Cortical thickness and hippocampal volume in adolescent children with obstructive sleep apnea.

STUDY OBJECTIVES: Intermittent hypoxia and sleep fragmentation due to obstructive sleep apnea (OSA) may contribute to oxidative tissue damage and apoptotic neuronal cell death, inflammation, and intracellular edema in the brain. We examined whether OSA in overweight and obese adolescent children is associated with cortical thickness and hippocampal structure compared to overweight and obese controls and whether OSA severity is associated with measures of brain integrity. METHODS: We calculated cortical thickness and hippocampal subfield volumes from T1-weighted images of 45 controls (age 15.43 ±â€…1.73 years, 21 male) and 53 adolescent children with OSA (age 15.26 ±â€…1.63 years, 32 male) to investigate the association of childhood OSA with the alteration of cortical structure and hippocampal subfield structural changes. In addition, we investigated the correlation between OSA severity and cortical thickness or hippocampal subfield volume using Pearson's correlation analysis. RESULTS: We found cortical thinning in the right superior parietal area of adolescent children with OSA (cluster size 32.29 mm2, cluster-wise corrected p-value = .030) that was negatively correlated with apnea-hypopnea index (AHI) (R=-0.27, p-value = .009) and arousal index (R=-0.25, p-value = .014). In addition, the volume of the right subiculum-head area of the hippocampus of adolescent children with OSA was larger than controls (0.19 ±â€…0.02 ml vs. 0.18 ±â€…0.02 ml, ß = 13.79, false discovery rate corrected p-value = .044), and it was positively correlated with AHI (R = 0.23, p-value = .026) and arousal index (R = 0.31, p-value = .002). CONCLUSIONS: Our findings provide evidence for OSA-associated brain structure alterations in adolescent children prior to the onset of treatment that likely have important implications for timely intervention and continued monitoring of health outcomes.

Altered cortical structure network in children with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent airway collapse during sleep, resulting in intermittent hypoxia and sleep fragmentation that may contribute to alternations in brain structure and function. We hypothesized that OSA in children reorganizes and alters cortical structure, which can cause changes in cortical thickness correlation between brain regions across subjects. METHODS: We constructed cortical structure networks based on cortical thickness measurements from 41 controls (age 15.54 ±â€…1.66 years, male 19) and 50 children with OSA (age 15.32 ±â€…1.65 years, male 29). The global (clustering coefficient [CC], path length, and small-worldness) and regional (nodal betweenness centrality, NBC) network properties and hub region distributions were examined between groups. RESULTS: We found increased CCs in OSA compared to controls across a wide range of network densities (p-value < .05) and lower NBC area under the curve in left caudal anterior cingulate, left caudal middle frontal, left fusiform, left transverse temporal, right pars opercularis, and right precentral gyri (p-value < .05). In addition, while most of the hub regions were the same between groups, the OSA group had fewer hub regions and a different hub distribution compared to controls. CONCLUSIONS: Our findings suggest that children with OSA exhibit altered global and regional network characteristics compared to healthy controls. Our approach to the investigation of cortical structure in children with OSA could prove useful in understanding the etiology of OSA-related brain functional disorders.

Insulin sensitivity and obstructive sleep apnea in adolescents with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) in adults is linked with insulin resistance (IR) and obstructive sleep apnea (OSA). However, less is known about these associations in adolescents. METHODS: We studied 3 groups of adolescents: 27 obese PCOS (OPCOS) (ages 13-21)11 normal-weight PCOS (NPCOS) (ages 13-21 years), and 8 healthy controls (ages 18-21 years). A hyperinsulinemic euglycemic clamp study was performed in all groups to determine IR by insulin sensitivity (M/I). Polysomnography was performed to assess for OSA in OPCOS and NPCOS groups. We compared indices of IR among all groups and OSA among OPCOS, and NPCOS. RESULTS: We noted that OPCOS and NPCOS and controls differed significantly in their IR. M/I was significantly lower in OPCOS vs. controls (p=0.0061), and also lower for NPCOS vs control but this approached but did not reach statistical significance (p=0.084). In addition, none of the NPCOS subjects had OSA compared to 42% of OPCOS (p=0.03). CONCLUSIONS: Our study suggests OPCOS adolescents have increased IR compared to controls and NPCOS subjects. Higher IR for NPCOS vs controls approached but did not reach statistical significance. Larger studies are needed. In addition, adolescents with OPCOS are at a high risk for OSA.

