination for the workup of pulmonary hypertension and the primary diagnosis of PE at the University of Wisconsin.

Chronic thromboembolic pulmonary hypertension is associated with a loss of total lung volume on computed tomography.

BACKGROUND: Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension (CTEPH), approximately 20%-29% of patients exhibit a restrictive pattern on pulmonary function testing. AIM: To quantify longitudinal changes in lung volume and cardiac cross-sectional area (CSA) in patients with CTEPH. METHODS: In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019, we evaluated 15 patients with CTEPH who had chest computed tomography (CT) performed at baseline and after at least 6 mo of therapy. We matched the CTEPH cohort with 45 control patients by age, sex, and observation period. CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test. RESULTS: Total, right lung, and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline (total, P = 0.004; right lung, P = 0.003; right lower lobe; P = 0.01). In the CTEPH group, the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group (total, P = 0.01; right lung, P = 0.007; right lower lobe, P = 0.01; CSA, P = 0.0002). There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort. CONCLUSION: After at least 6 mo of treatment, CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling.

Functional xenon-129 magnetic resonance imaging response to antifibrotic treatment in idiopathic pulmonary fibrosis.

A measure of regional gas exchange on HP 129Xe MRI was able to detect apparent improvements in IPF patients treated with antifibrotic medication after 1 year, while no such improvements were found in patients treated with conventional therapies https://bit.ly/3ZXipzD.

MRA as the Preferred Test for Pulmonary Embolism During the Iodinated Contrast Media Shortage of 2022: A Single-Center Experience.

BACKGROUND. Closure of a GE Healthcare facility in Shanghai, China, in 2022 disrupted the iodinated contrast media supply. Technologic advances have addressed limitations associated with the use of pulmonary MRA for diagnosis of pulmonary embolism (PE). OBJECTIVE. The purpose of this study was to describe a single institution's experience in the use of pulmonary MRA as an alternative to CTA for the diagnosis of PE in the general population during the iodinated contrast media shortage in 2022. METHODS. This retrospective single-center study included all CTA and MRA examinations performed to exclude PE from April 1 through July 31 (18 weekly periods) in 2019 (before the COVID-19 pandemic and contrast media shortage), 2021 (during the pandemic but before the shortage), and 2022 (during both the pandemic and the shortage). From early May through mid-July of 2022, MRA served as the preferred test for PE diagnosis, to preserve iodinated contrast media. CTA and MRA reports were reviewed. The total savings in iodinated contrast media volume resulting from preferred use of MRA was estimated. RESULTS. The study included 4491 examinations of 4006 patients (mean age, 57 ± 18 [SD] years; 1715 men, 2291 women): 1245 examinations (1111 CTA, 134 MRA) in 2019, 1547 examinations (1403 CTA, 144 MRA) in 2021, and 1699 examinations (1282 CTA, 417 MRA) in 2022. In 2022, the number of MRA examinations was four (nine when normalized to a 7-day period) in week 1, and this number increased to a maximum of 63 in week 10 and then decreased to 10 in week 18. During weeks 8-11, more MRA examinations (range, 45-63 examinations) than CTA examinations (range, 27-46 examinations) were performed. In 2022, seven patients with negative MRA underwent subsequent CTA within 2 weeks; CTA was negative in all cases. In 2022, 13.9% of CTA examinations (vs 10.3% of MRA examinations) were reported as having limited image quality. The estimated 4-month savings resulting from preferred use of MRA in 2022, under the assumption of uniform simple linear growth in CTA utilization annually and a CTA dose of 1 mL/kg, was 27 L of iohexol (350 mg I/mL). CONCLUSION. Preferred use of pulmonary MRA for PE diagnosis in the general population helped to conserve iodinated contrast media during the 2022 shortage. CLINICAL IMPACT. This single-center experience shows pulmonary MRA to be a practical substitute for pulmonary CTA in emergency settings.

Pulmonary MRA During Pregnancy: Early Experience With Ferumoxytol.

BACKGROUND: 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. PURPOSE: To describe our clinical experience with Fe-MRA in pregnant women with suspected PE. STUDY TYPE: Retrospective, observational, cohort. POPULATION: A total of 98 Fe-MRA exams (consecutive sample) performed in 94 pregnant women. FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T, 3D T1-weighted MRA. ASSESSMENT: 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. STATISTICAL TESTS: Continuous data are presented as mean ± standard deviation. The overall image quality and confidence score is given as the mean of three readers. RESULTS: 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. CONCLUSION: Ferumoxytol enhanced MRA is a radiation- and gadolinium-free alternative for diagnosis of PE during pregancy. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Skeletal Muscle Adiposity and Lung Function Trajectory in the Severe Asthma Research Program.

