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Background: Functional Respiratory Imaging (FRI) combines HRCT scans with computational fluid dynamics to provide objective and quantitative information about lung structure and function. FRI has proven its value in pulmonary diseases such as COPD and asthma, but limited studies have focused on cystic fibrosis (CF). This study aims to investigate the relation of multiple FRI parameters to validated imaging parameters and classical respiratory outcomes in a CF population., Methods: CF patients aged > 5 years scheduled for a chest CT were recruited in a cross-sectional study. FRI outcomes included regional airway volume, airway wall volume, airway resistance, lobar volume, air trapping and pulmonary blood distribution. Besides FRI, CT scans were independently evaluated by 2 readers using the CF-CT score. Spirometry and the 6-Minute Walk Test (6MWT) were also performed. Statistical tests included linear mixed-effects models, repeated measures correlations, Pearson and Spearman correlations., Results: 39 CT scans of 24 (17M/7F) subjects were analyzed. Patients were 24 ± 9 years old and had a ppFEV 1 of 71 ± 25% at the time of the first CT. All FRI parameters showed significant low-to-moderate correlations with the total CF-CT score, except for lobar volume. When considering the relation between FRI parameters and similar CF-CT subscores, significant correlations were found between parameters related to airway volume, air trapping and airway wall thickening. Air trapping, lobar volume after normal expiration and pulmonary blood distribution showed significant associations with all spirometric parameters and oxygen saturation at the end of 6MWT. In addition, air trapping was the only parameter related to the distance covered during 6MWT. A subgroup analysis showed considerably higher correlations in patients with mild lung disease (ppFEV 1  ≥ 70%) compared to patients with moderate to severe lung disease (ppFEV 1  < 70%) when comparing FRI to CF-CT scores., Conclusions: Multiple structural characteristics determined by FRI were associated with abnormalities determined by CF-CT score. Air trapping and pulmonary blood distribution appeared to be the most clinically relevant FRI parameters for CF patients due to their associations with classical outcome measures. The FRI methodology could particularly be of interest for patients with mild lung disease, although this should be confirmed in future research., (© 2021. The Author(s).)

Background: For patients with chronic obstructive pulmonary disease (COPD), greater improvements in lung function have been demonstrated for triple versus dual inhaled therapies in traditional spirometry studies. This study was the first to use functional respiratory imaging (FRI), known for increased sensitivity to airway changes versus spirometry, to assess the effect of the inhaled corticosteroid (ICS) component (budesonide) on lung function in patients with moderate-to-severe COPD and a blood eosinophil count > 150 cells/mm 3 ., Methods: Patients in this Phase IIIb (NCT03836677), randomized, double-blind, crossover study received twice-daily budesonide/glycopyrrolate/formoterol fumarate (BGF) 320/18/9.6 μg fixed-dose triple therapy and glycopyrrolate/formoterol fumarate (GFF) 18/9.6 μg fixed-dose dual therapy over 4 weeks, each delivered via a single metered dose Aerosphere inhaler. Primary endpoints were the improvements from baseline for each treatment in specific (i.e. corrected for lobar volume) image-based airway volume (siVaw) and resistance (siRaw) measured via FRI taken at total lung capacity (Day 29). Secondary outcomes included spirometry and body plethysmography. Adverse events were monitored throughout the study., Results: A total of 23 patients were randomized and included in the intent-to-treat analysis (mean age 64.9 years, 78.3% males, 43.5% current smokers, mean predicted post-bronchodilator forced expiratory volume in 1 s [FEV 1 ] 63.6%). BGF and GFF both statistically significantly increased siVaw from baseline at Day 29 (geometric mean ratio [GM], 95% confidence interval [CI]: 1.72 [1.38, 2.13] and 1.53 [1.28, 1.83], respectively, both p < 0.0001), with a greater increase observed for BGF versus GFF (GM, 95% CI 1.09 [1.03, 1.16], p = 0.0061). Statistically significant reductions in siRaw were also observed with both BGF and GFF (GM, 95% CI 0.50 [0.39, 0.63] and 0.52 [0.40, 0.67], respectively, both p < 0.0001). Additionally, significant improvements from baseline in post-dose FEV 1 were observed with BGF and GFF (mean 346 mL, p = 0.0003 and 273 mL, p = 0.0004, respectively). Safety findings were consistent with the known profiles of BGF and GFF., Conclusions: As observed using FRI, triple therapy with BGF resulted in greater increases in airway volume, and reductions in airway resistance versus long-acting muscarinic antagonist/long-acting β 2 -agonist (LAMA/LABA) dual therapy with GFF, reflecting the ICS component's contribution in patients with moderate-to-severe COPD., Trial Registration:  ClinicalTrials.gov, NCT03836677. Registered 11 February 2019, https://clinicaltrials.gov/ct2/show/NCT03836677.

