Characterizing Lung Parenchymal Aeration via Standardized Signal Intensity from Free-breathing 4D Dynamic MRI in Phantoms, Healthy Children, and Pediatric Patients with Thoracic Insufficiency Syndrome.

Purpose To investigate free-breathing thoracic bright-blood four-dimensional (4D) dynamic MRI (dMRI) to characterize aeration of parenchymal lung tissue in healthy children and patients with thoracic insufficiency syndrome (TIS). Materials and Methods All dMR images in patients with TIS were collected from July 2009 to June 2017. Standardized signal intensity (sSI) was investigated, first using a lung aeration phantom to establish feasibility and sensitivity and then in a retrospective research study of 40 healthy children (16 male, 24 female; mean age, 9.6 years ± 2.1 [SD]), 20 patients with TIS before and after surgery (11 male, nine female; mean age, 6.2 years ± 4.2), and another 10 healthy children who underwent repeated dMRI examinations (seven male, three female; mean age, 9 years ± 3.6). Individual lungs in 4D dMR images were segmented, and sSI was assessed for each lung at end expiration (EE), at end inspiration (EI), preoperatively, postoperatively, in comparison to normal lungs, and in repeated scans. Results Air content changes of approximately 6% were detectable in phantoms via sSI. sSI within phantoms significantly correlated with air occupation (Pearson correlation coefficient = -0.96 [P < .001]). For healthy children, right lung sSI was significantly lower than that of left lung sSI (at EE: 41 ± 6 vs 47 ± 6 and at EI: 39 ± 6 vs 43 ± 7, respectively; P < .001), lung sSI at EI was significantly lower than that at EE (P < .001), and left lung sSI at EE linearly decreased with age (r = -0.82). Lung sSI at EE and EI decreased after surgery for patients (although not statistically significantly, with P values of sSI before surgery vs sSI after surgery, left and right lung separately, in the range of 0.13-0.51). sSI varied within 1.6%-4.7% between repeated scans. Conclusion This study demonstrates the feasibility of detecting change in sSI in phantoms via bright-blood dMRI when air occupancy changes. The observed reduction in average lung sSI after surgery in pediatric patients with TIS may indicate postoperative improvement in parenchymal aeration. Keywords: MR Imaging, Thorax, Lung, Pediatrics, Thoracic Surgery, Lung Parenchymal Aeration, Free-breathing Dynamic MRI, MRI Intensity Standardization, Thoracic Insufficiency Syndrome Supplemental material is available for this article. © RSNA, 2024.

Do Rib-Based Anchors Impair Chest Wall Motion in Early Onset Scoliosis (EOS)?

Purpose: There is a concern in pediatric surgery practice that rib-based fixation may limit chest wall motion in early onset scoliosis (EOS). The purpose of this study is to address the above concern by assessing the contribution of chest wall excursion to respiration before and after surgery. Methods: Quantitative dynamic magnetic resonance imaging (QdMRI) is performed on EOS patients (before and after surgery) and normal children in this retrospective study. QdMRI is purely an image-based approach and allows free breathing image acquisition. Tidal volume parameters for chest walls (CWtv) and hemi-diaphragms (Dtv) were analyzed on concave and convex sides of the spinal curve. EOS patients (1-14 years) and normal children (5-18 years) were enrolled, with an average interval of two years for dMRI acquisition before and after surgery. Results: CWtv significantly increased after surgery in the global comparison including all EOS patients (p < 0.05). For main thoracic curve (MTC) EOS patients, CWtv significantly improved by 50.24% (concave side) and 35.17% (convex side) after age correction (p < 0.05) after surgery. The average ratio of Dtv to CWtv on the convex side in MTC EOS patients was not significantly different from that in normal children (p=0.78), although the concave side showed the difference to be significant. Conclusion: Chest wall component tidal volumes in EOS patients measured via QdMRI did not decrease after rib-based surgery, suggesting that rib-based fixation does not impair chest wall motion in pediatric patients with EOS.

Virtual Growing Child (VGC): A general normative comparative system via quantitative dynamic MRI for quantifying pediatric regional respiratory anomalies with application in thoracic insufficiency syndrome (TIS).

