Pilot study of paediatric regional lung function assessment via X-ray velocimetry (XV) imaging in children with normal lungs and in children with cystic fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry (XV) is a novel form of X-ray imaging that can generate lung ventilation data through the breathing cycle. XV technology has been validated in multiple animal models, including the ß-ENaC mouse model of CF lung disease. It has since been assessed in early-phase clinical trials in adult human subjects; however, there is a paucity of data in the paediatric cohort, including in CF. The aim of this pilot study was to investigate the feasibility of performing a single-centre cohort study in paediatric patients with CF and in those with normal lungs to demonstrate the appropriateness of proceeding with further studies of XV in these cohorts. METHODS AND ANALYSIS: This is a cross-sectional, single-centre, pilot study. It will recruit children aged 3-18 years to have XV lung imaging performed, as well as paired pulmonary function testing. The study will aim to recruit 20 children without CF with normal lungs and 20 children with CF. The primary outcome will be the feasibility of recruiting children and performing XV testing. Secondary outcomes will include comparisons between XV and current assessments of pulmonary function and structure. ETHICS AND DISSEMINATION: This project has ethical approval granted by The Women's and Children's Hospital Human Research Ethics Committee (HREC ID 2021/HRE00396). Findings will be disseminated through peer-reviewed publication and conferences. TRIAL REGISTRATION NUMBER: ACTRN12623000109606.

Usefulness of Muscle Ultrasonography in the Nutritional Assessment of Adult Patients with Cystic Fibrosis.

Background: Muscle ultrasonography of the quadriceps rectus femoris (QRF) is a technique on the rise in the assessment of muscle mass in application of nutritional assessment. The aim of the present study is to assess the usefulness of muscle ultrasonography in patients with cystic fibrosis, comparing the results with other body composition techniques such as anthropometry, bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and handgrip strength (HGS). At the same time, we intend to assess the possible association with the nutritional and respiratory status. Methods: This was a prospective observational study in adult patients with cystic fibrosis in a clinically stable situation. Muscle ultrasonography of the QRF was performed, and the results were compared with other measures of body composition: anthropometry, BIA, and DXA. HGS was used to assess muscle function. Respiratory parameters were collected, and nutritional status was assessed using Global Leadership Initiative on Malnutrition (GLIM) criteria. Results: A total of 48 patients were included, with a mean age of 34.1 ± 8.8 years. In total, 24 patients were men, and 24 patients were women. Mean BMI was 22.5 ± 3.8 kg/m2. Mean muscular area rectus anterior (MARA) was 4.09 ± 1.5 cm2, and mean muscular circumference rectus was 8.86 ± 1.61 cm. A positive correlation was observed between the MARA and fat-free mass index (FFMI) determined by anthropometry (r = 0.747; p < 0.001), BIA (r = 0.780; p < 0.001), and DXA (r = 0.678; p < 0.001), as well as muscle function (HGS: r = 0.790; p < 0.001) and respiratory parameters (FEV1; r = 0.445, p = 0.005; FVC: r = 0.376, p = 0.02; FEV1/FVC: r = 0.344, p = 0.037). A total of 25 patients (52.1%) were diagnosed with malnutrition according to GLIM criteria. Differences were observed when comparing the MARA based on the diagnosis of malnutrition (4.75 ± 1.65 cm2 in normo-nourished vs. 3.37 ± 1.04 in malnourished; p = 0.014). Conclusions: In adults with cystic fibrosis, the measurements collected by muscle ultrasound of the QRF correlate adequately with body composition techniques such as anthropometry, BIA, DXA, and handgrip strength. Muscle ultrasound measurements, particularly the MARA, are related to the nutritional status and respiratory function of these patients.

Assessment of Liver Fibrosis with the Use of Elastography in Paediatric Patients with Diagnosed Cystic Fibrosis.