Automatic upper airway segmentation in static and dynamic MRI via anatomy-guided convolutional neural networks.

PURPOSE: Upper airway segmentation on MR images is a prerequisite step for quantitatively studying the anatomical structure and function of the upper airway and surrounding tissues. However, the complex variability of intensity and shape of anatomical structures and different modes of image acquisition commonly used in this application makes automatic upper airway segmentation challenging. In this paper, we develop and test a comprehensive deep learning-based segmentation system for use on MR images to address this problem. MATERIALS AND METHODS: In our study, both static and dynamic MRI data sets are utilized, including 58 axial static 3D MRI studies, 22 mid-retropalatal dynamic 2D MRI studies, 21 mid-retroglossal dynamic 2D MRI studies, 36 mid-sagittal dynamic 2D MRI studies, and 23 isotropic dynamic 3D MRI studies, involving a total of 160 subjects and over 20 000 MRI slices. Samples of static and 2D dynamic MRI data sets were randomly divided into training, validation, and test sets by an approximate ratio of 5:2:3. Considering that the variability of annotation data among 3D dynamic MRIs was greater than for other MRI data sets, we increased the ratio of training data for these data to improve the robustness of the model. We designed a unified framework consisting of the following procedures. For static MRI, a generalized region-of-interest (GROI) strategy is applied to localize the partitions of nasal cavity and other portions of upper airway in axial data sets as two separate subobjects. Subsequently, the two subobjects are segmented by two separate 2D U-Nets. The two segmentation results are combined as the whole upper airway structure. The GROI strategy is also applied to other MRI modes. To minimize false-positive and false-negative rates in the segmentation results, we employed a novel loss function based explicitly on these rates to train the segmentation networks. An inter-reader study is conducted to test the performance of our system in comparison to human variability in ground truth (GT) segmentation of these challenging structures. RESULTS: The proposed approach yielded mean Dice coefficients of 0.84±0.03, 0.89±0.13, 0.84±0.07, and 0.86±0.05 for static 3D MRI, mid-retropalatal/mid-retroglossal 2D dynamic MRI, mid-sagittal 2D dynamic MRI, and isotropic dynamic 3D MRI, respectively. The quantitative results show excellent agreement with manual delineation results. The inter-reader study results demonstrate that the segmentation performance of our approach is statistically indistinguishable from manual segmentations considering the inter-reader variability in GT. CONCLUSIONS: The proposed method can be utilized for routine upper airway segmentation from static and dynamic MR images with high accuracy and efficiency. The proposed approach has the potential to be employed in other dynamic MRI-related applications, such as lung or heart segmentation.

Upper airway effective compliance during wakefulness and sleep in obese adolescents studied via two-dimensional dynamic MRI and semiautomated image segmentation.

Novel biomarkers of upper airway biomechanics may improve diagnosis of obstructive sleep apnea syndrome (OSAS). Upper airway effective compliance (EC), the slope of cross-sectional area versus pressure estimated using computational fluid dynamics (CFD), correlates with apnea-hypopnea index (AHI) and critical closing pressure (Pcrit). The study objectives are to develop a fast, simplified method for estimating EC using dynamic MRI and physiological measurements and to explore the hypothesis that OSAS severity correlates with mechanical compliance during wakefulness and sleep. Five obese children with OSAS and five control subjects with obesity aged 12-17 yr underwent anterior rhinomanometry, polysomnography, and dynamic MRI with synchronized airflow measurement during wakefulness and sleep. Airway cross section in retropalatal and retroglossal section images was segmented using a novel semiautomated method that uses optimized singular value decomposition (SVD) image filtering and k-means clustering combined with morphological operations. Pressure was estimated using rhinomanometry Rohrer's coefficients and flow rate, and EC was calculated from the area-pressure slope during five normal breaths. Correlations between apnea-hypopnea index (AHI), EC, and cross-sectional area (CSA) change were calculated using Spearman's rank correlation. The semiautomated method efficiently segmented the airway with average Dice Coefficient above 89% compared with expert manual segmentation. AHI correlated positively with EC at the retroglossal site during sleep (rs = 0.74, P = 0.014) and with change of EC from wake to sleep at the retroglossal site (rs = 0.77, P = 0.01). CSA change alone did not correlate significantly with AHI. EC, a mechanical biomarker which includes both CSA change and pressure variation, is a potential diagnostic biomarker for studying and managing OSAS.NEW & NOTEWORTHY This study investigated the dynamics of the upper airway at retropalatal and retroglossal sites during wakefulness and sleep by evaluating the effective compliance (EC) of each site and its correlation with apnea-hypopnea index (AHI) using novel semiautomated image processing. AHI correlated significantly with retroglossal EC during sleep and change of retroglossal EC from wake to sleep. The results suggest EC as a promising noninvasive diagnostic marker for estimating the mechanical properties of various upper airway regions in patients with OSAS.