Background: A normative database of regional respiratory structure and function in healthy children does not exist. Methods: VGC provides a database with four categories of regional respiratory measurement parameters including morphological, architectural, dynamic, and developmental. The database has 3,820 3D segmentations (around 100,000 2D slices with segmentations). Age and gender group analysis and comparisons for healthy children were performed using those parameters via two-sided t-testing to compare mean measurements, for left and right sides at end-inspiration (EI) and end-expiration (EE), for different age and gender specific groups. We also apply VGC measurements for comparison with TIS patients via an extrapolation approach to estimate the association between measurement and age via a linear model and to predict measurements for TIS patients. Furthermore, we check the Mahalanobis distance between TIS patients and healthy children of corresponding age. Findings: The difference between male and female groups (10-12 years) behave differently from that in other age groups which is consistent with physiology/natural growth behavior related to adolescence with higher right lung and right diaphragm tidal volumes for females(p<0.05). The comparison of TIS patients before and after surgery show that the right and left components are not symmetrical, and the left side diaphragm height and tidal volume has been significantly improved after surgery (p <0.05). The left lung volume at EE, and left diaphragm height at EI of TIS patients after surgery are closer to the normal children with a significant smaller Mahalanobis distance (MD) after surgery (p<0.05). Interpretation: The VGC system can serve as a reference standard to quantify regional respiratory abnormalities on dMRI in young patients with various respiratory conditions and facilitate treatment planning and response assessment. Funding: The grant R01HL150147 from the National Institutes of Health (PI Udupa).

Assessment of 3D hemi-diaphragmatic motion via free-breathing dynamic MRI in pediatric thoracic insufficiency syndrome.

Purpose: Thoracic insufficiency syndrome (TIS) affects ventilatory function due to spinal and thoracic deformities limiting lung space and diaphragmatic motion. Corrective orthopedic surgery can be used to help normalize skeletal anatomy, restoring lung space and diaphragmatic motion. This study employs free-breathing dynamic MRI (dMRI) and quantifies the 3D motion of each hemi-diaphragm surface in normal and TIS patients, and evaluates effects of surgical intervention. Materials and Methods: In a retrospective study of 149 pediatric patients with TIS and 190 healthy children, we constructed 4D images from free-breathing dMRI and manually delineated the diaphragm at end-expiration (EE) and end-inspiration (EI) time points. We automatically selected 25 points uniformly on each hemi-diaphragm surface, calculated their relative velocities between EE and EI, and derived mean velocities in 13 homologous regions for each hemi-diaphragm to provide measures of regional 3D hemi-diaphragm motion. T-testing was used to compare velocity changes before and after surgery, and to velocities in healthy controls. Results: The posterior-central region of the right hemi-diaphragm exhibited the highest average velocity post-operatively. Posterior regions showed greater velocity changes after surgery in both right and left hemi-diaphragms. Surgical reduction of thoracic Cobb angle displayed a stronger correlation with changes in diaphragm velocity than reduction in lumbar Cobb angle. Following surgery, the anterior regions of the left hemi-diaphragm tended to approach a more normal state. Conclusion: Quantification of regional motion of the 3D diaphragm surface in normal subjects and TIS patients via free-breathing dMRI is feasible. Derived measurements can be assessed in comparison to normal subjects to study TIS and the effects of surgery.

Assessment of Regional Functional Effects of Surgical Treatment in Thoracic Insufficiency Syndrome via Dynamic Magnetic Resonance Imaging.

BACKGROUND: Quantitative regional assessment of thoracic function would enable clinicians to better understand the regional effects of therapy and the degree of deviation from normality in patients with thoracic insufficiency syndrome (TIS). The purpose of this study was to determine the regional functional effects of surgical treatment in TIS via quantitative dynamic magnetic resonance imaging (MRI) in comparison with healthy children. METHODS: Volumetric parameters were derived via 129 dynamic MRI scans from 51 normal children (November 2017 to March 2019) and 39 patients with TIS (preoperatively and postoperatively, July 2009 to May 2018) for the left and right lungs, the left and right hemi-diaphragms, and the left and right hemi-chest walls during tidal breathing. Paired t testing was performed to compare the parameters from patients with TIS preoperatively and postoperatively. Mahalanobis distances between parameters of patients with TIS and age-matched normal children were assessed to evaluate the closeness of patient lung function to normality. Linear regression functions were utilized to estimate volume deviations of patients with TIS from normality, taking into account the growth of the subjects. RESULTS: The mean Mahalanobis distances for the right hemi-diaphragm tidal volume (RDtv) were -1.32 ± 1.04 preoperatively and -0.05 ± 1.11 postoperatively (p = 0.001). Similarly, the mean Mahalanobis distances for the right lung tidal volume (RLtv) were -1.12 ± 1.04 preoperatively and -0.10 ± 1.26 postoperatively (p = 0.01). The mean Mahalanobis distances for the ratio of bilateral hemi-diaphragm tidal volume to bilateral lung tidal volume (BDtv/BLtv) were -1.68 ± 1.21 preoperatively and -0.04 ± 1.10 postoperatively (p = 0.003). Mahalanobis distances decreased after treatment, suggesting reduced deviations from normality. Regression results showed that all volumes and tidal volumes significantly increased after treatment (p < 0.001), and the tidal volume increases were significantly greater than those expected from normal growth for RDtv, RLtv, BDtv, and BLtv (p < 0.05). CONCLUSIONS: Postoperative tidal volumes of bilateral lungs and bilateral hemi-diaphragms of patients with TIS came closer to those of normal children, indicating positive treatment effects from the surgical procedure. Quantitative dynamic MRI facilitates the assessment of regional effects of a surgical procedure to treat TIS. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