Background: Complications of cystic fibrosis-associated liver disease (CFLD) are a leading nonpulmonary cause of death. Noninvasive tests enabling early detection of liver changes, especially in children are sought. The aim of the study was to assess the scale of liver fibrosis with the use of elastography in paediatric patients with diagnosed cystic fibrosis (CF) and its comparison with other tests (APRI and Fibrotest). Methods: We examined 41 children, in the age range 2-21 years, with diagnosed CF. The analysis a included clinical picture, laboratory parameters of liver damage, and cholestasis. Aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrotest were done in all patients. Liver stiffness measurements were acquired using shear-wave elastography (SWE). Results: CFLD was diagnosed in 16/41 patients (39%). Abnormal elastography was observed in 19/41 patients (46.3%), and in 5/41 (12.2%), the changes were advanced (F4). Abnormal elastography was observed in 12/16 (75%) of the patients with CFLD, and in 7/25 (28%), there were no lesions observed in the liver in the course of cystic fibrosis. In all patients with F4, we observed abnormal results of the APRI and Fibrotest. In most patients with small changes in elastography, we found normal results of the APRI and Fibrotest. Conclusion: Elastography seems to be a noninvasive examination useful in everyday clinical work in detecting early liver changes and monitoring of progression in paediatric patients with diagnosed cystic fibrosis, ahead of changes in laboratory tests. The cost-effectiveness of this test, the possibility of its repetition, and its availability are additional benefits.

Assessment of hepatic involvement by two-dimensional shear wave elastography in paediatric patients with cystic fibrosis.

AIM: This study aimed to investigate parenchymal changes in the liver in paediatric patients with cystic fibrosis (CF) and to analyse diagnostic performance of two-dimensional shear wave elastography (2D-SWE) for the detection of hepatic involvement. METHODS: Patients with CF treated and followed at our centre were evaluated prospectively. All patients underwent liver tissue stiffness (TS) measurements by 2D-SWE, in addition to routine clinical assessments, laboratory work-up and abdominal ultrasound imaging. Data from patients with CF were compared with healthy control subjects. RESULTS: This study included 39 patients with CF and 37 healthy controls. Patients had a mean body weight of 29.9 (16.6-55) kg, mean age of 9 (5-17) years, mean height of 130 (107-172) cm and a mean body mass index of 16.1 (12.8-21.4) kg/m2 . Average SWE values of the liver were 1.02 (0.70-1.60) m/s in patients with CF (n = 39) and 0.89 (0.60-1.35) m/s in healthy controls (n = 37). Cystic fibrosis patients had significantly increased tissue stifness by liver elastography compared to controls (P = 0.005). CONCLUSION: Parenchymal liver changes may occur early in cystic fibrosis, which cannot be detected by conventional ultrasonography but may be demonstrated by 2D-SWE. Based on this cross-sectional study, 2D-SWE may be a promising, simple and non-invasive modality for objective monitoring of patients with cystic fibrosis who require lifelong follow-up, by providing numerical data for tissue stiffness early in the disease.

Effect of Salbutamol on Lung Ventilation in Children with Cystic Fibrosis: Comprehensive Assessment Using Spirometry, Multiple-Breath Washout, and Functional Lung Magnetic Resonance Imaging.

BACKGROUND: Inhalation therapy is one of the cornerstones of the daily treatment regimen in patients with cystic fibrosis (CF). Recommendations regarding the addition of bronchodilators, especially salbutamol are conflicting due to the lack of evidence. New diagnostic measures such as multiple-breath washout (MBW) and functional magnetic resonance imaging (MRI) have the potential to reveal new insights into bronchodilator effects in patients with CF. OBJECTIVE: The objective of the study was to comprehensively assess the functional response to nebulized inhalation with salbutamol in children with CF. METHODS: Thirty children aged 6-18 years with stable CF performed pulmonary function tests, MBW, and matrix pencil-MRI before and after standardized nebulized inhalation of salbutamol. RESULTS: Lung clearance index decreased (improved) by -0.24 turnover (95% confidence interval [CI]: -0.53 to 0.06; p = 0.111). Percentage of the lung volume with impaired fractional ventilation and relative perfusion decreased (improved) by -0.79% (CI: -1.99 to 0.42; p = 0.194) and -1.31% (CI: -2.28 to -0.35; p = 0.009), respectively. Forced expiratory volume (FEV1) increased (improved) by 0.41 z-score (CI: 0.24-0.58; p < 0.0001). We could not identify specific clinical factors associated with a more pronounced effect of salbutamol. CONCLUSIONS: There is a positive short-term effect of bronchodilator inhalation on FEV1 in patients with CF, which is independent of ventilation inhomogeneity. Heterogeneous response between patients suggests that for prediction of a therapeutic effect this should be tested by spirometry in every patient individually.