Prevalence of elevated right ventricular pressure in children with obstructive sleep apnea syndrome undergoing pulmonary hypertension screening.

STUDY OBJECTIVES: Our objective was to determine the prevalence of elevated right ventricular pressure (RVP) as a surrogate marker for pulmonary hypertension in children with obstructive sleep apnea syndrome (OSAS) undergoing echocardiography. METHODS: This was a retrospective chart review of children ages 2-21 years diagnosed with OSAS by an overnight polysomnogram who underwent cardiac echocardiogram to screen for pulmonary hypertension within 6 months of polysomnogram in a tertiary inner-city pediatric hospital. The primary outcome was elevated RVP defined by estimated RVP ≥ 25 mm Hg above right atrial pressure or ventricular septal configuration consistent with elevated RVP. RESULTS: A total of 174 children were included. The median (interquartile range) age was 8.9 (5.5-13.1) years with 59.2% male, 41.4% Hispanic, and 25.9% non-Hispanic Black patients. The prevalence of obesity was 72.0% and severe or very severe OSAS was present in 93.1%. The median (interquartile range) apnea-hypopnea index was 28.3 events/h (18.8-52.7 events/h). Seven children (4.0%) had elevated RVP. There was no association between elevated RVP and age, sex, race, body mass index percentile, apnea-hypopnea index, oxygen nadir, or severe OSAS (apnea-hypopnea index ≥ 10 events/h). CONCLUSIONS: Elevated RVP was rare and was not associated with OSAS severity. The prevalence in this cohort is higher than the prevalence of pulmonary hypertension noted in similar studies (0%-1.8%), which may be related to differences in methodology or unassessed cohort characteristics. Further effort to determine the optimal role for pulmonary hypertension screening in pediatric OSAS is needed. CITATION: Bitners AC, Arens R, Mahgerefteh J, et al. Prevalence of elevated right ventricular pressure in children with obstructive sleep apnea syndrome undergoing pulmonary hypertension screening. J Clin Sleep Med. 2021;17(11):2225-2232.

Segmentation of 4D images via space-time neural networks.

Medical imaging techniques currently produce 4D images that portray the dynamic behaviors and phenomena associated with internal structures. The segmentation of 4D images poses challenges different from those arising in segmenting 3D static images due to different patterns of variation of object shape and appearance in the space and time dimensions. In this paper, different network models are designed to learn the pattern of slice-to-slice change in the space and time dimensions independently. The two models then allow a gamut of strategies to actually segment the 4D image, such as segmentation following just the space or time dimension only, or following first the space dimension for one time instance and then following all time instances, or vice versa, etc. This paper investigates these strategies in the context of the obstructive sleep apnea (OSA) application and presents a unified deep learning framework to segment 4D images. Because of the sparse tubular nature of the upper airway and the surrounding low-contrast structures, inadequate contrast resolution obtainable in the magnetic resonance (MR) images leaves many challenges for effective segmentation of the dynamic airway in 4D MR images. Given that these upper airway structures are sparse, a Dice coefficient (DC) of ~0.88 for their segmentation based on our preferred strategy is similar to a DC of >0.95 for large non-sparse objects like liver, lungs, etc., constituting excellent accuracy.

Effect of sleep on upper airway dynamics in obese adolescents with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: The biomechanical basis of obstructive sleep apnea syndrome (OSAS) may influence upper airway dynamics. In this study, we investigate dynamic changes during respiration in wakefulness and sleep in obese adolescents with and without OSAS. METHODS: Respiratory-gated dynamic magnetic resonance imaging (MRI) at the retropalatal and retroglossal regions was performed with simultaneous measurement of SpO2 and nasal-oral mask airflow and pressure. Airway cross-sectional area (CSA) was determined using AMIRA. Percent change in CSA was calculated from five continuous tidal breaths in states of wakefulness and sleep. Mixed effects models were used to evaluate interactions between group (OSAS/control), site (retropalatal/retroglossal), and stage (wake/sleep). RESULTS: We studied 24 children with OSAS (mean age 15.49 ± 2.00 years, mean apnea-hypopnea index [AHI] 16.53 ± 8.72 events/h) and 19 controls (mean age 14.86 ± 1.75 years, mean AHI 2.12 ± 1.69 events/h). Groups were similar in age, sex, height, weight, and BMI Z-score. Participants with OSAS had a 48.17% greater increase in percent change of airway CSA during sleep than controls (p < 0.0001), while there was no difference between groups during wakefulness (p = 0.6589). Additionally, participants with OSAS had a 48.80% increase in percent change of airway CSA during sleep as compared with wakefulness (p < 0.0001), whereas no such relationship was observed in controls (p = 0.5513). CONCLUSIONS: This study demonstrates significant effects of sleep on upper airway dynamics in obese children with OSAS. Dynamic MRI with physiological data can potentially provide further insight into the biomechanical basis of OSAS and assist in more effective management.

