Magnetic Resonance Imaging of Pulmonary and Paranasal Sinus Abnormalities in Children with Primary Ciliary Dyskinesia Compared to Children with Cystic Fibrosis.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are characterized by inherited impaired mucociliary clearance leading to chronic progressive lung disease as well as chronic rhinosinusitis (CRS). The diseases share morphological and functional commonalities on magnetic resonance imaging (MRI) of the lungs and paranasal sinuses, but comparative MRI studies are lacking. Objectives: To determine whether PCD shows different associations of pulmonary and paranasal sinus abnormalities on MRI and lung function test results in children (infants to adolescents) compared with children with CF. Methods: Eighteen children with PCD (median age, 9.5 [IQR, 3.4-12.7] yr; range, 0-18 yr) and 36 age-matched CF transmembrane conductance regulator modulator-naive children with CF (median age, 9.4 [3.4-13.2] yr; range, 0-18 yr) underwent same-session chest and paranasal sinus MRI as well as spirometry (to determine forced expiratory volume in 1 s percent predicted) and multiple-breath washout (to determine lung clearance index z-score). Pulmonary and paranasal sinus abnormalities were assessed using previously validated chest MRI and CRS-MRI scoring systems. Results: Mean chest MRI global score was similar in children with PCD and CF (15.0 [13.5-20.8] vs. 15.0 [9.0-15.0]; P = 0.601). Consolidations were more prevalent and severe in children with PCD (56% vs. 25% and 1.0 [0.0-2.8] vs. 0.0 [0.0-0.3], respectively; P < 0.05). The chest MRI global score correlated moderately with forced expiratory volume in 1 second percent predicted in children with PCD and children with CF (r = -0.523 and -0.687; P < 0.01) and with lung clearance index in children with CF (r = 0.650; P < 0.001) but not in PCD (r = 0.353; P = 0.196). CRS-MRI sum score and mucopyocele subscore were lower in children with PCD than in children with CF (27.5 [26.3-32.0] vs. 37.0 [37.8-40.0] and 2.0 [0.0-2.0] vs. 7.5 [4.8-9.0], respectively; P < 0.01). CRS-MRI sum score did not correlate with chest MRI score in PCD (r = 0.075-0.157; P = 0.557-0.788) but correlated moderately with MRI morphology score in CF (r = 0.437; P < 0.01). Conclusions: MRI detects differences in lung and paranasal sinus abnormalities between children with PCD and those with CF. Lung disease does not correlate with CRS in PCD but correlates in CF.

Elexacaftor/tezacaftor/ivacaftor improves chronic rhinosinusitis detected by magnetic resonance imaging in children with cystic fibrosis on long-term therapy with lumacaftor/ivacaftor.

INTRODUCTION: Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of chronic rhinosinusitis (CRS) from infancy to school age, and response to lumacaftor/ivacaftor (LUM/IVA) therapy in children with cystic fibrosis (CF). However, the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CRS detected by MRI in children with CF and at least one F508del mutation, and potential incremental effects of ELX/TEZ/IVA compared to LUM/IVA in F508del homozygous children have not been studied. METHODS: 30 children with CF with at least one F508del mutation underwent three longitudinal paranasal sinus MRI before (MRI1), without (n = 16) or with LUM/IVA therapy (n = 14, MRI2), and with ELX/TEZ/IVA therapy (MRI3, mean age at therapy initiation 11.1 ± 3.4y, range 6-16y). MRI were evaluated using the CRS-MRI score. RESULTS: After therapy initiation with ELX/TEZ/IVA, the prevalence and in maxillary and sphenoid sinuses the dominance of mucopyoceles decreased (35% vs. 0 %, p<0.001 and 26% vs. 8 %, p < 0.05, respectively). This leads to a reduction in mucopyocele subscore (-3.4 ± 1.9, p < 0.001), and sinus subscores in MRI3 (maxillary sinus: -5.3 ± 3.1, p < 0.001, frontal sinus: -1.0 ± 1.9, p < 0.01, sphenoid subscore: -2.8 ± 3.5, p < 0.001, ethmoid sinus: -1.7 ± 1.9, p < 0.001). The CRS-MRI sum score decreased after therapy initiation with ELX/TEZ/IVA by -9.6 ± 5.5 score points (p < 0.001). The strength in reduction of mucopyoceles subscore and CRS-MRI sum score was independent of a pretreatment with LUM/IVA from MRI1-MRI2 (p = 0.275-0.999). CONCLUSIONS: ELX/TEZ/IVA therapy leads to improvement of CRS in eligible children with CF. Our data support the role of MRI for comprehensive monitoring of CRS disease severity and response to therapy in children with CF.