Assessment of Right Heart Functions in Children with Mild Cystic Fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystemic disease that prevalently involves the lungs. Hypoxemia occurs due to the existing of progressive damage to the pulmonary parenchyma and pulmonary vessels. The condition may cause systolic and diastolic dysfunction to the right ventricle due to the effects of high pulmonary artery systolic pressure (PASP). The study aimed to determine echocardiographic alterations in PASP, right ventricle (RV) anatomy, and functions in mild CF children. MATERIALS AND METHODS: RV anatomy, systolic, and diastolic functions were evaluated with conventional echocardiographic measurements. Estimated PASP was used measured with new echocardiographic modalities, including pulmonary artery acceleration time (PAAT), right ventricular ejection time (RVET), and their ratio (PAAT/RVET). The obtained echocardiographic data were statistically compared between the patient group and the control group. RESULTS: The study consisted of 30 pediatric patients with mild CF and 30 healthy children with similar demographics. In patient group, conventional parameters disclosed differences in RV anatomy, both systolic and diastolic functions of RV compared with the healthy group. We did not compare the patient group with published standard data because of the wide range variability. However, new echocardiographic parameters showed notable increase in pulmonary artery pressure compared with values of control group and published standard data (p<0.001). CONCLUSION: Elevated PASP, RV failure, and Cor pulmonale usually begin early in children with mild CF. In addition to routine echocardiographic measurements to evaluate RV, we recommend the use of new echocardiographic modalities for routine examinations and in the follow up of children with mild CF.

Longitudinal Assessment of Patients With Cystic Fibrosis Lung Disease With Multivolume Noncontrast MRI and Spirometry.

BACKGROUND: MRI has been suggested as a radiation-free imaging modality to investigate early structural alterations and regional functional impairment in cystic fibrosis (CF) lung disease. PURPOSE/HYPOTHESIS: To compare functional and morphological MRI changes over the course of the disease to changes in spirometry. STUDY TYPE: Longitudinal retrospective study. POPULATION: Twenty patients with CF lung disease (at baseline, age = 16.5 (13.3-20.6) years, forced expiratory volume in 1 second (as % of predicted [%pred]) FEV1 = 71 (59-87) %pred, forced expiratory flow at 25-75% of forced vital capacity FEF25-75 = 39 (25-63) %pred. FIELD STRENGTH/SEQUENCE: 1.5T / T2 -weighted HASTE; T2 -weighted TSE-PROPELLER; T2 -weighted bSSFP; T1 -weighted 3D GRE. ASSESSMENT: Nonenhanced chest MRI and spirometry were retrospectively collected over a 3-year period from the initial recruitment visit. Images acquired at end-inspiration and end-expiration were registered by software using the optical flow method to measure expiratory-inspiratory differences in MR signal-intensity (Δ1 H-MRI). Measures of CF functional impairment were defined from Δ1 H-MRI: Δ1 H-MRI median, Δ1 H-MRI quartile coefficient of variation (QCV), and percent low-signal-variation volume (LVV). MR images were also evaluated by three readers using a CF-specific scoring system. STATISTICAL TESTS: Spearman correlation analysis, Spearman rank correlation analysis, linear mixed-effect model analysis, intraclass correlation coefficient. RESULTS: Functional imaging parameters and total morphological score correlated with all spirometric measures, as did subscores of bronchial wall thickening/bronchiectasis, mucus plugging, and consolidation. Overall, the percent change of Δ1H-MRI median correlated with the percent change of FEV1 (ΔFEV1 , r = 0.41, P < 0.01) and the percent change of FEF25-75 (ΔFEF25-75%, r = 0.38, P < 0.01). The percent change of LVV correlated with ΔFEV1 (r = -0.47, P < 0.001) and ΔFEF25-75 (r = -0.50, P < 0.001). DATA CONCLUSION: These preliminary results suggest that nonenhanced multivolume MRI may provide a feasible tool to regionally map early pulmonary alterations for longitudinal evaluation of CF lung disease, without exposing the patients to ionizing radiation. LEVEL OF EVIDENCE: 3T TECHNICAL EFFICACY STAGE: 5.