Rationale: Extrapulmonary manifestations of asthma, including fatty infiltration in tissues, may reflect systemic inflammation and influence lung function and disease severity. Objectives: To determine if skeletal muscle adiposity predicts lung function trajectory in asthma. Methods: Adult SARP III (Severe Asthma Research Program III) participants with baseline computed tomography imaging and longitudinal postbronchodilator FEV1% predicted (median follow-up 5 years [1,132 person-years]) were evaluated. The mean of left and right paraspinous muscle density (PSMD) at the 12th thoracic vertebral body was calculated (Hounsfield units [HU]). Lower PSMD reflects higher muscle adiposity. We derived PSMD reference ranges from healthy control subjects without asthma. A linear multivariable mixed-effects model was constructed to evaluate associations of baseline PSMD and lung function trajectory stratified by sex. Measurements and Main Results: Participants included 219 with asthma (67% women; mean [SD] body mass index, 32.3 [8.8] kg/m2) and 37 control subjects (51% women; mean [SD] body mass index, 26.3 [4.7] kg/m2). Participants with asthma had lower adjusted PSMD than control subjects (42.2 vs. 55.8 HU; P < 0.001). In adjusted models, PSMD predicted lung function trajectory in women with asthma (ß = -0.47 Δ slope per 10-HU decrease; P = 0.03) but not men (ß = 0.11 Δ slope per 10-HU decrease; P = 0.77). The highest PSMD tertile predicted a 2.9% improvement whereas the lowest tertile predicted a 1.8% decline in FEV1% predicted among women with asthma over 5 years. Conclusions: Participants with asthma have lower PSMD, reflecting greater muscle fat infiltration. Baseline PSMD predicted lung function decline among women with asthma but not men. These data support an important role of metabolic dysfunction in lung function decline.

Hyperpolarized 129Xe MR Spectroscopy in the Lung Shows 1-year Reduced Function in Idiopathic Pulmonary Fibrosis.

Background Idiopathic pulmonary fibrosis (IPF) is a temporally and spatially heterogeneous lung disease. Identifying whether IPF in a patient is progressive or stable is crucial for treatment regimens. Purpose To assess the role of hyperpolarized (HP) xenon 129 (129Xe) MRI measures of ventilation and gas transfer in IPF generally and as an early signature of future IPF progression. Materials and Methods In a prospective study, healthy volunteers and participants with IPF were consecutively recruited between December 2015 and August 2019 and underwent baseline HP 129Xe MRI and chest CT. Participants with IPF were followed up with forced vital capacity percent predicted (FVC%p), diffusing capacity of the lungs for carbon monoxide percent predicted (DLco%p), and clinical outcome at 1 year. IPF progression was defined as reduction in FVC%p by at least 10%, reduction in DLco%p by at least 15%, or admission to hospice care. CT and MRI were spatially coregistered and a measure of pulmonary gas transfer (red blood cell [RBC]-to-barrier ratio) and high-ventilation percentage of lung volume were compared across groups and across fibrotic versus normal-appearing regions at CT by using Wilcoxon signed rank tests. Results Sixteen healthy volunteers (mean age, 57 years ± 14 [SD]; 10 women) and 22 participants with IPF (mean age, 71 years ± 9; 15 men) were evaluated, as follows: nine IPF progressors (mean age, 72 years ± 7; five women) and 13 nonprogressors (mean age, 70 years ± 10; 11 men). Reduction of high-ventilation percent (13% ± 6.1 vs 8.2% ± 5.9; P = .03) and RBC-to-barrier ratio (0.26 ± 0.06 vs 0.20 ± 0.06; P = .03) at baseline were associated with progression of IPF. Participants with progressive disease had reduced RBC-to-barrier ratio in structurally normal-appearing lung at CT (0.21 ± 0.07 vs 0.28 ± 0.05; P = .01) but not in fibrotic regions of the lung (0.15 ± 0.09 vs 0.14 ± 0.04; P = .62) relative to the nonprogressive group. Conclusion In this preliminary study, functional measures of gas transfer and ventilation measured with xenon 129 MRI and the extent of fibrotic structure at CT were associated with idiopathic pulmonary fibrosis disease progression. Differences in gas transfer were found in regions of nonfibrotic lung. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gleeson and Fraser in this issue.

The Impact of Insulin Resistance on Loss of Lung Function and Response to Treatment in Asthma.