The relationship of hypertension with obesity and obstructive sleep apnea in adolescents.

OBJECTIVES: To assess the independent relationships of obesity and obstructive sleep apnea (OSA) with hypertension/elevated blood pressure (EBP) in adolescent patients. STUDY DESIGN: A retrospective cohort analysis was performed on 501 patients (age 13-21 years) with three separate blood pressure measurements within 6 months of polysomnography. EBP was defined as average systolic blood pressure (SBP) ≤120 mm Hg; obesity as body mass index Z-score ≤1.65; and OSA as obstructive apnea-hypopnea index <1. Pearson correlations and multivariable analyses were performed to assess the independent effects of the apnea-hypopnea index and body mass index Z-score on SBP. RESULTS: Of 501 patients (mean age 16 ± 2 years), 246 (49%) were male. OSA was present in 329 (66%) patients, obesity in 337 (67%), and EBP in 262 (52%). EBP was present in 70% of obese adolescents and 60% of adolescents with OSA. Univariable correlation showed a significant relationship between SBP, body mass index Z-score, and apnea-hypopnea index. Multivariable linear regression analysis showed blood pressure was significantly associated with body mass index Z-score (ß = .46; P < .01), age (ß = .25; P < .01), and height Z-score (ß = .14; P < .01), but not apnea-hypopnea index (ß = .01; P = .72). CONCLUSIONS: The relationship between OSA and EBP in adolescents is most closely associated with the degree of obesity. Further studies are needed to assess the effect of the treatment of obesity and OSA on blood pressure in adolescents.

Association Between Periodic Limb Movements in Sleep and Cerebrovascular Changes in Children With Sickle Cell Disease.

STUDY OBJECTIVES: Periodic limb movements (PLMs) have been associated with increased risk of stroke, but there is currently scarce research exploring this relationship in the setting of sickle cell disease (SCD). The aim of this study was to explore whether increased PLMs in children with SCD are associated with increased risk of cerebrovascular disease and to determine if there are any clinical or laboratory differences between children with SCD with elevated periodic limb movement index (PLMI) versus those with normal PLMI. METHODS: This study is a comprehensive review of medical records of 129 children with SCD (aged ≤ 18 years) who had undergone polysomnography for evaluation of sleep-disordered breathing. RESULTS: Elevated PLMI (PLMI > 5 events/h) was present in 42% (54/129) of children with SCD. Children with elevated PLMI were found to have higher percentage of hemoglobin S, lower total iron, higher arousal index and tendency toward elevated transcranial Doppler velocity (P = .063, odds ratio = 3.9, 95% CI 0.93-16.22). While association between elevated PLMI and isolated cerebrovascular stenosis (P = .050, odds ratio 5.6, 95% CI 1.0-31.10) trended toward significance, there was significantly greater proportion of children with elevated PLMI who had cerebrovascular stenosis with Moyamoya disease (P = .046) as demonstrated by magnetic resonance imaging (MRI). CONCLUSIONS: The prevalence of elevated PLMI in children with SCD was higher than in previously published data. Elevated PLMI was significantly associated with greater rates of cerebrovascular disease as detected by MRI.

Biomechanics of the soft-palate in sleep apnea patients with polycystic ovarian syndrome.