The remaining barriers to normalcy in CF: Advances in assessment of CF lung disease.

Despite early diagnosis of cystic fibrosis (CF) through newborn screening, a substantial proportion of infants and young children with CF still demonstrate physiologic and structural evidence of lung disease progression, such as obstructive airway disease and bronchiectasis. The growing availability of highly effective CF transmembrane conductance regulatory modulator therapy to the vast majority of people with CF has led to the potential to alter the natural history of CF lung disease, but to assess the full impact of these therapies on CF lung disease and to help guide treatment, sensitive measures of early and mild disease are needed. Chest imaging using computed tomography or magnetic resonance imaging is one approach, but technologic barriers and/or concern about exposure to ionizing radiation may limit its use. However, advances in physiologic measurement techniques and exhaled breath analysis offer another option for assessment of CF lung disease.

Predictive value of the modified Bhalla score for assessment of pulmonary exacerbations in adults with cystic fibrosis.

OBJECTIVES: The objective of this study was to analyze the predictive value of the modified Bhalla score in high-resolution computed tomography (HRCT) for assessment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) patients. We also describe the relationship between this score and pulmonary function test results. METHODS: We performed a multicenter and prospective study where adult patients with CF were included consecutively over 18 months. All patients underwent HRCT with acquisition in inspiration and expiration. The results were analyzed by an expert radiologist who assigned a modified Bhalla score value. Lung function was also assessed, and clinical variables were collected. Follow-up lasted approximately 1 year, and PEx were registered. RESULTS: The study population comprised 160 subjects selected from 360 CF patients monitored in the participating CF units. The mean age was 28 years, 47.5% were women, and mean forced expiratory volume in 1 s (FEV1) was 67.5%. The mean global modified Bhalla score was 14.5 ± 0.31 points. Pulmonary function test (PFT) results and the modified Bhalla score correlated well, mainly forced vital capacity (FVC) and FEV1. We constructed a statistical model based on the overall Bhalla score to predict the number of PEx. CONCLUSIONS: The overall modified Bhalla score can predict future PEx in CF patients. This useful tool can help to prevent PEx in higher risk patients. KEY POINTS: • Pulmonary function test results and the modified Bhalla score correlated well with FVC and FEV1. • The total modified Bhalla score can predict the number of exacerbations in adult CF patients. • Our findings highlight the need to establish a unified protocol for chest HRCT during the follow-up of adult patients with CF in order to anticipate possible complications and determine their impact on pulmonary function.