Long-term effects of lumacaftor/ivacaftor on paranasal sinus abnormalities in children with cystic fibrosis detected with magnetic resonance imaging.

Introduction: Chronic rhinosinusitis (CRS) usually presents with nasal congestion, rhinorrhea and anosmia impacts quality of life in cystic fibrosis (CF). Especially mucopyoceles pathognomonic for CRS in CF may cause complications such as spread of infection. Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of CRS from infancy to school age in patients with CF, and mid-term improvements of CRS in preschool and school-age children with CF treated with lumacaftor/ivacaftor for at least 2 months. However, long-term data on treatment effects on paranasal sinus abnomalities in preschool and school-age children with CF are lacking. Methods: 39 children with CF homozygous for F508del (mean age at baseline MRI 5.9 ± 3.0 years, range 1-12 years) underwent MRI before (MRI1) and about 7 months after starting lumacaftor/ivacaftor and then annually (median 3 follow-up MRI, range 1-4) (MRI2-4). MRI were evaluated using the previously evaluated CRS-MRI score with excellent inter-reader agreement. For intraindividual analysis ANOVA mixed-effects analysis including Geisser-Greenhouse correction and Fisher's exact test, and for interindividual group analysis Mann-Whitney test were used. Results: The CRS-MRI sum score at baseline was similar in children starting lumacaftor/ivacaftor in school age and children starting therapy at preschool age (34.6 ± 5.2 vs.32.9 ± 7.8, p = 0.847). Mucopyoceles were the dominant abnormality in both, especially in maxillary sinus (65% and 55%, respectively). In children starting therapy in school age the CRS-MRI sum score decreased longitudinally from MRI1 to MRI2 (-2.1 ± 3.5, p < 0.05), MRI3 (-3.0 ± 3.7, p < 0.01) and MRI4 (-3.6 ± 4.7, p < 0.01), mainly due to a decrease in the mucopyoceles subscore (-1.0 ± 1.5, p = 0.059; -1.2 ± 2.0, p < 0.05; -1.6 ± 1.8, p < 0.01; and -2.6 ± 2.8, p = 0.417, respectively). In children starting lumacaftor/ivacaftor in preschool age, the CRS-MRI sum score remained stable under therapy over all three follow-up MRI (0.6 ± 3.3, p = 0.520; 2.4 ± 7.6, p = 0.994; 2.1 ± 10.5, p > 0.999 and -0.5 ± 0.5, p = 0.740; respectively). Conclusion: Longitudinal paranasal sinus MRI shows improvements in paranasal sinus abnormalities in children with CF starting lumacaftor/ivacaftor therapy at school age. Further, MRI detects a prevention of an increase in paranasal sinus abnormalities in children with CF starting lumacaftor/ivacaftor therapy at preschool age. Our data support the role of MRI for comprehensive non-invasive therapy and disease monitoring of paranasal sinus abnormalities in children with CF.

Magnetic resonance imaging detects onset and association with lung disease severity of bronchial artery dilatation in cystic fibrosis.