Highly compliant tissue supporting the pharynx and low muscle tone enhance the possibility of upper airway occlusion in children with obstructive sleep apnea (OSA). The present study describes subject-specific computational modeling of flow-induced velopharyngeal narrowing in a female child with polycystic ovarian syndrome (PCOS) with OSA and a non-OSA control. Anatomically accurate three-dimensional geometries of the upper airway and soft-palate were reconstructed for both subjects using magnetic resonance (MR) images. A fluid-structure interaction (FSI) shape registration analysis was performed using subject-specific values of flow rate to iteratively compute the biomechanical properties of the soft-palate. The optimized shear modulus for the control was 38 percent higher than the corresponding value for the OSA patient. The proposed computational FSI model was then employed for planning surgical treatment for the apneic subject. A virtual surgery comprising of a combined adenoidectomy, palatoplasty and genioglossus advancement was performed to estimate the resulting post-operative patterns of airflow and tissue displacement. Maximum flow velocity and velopharyngeal resistance decreased by 80 percent and 66 percent respectively following surgery. Post-operative flow-induced forces on the anterior and posterior faces of the soft-palate were equilibrated and the resulting magnitude of tissue displacement was 63 percent lower compared to the pre-operative case. Results from this pilot study indicate that FSI computational modeling can be employed to characterize the mechanical properties of pharyngeal tissue and evaluate the effectiveness of various upper airway surgeries prior to their application.

Sleep and Breathing the First Night After Adenotonsillectomy in Obese Children With Obstructive Sleep Apnea.

STUDY OBJECTIVES: There are few studies measuring postoperative respiratory complications in obese children with obstructive sleep apnea (OSA) undergoing adenotonsillectomy (AT). These complications are further compounded by perioperative medications. Our objective was to study obese children with OSA for their respiratory characteristics and sleep architecture on the night of AT. METHODS: This was a prospective study at a tertiary pediatric hospital between January 2009-February 2012. Twenty obese children between 8-17 years of age with OSA and adenotonsillar hypertrophy were recruited. Patients underwent baseline polysomnography (PSG) and AT with or without additional debulking procedures, followed by a second PSG on the night of surgery. Demographic and clinical variables, surgical details, perioperative anesthetics and analgesics, and PSG respiratory and sleep architecture parameters were recorded. Statistical tests included Pearson correlation coefficient for correlation between continuous variables and chi-square and Wilcoxon rank-sum tests for differences between groups. RESULTS: Baseline PSG showed OSA with mean obstructive apnea-hypopnea index (oAHI) 27.1 ± 22.9, SpO2 nadir 80.1 ± 7.9%, and sleep fragmentation-arousal index 25.5 ± 22.0. Postoperatively, 85% of patients had abnormal sleep studies similar to baseline, with postoperative oAHI 27.0 ± 34.3 (P = .204), SpO2 nadir, 82.0 ± 8.7% (P = .462), and arousal index, 24.3 ± 24.0 (P = .295). Sleep architecture was abnormal after surgery, showing a significant decrease in REM sleep (P = .003), and a corresponding increase in N2 (P = .017). CONCLUSIONS: Obese children undergoing AT for OSA are at increased risk for residual OSA on the night of surgery. Special considerations should be taken for postoperative monitoring and treatment of these children. COMMENTARY: A commentary on this article appears in this issue on page 775.

The Effects of Obstructive Sleep Apnea Syndrome on the Dentate Gyrus and Learning and Memory in Children.

Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but the underlying pathology is unknown. We hypothesized that OSAS would affect the dentate gyrus, a hippocampal subdivision essential to neurogenesis and cognition, and that this impact would further affect cognitive function in children. In children with OSAS (n = 11) and control subjects (n = 12; age and sex matched), we performed diffusion tensor imaging and structural MRI, polysomnography, and neuropsychological assessments. We found that OSAS was associated with decreased mean diffusivity of the left dentate gyrus (p = 0.002; false discovery rate corrected; adjusting for sex, age, and body mass index), showing a large effect size (partial η2 = 0.491), but not with any other structural measures across the brain. Decreased dentate gyrus mean diffusivity correlated with a higher apnea hypopnea index (Spearman's r = -0.50, p = 0.008) and a greater arousal index (r = -0.44, p = 0.017). OSAS did not significantly affect neuropsychological measures (p values >0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity (r = 0.54, p = 0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on verbal learning capacity. Finally, the diagnostic accuracy of a regression model based on dentate gyrus mean diffusivity reached 85.8% (cross validated). This study demonstrates a likely pathway of effects of OSAS on neurocognitive function in children, as well as potential utility of the dentate gyrus mean diffusivity as an early marker of brain pathology in children with OSAS.SIGNIFICANCE STATEMENT In this study we investigate the relationships between dentate gyrus structure, hippocampus-dependent cognition, and obstructive sleep apnea syndrome (OSAS). We demonstrate lower mean diffusivity of the dentate gyrus in children with OSAS, which correlates with a lower verbal learning and memory score. This study provides new evidence of disrupted microstructure of the dentate gyrus in children with OSAS that may help explain some of the neurocognitive deficits described in these children.