Tissue Doppler and speckle tracking echocardiography assessment of left ventricular function in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis may lead to left ventricular (LV) dysfunction. This dysfunction can be documented by methods such as tissue Doppler echocardiographic (TDI) imaging and two-dimensional speckle tracking echocardiography (STE) in early stage. STUDY DESIGN: This was prospective cohort study. METHODS: A total of 34 patients diagnosed with cystic fibrosis (mean age and SD 9.9 ± 4.9 years) and 37 healthy control subjects with a comparable gender and age distribution (mean age 9.8 ± 4.3) were studied. The results for the two groups were compared along with the results of published reports. RESULTS: No significant relationship was found between the groups in terms of systolic and diastolic measurements of the interventricular septum and posterior left ventricular wall, and ejection fraction (P > .05). Myocardial performance indexes of left ventricular free wall and interventricular septum increased in the patient group compared with the controls (P < .05). As measured by STE, seven segments in the LV myocardial longitudinal strain and three segments in the LV myocardial circumferential strain showed significant reductions in patients with cystic fibrosis compared with controls (P < .05). The longitudinal global, circumferential global, and total global strain values had no significant difference between the groups (P > .05). Longitudinal strain rates and circumferential strain rates were both lower in five segments in the patient group (P < .05). CONCLUSIONS: Tissue Doppler echocardiographic imaging and STE may help identifying subclinical LV dysfunction in cystic fibrosis patients with unremarkable conventional echocardiography. They may be considered for the routine follow-up of cystic fibrosis patients.

[Assessment of lung impairment in patients with cystic fibrosis : Novel magnetic resonance imaging methods]. / Detektion von Lungenveränderungen bei Patienten mit Mukoviszidose : Innovationen der Magnetresonanztomographie des Thorax.

CLINICAL/METHODOLOGICAL ISSUE: The differentiated assessment of respiratory mechanics, gas exchange and pulmonary circulation, as well as structural impairment of the lung are essential for the treatment of patients with cystic fibrosis (CF). Clinical lung function measurements are often not sufficiently specific and are often difficult to perform. STANDARD RADIOLOGICAL METHODS: The standard procedures for pulmonary imaging are chest X­ray and computed tomography (CT) for assessing lung morphology. In more recent studies, an increasing number of centers are using magnetic resonance imaging (MRI) to assess lung structure and function. However, functional imaging is currently limited to specialized centers. METHODOLOGICAL INNOVATIONS: In patients with CF, studies showed that MRI with hyperpolarized gases and Fourier decomposition/matrix pencil MRI (FD/MP-MRI) are feasible for assessing pulmonary ventilation. For pulmonary perfusion, dynamic contrast-enhanced MRI (DCE-MRI) or contrast-free methods, e.g., FD-MRI, can be used. PERFORMANCE: Functional MRI provides more accurate insight into the pathophysiology of pulmonary function at the regional level. Advantages of MRI over X­ray are its lack of ionizing radiation, the large number of lung function parameters that can be extracted using different contrast mechanisms, and ability to be used repeatedly over time. ACHIEVEMENTS: Early assessment of lung function impairment is needed as the structural changes usually occur later in the course of the disease. However, sufficient experience in clinical application exist only for certain functional lung MRI procedures. PRACTICAL RECOMMENDATIONS: Clinical application of the aforementioned techniques, except for DCE-MRI, should be restricted to scientific studies.

Cystic Fibrosis from Childhood to Adulthood: What Is New in Imaging Assessment?

Advanced pulmonary disease continues to remain the leading cause of morbidity and mortality in patients with cystic fibrosis (CF), with pulmonary imaging playing a crucial role in early detection, longitudinal monitoring, as well as prelung and postlung transplant evaluation. This article reviews the specific imaging features of CF using conventional imaging modalities (chest radiographs and high-resolution computed tomography [HRCT]) as well as emerging imaging technologies (digital chest tomosynthesis and MR imaging). In addition, the authors review the CF-specific HRCT imaging findings that are essential in the evaluation of these patients in the pre-lung transplant and post-lung transplant settings.

Utility and validity of dynamic chest radiography in cystic fibrosis (dynamic CF): an observational, non-controlled, non-randomised, single-centre, prospective study.