Background: Bronchial artery dilatation (BAD) is associated with haemoptysis in advanced cystic fibrosis (CF) lung disease. Our aim was to evaluate BAD onset and its association with disease severity by magnetic resonance imaging (MRI). Methods: 188 CF patients (mean±sd age 13.8±10.6 years, range 1.1-55.2 years) underwent annual chest MRI (median three exams, range one to six exams), contributing a total of 485 MRI exams including perfusion MRI. Presence of BAD was evaluated by two radiologists in consensus. Disease severity was assessed using the validated MRI scoring system and spirometry (forced expiratory volume in 1 s (FEV1) % pred). Results: MRI demonstrated BAD in 71 (37.8%) CF patients consistently from the first available exam and a further 10 (5.3%) patients first developed BAD during surveillance. Mean MRI global score in patients with BAD was 24.5±8.3 compared with 11.8±7.0 in patients without BAD (p<0.001) and FEV1 % pred was lower in patients with BAD compared with patients without BAD (60.8% versus 82.0%; p<0.001). BAD was more prevalent in patients with chronic Pseudomonas aeruginosa infection versus in patients without infection (63.6% versus 28.0%; p<0.001). In the 10 patients who newly developed BAD, the MRI global score increased from 15.1±7.8 before to 22.0±5.4 at first detection of BAD (p<0.05). Youden indices for the presence of BAD were 0.57 for age (cut-off 11.2 years), 0.65 for FEV1 % pred (cut-off 74.2%) and 0.62 for MRI global score (cut-off 15.5) (p<0.001). Conclusions: MRI detects BAD in patients with CF without radiation exposure. Onset of BAD is associated with increased MRI scores, worse lung function and chronic P. aeruginosa infection, and may serve as a marker of disease severity.

Longitudinal Magnetic Resonance Imaging Detects Onset and Progression of Chronic Rhinosinusitis from Infancy to School Age in Cystic Fibrosis.

Rationale: Chronic rhinosinusitis (CRS) contributes to morbidity in patients with cystic fibrosis (CF). However, longitudinal data on CRS onset and progression is lacking. Objectives: To longitudinally evaluate CRS in CF from infancy to school age with paranasal sinus magnetic resonance imaging (MRI). Methods: A total of 64 children with CF (mean age at baseline, 1.1 ± 1.6 yr; range, 0-5 yr) underwent a mean of 5.8 ± 2.2 (range, 3-11 yr) subsequent annual MRI examinations. Additional 24 children (9.2 ± 4.4 yr; range, 3-17 yr) homozygous for the F508del mutation underwent MRI before and at least 2 months after starting lumacaftor/ivacaftor. MRI was assessed using the previously evaluated CRS-MRI score. Results: In infancy, 65-87% of paranasal sinuses were opacified, and mucosal swelling was the dominant abnormality (58-97%). At preschool age (1-5 yr), 79-94% of sinuses were opacified (P < 0.05 vs. infancy), and mucosal swelling was the most dominant abnormality (79-94%; P < 0.05). At school age (at least 6 yr), almost all sinuses were opacified (71-99%; P < 0.001-0.357 vs. preschool age), and mucopyoceles were the dominant abnormality in maxillary and frontal sinuses (53-56%; P < 0.05-0.808). The CRS-MRI sum score increased from 22.4 ± 9.6 in infancy to 34.2 ± 9.6 in preschool age (P < 0.001) and was 34.0 ± 5.7 in school age (P = 0.052). In children under lumacaftor/ivacaftor therapy, the CRS-MRI sum score (-0.5 ± 3.3; P < 0.05) and maxillary sinus subscore (-0.5 ± 1.5; P < 0.05) improved. Conclusions: Longitudinal paranasal sinus MRI detects an early onset and progression of the severity of CRS from infancy to school age, and response to lumacaftor/ivacaftor therapy in children with CF. Our data support its role in the comprehensive noninvasive monitoring of CRS in children with CF. Clinical trial registered with www.clinicaltrials.gov (NCT02270476).

Near-Adult Heights and Adult Height Predictions Using Automated and Conventional Greulich-Pyle Bone Age Determinations in Children with Chronic Endocrine Diseases.