Background: Idiopathic pulmonary fibrosis (IPF) is chronic fibrosing pneumonia with an unpredictable natural disease history. Functional respiratory imaging (FRI) has potential to better characterize this disease. The aim of this study was to identify FRI parameters, which predict FVC decline in patients with IPF., Methods: An IPF-cohort (treated with pamrevlumab for 48 weeks) was retrospectively studied using FRI. Serial CT's were compared from 66 subjects. Post-hoc analysis was performed using FRI, FVC and mixed effects models., Results: Lung volumes, determined by FRI, correlated with FVC (lower lung volumes with lower FVC) (R 2  = 0.61, p < 0.001). A negative correlation was observed between specific image based airway radius (siRADaw) at total lung capacity (TLC) and FVC (R 2  = 0.18, p < 0.001). Changes in FVC correlated significantly with changes in lung volumes (R 2  = 0.18, p < 0.001) and siRADaw (R 2  = 0.15, p = 0.002) at week 24 and 48, with siRADaw being more sensitive to change than FVC. Loss in lobe volumes (R 2  = 0.33, p < 0.001), increasing fibrotic tissue (R 2  = 0.33, p < 0.001) and airway radius (R 2  = 0.28, p < 0.001) at TLC correlated with changes in FVC but these changes already occur in the lower lobes when FVC is still considered normal., Conclusion: This study indicates that FRI is a superior tool than FVC in capturing of early and clinically relevant, disease progression in a regional manner.

Rationale and Objectives: Long-term survival after lung transplantation (LTx) is limited by bronchiolitis obliterans syndrome (BOS), defined as a sustained decline in forced expiratory volume in the first second (FEV 1 ) not explained by other causes. We assessed whether machine learning (ML) utilizing quantitative computed tomography (qCT) metrics can predict eventual development of BOS., Materials and Methods: Paired inspiratory-expiratory CT scans of 71 patients who underwent LTx were analyzed retrospectively (BOS [n = 41] versus non-BOS [n = 30]), using at least two different time points. The BOS cohort experienced a reduction in FEV 1 of >10% compared to baseline FEV 1 post LTx. Multifactor analysis correlated declining FEV 1 with qCT features linked to acute inflammation or BOS onset. Student t test and ML were applied on baseline qCT features to identify lung transplant patients at baseline that eventually developed BOS., Results: The FEV 1 decline in the BOS cohort correlated with an increase in the lung volume (P = .027) and in the central airway volume at functional residual capacity (P = .018), not observed in non-BOS patients, whereas the non-BOS cohort experienced a decrease in the central airway volume at total lung capacity with declining FEV 1 (P = .039). Twenty-three baseline qCT parameters could significantly distinguish between non-BOS patients and eventual BOS developers (P < .05), whereas no pulmonary function testing parameters could. Using ML methods (support vector machine), we could identify BOS developers at baseline with an accuracy of 85%, using only three qCT parameters., Conclusions: ML utilizing qCT could discern distinct mechanisms driving FEV 1 decline in BOS and non-BOS LTx patients and predict eventual onset of BOS. This approach may become useful to optimize management of LTx patients., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: Severe exacerbations associated with chronic obstructive pulmonary disease (COPD) that require hospitalization significantly contribute to morbidity and mortality. Definitions for exacerbations are very broad, and it is unclear whether there is one predominant underlying mechanism that leads to them. Functional respiratory imaging (FRI) with modeling provides detailed information about airway resistance, hyperinflation, and ventilation-perfusion (V/Q) mismatch during and following an acute exacerbation., Materials and Methods: Forty-two patients with COPD participating in a multicenter study were assessed by FRI, pulmonary function tests, and self-reported outcome measures during an acute exacerbation and following resolution. Arterial blood gasses and lung function parameters were measured., Results: A significant correlation was found between alveolar-arterial gradient and image-based V/Q (iV/Q), suggesting that iV/Q represents V/Q mismatch during an exacerbation ( p <0.05)., Conclusion: Recovery of an exacerbation is due to decreased (mainly distal) airway resistance ( p <0.05). Improvement in patient-reported outcomes were also associated with decreased distal airway resistance ( p <0.05), but not with forced expiratory volume. FRI is, therefore, a sensitive tool to describe changes in airway caliber, ventilation, and perfusion during and after exacerbation. On the basis of the fact that FRI increased distal airway resistance seems to be the main cause of an exacerbation, therapy should mainly focus on decreasing it during and after the acute event., Competing Interests: Disclosure J De Backer and W Vos are affiliated with FLUIDDA NV. The authors report no other conflicts of interest in this work.

