Changes in Pulmonary Function and Controlled Ventilation-High Resolution CT of Chest After Antibiotic Therapy in Infants and Young Children with Cystic Fibrosis.

BACKGROUND: Infants with cystic fibrosis (CF) develop early progressive lung disease which may be asymptomatic. Infant pulmonary function tests (IPFT) and controlled ventilation-high resolution computed tomography (CV-HRCT) of chest can detect early asymptomatic lung disease. It is not well established that these objective measures can detect changes in lung disease after clinical interventions. OBJECTIVE: The purpose of this study was to evaluate usefulness of IPFT and CV-HRCT to detect changes in lung disease after intravenous (IV) antibiotic therapy in infants with early CF-related lung disease. STUDY DESIGN: IPFTs and CV-HRCT done before and after 2 weeks of IV antibiotics in infants at our institution over the last 12 years were compared. CV-HRCTs were compared using the modified Brody scoring system. RESULTS: The sample included 21 infants, mean age 85.2 ± 47.6 weeks. Mean change in weight was 0.4 ± 0.38 kg (p = 0.001). Significant changes in IPFT included mean % predicted FEV(0.5) (+13.5 %, p = 0.043), mean %FEF(25-75) (+30.2 %, p = 0.008), mean %RV/TLC (-11.2 %, p = 0.008), and mean %FRC/TLC (-4.5 %, p = 0.001). Total Brody scores improved from a median of 10 to 5 (p < 0.001) as did mean scores for airway wall thickening (p = 0.050), air trapping (p < 0.001), and parenchymal opacities (p = 0.003). CONCLUSION: IPFT and CV-HRCT can be used as objective measures of improvement in lung disease for infants with CF treated with antibiotics.

Image analysis for cystic fibrosis: computer-assisted airway wall and vessel measurements from low-dose, limited scan lung CT images.

Cystic fibrosis (CF) is a life-limiting genetic disease that affects approximately 30,000 Americans. When compared to those of normal children, airways of infants and young children with CF have thicker walls and are more dilated in high-resolution computed tomographic (CT) imaging. In this study, we develop computer-assisted methods for assessment of airway and vessel dimensions from axial, limited scan CT lung images acquired at low pediatric radiation doses. Two methods (threshold- and model-based) were developed to automatically measure airway and vessel sizes for pairs identified by a user. These methods were evaluated on chest CT images from 16 pediatric patients (eight infants and eight children) with different stages of mild CF related lung disease. Results of threshold-based, corrected with regression analysis, and model-based approaches correlated well with both electronic caliper measurements made by experienced observers and spirometric measurements of lung function. While the model-based approach results correlated slightly better with the human measurements than those of the threshold method, a hybrid method, combining these two methods, resulted in the best results.

Structural lung disease in preschool children with cystic fibrosis: An 18 month natural history study.

BACKGROUND: This study was performed to describe the natural history of CF lung disease in young children over an 18 month period to assess the use of CT scanning as an outcome measure for intervention trials. METHODS: Chest CT scans were obtained at baseline and after 18 months in 42 two- to six-year-old children with CF. CT scans were scored by 2 experienced radiologists for the presence and severity of bronchiectasis, mucous plugging, and air trapping. RESULTS: Mean age at baseline 3.5 (1.3) (mean, sd) years. One or more findings of CF lung disease was seen on the first CT in 27 (64%) and at 18 months in 30 (75%). From baseline to 18 months bronchiectasis, mucous plugging, and air trapping increased from 50% to 53%, 14% to 28%, and 48% to 58% respectively. There was marked variability in the rate of progression, with subjects commonly showing improvement in lung disease. Bronchiectasis worsened in 14 (33%) and improved in 13 (31%). Single subjects with F508del/class III and F508del/class V demonstrated greater worsening and improvement respectively than F508del homozygous and class I genotypes. CONCLUSIONS: The natural history of CF lung disease over 18 months varies widely between subjects. Factors including genotype may affect natural history as well as the effectiveness of mediators and could be an important confounder if not recognized. These findings suggest that the use of CT scanning as an outcome surrogate for CF lung disease in young children may be more challenging than has been previously recognized.