MR Image Analytics to Characterize the Upper Airway Structure in Obese Children with Obstructive Sleep Apnea Syndrome.

PURPOSE: Quantitative image analysis in previous research in obstructive sleep apnea syndrome (OSAS) has focused on the upper airway or several objects in its immediate vicinity and measures of object size. In this paper, we take a more general approach of considering all major objects in the upper airway region and measures pertaining to their individual morphological properties, their tissue characteristics revealed by image intensities, and the 3D architecture of the object assembly. We propose a novel methodology to select a small set of salient features from this large collection of measures and demonstrate the ability of these features to discriminate with very high prediction accuracy between obese OSAS and obese non-OSAS groups. MATERIALS AND METHODS: Thirty children were involved in this study with 15 in the obese OSAS group with an apnea-hypopnea index (AHI) = 14.4 ± 10.7) and 15 in the obese non-OSAS group with an AHI = 1.0 ± 1.0 (p<0.001). Subjects were between 8-17 years and underwent T1- and T2-weighted magnetic resonance imaging (MRI) of the upper airway during wakefulness. Fourteen objects in the vicinity of the upper airways were segmented in these images and a total of 159 measurements were derived from each subject image which included object size, surface area, volume, sphericity, standardized T2-weighted image intensity value, and inter-object distances. A small set of discriminating features was identified from this set in several steps. First, a subset of measures that have a low level of correlation among the measures was determined. A heat map visualization technique that allows grouping of parameters based on correlations among them was used for this purpose. Then, through T-tests, another subset of measures which are capable of separating the two groups was identified. The intersection of these subsets yielded the final feature set. The accuracy of these features to perform classification of unseen images into the two patient groups was tested by using logistic regression and multi-fold cross validation. RESULTS: A set of 16 features identified with low inter-feature correlation (< 0.36) yielded a high classification accuracy of 96% with sensitivity and specificity of 97.8% and 94.4%, respectively. In addition to the previously observed increase in linear size, surface area, and volume of adenoid, tonsils, and fat pad in OSAS, the following new markers have been found. Standardized T2-weighted image intensities differed between the two groups for the entire neck body region, pharynx, and nasopharynx, possibly indicating changes in object tissue characteristics. Fat pad and oropharynx become less round or more complex in shape in OSAS. Fat pad and tongue move closer in OSAS, and so also oropharynx and tonsils and fat pad and tonsils. In contrast, fat pad and oropharynx move farther apart from the skin object. CONCLUSIONS: The study has found several new anatomic bio-markers of OSAS. Changes in standardized T2-weighted image intensities in objects may imply that intrinsic tissue composition undergoes changes in OSAS. The results on inter-object distances imply that treatment methods should respect the relationships that exist among objects and not just their size. The proposed method of analysis may lead to an improved understanding of the mechanisms underlying OSAS.

Computational fluid dynamics upper airway effective compliance, critical closing pressure, and obstructive sleep apnea severity in obese adolescent girls.

Obstructive sleep apnea syndrome (OSAS) is associated with anatomical abnormalities restricting upper airway size and functional factors decreasing pharyngeal dilator activity in sleep. In this study we hypothesized that OSAS is also associated with altered pharyngeal mechanical compliance during wakefulness. Five OSAS and six control obese girls between 14 and 18 years of age were studied. All underwent polysomnography, critical closing pressure (Pcrit) studies, and dynamic MRI of the upper airway during awake tidal breathing. Effective airway compliance was defined as the slope of cross-sectional area vs. average pressure between maximum inspiration and maximum expiration along the pharyngeal airway. Pharyngeal pressure fields were calculated by using image-based computational fluid dynamics and nasal resistance. Spearman correlations were calculated to test associations between apnea-hypopnea index (AHI), Pcrit, and airway compliance. Effective compliances in the nasopharynx (CNP) and velopharynx (CVP) were lower and negative in OSAS compared with controls: -4.4 vs. 1.9 (mm2/cmH2O, P = 0.012) and -2.1 vs. 3.9 (mm2/cmH2O, P = 0.021), respectively, suggesting a strong phasic pharyngeal dilator activity during inspiration in OSAS compared with controls. For all subjects, CNP and AHI correlated negatively (rS = -0.69, P = 0.02), and passive Pcrit correlated with CNP (rS = -0.76, P = 0.006) and with AHI (rS = 0.86, P = 0.0006). Pharyngeal mechanics obtained during wakefulness could be used to characterize subjects with OSAS. Moreover, negative effective compliance during wakefulness and its correlation to AHI and Pcrit suggest that phasic dilator activity of the upper pharynx compensates for negative pressure loads in these subjects.