OBJECTIVES: To validate adult height predictions (BX) using automated and Greulich-Pyle bone age determinations in children with chronic endocrine diseases. METHODS: Heights and near-adult heights were measured in 82 patients (48 females) with chronic endocrinopathies at the age of 10.45 ± 2.12 y and at time of transition to adult care (17.98 ± 3.02 y). Further, bone age (BA) was assessed using the conventional Greulich-Pyle (GP) method by three experts, and by BoneXpert™. PAH were calculated using conventional BP tables and BoneXpert™. RESULTS: The conventional and the automated BA determinations revealed a mean difference of 0.25 ± 0.72 y (p = 0.0027). The automated PAH by BoneXpert™ were 156.26 ± 0.86 cm (SDS - 2.01 ± 1.07) in females and 171.75 ± 1.6 cm (SDS - 1.29 ± 1.06) in males, compared to 153.95 ± 1.12 cm (SDS - 2.56 ± 1.5) in females and 169.31 ± 1.6 cm (SDS - 1.66 ± 1.56) in males by conventional BP, respectively and in comparison to near-adult heights 156.38 ± 5.84 cm (SDS - 1.91 ± 1.15) in females and 168.94 ± 8.18 cm (SDS - 1.72 ± 1.22) in males, respectively. CONCLUSION: BA ratings and adult height predictions by BoneXpert™ in children with chronic endocrinopathies abolish rater-dependent variability and enhance reproducibility of estimates thereby refining care in growth disorders. Conventional methods may outperform automated analyses in specific cases.

Echo Time-Dependence of Observed Lung T1 in Patients With Cystic Fibrosis and Correlation With Clinical Metrics.

BACKGROUND: Noninvasive monitoring of early abnormalities and therapeutic intervention in cystic fibrosis (CF) lung disease using MRI is important. Lung T1 mapping has shown potential for local functional imaging without contrast material. Recently, it was discovered that observed lung T1 depends on the measurement echo time (TE). PURPOSE: To examine TE-dependence of observed T1 in patients with CF and its correlation with clinical metrics. STUDY TYPE: Prospective. POPULATION: In all, 75 pediatric patients with CF (8.6 ± 6.1 years, range 0.1-23 years), with 32 reexamined after 1 year. FIELD STRENGTH/SEQUENCE: Patients were examined at 1.5T using an established MRI protocol and a multiecho inversion recovery 2D ultrashort echo time (UTE) sequence for T1 (TE) mapping at five TEs including TE1 = 70 µs. ASSESSMENT: Morphological and perfusion MRI were assessed by a radiologist (M.W.) with 11 years of experience using an established CF-MRI scoring system. T1 (TE) was quantified automatically. Clinical data including spirometry (FEV1pred%) and lung clearance index (LCI) were collected. STATISTICAL TESTS: T1 (TE) was correlated with the CF-MRI score, clinical data, and LCI. RESULTS: T1 (TE) showed a different curvature in CF than in healthy adults: T1 at TE1 was shorter in CF (1157 ms ± 73 ms vs. 1047 ms ± 70 ms, P < 0.001), but longer at TE3 (1214 ms ± 72 ms vs. 1314 ms ± 68 ms, P < 0.001) and later TEs. The correlations of T1 (TE) with patient age (ρTE1-TE5 = -0.55, -0.44, -0.24, -0.30, -0.22), and LCI (ρTE1-TE5 = -0.43, -0.42, -0.33, 0.27, -0.22) were moderate at ultra-short to short TE (P < 0.001) but decreased for longer TE. Moderate but similar correlations at all TE were found with MRI perfusion score (ρTE1-TE5 = -0.43, -0.51, -0.47, -0.46, -0.44) and FEV1pred% (ρTE1-TE5 = +0.44, +0.44, +0.43, +0.40, +0.39) (P < 0.05). DATA CONCLUSION: TE should be considered when measuring lung T1 , since observed differences between CF and healthy subjects strongly depend on TE. The different variation of correlation coefficients with TE for structural vs. functional metrics implies that TE-dependence holds additional information which may help to discern effects of tissue structural abnormalities and abnormal perfusion. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1645-1654.

The value of chest magnetic resonance imaging compared to chest radiographs with and without additional lung ultrasound in children with complicated pneumonia.