Volume-monitored chest CT: a simplified method for obtaining motion-free images near full inspiratory and end expiratory lung volumes.

BACKGROUND: Lung inflation and respiratory motion during chest CT affect diagnostic accuracy and reproducibility. OBJECTIVE: To describe a simple volume-monitored (VM) method for performing reproducible, motion-free full inspiratory and end expiratory chest CT examinations in children. MATERIALS AND METHODS: Fifty-two children with cystic fibrosis (mean age 8.8 ± 2.2 years) underwent pulmonary function tests and inspiratory and expiratory VM-CT scans (1.25-mm slices, 80-120 kVp, 16-40 mAs) according to an IRB-approved protocol. The VM-CT technique utilizes instruction from a respiratory therapist, a portable spirometer and real-time documentation of lung volume on a computer. CT image quality was evaluated for achievement of targeted lung-volume levels and for respiratory motion. RESULTS: Children achieved 95% of vital capacity during full inspiratory imaging. For end expiratory scans, 92% were at or below the child's end expiratory level. Two expiratory exams were judged to be at suboptimal volumes. Two inspiratory (4%) and three expiratory (6%) exams showed respiratory motion. Overall, 94% of scans were performed at optimal volumes without respiratory motion. CONCLUSION: The VM-CT technique is a simple, feasible method in children as young as 4 years to achieve reproducible high-quality full inspiratory and end expiratory lung CT images.

Mucus plugging, air trapping, and bronchiectasis are important outcome measures in assessing progressive childhood cystic fibrosis lung disease.

OBJECTIVE: To determine which outcome measures could detect early progression of disease in school-age children with mild cystic fibrosis (CF) lung disease over a two-year time interval utilizing chest computed tomography (CT) scores, quantitative CT air trapping (QAT), and spirometric measurements. METHODS: Thirty-six school-age children with mild CF lung disease (median [interquartile range] age 12 [3.7] years; percent predicted forced expiratory volume in 1 second (ppFEV1 ) 99 [12.5]) were evaluated by serial spirometer-controlled chest CT scans and spirometry at baseline, 3-month, 1- and 2-years. RESULTS: No significant changes were noted at 3-month for any variable except for decreased ppFEV1 . Mucus plugging score (MPS) and QATA1andA2 increased at 1- and 2-years. The bronchiectasis score (BS), and total score (TS) were increased at 2-year. All variables tested with the exception of bronchial wall thickness score, parenchymal score (PS), and ppFEV1 , were consistent with longitudinal worsening of lung disease. Multivariate analysis revealed baseline PS, baseline TS, and 1-year changes in BS and air trapping score were predictive of 2-year changes in BS. CONCLUSIONS: MPS and QATA1-A2 were the most sensitive indicators of progressive childhood CF lung disease. The 1-year change in the bronchiectasis score had the most positive predictive power for 2-year change in bronchiectasis.

Multivariate analysis applied to the study of spatial distributions found in drug-eluting stent coatings by confocal Raman microscopy.

Multivariate data analysis was applied to confocal Raman measurements on stents coated with the polymers and drug used in the CYPHER Sirolimus-eluting Coronary Stents. Partial least-squares (PLS) regression was used to establish three independent calibration curves for the coating constituents: sirolimus, poly(n-butyl methacrylate) [PBMA], and poly(ethylene-co-vinyl acetate) [PEVA]. The PLS calibrations were based on average spectra generated from each spatial location profiled. The PLS models were tested on six unknown stent samples to assess accuracy and precision. The wt % difference between PLS predictions and laboratory assay values for sirolimus was less than 1 wt % for the composite of the six unknowns, while the polymer models were estimated to be less than 0.5 wt % difference for the combined samples. The linearity and specificity of the three PLS models were also demonstrated with the three PLS models. In contrast to earlier univariate models, the PLS models achieved mass balance with better accuracy. This analysis was extended to evaluate the spatial distribution of the three constituents. Quantitative bitmap images of drug-eluting stent coatings are presented for the first time to assess the local distribution of components.