Rationale: The role of obesity-associated insulin resistance (IR) in airflow limitation in asthma is uncertain. Objectives: Using data in the Severe Asthma Research Program 3 (SARP-3), we evaluated relationships between homeostatic measure of IR (HOMA-IR), lung function (cross-sectional and longitudinal analyses), and treatment responses to bronchodilators and corticosteroids. Methods: HOMA-IR values were categorized as without (<3.0), moderate (3.0-5.0), or severe (>5.0). Lung function included FEV1 and FVC measured before and after treatment with inhaled albuterol and intramuscular triamcinolone acetonide and yearly for 5 years. Measurements and Main Results: Among 307 participants in SARP-3, 170 (55%) were obese and 140 (46%) had IR. Compared with patients without IR, those with IR had significantly lower values for FEV1 and FVC, and these lower values were not attributable to obesity effects. Compared with patients without IR, those with IR had lower FEV1 responses to ß-adrenergic agonists and systemic corticosteroids. The annualized decline in FEV1 was significantly greater in patients with moderate IR (-41 ml/year) and severe IR (-32 ml/year,) than in patients without IR (-13 ml/year, P < 0.001 for both comparisons). Conclusions: IR is common in asthma and is associated with lower lung function, accelerated loss of lung function, and suboptimal lung function responses to bronchodilator and corticosteroid treatments. Clinical trials in patients with asthma and IR are needed to determine if improving IR might also improve lung function.

Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts.

Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes. Materials and Methods A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models. Results A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001). Conclusion Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.

Dynamic contrast enhanced MRI for the evaluation of lung perfusion in idiopathic pulmonary fibrosis.

BACKGROUND: The objective of this work was to apply quantitative and semiquantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) methods to evaluate lung perfusion in idiopathic pulmonary fibrosis (IPF). METHODS: In this prospective trial 41 subjects, including healthy control and IPF subjects, were studied using DCE-MRI at baseline. IPF subjects were then followed for 1 year; progressive IPF (IPFprog) subjects were distinguished from stable IPF (IPFstable) subjects based on a decline in percent predicted forced vital capacity (FVC % pred) or diffusing capacity of the lung for carbon monoxide (D LCO % pred) measured during follow-up visits. 35 out of 41 subjects were retained for final baseline analysis (control: n=15; IPFstable: n=14; IPFprog: n=6). Seven measures and their coefficients of variation (CV) were derived using temporally resolved DCE-MRI. Two sets of global and regional comparisons were made: control versus IPF groups and control versus IPFstable versus IPFprog groups, using linear regression analysis. Each measure was compared with FVC % pred, D LCO % pred and the lung clearance index (LCI % pred) using a Spearman rank correlation. RESULTS: DCE-MRI identified regional perfusion differences between control and IPF subjects using first moment transit time (FMTT), contrast uptake slope and pulmonary blood flow (PBF) (p≤0.05), while global averages did not. FMTT was shorter for IPFprog compared with both IPFstable (p=0.004) and control groups (p=0.023). Correlations were observed between PBF CV and D LCO % pred (rs= -0.48, p=0.022) and LCI % pred (rs= +0.47, p=0.015). Significant group differences were detected in age (p<0.001), D LCO % pred (p<0.001), FVC % pred (p=0.001) and LCI % pred (p=0.007). CONCLUSIONS: Global analysis obscures regional changes in pulmonary haemodynamics in IPF using DCE-MRI in IPF. Decreased FMTT may be a candidate marker for IPF progression.

Mucus Plugs Persist in Asthma, and Changes in Mucus Plugs Associate with Changes in Airflow over Time.

Rationale: Cross-sectional analysis of mucus plugs in computed tomography (CT) lung scans in the Severe Asthma Research Program (SARP)-3 showed a high mucus plug phenotype. Objectives: To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function. Methods: In a longitudinal analysis of baseline and Year 3 CT lung scans in SARP-3 participants, radiologists generated mucus plug scores to assess mucus plug persistence over time. Changes in mucus plug score were analyzed in relation to changes in lung function and CT air trapping measures. Measurements and Main Results: In 164 participants, the mean (range) mucus plug score was similar at baseline and Year 3 (3.4 [0-20] vs. 3.8 [0-20]). Participants and bronchopulmonary segments with a baseline plug were more likely to have plugs at Year 3 than those without baseline plugs (risk ratio, 2.8; 95% confidence interval [CI], 2.0-4.1; P < 0.001; and risk ratio, 5.0; 95% CI, 4.5-5.6; P < 0.001, respectively). The change in mucus plug score from baseline to Year 3 was significantly negatively correlated with change in FEV1% predicted (rp = -0.35; P < 0.001) and with changes in CT air trapping measures (all P values < 0.05). Conclusions: Mucus plugs identify a persistent asthma phenotype, and susceptibility to mucus plugs occurs at the subject and the bronchopulmonary segment level. The association between change in mucus plug score and change in airflow over time supports a causal role for mucus plugs in mechanisms of airflow obstruction in asthma.