INTRODUCTION: In children with pneumonia, chest x-ray (CXR) is typically the first imaging modality used for diagnostic work-up. Repeated CXR or computed tomography (CT) are often necessary if complications such as abscesses or empyema arise, thus increasing radiation exposure. The aim of this retrospective study was to evaluate the potential of radiation-free chest magnetic resonance imaging (MRI) to detect complications at baseline and follow-up, compared to CXR with and without additional lung ultrasound (LUS). METHODS: Paired MRI and CXR scans were retrospectively reviewed by two blinded readers for presence and severity of pulmonary abscess, consolidation, bronchial wall thickening, mucus plugging and pleural effusion/empyema using a chest MRI scoring system. The scores for MRI and CXR were compared at baseline and follow-up. Furthermore, the MRI scores at baseline with and without contrast media were evaluated. RESULTS: 33 pediatric patients (6.3±4.6 years), who had 33 paired MRI and CXR scans at baseline and 12 at follow-up were included. MRI detected significantly more lung abscess formations with a prevalence of 72.7% compared to 27.3% by CXR at baseline (p = 0.001), whereas CXR+LUS was nearly as good as MRI. MRI also showed a higher sensitivity in detecting empyema (p = 0.003). At follow-up, MRI also showed a slightly better sensitivity regarding residual abscesses. The overall severity of disease was rated higher on MRI. Contrast material did not improve detection of abscesses or empyema by MRI. CONCLUSION: CXR and LUS seem to be sufficient in most cases. In cases where LUS cannot be realized or the combination of CXR+LUS might be not sufficient, MRI, as a radiation free modality, should be preferred to CT. Furthermore, the admission of contrast media is not mandatory in this context.

Non-contrast enhanced magnetic resonance imaging detects mosaic signal intensity in early cystic fibrosis lung disease.

OBJECTIVES: To determine if morphological non-contrast enhanced magnetic resonance imaging (MRI) of the lung is sensitive to detect mosaic signal intensity in infants and preschool children with cystic fibrosis (CF). MATERIALS AND METHODS: 50 infant and preschool CF patients (mean age 3.5 ±â€¯1.4y, range 0-6y) routinely underwent morphological (T2-weighted turbo-spin echo sequence with half-Fourier acquisition, HASTE) and contrast-enhanced 4D perfusion MRI (gradient echo sequence with parallel imaging and echo sharing, TWIST). MRI studies were independently scored by two readers blinded for patient age and clinical data (experienced Reader 1 = R1, inexperienced Reader 2 = R2). The extent of lung parenchyma signal abnormalities on HASTE was rated for each lobe from 0 (normal), 1 (<50% of lobe affected) to 2 (≥50% of lobe affected). Perfusion MRI was rated according to the previously established MRI score, and served as the standard of reference. RESULTS: Inter-method agreement between MRI mosaic score and perfusion score was moderate with κ = 0.58 (confidence interval 0.45-0.71) for R1, and with κ = 0.59 (0.46-0.72) for R2. Bland-Altman analysis revealed a slight tendency of the mosaic score to underestimate perfusion abnormalities with a score bias of 0.48 for R1 and 0.46 for R2. Inter-reader agreement for mosaic score was substantial with κ = 0.71 (0.62-0.79), and a low bias of 0.02. CONCLUSIONS: This study demonstrates that non-contrast enhanced MRI reliably detects mosaic signal intensity in infants and preschool children with CF, reflecting pulmonary blood volume distribution. It may thus be used as a surrogate for perfusion MRI if contrast material is contra-indicated or alternative techniques are not available.

Point shear wave elastography (pSWE) using Acoustic Radiation Force Impulse (ARFI) imaging: a feasibility study and norm values for renal parenchymal stiffness in healthy children and adolescents.

AIMS: To evaluate the applicability of point shear wave elastography (pSWE) for measuring renal parenchymal stiffness in healthy children and adolescents and to establish norm values for shear wave speed (SWS) using two ARFI methods and ultrasound probes. MATERIAL AND METHODS: We prospectively investigated 264 children (43.9% males). pSWE (Virtual TouchTM Quantification and Virtual TouchTM Imaging Quantification (VTQ and VTIQ; Siemens, Germany)) was performed in the renal cortex of 528 healthy kidneys using a 1-6 MHz convex and a 4-9 MHz linear ultrasound probe in ventrolateral and dorsal examinations. Feasibility and reproducibility of pSWE measurements were evaluated. SWS values were analysed with regard to age, body dimensions, kidney volume and measuring depth. RESULTS: pSWE measurements were successful in >95% of subjects using the low and in <60% using the high-frequency probe. Mean SWS values (m/s) differed by method and probe: 2.10±0.43 (VTQ1-6MHz, convex, ventrolateral), 2.30±0.37 (VTQ1-6MHz, convex, dorsal), 1.58±0.44 (VTQ4-9MHz, linear, dorsal) and 1.96±0.27 (VTIQ4-9MHz, linear, dorsal). SWS was positively correlated with age, weight and body height, but independent of sex, BMI, or kidney volume and depth. CONCLUSIONS: pSWE (VTQ) is a feasible method to evaluate renal parenchymal stiffness in children of all ages. SWS values are age and weight dependent and differ significantly between high- and low-frequency probes. High-frequency probes and VTIQ should only be used in children <10 years.