QdMRI: A system for comprehensive analysis of thoracic dynamics via dynamic MRI.

Quantitative thoracic dynamic magnetic resonance imaging (QdMRI), a recently developed technique, provides a potential solution for evaluating treatment effects in thoracic insufficiency syndrome (TIS). In this paper, we integrate all related algorithms and modules during our work from the past 10 years on TIS into one system, named QdMRI, to address the following questions: (1) How to effectively acquire dynamic images? For many TIS patients, subjects are unable to cooperate with breathing instructions during image acquisition. Image acquisition can only be implemented under free-breathing conditions, and it is not feasible to use a surrogate device for tracing breathing signals. (2) How to assess the thoracic structures from the acquired image, such as lungs, left and right, separately? (3) How to depict the dynamics of thoracic structures due to respiration motion? (4) How to use the structural and functional information for the quantitative evaluation of surgical TIS treatment and for the design of the surgery plan? The QdMRI system includes 4 major modules: dynamic MRI (dMRI) acquisition, 4D image construction, image segmentation (from 4D image), and visualization of segmentation results, dynamic measurements, and comparisons of measurements from TIS patients with those from normal children. Scanning/image acquisition time for one subject is ~20 minutes, 4D image construction time is ~5 minutes, image segmentation of lungs via deep learning is 70 seconds for all time points (with the average DICE 0.96 in healthy children), and measurement computation time is 2 seconds.

OFx: A method of 4D image construction from free-breathing non-gated MRI slice acquisitions of the thorax via optical flux.

PURPOSE: Since real-time 4D dynamic magnetic resonance imaging (dMRI) methods with adequate spatial and temporal resolution for imaging the pediatric thorax are currently not available, free-breathing slice acquisitions followed by appropriate 4D construction methods are currently employed. Self-gating methods, which extract breathing signals only from image information without any external gating technology, have much potential for this purpose, such as for use in studying pediatric thoracic insufficiency syndrome (TIS). Patients with TIS frequently suffer from extreme malformations of the chest wall, diaphragm, and spine, leading to breathing that is very complex, including deep or shallow respiratory cycles. Existing 4D construction methods cannot perform satisfactorily in this scenario, and most are not fully automatic, requiring manual interactive operations. In this paper, we propose a novel fully automatic 4D image construction method based on an image-derived concept called flux to address these challenges. METHODS: We utilized 25 dMRI data sets from 25 pediatric subjects with no known thoracic anomalies and 58 dMRI data sets from 29 patients with TIS where each patient had a dMRI scan before and after surgery. A time sequence of 80 slices are acquired at each sagittal location continuously at a rate of ~480 ms per slice under free-breathing conditions, with 30-40 sagittal locations across the chest for each subject depending on the thoracic size. In our approach, we first extract the breathing signal for each sagittal location based on the flux of the optical flow vector field of the body region from the image time series. Here, for each time point of respiratory phase, the net flux of the body region can be regarded as the flux going into or out of the body region, which we term Optical Flux (OFx). OFx provides a very robust representation of the real breathing motion of the thorax. OFx allows us to perform a full analysis of all respiratory cycles, extract only normal cycles in a robust manner, and map all extracted normal cycles on to one cosine respiration model for each sagittal location. Subsequently, we re-sample one normal cycle from the respiration model for each location independently. The normal cycle models associated with the different sagittal locations are finally composited to form the final constructed 4D image. RESULTS: We employ several metrics to evaluate the quality of the 4D construction results: Eie - error in locating time instants corresponding to end inspiration and end expiration; Eto - deviation from correct temporal order in each detected normal cycle; Ess - deviation in spatial smoothness; and Esc - deviation from spatial continuity as scored by a reader. The means and standard deviations of these metrics for normal subjects and TIS patients are found to be, respectively: Eie: 0.25 ± 0.05 and 0.38 ± 0.16 in units of time instance (ideal value = 0); Eto: 2.7% ± 2.3% and 1.8% ± 2% (ideal value = 0%); Ess: 0.5 ± 0.17 and 0.54 ± 0.25 in pixel units (ideal value = 0); Esc: 4.6 ± 0.48 and 4.56 ± 0.98 (score range: best = 5, worst = 1). The results show that the OFx method achieves excellent spatial and temporal continuity and its yield was 100% meaning that it successfully performed 4D construction on every data set tested. Compared to a recently published method, OFx is fully automatic requiring about 5 min of computational time per study starting from acquired dMRI scans. The method achieves high temporal and spatial continuity even on complex TIS data sets that include many abnormal respiratory cycles. CONCLUSIONS: A new 4D dMRI construction method based on the concept of optical flux is presented which is fully automatic and very robust in deriving respiratory signals purely from dynamic image sequences even when presented with complex breathing patterns due to severe disease conditions like TIS. Evaluations show that its accuracy is comparable to the variations found in manual annotations. An important characteristic of the method is that it is independent of the number of sagittal locations used in the construction process, which suggests that it is applicable to imaging techniques where data are acquired at only a few sagittal locations instead of the full width of the thorax. The method is not tied to any specific imaging modality, as demonstrated in this paper on not just dMRI but dynamic computed tomography (CT) as well.