Usefulness of multidetector CT imaging to assess vascular stents in children with congenital heart disease: an in vivo and in vitro study.

OBJECTIVE: To evaluate varying CT settings to visualize pediatric vascular stents in comparison to digital angiography (DA). BACKGROUND: There is a great clinical interest in substituting noninvasive methods to follow up children with congenital heart disease after interventional treatment. MATERIALS AND METHODS: CT studies in small children with transcatheter placed stents were reviewed, retrospectively. Furthermore, eight stents were implanted in tubes and partially obstructed. CT exams were performed on varying scanners (4 up to 64 slices) with corresponding tube settings. The effects of dose on image quality were evaluated regarding stent size, strut thickness, and in-stent stenoses in comparison to DA. RESULTS: Fourteen children with 28 implanted stents were identified. Significant differences between higher and lower radiation settings were not found, corresponding with the phantom, where moderate tube setting showed the best results. In vitro, there was an improvement with increasing number of detector rows, which resulted in a decrease of stent strut overestimation (295% down to 201%; P < 0.0001) and a better agreement with DA measurements for mild (78% up to 91%; P = 0.003) and moderate in-stent stenoses (80% up to 99%; P = 0.0001). CONCLUSION: Higher radiation exposure settings did not improve image quality, suggesting that the exams could be performed at a lower radiation dose.

CT of pediatric vascular stents used to treat congenital heart disease.

OBJECTIVE: The purpose of our study was to assess the visibility of lumen narrowing of pediatric vascular stents using various CT dose parameters in an in vitro model. MATERIALS AND METHODS: Ten steel stents of varying designs and sizes commonly used in the treatment of congenital heart disease were implanted in polyvinyl chloride (PVC) tubes and three of the 10 stents were partially obstructed with wax by filling 25% (mild) to 60% (moderate) of the lumen with contrast material. On a 64-MDCT scanner, the stents were scanned at tube voltages (kVp) of 80, 100, and 120 and at tube currents (mA) of 40, 80, 120, and 160. CT measurements of inner-stent diameter, strut thickness, and percent lumen (in-stent) stenoses were compared with biplane fluoroscopy of digital angiography. RESULTS: The stent diameter and percent stenosis on all CT images were consistently smaller than measured on digital angiography but were highly correlated (r = 0.97; p < 0.0001) with improvement as stent diameter increased (93% agreement with digital angiography for 4-mm stent, up to 99% for 25-mm stent; p = 0.001). Moderate stenosis could be assessed better than mild stenosis (99% vs 91% agreement with digital angiography; p = 0.003). Increasing exposure settings improved CT correlation of all measurements for mA up to 120 and kVp up to 100 (98.1% agreement). Higher settings did not improve accuracy (93.9% for 160 mA at 120 kVp; p = 0.03). CONCLUSION: CT is feasible to assess lumen narrowing of pediatric vascular stents at a wide range of tube settings. The study suggests that it is possible to lower the radiation exposure settings without loss in image quality or accuracy in detecting in-stent stenoses.

Imaging evolution of airway disorders in children.

This article discusses and illustrates the insights gained from CT imaging of the lungs in infants and young children who do not have respiratory motion and at end-inspiratory and resting end-expiratory lung volumes using noninvasive controlled ventilation CT technique. The potential role of noninvasive controlled ventilation CT in developing quantitative measures of airway disease is highlighted and clinical examples demonstrating the use of the technique are shown.

Computed tomography correlates with improvement with ivacaftor in cystic fibrosis patients with G551D mutation.