3D Geometric Analysis of the Pediatric Aorta in 3D MRA Follow-Up Images with Application to Aortic Coarctation.

BACKGROUND: Coarctation of the aorta is one of the most common congenital heart diseases. Despite different treatment opportunities, long-term outcome after surgical or interventional therapy is diverse. Serial morphologic follow-up of vessel growth is necessary, because vessel growth cannot be predicted by primer morphology or a therapeutic option. OBJECTIVES: For the analysis of the long-term outcome after therapy of congenital diseases such as aortic coarctation, accurate 3D geometric analysis of the aorta from follow-up 3D medical image data such as magnetic resonance angiography (MRA) is important. However, for an objective, fast, and accurate 3D geometric analysis, an automatic approach for 3D segmentation and quantification of the aorta from pediatric images is required. METHODS: We introduce a new model-based approach for the segmentation of the thoracic aorta and its main branches from follow-up pediatric 3D MRA image data. For robust segmentation of vessels even in difficult cases (e.g., neighboring structures), we propose a new extended parametric cylinder model that requires only relatively few model parameters. Moreover, we include a novel adaptive background-masking scheme used for least-squares model fitting, we use a spatial normalization scheme to align the segmentation results from follow-up examinations, and we determine relevant 3D geometric parameters of the aortic arch. RESULTS: We have evaluated our proposed approach using different 3D synthetic images. Moreover, we have successfully applied the approach to follow-up pediatric 3D MRA image data, we have normalized the 3D segmentation results of follow-up images of individual patients, and we have combined the results of all patients. We also present a quantitative evaluation of our approach for four follow-up 3D MRA images of a patient, which confirms that our approach yields accurate 3D segmentation results. An experimental comparison with two previous approaches demonstrates that our approach yields superior results. CONCLUSIONS: From the results, we found that our approach is well suited for the quantification of the 3D geometry of the aortic arch from follow-up pediatric 3D MRA image data. In future work, this will enable to investigate the long-term outcome of different surgical and interventional therapies for aortic coarctation.

Long-term investigation of kidney ultrasound in cases of hemolytic uremic syndrome in children.

PURPOSE: The aim is to describe the changes in initial findings of kidney ultrasound examinations in cases of hemolytic uremic syndrome (HUS) in children and to evaluate the respective importance of three sonographical parameters: echogenicity, corticomedullary differentiation (CMD), and kidney size. The correlation with laboratory parameters and proteinuria is analysed. METHODS: Reports containing ultrasound examinations and laboratory values from 1989 through 2012 of 39 children (13 cases of atypical HUS and 26 cases of typical HUS, first diagnosis at age 4 months to 10 2/12 years) suffering from HUS were analysed retrospectively. Ultrasound scans of the right kidney (n = 312) were evaluated with regard to the factors echogenicity, CMD, and kidney volume (ml, percentile). Laboratory parameters included serum creatinine, endogenous creatinine clearance in 24-h urine collection, eGFR according to Schwartz, and the protein content of the 24-h urine collection. RESULTS: All patients initially had increased echogenicity of the kidneys. All kidney volumes were ranged in the higher percentiles (the median percentile was the 85th). For assessment of long-term progression, the echogenicity proved to be of higher importance than the CMD due to a significant correlation between laboratory parameters of kidney function and the echogenicity. CONCLUSION: Ultrasound examination of the kidneys is an important method in follow-up examinations of patients with HUS. Renal morphology correlates with laboratory parameters of kidney function.