Understanding Respiratory Restrictions as a Function of the Scoliotic Spinal Curve in Thoracic Insufficiency Syndrome: A 4D Dynamic MR Imaging Study.

BACKGROUND: Over the past 100 years, many procedures have been developed for correcting restrictive thoracic deformities which cause thoracic insufficiency syndrome. However, none of them have been assessed by a robust metric incorporating thoracic dynamics. In this paper, we investigate the relationship between radiographic spinal curve and lung volumes derived from thoracic dynamic magnetic resonance imaging (dMRI). Our central hypothesis is that different anteroposterior major spinal curve types induce different restrictions on the left and right lungs and their dynamics. METHODS: Retrospectively, we included 25 consecutive patients with thoracic insufficiency syndrome (14 neuromuscular, 7 congenital, 4 other) who underwent vertical expandable prosthetic titanium rib surgery and received preimplantation and postimplantation thoracic dMRI for clinical care. We measured thoracic and lumbar major curves by the Cobb measurement method from anteroposterior radiographs and classified the curves as per Scoliosis Research Society (SRS)-defined curve types. From 4D dMRI images, we derived static volumes and tidal volumes of left and right lung, along with left and right chest wall and left and right diaphragm tidal volumes (excursions), and analyzed their association with curve type and major curve angles. RESULTS: Thoracic and lumbar major curve angles ranged from 0 to 136 and 0 to 116 degrees, respectively. A dramatic postoperative increase in chest wall and diaphragmatic excursion was seen qualitatively. All components of volume increased postoperatively by up to 533%, with a mean of 70%. As the major curve, main thoracic curve (MTC) was associated with higher tidal volumes (effect size range: 0.7 to 1.0) than thoracolumbar curve (TLC) in preoperative and postoperative situation. Neither MTC nor TLC showed any meaningful correlation between volumes and major curve angles preoperatively or postoperatively. Moderate correlations (0.65) were observed for specific conditions like volumes at end-inspiration or end-expiration. CONCLUSIONS: The relationships between component tidal volumes and the spinal curve type are complex and are beyond intuitive reasoning and guessing. TLC has a much greater influence on restricting chest wall and diaphragm tidal volumes than MTC. Major curve angles are not indicative of passive resting volumes or tidal volumes. LEVEL OF EVIDENCE: Level II-diagnostic.

Thoracic growth deficiency in childhood cancer survivors may cause overestimation of lung disease.

INTRODUCTION: Survivors of childhood cancers undergo routine pulmonary function testing as they are at an increased lifetime risk for significant lung disease. However, this population also demonstrates growth abnormalities that could influence the interpretation of these tests, as reference equations are based on standing height. We aim to determine the impact of the relative thoracic growth deficiency in childhood cancer survivors on the interpretation of pulmonary function testing. METHODS: Standing height and upper segment length (USL) in childhood cancer survivors undergoing pulmonary function testing at a single academic center were compared to age-matched historical standards. Additionally, pulmonary function tests were compared to reference values generated from standing height and doubled USL. RESULTS: Data were obtained from 107 cancer survivors. While the subjects demonstrated an overall 6.8% lower standing height vs historical standards, they also demonstrated relative thoracic growth abnormality with a further 9.9% decrement in the ratio USL to standing height. The use of doubled upper segment length as a surrogate measure for standing height in pulmonary function reference equations decreased the number of patients with restrictive lung disease as indicated by spirometry. CONCLUSIONS: Childhood cancer survivors have disproportionately worse thoracic growth deficiency vs appendicular growth deficiency. As a result, their USL is disproportionately short for their standing height, which is most commonly used in pulmonary function testing reference equations. This leads to an increased likelihood in these patients meeting pulmonary function test criteria for restrictive lung disease.