BACKGROUND: Ivacaftor corrects the cystic fibrosis transmembrane conductance regulator (CFTR) gating defect associated with G551D mutation and is quickly becoming an important treatment in patients with cystic fibrosis (CF) due to this genetic mutation. METHODS: A single-center study was performed in CF patients receiving ivacaftor to evaluate the usefulness of high resolution computed tomography (HRCT) of the chest as a way to gauge response to ivacaftor therapy. RESULTS: Ten patients with CF were enrolled for at least one year before and after starting ivacaftor. At time of enrollment, mean age was 20.9 ± 10.8 (range 10-44) years. There were significant improvements from baseline to 6 months in mean %FVC (93 ± 16 to 99 ± 16) and %FEV1 (79 ± 26 to 87 ± 28) but reverted to baseline at one year. Mean sweat chloride levels decreased significantly from baseline to one year. Mean weight and BMI improved at 6 months. Weight continued to improve with stabilization of BMI at one year. Chest HRCT showed significant improvement at one year in mean modified Brody scores for bronchiectasis, mucous plugging, airway wall thickness, and total Brody scores. Elevated bronchiectasis and airway wall thickness scores correlated significantly with lower %FEV1, while higher airway wall thickness and mucus plugging scores correlated with more pulmonary exacerbations requiring IV and oral antibiotics respectively. CONCLUSIONS: Based on our findings, HRCT imaging is a useful tool in monitoring response to ivacaftor therapy that corrects the gating defect associated with the G551D-CFTR mutation.

Detrimental effects of secondhand smoke exposure on infants with cystic fibrosis.

RATIONALE: Secondhand smoke (SHS) has deleterious respiratory, immune, and nutritional effects in children, but there is little data regarding the effects of SHS exposure in infants with cystic fibrosis (CF). METHODS: A retrospective chart review was undertaken from 2008 to 2012 of 75 infants with CF. Growth, lung function, Chest CT imaging, and microbiologic characteristics were compared between 4 and 12 months for SHS and non-SHS exposed patients. RESULTS: SHS exposed infants with CF had decreased growth between 4 and 12 months compared to non-SHS exposed infants. SHS exposure was associated with increased bronchodilator responsiveness and air trapping, but no other lung function or radiologic differences. SHS exposure was also associated with increased methicillin resistant Staphylococcus aureus (MRSA) and anaerobic growth on respiratory culture. There was no difference in Pseudomonas aeruginosa between groups. There were no differences in antibiotic use or hospitalizations between the groups. CONCLUSIONS: SHS exposure in CF infants is associated with diminished growth, increased air trapping and bronchodilator responsiveness, and propensity to culture MRSA and facultative anaerobic bacteria, suggesting the need for early, aggressive parental smoking cessation interventions to prevent SHS exposure complications.

Lateral thoracic expansion for Jeune syndrome: evidence of rib healing and new bone formation.

BACKGROUND: Lateral thoracic expansion is a procedure that has been described to enlarge the thoracic cage in patients with Jeune's asphyxiating thoracic dystrophy. The procedure involves separating ribs from their periosteum and plating them together in an expanded fashion with titanium struts. We have speculated that the ribs heal in this situation, despite the absence of surrounding periosteum, and that new rib formation occurs in the liberated periosteum. METHODS: Radiographic studies of patients who have undergone lateral thoracic expansion were reviewed for evidence of rib healing or periosteal new bone formation. RESULTS: This study presents radiologic evidence that rib healing actually occurs, as does periosteal ossification. CONCLUSIONS: Lateral thoracic expansion creates additional chest wall that is formed of autologous tissue, fully healed, and not ultimately dependent on titanium struts.

Image analysis for cystic fibrosis: automatic lung airway wall and vessel measurement on CT images.

Cystic Fibrosis (CF) is the most common lethal genetic disorder in the Caucasian population, affecting about 30,000 people in the United States. It results in inflammation, hence thickening of airway (AW) walls. It has been demonstrated that AW inflammation begins early in life producing structural AW damage. Because this damage can be present in patients who are relatively asymptomatic, lung disease can progress insidiously. High-resolution computed tomographic imaging has also shown that the AWs of infants and young children with CF have thicker walls and are more dilated than those of normal children. The purpose of this study was to develop computerized methods which allow rapid, efficient and accurate assessment of computed tomographic AW and vessel (V) dimensions from axial CT lung images. For this purpose, a full-width-half-max based automatic AW and V size measurement method was developed. The only user input required is approximate center marking of AW and V by an expert. The method was evaluated on a patient population of 4 infants and 4 children with different stages of mild CF related lung disease. This new automated method for assessing early AW disease in infants and children with CF represents a potentially useful outcome measure for future intervention trials.

