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Background: There is an unmet need for an objective biomarker to predict asthma exacerbations., Objective: Our aim was to assess the ventilation defect percent (VDP) on hyperpolarized helium-3 magnetic resonance imaging as a predictor of exacerbation frequency following imaging., Methods: Subjects underwent hyperpolarized helium-3 and conventional clinical measurements, including pulmonary function tests, during a period of disease stability, and exacerbations were recorded prospectively over the following 2 years. We used a Poisson regression tree model to estimate an optimal VDP threshold for classifying subjects into high- versus low-exacerbation groups and then used statistical regression to compare this VDP threshold against conventional clinical measures as predictors of exacerbations., Results: A total of 67 individuals with asthma (27 males and 40 females, 28 with mild-to-moderate asthma and 39 with severe asthma) had a median VDP of 3.75% (1.2% [first quartile]-7.9% [third quartile]). An optimal VDP threshold of 4.28% was selected on the basis of the maximum likelihood estimation of the regression tree model. Subjects with a VDP greater than 4.28% (n = 32) had a median of 1.5 exacerbations versus 0.0 for subjects with a VDP less than 4.28% (n = 35). In a stepwise multivariate regression model, a VDP greater than 4.28% was associated with an exacerbation incidence rate ratio of 2.5 (95% CI = 1.3-4.7) versus a VDP less than or equal to 4.28%. However, once individual medical history was included in the model, VDP was no longer significant. Nonetheless, VDP may provide an objective and complementary quantitative marker of individual exacerbation risk that is useful for monitoring individual change in disease status, selecting patients for therapy, and assessing treatment response., Conclusion: VDP measured with magnetic resonance imaging shows promise as a biomarker of prospective asthma exacerbations., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Quantitative computed tomographic (QCT) biomarkers of airway morphology hold potential for understanding and monitoring regional airway remodeling in asthmatic patients., Objective: We sought to determine whether the change in airway lumen area between total lung capacity (TLC) and functional residual capacity (FRC) lung volumes measured from CT imaging data was correlated with severe outcomes in asthmatic patients., Methods: We studied 152 asthmatic patients (90 female and 62 male patients) and 33 healthy subjects (12 female and 21 male subjects) using QCT. Postprocessing of airways at generations 1 to 5 (1 = trachea) was performed for wall area percentage, wall thickness percentage (WT%), lumen area at baseline total lung capacity (LA TLC ), lumen area at baseline functional residual capacity (LA FRC ), and low attenuation area at FRC. A new metric (reflecting remodeling, distal air trapping, or both), Delta Lumen, was determined as follows: Percentage difference in lumen area (LA TLC  - LA FRC )/LA TLC  × 100., Results: Postprocessing of 4501 airway segments was performed (3681 segments in the 152 patients with asthma and 820 segments in the 33 healthy subjects; range, 17-28 segments per subject). Delta Lumen values were negatively correlated with WT% and low attenuation area (P < .01) in asthmatic patients. Delta Lumen values were significantly lower for airway generations 3 to 5 (segmental airways) in subjects undergoing hospitalization because of exacerbation and in patients with refractory asthma requiring treatment with systemic corticosteroids. WT% and low attenuation area were positively and Delta Lumen values were negatively associated with systemic corticosteroid treatment (P < .05), suggesting that a reduced Delta Lumen value is a potential outcome biomarker in patients with severe asthma., Conclusion: Reduced Delta Lumen value in the central airways measured by using QCT is a promising exploratory biomarker of unstable refractory asthma that warrants further study., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Imaging variables, including airway diameter, wall thickness, and air trapping, have been found to be important metrics when differentiating patients with severe asthma from those with nonsevere asthma and healthy subjects., Objective: The objective of this study was to identify imaging-based clusters and to explore the association of the clusters with existing clinical metrics., Methods: We performed an imaging-based cluster analysis using quantitative computed tomography-based structural and functional variables extracted from the respective inspiration and expiration scans of 248 asthmatic patients. The imaging-based metrics included a broader set of multiscale variables, such as inspiratory airway dimension, expiratory air trapping, and registration-based lung deformation (inspiration vs expiration). Asthma subgroups derived from a clustering method were associated with subject demographics, questionnaire results, medication history, and biomarker variables., Results: Cluster 1 was composed of younger patients with early-onset