Identifying and treating intrinsic PEEP in infants with severe bronchopulmonary dysplasia.

RATIONALE: Infants with severe bronchopulmonary dysplasia (sBPD) and airway obstruction may develop dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi ), which impairs patient/ventilator synchrony. OBJECTIVES: To determine if PEEPi is present in infants with sBPD during spontaneous breathing and if adjusting ventilator PEEP improves patient/ventilator synchrony and comfort. METHODS: Interventional study in infants with sBPD. PEEPi measured by esophageal pressure (Pes) and pneumotachometer, during pressure-supported breaths. PEEP i defined as the difference between Pes at start of the inspiratory effort minus Pes at onset of inspiratory flow. The set PEEP was adjusted to minimize PEEP i . "Best PEEP" was the setting with minimal wasted efforts (WE), an inspiratory effort seen on the Pes waveform without a corresponding ventilator breath. FiO 2 and SpO 2 measured pre- and post-PEEP adjustment. Sedation requirements evaluated 72 hours preprocedure and postprocedure. RESULTS: Twelve infants were assessed (gestational age, 24.9 ± 1.4 weeks; study age, 48.8 ± 1.5 weeks, postmenstrual age). Mean baseline ventilator PEEP was 16.4 cm H2 O (14-20 cm H 2 O). Eight infants required an increase, one, a reduction, and three, no change in the set PEEP. For the eight infants requiring an increase in set PEEP, there was an 18.9% reduction in WE and a reduction in FiO 2 (0.084 ± 0.058) requirements in the subsequent 24 hours. Conditional sedation was reduced in five infants postprocedure. No adverse events occurred during testing. CONCLUSION: PEEPi is measurable in infants with sBPD with concurrent esophageal manometry and flow-time tracings without the need for pharmacological paralysis. In those with PEEP i , increasing ventilator PEEP to offset PEEP i improves synchrony.

Quantitative dynamic MRI (QdMRI) Volumetric Analysis of Pediatric Patients with Thoracic Insufficiency Syndrome.

The lack of standardizable objective diagnostic measurement techniques is a major hurdle in the assessment and treatment of pediatric patients with thoracic insufficiency syndrome (TIS). The aim of this paper is to explore quantitative dynamic MRI (QdMRI) volumetric parameters derived from thoracic dMRI in pediatric patients with TIS and the relationships between dMRI parameters and clinical measurements. 25 TIS patients treated with vertical expandable prosthetic titanium rib (VEPTR) surgery are included in this retrospective study. Left and right lungs at end-inspiration and end-expiration are segmented from constructed 4D dMRI images. Lung volumes and excursion (or tidal) volumes of the left/right chest wall and hemi-diaphragms are computed. Commonly used clinical parameters include thoracic and lumbar Cobb angles and respiratory measurements from pulmonary function testing (PFT). 200 3D lungs in total (left & right, pre-operative & post-operative, end-inspiration & end-expiration) are segmented for analysis. Our analysis indicates that change of resting breathing rate (RR) following surgery is negatively correlated with that of QdMRI parameters. Chest wall tidal volumes and hemi-diaphragm tidal volumes increase significantly following surgery. Clinical parameter RR reduced after surgical treatment with P values around 0.06 but no significant differences were found on other clinical parameters. The significant increase in post-operative tidal volumes suggests a treatment-related improvement in lung capacity. The reduction of RR following surgery shows that breathing function is improved. The QdMRI parameters may offer an objective marker set for studying TIS, which is currently lacking.

Upper Airway Vibration Perception in School-Aged Children with Obstructive Sleep Apnea.