An airway phantom to standardize CT acquisition in multicenter clinical trials.

RATIONALE AND OBJECTIVES: The purpose of this study was to demonstrate the use of a phantom to standardize low-dose chest computed tomographic (CT) protocols in children with cystic fibrosis. MATERIALS AND METHODS: Spiral chest CT scans of a Plexiglas phantom simulating airway sizes (internal diameter, 1.1-16.4 mm; wall thickness, 0.4-4.6 mm) in children with cystic fibrosis were obtained using two multidetector CT (MDCT) scanners (GE VCT and Siemens Sensation 64). Quantitative airway measurements from both scanners were compared with micro-CT airway measurements over a range of doses (0.2-1.8 mSv) to evaluate bias and variance of measurements. The effective doses for CT protocols were estimated using the ImPACT CT Patient Dosimetry Calculator. RESULTS: Both MDCT scanners were able to accurately measure airway sizes down to 3 mm internal diameter and 1.3 mm airway wall thickness, with errors of <3.5%. ImPACT estimates of effective dose were different for the MDCT scanners for a given peak tube voltage and product of tube current and exposure time. Accuracy and precision were not found to be associated with dose parameters for either machine. Bias in all measurements was strongly associated with airway diameter (P values < .00001), but the magnitude of bias was small (mean, 0.07 mm; maximum, 0.21 mm). Differences between machines in error components were on the order of a few micrometers. CONCLUSIONS: The use of a standard airway phantom confirms that different MDCT scanners have similar results within dose ranges planned for potential future clinical trials. Standardized protocols can be developed that adjust for differences in radiation exposure for different MDCT scanners.

High-resolution computed tomography of the lung in children with cystic fibrosis: technical factors.

A standard technique that controls for respiratory motion and lung volumes during imaging is necessary if high-resolution computed tomography is to be used as an outcome measure in children with cystic fibrosis. End-inspiratory and expiratory imaging allows for the detection and differentiation of early lung disease. In children ages 0-5 years, a noninvasive controlled ventilation technique is ideal, and can be used in combination with raised-volume infant pulmonary function tests. In older children, a spirometric-assisted or spirometric-triggered technique should be used. With optimal technique, radiation dose settings (kVp and mA) can be lowered to achieve a diagnostic screening high-resolution computed tomography of the lungs at a dose equivalent to that of the chest radiograph.

Computed tomography dose and variability of airway dimension measurements: how low can we go?

BACKGROUND: Quantitative CT shows promise as an outcome measure for cystic fibrosis (CF) lung disease in infancy, but must be accomplished at a dose as low as reasonably achievable. OBJECTIVE: To determine the feasibility of ultra-low-dose CT for quantitative measurements of airway dimensions. MATERIALS AND METHODS: Two juvenile pigs were anesthetized and their lungs scanned at 25 cm H(2)O face-mask pressure in apnoea using beam currents of 5, 10, 20, 40 and 100 mAs. The lumen diameters and wall thicknesses of matched airways (n=22) at each dose were measured by two observers using validated software. Measurement variability at each dose was compared to that at 100 mAs (reference dose) for large and small airways (lumen diameter <2.5 mm). RESULTS: Lowering CT dose (mAs) affected measurement variability for lumen diameter of small and large airways (P<0.001) and for wall thickness of small (P<0.001), but not large (P=0.63), airways. To obtain the same measurement variability at 5 mAs as at 100 mAs, four to six small airways or one to three large airways have to be measured and averaged. CONCLUSION: Quantitative airway measurements are feasible on images obtained at as low as 5 mAs, but more airways need to be measured to compensate for greater measurement variability.

Monozygotic twins with discordant intestinal rotation.

Previous case reports have suggested a strong concordance of intestinal malrotation among identical twins. This has led to the recommendation that the asymptomatic twin undergo screening when malrotation is discovered in the identical sibling. We present a case of monozygotic twins in which one twin presented with intestinal malrotation with midgut volvulus while the other twin was found to have normal gastrointestinal anatomy.