INTRODUCTION: Dynamic chest radiography (DCR) uses novel, low-dose radiographic technology to capture images of the thoracic cavity while in motion. Pulmonary function testing is important in cystic fibrosis (CF). The tolerability, rapid acquisition and lower radiation and cost compared with CT imaging may make DCR a useful adjunct to current standards of care. METHODS AND ANALYSIS: This is an observational, non-controlled, non-randomised, single-centre, prospective study. This study is conducted at the Liverpool Heart and Chest Hospital (LHCH) adult CF unit. Participants are adults with CF. This study reviews DCR taken during routine CF Annual Review (n=150), validates DCR-derived lung volumes against whole body plethysmography (n=20) and examines DCR at the start and end of pulmonary exacerbations of CF (n=20). The primary objectives of this study are to examine if DCR provides lung function information that correlates with PFT, and lung volumes that correlate whole body plethysmography. ETHICS AND DISSEMINATION: This study has received the following approvals: HRA REC (11 December 2019) and LHCH R&I (11 October 2019). Results are made available to people with CF, the funders and other researchers. Processed, anonymised data are available from the research team on request. TRIAL REGISTRATION NUMBER: ISRCTN 64994816.

Assessment of early lung disease in young children with CF: A comparison between pressure-controlled and free-breathing chest computed tomography.

BACKGROUND: Chest computed tomography (CT) in children with cystic fibrosis (CF) is sensitive in detecting early airways disease. The pressure-controlled CT-protocol combines a total lung capacity scan (TLC PC-CT) with a near functional residual capacity scan (FRC PC-CT) under general anesthesia, while another CT-protocol is acquired during free breathing (FB-CT) near functional residual capacity. The aim of this study was to evaluate the sensitivity in detecting airways disease of both protocols in two cohorts. METHODS: Routine PC-CTs (Princess Margaret Children's Hospital) and FB-CTs (Erasmus MC-Sophia Children's Hospital) were retrospectively collected from CF children aged 2 to 6 years. Total airways disease (%disease), bronchiectasis (%Bx), and low attenuation regions (%LAR) were scored on CTs using the Perth-Rotterdam annotated grid morphometric analysis-CF method. The Wilcoxon signed-rank test was used for differences between TLC and FRC PC-CTs and the Wilcoxon rank-sum test for differences between FRC PC-CTs and FB-CTs. RESULTS: Fifty patients with PC-CTs (21 male, aged 2.5-5.5 years) and 42 patients with FB-CTs (26 male, aged 2.3-6.8 years) were included. %Disease was higher on TLC PC-CTs compared with FRC PC-CTs (median 4.51 vs 2.49; P < .001). %Disease and %Bx were not significantly different between TLC PC-CTs and FB-CTs (median 4.51% vs 3.75%; P = .143 and 0.52% vs 0.57%; P = .849). %Disease, %Bx, and %LAR were not significantly different between FRC PC-CTs and FB-CTs (median 2.49% vs 3.75%; P = .055, 0.54% vs 0.57%; P = .797, and 2.49% vs 1.53%; P = .448). CONCLUSIONS: Our data suggest that FRC PC-CTs are less sensitive than TLC PC-CTs and that FB-CTs have similar sensitivity to PC-CTs in detecting lung disease. FB-CTs seem to be a viable alternative for PC-CTs to track CF lung disease in young patients with CF.

Lung T1 mapping magnetic resonance imaging in the assessment of pulmonary disease in children with cystic fibrosis: a pilot study.