STUDY OBJECTIVES: Children with the obstructive sleep apnea (OSA) have impaired upper airway two-point discrimination compared to controls. In addition, blunted vibration threshold detection (VT) in the palate has been recognized in adults with OSA, but has not been studied in children. Both findings are indicative of a defect in the afferent limb of the upper airway dilator reflex that could prevent upper airway dilation secondary to airway loading, resulting in airway collapse. We hypothesized that children with OSA have impaired palate VT compared to controls, and that this improves after OSA treatment. METHODS: Case-control study. Children with OSA and healthy non-snoring controls underwent polysomnography and palate VT measurements. Children with OSA were retested after adenotonsillectomy. RESULTS: 29 children with OSA (median [interquartile range] age = 9.5 [7.5-12.6] years, obstructive apnea-hypopnea index [OAHI] = 11.3 [5.7-19.5] events/h, BMI z = 1.8 [1.3-2.1]) and 32 controls (age = 11.2 [9.3-13.5] years, P = 0.1; OAHI = 0.5 [0.1-0.7] events/h, P < 0.001; BMI z = 1 [0.3-1.7], P = 0.004) were tested. OSA palate VT (1.0 [0.8-1.5] vibration units) was similar to that of controls (1 [0.8-1.3], P = 0.37). 20 children with OSA were retested 4.4 (3.2-7.1) months after treatment. OAHI decreased from 13.1 (5.8-19) to 0.6 (0.2-2.5) events per hour (P < 0.001) postoperatively, but palate VT did not change (before = 1 [0.7-1.5], after = 1.2 [0.8-1.4], P = 0.37). CONCLUSIONS: Children with OSA and controls have similar palate VT. Unlike in adults, palate VT does not seem to be affected by childhood OSA.

Airway Resistance in Children with Obstructive Sleep Apnea Syndrome.

STUDY OBJECTIVES: Enlarged tonsils and adenoids, the main cause of obstructive sleep apnea syndrome (OSAS) in children, results in upper airway (UA) loading. This contributes to the imbalance between structural and neuromotor factors ultimately leading to UA collapse during sleep. However, it is unknown whether this UA loading can cause elevated airway resistance (AR) during wakefulness. We hypothesized that children with OSAS have elevated AR compared to controls and that this improves after OSAS treatment. METHODS: Case control study performed at an academic hospital. Children with OSAS and nonsnoring healthy controls underwent baseline polysomnography and spirometry, and AR measurement by body plethysmography while breathing via an orofacial mask. Children with OSAS repeated the previously mentioned tests after adenotonsillectomy. RESULTS: 31 OSAS participants (mean age ± SD = 9.7 ± 3.0 y, obstructive apnea-hypopnea index (OAHI) median [range] = 14.9 [2-58.7] events/h, body mass index [BMI] z = 1.5 ± 1) and 31 controls (age = 10.5 ± 2.5 y, P = 0.24; OAHI = 0.4 [0-1.4], P < 0.001; BMI z = 0.9 ± 1, P = 0.01) were tested. OSAS AR at baseline was 3.9 [1.5-10.3] cmH2O/L/sec and controls 2.8 [1.4 - 6.2] (P = 0.027). Both groups had similar spirometry results. 20 patients with OSAS were tested 6.4 ± 6.6 mo after adenotonsillectomy. OAHI decreased from 15.2 [2.1-58.7] to 0.5 [0 - 5.1] events/h postoperatively (P < 0.001), and AR decreased from 4.3 [1.5 - 10.3] to 2.8 [1.7 - 4.7] cmH2O/L/sec (P = 0.009). CONCLUSIONS: Children with OSAS have elevated AR that decreases after treatment. This is likely because of upper airway loading secondary to adenotonsillar hypertrophy and may contribute to the increased frequency of respiratory diseases in untreated children with OSAS.

Respiratory cortical processing to inspiratory resistances during wakefulness in children with the obstructive sleep apnea syndrome.

Children with the obstructive sleep apnea syndrome (OSAS) have impaired respiratory afferent cortical processing during sleep that persists after treatment of OSAS. However, it is unknown whether this impairment is present during wakefulness and, if so, whether it improves after OSAS treatment. We hypothesized that children with OSAS, during wakefulness, have abnormal cortical processing of respiratory stimuli manifested by blunted respiratory-related evoked potentials (RREP) and that this resolves after OSAS treatment. We measured RREP during wakefulness in 26 controls and 21 children with OSAS before and after treatment. Thirteen participants with OSAS repeated testing 3-6 mo after adenotonsillectomy. RREP were elicited by interruption of inspiration by total occlusion and 30 and 20 cmH2O/l per s resistances. Nf at Fz latency elicited by occlusion was longer in children with OSAS at baseline compared with controls (78.8 ± 24.8 vs. 63.9 ± 19.7 ms, P = 0.05). All other peak amplitudes and latencies were similar between the two groups. After OSAS treatment, Nf at Fz latency elicited by 30 cmH2O/l per s decreased significantly (before, 88 ± 26 vs. after, 71 ± 25 ms, P = 0.02), as did that elicited by 20 cmH2O/l per s (85 ± 27 vs. 72 ± 24 ms, P = 0.004). The amplitude of N1 at Cz elicited by occlusion increased from -3.4 ± 5.6 to -7.4 ± 3 µV (P = 0.049) after treatment. We concluded that children with OSAS have partial delay of respiratory afferent cortical processing during wakefulness that improves after treatment.