nonsevere asthma and reversible airflow obstruction and normal airway structure. Cluster 2 was composed of patients with a mix of patients with nonsevere and severe asthma with marginal inflammation who exhibited airway luminal narrowing without wall thickening. Clusters 3 and 4 were dominated by patients with severe asthma. Cluster 3 patients were obese female patients with reversible airflow obstruction who exhibited airway wall thickening without airway narrowing. Cluster 4 patients were late-onset older male subjects with persistent airflow obstruction who exhibited significant air trapping and reduced regional deformation. Cluster 3 and 4 patients also showed decreased lymphocyte and increased neutrophil counts, respectively., Conclusions: Four image-based clusters were identified and shown to be correlated with clinical characteristics. Such clustering serves to differentiate asthma subgroups that can be used as a basis for the development of new therapies., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Ventricular kinetic energy measurements may provide a novel imaging biomarker of declining ventricular efficiency in patients with repaired tetralogy of Fallot. Our purpose was to assess differences in ventricular kinetic energy with 4-dimensional flow magnetic resonance imaging between patients with repaired tetralogy of Fallot and healthy volunteers., Methods: Cardiac magnetic resonance, including 4-dimensional flow magnetic resonance imaging, was performed at rest in 10 subjects with repaired tetralogy of Fallot and 9 healthy volunteers using clinical 1.5T and 3T magnetic resonance imaging scanners. Right and left ventricular kinetic energy (KERV and KELV), main pulmonary artery flow (QMPA), and aortic flow (QAO) were quantified using 4-dimensional flow magnetic resonance imaging data. Right and left ventricular size and function were measured using standard cardiac magnetic resonance techniques. Differences in peak systolic KERV and KELV in addition to the QMPA/KERV and QAO/KELV ratios between groups were assessed. Kinetic energy indices were compared with conventional cardiac magnetic resonance parameters., Results: Peak systolic KERV and KELV were higher in patients with repaired tetralogy of Fallot (6.06 ± 2.27 mJ and 3.55 ± 2.12 mJ, respectively) than in healthy volunteers (5.47 ± 2.52 mJ and 2.48 ± 0.75 mJ, respectively), but were not statistically significant (P = .65 and P = .47, respectively). The QMPA/KERV and QAO/KELV ratios were lower in patients with repaired tetralogy of Fallot (7.53 ± 5.37 mL/[cycle mJ] and 9.65 ± 6.61 mL/[cycle mJ], respectively) than in healthy volunteers (19.33 ± 18.52 mL/[cycle mJ] and 35.98 ± 7.66 mL/[cycle mJ], respectively; P < .05). QMPA/KERV and QAO/KELV were weakly correlated to ventricular size and function., Conclusions: Greater ventricular kinetic energy is necessary to generate flow in the pulmonary and aortic circulations in repaired tetralogy of Fallot. Quantification of ventricular kinetic energy in patients with repaired tetralogy of Fallot is a new observation. Future studies are needed to determine whether changes in ventricular kinetic energy can provide earlier evidence of ventricular dysfunction and guide future medical and surgical interventions., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to evaluate alterations in flow patterns in thoracic aortic dissections using 4-dimensional, flow-sensitive magnetic resonance imaging., Methods: This prospective study was conducted at 2 academic tertiary referral medical centers. Thirteen 4-dimensional flow magnetic resonance imaging studies were performed in 12 subjects (4 female, aged 25-71 years) with thoracic aortic dissection using 3.0T clinical scanners. Qualitative assessment of flow patterns in the true and false lumina was performed in consensus by 3 cardiovascular radiologists. Quantitative analysis included measurement of net flow, retrograde flow, peak flow, and time-to-peak flow in the true and false lumina in the ascending aorta, aortic arch, and descending aorta. Differences in flow through the true and false lumina at each analysis plane were compared with the 2-tailed, paired Student t test., Results: Flow patterns were significantly altered in association with different extents of disease, vessel dilatation, and post-therapeutic anatomy. Total flow per cardiac cycle and peak flow were higher in the true lumen than in the false lumen (P < .01). Retrograde flow was less in the true lumen than in the false lumen (P ≤ .01). Time-to-peak flow in the true lumen occurred later than in the false lumen (P = .05-.08)., Conclusions: Four-dimensional, flow-sensitive magnetic resonance imaging at 3.0T provided qualitative and quantitative information on alterations of aortic flow in patients with thoracic aortic dissection. Future application of this magnetic resonance flow methodology may help provide insights into the pathophysiology and effects of flow alterations and establish prognostic indicators for the development of complications or aneurysm growth in patients with aortic dissection., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)