Minimally interactive segmentation of 4D dynamic upper airway MR images via fuzzy connectedness.

PURPOSE: There are several disease conditions that lead to upper airway restrictive disorders. In the study of these conditions, it is important to take into account the dynamic nature of the upper airway. Currently, dynamic magnetic resonance imaging is the modality of choice for studying these diseases. Unfortunately, the contrast resolution obtainable in the images poses many challenges for an effective segmentation of the upper airway structures. No viable methods have been developed to date to solve this problem. In this paper, the authors demonstrate a practical solution by employing an iterative relative fuzzy connectedness delineation algorithm as a tool. METHODS: 3D dynamic images were collected at ten equally spaced instances over the respiratory cycle (i.e., 4D) in 20 female subjects with obstructive sleep apnea syndrome. The proposed segmentation approach consists of the following steps. First, image background nonuniformities are corrected which is then followed by a process to correct for the nonstandardness of MR image intensities. Next, standardized image intensity statistics are gathered for the nasopharynx and oropharynx portions of the upper airway as well as the surrounding soft tissue structures including air outside the body region, hard palate, soft palate, tongue, and other soft structures around the airway including tonsils (left and right) and adenoid. The affinity functions needed for fuzzy connectedness computation are derived based on these tissue intensity statistics. In the next step, seeds for fuzzy connectedness computation are specified for the airway and the background tissue components. Seed specification is needed in only the 3D image corresponding to the first time instance of the 4D volume; from this information, the 3D volume corresponding to the first time point is segmented. Seeds are automatically generated for the next time point from the segmentation of the 3D volume corresponding to the previous time point, and the process continues and runs without human interaction and completes in 10 s for segmenting the airway structure in the whole 4D volume. RESULTS: Qualitative evaluations performed to examine smoothness and continuity of motions of the entire upper airway as well as its transverse sections at critical anatomic locations indicate that the segmentations are consistent. Quantitative evaluations of the separate 200 3D volumes and the 20 4D volumes yielded true positive and false positive volume fractions around 95% and 0.1%, respectively, and mean boundary placement errors under 0.5 mm. The method is robust to variations in the subjective action of seed specification. Compared with a segmentation approach based on a registration technique to propagate segmentations, the proposed method is more efficient, accurate, and less prone to error propagation from one respiratory time point to the next. CONCLUSIONS: The proposed method is the first demonstration of a viable and practical approach for segmenting the upper airway structures in dynamic MR images. Compared to registration-based methods, it effectively reduces error propagation and consequently achieves not only more accurate segmentations but also more consistent motion representation in the segmentations. The method is practical, requiring minimal user interaction and computational time.

Intracapsular and Extracapsular Tonsillectomy and Adenoidectomy in Pediatric Obstructive Sleep Apnea.

IMPORTANCE: Limited information exists regarding clinical outcomes of children undergoing extracapsular tonsillectomy and adenoidectomy (ETA) or intracapsular tonsillectomy and adenoidectomy (ITA) for treatment of obstructive sleep apnea syndrome (OSAS). OBJECTIVES: To quantify polysomnography (PSG) and clinical outcomes of ETA and ITA in children with OSAS and to assess the contribution of comorbid conditions of asthma and obesity. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using medical records at a tertiary pediatrics inner-city hospital. Medical records from 89 children who underwent ETA or ITA between October 1, 2008, and December 31, 2013, were analyzed. The dates of our analysis were January 6, 2014, to April 11, 2014. Inclusion criteria required no evidence of craniofacial or neurological disorders, confirmation of OSAS by PSG within the 2 years before surgery, and a second PSG within the 2 years after surgery. INTERVENTIONS: Each child underwent ETA or ITA after being evaluated by a pediatric otolaryngologist and obtaining written parental informed consent. MAIN OUTCOMES AND MEASURES: Main primary outcomes were derived from PSG. Secondary outcomes included treatment failure, defined as residual OSAS with an obstructive apnea-hypopnea index of at least 5 events per hour. Comparisons were made between and within groups. Logistic regression was used to identify factors associated with treatment failure. RESULTS: Fifty-two children underwent ETA, and 37 children underwent ITA. Children in the ETA group were older (7.5 vs 5.2 years, P = .001) and more obese (60% [31 of 52] vs 30% [11 of 37], P = .004). However, both groups had similar severity of OSAS, with median preoperative obstructive apnea-hypopnea indexes of 17.0 in the ETA group and 24.1 in the ITA group (P = .21), and similar prevalences of asthma (38% [20 of 52] vs 38% [14 of 37]). After surgery, significant improvement was noted on PSG in both groups, with no differences in any clinical outcomes. There was no association between procedure type, age, or body mass index z score and treatment failure. However, in a subset of patients with asthma and obesity, ITA was associated with residual OSAS (odds ratio, 16.5; 95% CI, 1.1-250.2; P = .04). CONCLUSIONS AND RELEVANCE: Both ETA and ITA are effective modalities to treat OSAS, with comparable surgical outcomes on short-term follow-up. However, when comorbid diagnoses of both asthma and obesity exist, OSAS is likely to be refractory to treatment with ITA compared with ETA.