Pilot study of nasal expiratory positive airway pressure devices for the treatment of childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Alternative therapies for childhood obstructive sleep apnea syndrome (OSAS) are needed as OSAS may persist despite adenotonsillectomy, and continuous positive airway pressure (CPAP) adherence is low. Nasal expiratory positive airway pressure (NEPAP) devices have not been studied in children. We hypothesized that NEPAP would result in polysomnographic improvement. Further, we aimed to determine NEPAP adherence, effects on sleepiness, behavior, and quality of life. METHODS: A randomized, double-blind, placebo-controlled, crossover pilot study was performed. CPAP candidates, 8-16 years old, underwent NEPAP and placebo polysomnograms. Subjects with ≥ 50% reduction in the apnea hypopnea index (AHI) from placebo to NEPAP night or AHI < 5/h on NEPAP night wore NEPAP at home for 30 days. Adherence was assessed by daily phone calls/emails and collecting used devices. RESULTS: Fourteen subjects (age 13.4 ± 1.9 years, BMI z-scores 2.2 ± 1 [mean ± SD]) were studied. There was significant improvement in the obstructive apnea index with NEPAP vs. placebo: 0.6 (0-21.1)/h vs. 4.2 (0-41.9)/h (median [range], p = 0.010) and trends for improvement in other polysomnographic parameters. However, responses were variable, with 3 subjects not improving and 2 worsening. Older children and those with less hypercapnia had a better response. Eight subjects were sent home with devices; one was lost to follow-up, and adherence in the remainder was 83% of nights; these subjects had a significant improvement in sleepiness and quality of life. CONCLUSIONS: NEPAP devices are a potential alternative therapy for OSAS in a small subset of children. Due to variability in individual responses, efficacy of NEPAP should be evaluated with polysomnography. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT01768065.

Computational fluid dynamics endpoints for assessment of adenotonsillectomy outcome in obese children with obstructive sleep apnea syndrome.

BACKGROUND: Improvements in obstructive sleep apnea syndrome (OSAS) severity may be associated with improved pharyngeal fluid mechanics following adenotonsillectomy (AT). The study objective is to use image-based computational fluid dynamics (CFD) to model changes in pharyngeal pressures after AT, in obese children with OSAS and adenotonsillar hypertrophy. METHODS: Three-dimensional models of the upper airway from nares to trachea, before and after AT, were derived from magnetic resonance images obtained during wakefulness, in a cohort of 10 obese children with OSAS. Velocity, pressure, and turbulence fields during peak tidal inspiratory flow were computed using commercial software. CFD endpoints were correlated with polysomnography endpoints before and after AT using Spearman׳s rank correlation (rs). RESULTS: Apnea hypopnea index (AHI) decreases after AT was strongly correlated with reduction in maximum pressure drop (dPTAmax) in the region where tonsils and adenoid constrict the pharynx (rs=0.78, P=0.011), and with decrease of the ratio of dPTAmax to flow rate (rs=0.82, P=0.006). Correlations of AHI decrease to anatomy, negative pressure in the overlap region (including nasal flow resistance), or pressure drop through the entire pharynx, were not significant. In a subgroup of subjects with more than 10% improvement in AHI, correlations between flow variables and AHI decrease were stronger than in all subjects. CONCLUSIONS: The correlation between change in dPTAmax and improved AHI suggests that dPTAmax may be a useful index for internal airway loading due to anatomical narrowing, and may be better correlated with AHI than direct airway anatomic measurements.

Computational fluid dynamics endpoints to characterize obstructive sleep apnea syndrome in children.