Introduction: Patients with severe COPD often develop chronic hypercapnic respiratory failure. Their prognosis worsens and they are more likely to develop exacerbations. This has major influence on the health-related quality of life. Currently, there is no information about the success of long-term noninvasive ventilation (NIV) among patients who receive NIV in acute settings. Also, little is known about the pathophysiological mechanism of NIV., Methods: Ten Global Initiative for Obstructive Lung Disease stage III and IV COPD patients with respiratory failure who were hospitalized following acute exacerbation were treated with NIV using a Synchrony BiPAP device for 6 months. Arterial blood gases and lung function parameters were measured. Low-dose computed tomography of the thorax was performed and used for segmentation. Further analyses provided lobe volume, airway volume, and airway resistance, giving an overall functional description of the separate airways and lobes. Ventilation perfusion (VQ) was calculated. Patient-reported outcomes were evaluated., Results: PaCO 2 significantly improved from 50.03 mmHg at baseline to 44.75 mmHg after 1 month and 43.37 mmHg after 6 months ( P =0.006). Subjects showed improvement in the 6-minute walk tests (6MWTs) by an average of 51 m (from 332 m at baseline to 359 m at 1 month and 383 m at 6 months). Patients demonstrated improvement in self-reported anxiety ( P =0.018). The improvement in image-based VQ was positively associated with the 6MWT and the anxiety domain of the Severe Respiratory Insufficiency Questionnaire., Conclusion: Though previous studies of long-term NIV have shown conflicting results, this study demonstrates that patients can benefit from long-term NIV treatment, resulting in improved VQ, gas exchange, and exercise tolerance., Competing Interests: Disclosure J De Backer, W Vos, F Ferreira, and KC Barboza are affiliated with Fluidda NV. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Objective: We aim to investigate if anatomical and functional properties of the upper airway using computerized 3D models derived from computed tomography (CT) scans better predict obstructive sleep apnea (OSA) severity than standard clinical markers., Methods: Consecutive children with suspected OSA underwent polysomnography, clinical assessment of upper airway patency, and a CT scan while awake. A three-dimensional (3D) reconstruction of the pharyngeal airway was built from these images, and computational fluid dynamics modeling of low inspiratory flow was performed using open-source software., Results: Thirty-three children were included (23 boys; mean age, was 6.0±3.2y). OSA was diagnosed in 23 patients. Children with OSA had a significantly lower volume of the overlap region between tonsils and the adenoids (median volume, 1408 mm compared to 2173 mm; p=0.04), a lower mean cross-sectional area at this location (median volume, 69.3mm(2) compared to 114.3mm2; p=0.04), and a lower minimal cross-sectional area (median volume, 17.9 mm2 compared to 25.9 mm2; p=0.05). Various significant correlations were found between several imaging parameters and the severity of OSA, most pronounced for upper airway conductance (r=-0.46) (p<0.01) for correlation between upper airway conductance and the apnea-hypopnea index. No differences or significant correlations were observed with clinical parameters of upper airway patency. Preliminary data after treatment showed that none of the patients with residual OSA had their smallest cross-sectional area located in segment 3, and this frequency was significantly lower than in their peers whose sleep study normalized (64%; p=0.05)., Conclusion: Functional imaging parameters are highly correlated with OSA severity and are a more powerful correlate than clinical scores of upper airway patency. Preliminary data also showed that we could identify differences in the upper airway of those subjects who did not benefit from a local upper airway treatment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: Chest physiotherapy enhances sputum evacuation in COPD patients. It can be applied as a single technique or as a combination of techniques including intrapulmonary percussive ventilation (IPV). Recently developed assessment techniques may provide new insights into the effect of airway clearance techniques., Participants: Five moderate to severe COPD patients (three females and two males; mean forced expiratory volume in 1 second of 39.49% predicted) who were admitted in the hospital for an acute exacerbation were included in this study., Methods: A novel imaging technique was used, together with other conventional techniques, to visualize the short-term effects of a single IPV treatment in COPD patients., Results: No significant changes were noted in the lung function parameters or arterial blood gases measured within 1 hour after the end of the IPV session. Computed tomography images detected changes in the airway patency after the IPV treatment compared with before treatment. Local resistances, calculated for the three-dimensional models, showed local changes in airway resistance., Conclusion: The effects of a single IPV session can be visualized by functional imaging. This functional imaging allows a calculation of changes in local airway resistance and local changes in airway volume in COPD patients without affecting conventional lung function parameters.