BACKGROUND: Assessment tools for early cystic fibrosis (CF) lung disease are limited. Detecting early pulmonary disease is crucial to increasing life expectancy by starting interventions to slow the progression of the pulmonary disease with the many treatment options available. OBJECTIVE: To compare the utility of lung T1-mapping MRI with ultrashort echo time (UTE) MRI in children with cystic fibrosis in detecting early stage lung disease and monitoring pulmonary exacerbations. MATERIALS AND METHODS: We performed a prospective study in 16 children between September 2017 and January 2018. In Phase 1, we compared five CF patients with normal spirometry (mean 11.2 years) to five age- and gender-matched healthy volunteers. In Phase 2, we longitudinally evaluated six CF patients (median 11 years) in acute pulmonary exacerbation. All children had non-contrast lung T1-mapping and UTE MRI and spirometry testing. We compared the mean normalized T1 value and percentage lung volume without T1 value in CF patients and healthy subjects in Phase 1 and during treatment in Phase 2. We also performed cystic fibrosis MRI scoring. We evaluated differences in continuous variables using standard statistical tests. RESULTS: In Phase 1, mean normalized T1 values of the lung were significantly lower in CF patients in comparison to healthy controls (P=0.02) except in the right lower lobe (P=0.29). The percentage lung volume without T1 value was also significantly higher in CF patients (P=0.006). UTE MRI showed no significant differences between CF patients and healthy volunteers (P=0.11). In Phase 2, excluding one outlier case who developed systemic disease in the course of treatment, the whole-lung T1 value increased (P=0.001) and perfusion scoring improved (P=0.02) following therapy. We observed no other significant changes in the MRI scoring. CONCLUSION: Lung T1-mapping MRI can detect early regional pulmonary CF disease in children and might be helpful in the assessment of acute pulmonary exacerbations.

New severity assessment in cystic fibrosis: signal intensity and lung volume compared to LCI and FEV1: preliminary results.

OBJECTIVES: Magnetic resonance imaging (MRI) aids diagnosis in cystic fibrosis (CF) but its use in quantitative severity assessment is under research. This study aims to assess changes in signal intensity (SI) and lung volumes (Vol) during functional MRI and their use as a severity assessment tool in CF patients. METHODS: The CF intra-hospital standard chest 1.5 T MRI protocol comprises of very short echo-time sequences in submaximal in- and expiration for functional information. Quantitative measurements (Vol/SI at in- and expiration, relative differences (Vol_delta/SI_delta), and cumulative histograms for normalized SI values across the expiratory lung volume) were assessed for correlation to pulmonary function: lung clearance index (LCI) and forced expiratory volume in 1 s (FEV1). RESULTS: In 49 patients (26 male, mean age 17 ± 7 years) significant correlation of Vol_delta and SI_delta (R = 0.86; p < 0.0001) during respiration was observed. Individual cumulated histograms enabled severity disease differentiation (mild, severe) to be visualized (defined by functional parameter: LCI > 10). The expiratory volume at a relative SI of 100% correlated significantly to LCI (R = 0.676 and 0.627; p < 0.0001) and FEV1 (R = - 0.847 and - 0.807; p < 0.0001). Clustering patients according to Vol_SI_100 showed that an amount of ≤ 4% was related to normal, while an amount of > 4% was associated with pathological pulmonary function values. CONCLUSION: Functional pulmonary MRI provides a radiation-free severity assessment tool and can contribute to early detection of lung impairment in CF. Lung volume with SI below 100% of the inspiratory volume represents overinflated tissue; an amount of 4% of the expiratory lung volume was a relevant turning point. KEY POINTS: • Signal intensity and lung volumes are used as potential metric parameters for lung impairment. • Quantification of trapped air impacts on therapy management. • Functional pulmonary MRI can contribute to early detection of lung impairment.

Current state of the art MRI for the longitudinal assessment of cystic fibrosis.