Clinical utility of magnetic resonance imaging and ultrasonography for diagnosis of polycystic ovary syndrome in adolescent girls.

OBJECTIVE: To evaluate ovarian morphology using three-dimensional magnetic resonance imaging (MRI) in adolescent girls with and without polycystic ovary syndrome (PCOS). Also compare the utility of MRI versus ultrasonography (US) for diagnosis of PCOS. DESIGN: Cross-sectional study. SETTING: Urban academic tertiary-care children's hospital. PATIENT(S): Thirty-nine adolescent girls with untreated PCOS and 22 age/body mass index (BMI)-matched controls. INTERVENTION(S): Magnetic resonance imaging and/or transvaginal/transabdominal US. MAIN OUTCOME MEASURE(S): Ovarian volume (OV); follicle number per section (FNPS); correlation between OV on MRI and US; proportion of subjects with features of polycystic ovaries (PCOs) on MRI and US. RESULT(S): Magnetic resonance imaging demonstrated larger OV and higher FNPS in subjects with PCOS compared with controls. Within the PCOS group, median OV was 11.9 (7.7) cm(3) by MRI compared with 8.8 (7.8) cm(3) by US. Correlation coefficient between OV by MRI and US was 0.701. Due to poor resolution, FNPS could not be determined by US or compared with MRI. The receiver operating characteristic curve analysis for MRI demonstrated that increasing volume cutoffs for PCOs from 10-14 cm(3) increased specificity from 77%-95%. For FNPS on MRI, specificity increased from 82%-98% by increasing cutoffs from ≥ 12 to ≥ 17. Using Rotterdam cutoffs, 91% of subjects with PCOS met PCO criteria on MRI, whereas only 52% met criteria by US. CONCLUSION(S): Ultrasonography measures smaller OV than MRI, cannot accurately detect follicle number, and is a poor imaging modality for characterizing PCOs in adolescents with suspected PCOS. For adolescents in whom diagnosis of PCOS remains uncertain after clinical and laboratory evaluation, MRI should be considered as a diagnostic imaging modality.

Body-wide hierarchical fuzzy modeling, recognition, and delineation of anatomy in medical images.

To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide Automatic Anatomy Recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions - thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) - involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and testing data sets are divided into equal size in all cases except for the neck. Overall the AAR method achieves a mean accuracy of about 2 voxels in localizing non-sparse blob-like objects and most sparse tubular objects. The delineation accuracy in terms of mean false positive and negative volume fractions is 2% and 8%, respectively, for non-sparse objects, and 5% and 15%, respectively, for sparse objects. The two object groups achieve mean boundary distance relative to ground truth of 0.9 and 1.5 voxels, respectively. Some sparse objects - venous system (in the thorax on CT), inferior vena cava (in the abdomen on CT), and mandible and naso-pharynx (in neck on MRI, but not on CT) - pose challenges at all levels, leading to poor recognition and/or delineation results. The AAR method fares quite favorably when compared with methods from the recent literature for liver, kidneys, and spleen on CT images. We conclude that separation of modality-independent from dependent aspects, organization of objects in a hierarchy, encoding of object relationship information explicitly into the hierarchy, optimal threshold-based recognition learning, and fuzzy model-based IRFC are effective concepts which allowed us to demonstrate the feasibility of a general AAR system that works in different body regions on a variety of organs and on different modalities.

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.