Background: Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD). However, their bronchodilating effect has not yet been compared in the central and distal airways. Functional imaging using computational fluid dynamics offers the possibility of making such a comparison. The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways., Methods: Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments. Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging. Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography., Results: Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product. On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways. Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient. Salbutamol was more effective in the other patients., Conclusion: This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics.

Purpose: To compare the results obtained by using numerical flow simulations with the results of combined single photon emission computed tomography (SPECT) and computed tomography (CT) and to demonstrate the importance of correct boundary conditions for the numerical methods to account for the large amount of interpatient variability in airway geometry., Materials and Methods: This study was approved by all relevant institutional review boards. All patients gave their signed informed consent. In this study, six patients with mild asthma (three men; three women; overall mean age, 46 years ± 17 [standard deviation]) underwent CT at functional residual capacity and total lung capacity, as well as SPECT/CT. CT data were used for segmentation and computational fluid dynamics (CFD) simulations. A comparison was made between airflow distribution, as derived with (a) SPECT/CT through tracer concentration analysis, (b) CT through lobar expansion measurement, and (c) CFD through flow computer simulation. Also, the heterogeneity of the ventilation was examined., Results: Good agreement was found between SPECT/CT, CT, and CFD in terms of airflow distribution and hot spot detection. The average difference for the internal airflow distribution was less than 3% for CFD and CT versus SPECT/CT. Heterogeneity in ventilation patterns could be detected with SPECT/CT and CFD., Conclusion: This results of this study show that patient-specific computer simulations with appropriate boundary conditions yield information that is similar to that obtained with functional imaging tools, such as SPECT/CT., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100322/-/DC1., (© RSNA, 2010)

Patients with sleep related breathing disorders (SRBD) can be treated with nasal continuous positive airway pressure (nCPAP) or with several upper airway (UA) interventions. While nCPAP is almost always effective when clinically well tolerated, the therapeutic outcome of UA surgery and UA devices is difficult to predict. The improvement of our capability to perform the latter predictions more accurately is of great clinical importance since it will prevent patients to be treated with ineffective, sometimes irreversible, techniques. In this review we describe the importance of new imaging methods in this respect. We first refer to the most important pathophysiological mechanisms known so far to play a role in SRBD, indicating that functional imaging could elucidate these mechanisms in a patient specific manner. Then we describe the new technologies that make UA imaging more functional referring to the data as they are presently available. Finally we summarise the studies that do indicate that the use of functional imaging of the UA in SRBD patients may significantly help to predict the clinical outcome after UA interventions.

The effect of a bronchodilator in asthmatics is only partially described by changes in spirometric values since no information on regional differences can be obtained. Imaging techniques like high-resolution computed tomography (HRCT) provide further information but lack detailed information on specific airway responses. The aim of the present study was to improve the actual imaging techniques by subsequent analysis of the imaging data using computational fluid dynamics (CFD). We studied 14 mild to moderately severe asthmatics. Ten patients underwent HRCT before and 4h after inhalation of a novel long acting beta(2) agonist (LABA) that acts shortly after inhalation. Four patients were studied for chronic effects and underwent CT scans twice after adequate wash-out of bronchodilators. In the active group, a significant bronchodilator response was seen with a forced expiratory volume in 1s (FEV1) increase of 8.78 +/- -6.27% pred vs -3.38 +/- 6.87% pred in the control group. The changes in FEV1 correlated significantly with the changes in distal airway volume (r = 0.69, p = 0.007), total airway resistance (r = -0.73, p = 0.003) and distal airway resistance (r = -0.76, p = 0.002) as calculated with the CFD method. The changes in distal R(aw) were not fully homogeneous. In some patients with normal FEV1 at baseline, CFD-based changes in R(aw) were still detectable. We conclude that CFD calculations, based on airway geometries of asthmatic patients, provide additional information about changes in regional R(aw). All changes in the CFD-based calculated R(aw) significantly correlate with the observed changes in spirometric values therefore validating the CFD method for the studied application.