Pulmonary MRI can now provide high-resolution images that are sensitive to early disease and specific to inflammation in cystic fibrosis (CF) lung disease. With specificity and function limited via computed tomography (CT), there are significant advantages to MRI. Many of the modern MRI techniques can be performed throughout life, and can be employed to understand changes over time, in addition to quantification of treatment response. Proton density and T1 /T2 contrast images can be obtained within a single breath-hold, providing depiction of structural abnormalities and active inflammation. Modern radial and/or spiral ultrashort echo-time (UTE) techniques rival CT in resolution for depiction and quantification of structure, for both airway and parenchymal abnormalities. Contrast perfusion MRI techniques are now utilized routinely to visualize changes in pulmonary and bronchial circulation that routinely occur in CF lung disease, and noncontrast techniques are moving closer to clinical translation. Functional information can be obtained from noncontrast proton images alone, using techniques such as Fourier decomposition. Hyperpolarized-gas MRI, increasingly using 129 Xe, is now becoming more widespread and has been demonstrated to have high sensitivity to early airway obstruction in CF via ventilation MRI. The sensitivity of 129 Xe MRI promises future use in personalized medicine, management of early CF lung disease, and in future clinical trials. By combining structural and functional techniques, with or without hyperpolarized gases, regional structure-function relationships can be obtained, giving insight into the pathophysiology of disease and improved clinical management. This article reviews the modern MRI techniques that can routinely be employed for CF lung disease in nearly any large medical center. Level of Evidence: 4 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019.

Efficacy of model-based iterative reconstruction in cystic fibrosis assessment using CT.

AIM: To evaluate the efficacy of model-based iterative reconstruction (MBIR) constructed non-enhanced ultra-low dose (ULD) computed tomography (CT) of the chest to evaluate cystic fibrosis (CF) pathology. MATERIALS AND METHODS: ULD-CT was compared with chest X-ray and standard adaptive statistical iterative reconstructed (ASIR) non-enhanced low-dose CT (LD-CT). The effective radiation dose was calculated from the recorded dose-length product (DLP) values and compared between the two CT methods. Identification of pathology was compared between ULD-CT and chest X-ray. It was hypothesised that ULD-CT would be superior to chest X-ray in the identification of CF pathology at lower doses than LD-CT. RESULTS: The mean effective radiation dose of ULD-CT was 0.073 mSv, comparable to one chest X-ray, which was a 94% reduction compared to LD-CT. Compared to chest X-ray, ULD-CT detected on average, 2.3 more regions of bronchiectasis per study and better delineated varicose and cystic forms of bronchiectasis (p≤0.0001). ULD-CT identified four-times more mucous plugging than chest X-ray (p<0.000001) and twice the amount of consolidation (p=0.0002). CONCLUSION: ULD-CT is superior to chest X-ray in quantifying CF disease and achieves remarkable radiation doses significantly lower than LD-CT, comparable to one chest radiograph. The present results suggest that MBIR-constructed ULD-CT is an effective imaging technique for CF surveillance, with potential applications in other disease settings.

Congruence Between Pulmonary Function and Computed Tomography Imaging Assessment of Cystic Fibrosis Severity.

In cystic fibrosis, pulmonary function tests (PFTs) and computed tomography are used to assess lung function and structure, respectively. Although both techniques of assessment are congruent there are lingering doubts about which PFTs variables show the best congruence with computed tomography scoring. In this study we addressed the issue by reinvestigating the association between PFTs variables and the score of changes seen in computed tomography scans in patients with cystic fibrosis with and without pulmonary exacerbation. This retrospective study comprised 40 patients in whom PFTs and computed tomography were performed no longer than 3 weeks apart. Images (inspiratory: 0.625 mm slice thickness, 0.625 mm interval; expiratory: 1.250 mm slice thickness, 10 mm interval) were evaluated with the Bhalla scoring system. The most frequent structural abnormality found in scans were bronchiectases and peribronchial thickening. The strongest relationship was found between the Bhalla sore and forced expiratory volume in 1 s (FEV1). The Bhalla sore also was related to forced vital capacity (FVC), FEV1/FVC ratio, residual volume (RV), and RV/total lung capacity (TLC) ratio. We conclude that lung structural data obtained from the computed tomography examination are highly congruent to lung function data. Thus, computed tomography imaging may supersede functional assessment in cases of poor compliance with spirometry procedures in the lederly or children. Computed tomography also seems more sensitive than PFTs in the assessment of cystic fibrosis progression. Moreover, in early phases of cystic fibrosis, computed tomography, due to its excellent resolution, may be irreplaceable in monitoring pulmonary damage.