Computational fluid dynamics (CFD) analysis may quantify the severity of anatomical airway restriction in obstructive sleep apnea syndrome (OSAS) better than anatomical measurements alone. However, optimal CFD model endpoints to characterize or assess OSAS have not been determined. To model upper airway fluid dynamics using CFD and investigate the strength of correlation between various CFD endpoints, anatomical endpoints, and OSAS severity, in obese children with OSAS and controls. CFD models derived from magnetic resonance images were solved at subject-specific peak tidal inspiratory flow; pressure at the choanae was set by nasal resistance. Model endpoints included airway wall minimum pressure (Pmin), flow resistance in the pharynx (Rpharynx), and pressure drop from choanae to a minimum cross section where tonsils and adenoids constrict the pharynx (dPTAmax). Significance of endpoints was analyzed using paired comparisons (t-test or Wilcoxon signed rank test) and Spearman correlation. Fifteen subject pairs were analyzed. Rpharynx and dPTAmax were higher in OSAS than control and most significantly correlated to obstructive apnea-hypopnea index (oAHI), r = 0.48 and r = 0.49, respectively (P < 0.01). Airway minimum cross-sectional correlation to oAHI was weaker (r = -0.39); Pmin was not significantly correlated. CFD model endpoints based on pressure drops in the pharynx were more closely associated with the presence and severity of OSAS than pressures including nasal resistance, or anatomical endpoints. This study supports the usefulness of CFD to characterize anatomical restriction of the pharynx and as an additional tool to evaluate subjects with OSAS.

Changes in gastric pressure and volume during mechanical in-exsufflation.

BACKGROUND/PURPOSE: A mechanical insufflator-exsufflator (MI-E) is used to replicate spontaneous cough in weak or neurologically impaired patients. Its use is often withheld after abdominal surgery because of concerns for potential wound dehiscence from abdominal distension or development of excessive abdominal positive pressure. We hypothesized that gastric pressure during MI-E use would not exceed usual pressures generated during a spontaneous cough. METHODS: Thirteen subjects 0.8-23.1 years (mean 10.5 years) with neuromuscular weakness, pre-existing gastrostomy tube, and established MI-E routine were studied. A pressure transducer through the gastrostomy tube measured gastric pressure (Pgas) during MI-E treatment. Chest and abdominal volume change was assessed by respiratory inductance plethysmography. In three subjects, the same measurements were made during spontaneous cough. RESULTS: The maximum Pgas was 24 cm with applied pressures of 20-40 cm. In the three subjects able to cough, the maximum Pgas achieved during the spontaneous maneuver was 25 cm, a value higher than they achieved with MI-E treatment. CONCLUSION: MI-E resulted in less positive abdominal pressure than has been described in healthy subjects during spontaneous coughing. As such, use of an MI-E device should be considered safe to use in the post-operative period following abdominal surgery in patients with neuromuscular weakness.

Upper airway lymphoid tissue size in children with sickle cell disease.

BACKGROUND: The prevalence of obstructive sleep apnea syndrome (OSAS) is higher in children with sickle cell disease (SCD) as compared with the general pediatric population. It has been speculated that overgrowth of the adenoid and tonsils is an important contributor. METHODS: The current study used MRI to evaluate such an association. We studied 36 subjects with SCD (aged 6.9 ± 4.3 years) and 36 control subjects (aged 6.6 ± 3.4 years). RESULTS: Compared with control subjects, children with SCD had a significantly smaller upper airway (2.8 ± 1.2 cm(3) vs 3.7 ± 1.6 cm(3), P < .01), and significantly larger adenoid (8.4 ± 4.1 cm(3) vs 6.0 ± 2.2 cm(3), P < .01), tonsils (7.0 ± 4.3 cm(3) vs 5.1 ± 1.9 cm(3), P < .01), retropharyngeal nodes (3.0 ± 1.9 cm(3) vs 2.2 ± 0.9 cm(3), P < .05), and deep cervical nodes (15.7 ± 5.7 cm(3) vs 12.7 ± 4.0 cm(3), P < .05). Polysomnography showed that 19.4% (seven of 36) of children with SCD had OSAS compared with 0% (zero of 20) of control subjects (P < .05) and that in children with SCD the apnea-hypopnea index correlated positively with upper airway lymphoid tissues size (r = 0.57, P < 001). In addition, children with SCD had lower arterial oxygen saturation nadir (84.3% ± 12.3% vs 91.2% ± 4.2%, P < .05), increased peak end-tidal CO(2) (53.4 ± 8.5 mm Hg vs 42.3 ± 5.3 mm Hg, P < .001), and increased arousals (13.7 ± 4.7 events/h vs 10.8 ± 3.8 events/h, P < .05). CONCLUSIONS: Children with SCD have reduced upper airway size due to overgrowth of the surrounding lymphoid tissues, which may explain their predisposition to OSAS.

Upper airway structure and body fat composition in obese children with obstructive sleep apnea syndrome.

RATIONALE: Mechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood. OBJECTIVES: The aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS. METHODS: Magnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS. MEASUREMENTS AND MAIN RESULTS: We studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues. CONCLUSIONS: Upper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.