Anatomic predictors of response and mechanism of action of upper airway stimulation therapy in patients with obstructive sleep apnea.

Study Objectives: Upper airway stimulation has been shown to be an effective treatment for some patients with obstructive sleep apnea. However, the mechanism by which hypoglossal nerve stimulation increases upper airway caliber is not clear. Therefore, the objective of this study was to identify the mechanism of action of upper airway stimulation. We hypothesized that, with upper airway stimulation, responders would show greater airway opening in the retroglossal (base of the tongue) region, greater hyoid movement toward the mandible, and greater anterior motion in the posterior, inferior region of the tongue compared with nonresponders. Methods: Seven participants with obstructive sleep apnea who had been successfully treated with upper airway stimulation (responders) and six participants who were not successfully treated (nonresponders) underwent computed tomography imaging during wakefulness with and without hypoglossal nerve stimulation. Responders reduced their apnea-hypopnea index (AHI) by 22.63 ± 6.54 events per hour, whereas nonresponders had no change in their AHI (0.17 ± 14.04 events per hour). We examined differences in upper airway caliber, the volume of the upper airway soft tissue structures, craniofacial relationships, and centroid tongue and soft palate movement between responders and nonresponders with and without hypoglossal nerve stimulation. Results: Our data indicate that compared with nonresponders, responders had a smaller baseline soft palate volume and, with stimulation, had (1) a greater increase in retroglossal airway size; (2) increased shortening of the mandible-hyoid distance; and (3) greater anterior displacement of the tongue. Conclusions: These results suggest that smaller soft palate volumes at baseline and greater tongue movement anteriorly with stimulation improve the response to upper airway stimulation.

Patient-specific modeling of regional antibiotic concentration levels in airways of patients with cystic fibrosis: are we dosing high enough?

BACKGROUND: Pseudomonas aeruginosa (Pa) infection is an important contributor to the progression of cystic fibrosis (CF) lung disease. The cornerstone treatment for Pa infection is the use of inhaled antibiotics. However, there is substantial lung disease heterogeneity within and between patients that likely impacts deposition patterns of inhaled antibiotics. Therefore, this may result in airways below the minimal inhibitory concentration of the inhaled agent. Very little is known about antibiotic concentrations in small airways, in particular the effect of structural lung abnormalities. We therefore aimed to develop a patient-specific airway model to predict concentrations of inhaled antibiotics and to study the impact of structural lung changes and breathing profile on local concentrations in airways of patients with CF. METHODS: In- and expiratory CT-scans of children with CF (5-17 years) were scored (CF-CT score), segmented and reconstructed into 3D airway models. Computational fluid dynamic (CFD) simulations were performed on 40 airway models to predict local Aztreonam lysine for inhalation (AZLI) concentrations. Patient-specific lobar flow distribution and nebulization of 75 mg AZLI through a digital Pari eFlow model with mass median aerodynamic diameter range were used at the inlet of the airway model. AZLI concentrations for central and small airways were computed for different breathing patterns and airway surface liquid thicknesses. RESULTS: In most simulated conditions, concentrations in both central and small airways were well above the minimal inhibitory concentration. However, small airways in more diseased lobes were likely to receive suboptimal AZLI. Structural lung disease and increased tidal volumes, respiratory rates and larger particle sizes greatly reduced small airway concentrations. CONCLUSIONS: CFD modeling showed that concentrations of inhaled antibiotic delivered to the small airways are highly patient specific and vary throughout the bronchial tree. These results suggest that anti-Pa treatment of especially the small airways can be improved.

Upper airway imaging in pediatric obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome in children is a manifestation of sleep-disordered breathing and associated with a number of complications. Structural narrowing of the upper airway in combination with inadequate compensation for a decrease in neuromuscular tone is an important factor in the pathogenesis. Adenotonsillar hypertrophy is the most important predisposing factor. However, many other causes of craniofacial defects may coexist. Additionally, the pathogenesis of narrowing is more complex in certain subgroups such as children with obesity, craniofacial malformations, Down syndrome or neuromuscular disorders. The diagnosis of obstructive sleep apnea is based on an overnight polysomnography. This investigation is expensive, time consuming and not widely available. In view of the major role of structural narrowing, upper airway imaging could be a useful tool for investigating obstructive sleep apnea and in establishing the site(s) of obstruction. Several radiological techniques (lateral neck radiography, cephalometry, computerized tomography, magnetic resonance imaging and post-processing of these images using computational fluid dynamics) have been used to investigate the role of structural alterations in the pathogenesis. We reviewed the literature to examine if upper airway imaging could replace polysomnography in making the diagnosis and if imaging could predict the effect of treatment with a focus on adenotonsillectomy. There is a limited number of high quality studies of imaging predicting the effect of treatment. To avoid unnecessary risks and ineffective surgeries, it seems crucial to couple the exact individual anatomical risk factor with the most appropriate treatment. We conclude that imaging could be a non-invasive tool that could assist in selection of treatment.

Functional respiratory imaging as a tool to personalize respiratory treatment in patients with unilateral diaphragmatic paralysis.

A completely different treatment approach was chosen for 2 patients with unilateral diaphragmatic paralysis and complaints of dyspnea despite similar anatomic and physiologic abnormalities. These decisions were supported by results obtained by functional respiratory imaging (FRI). FRI generated functional information on lobar ventilation and local drug deposition. In the first patient, some lobes were poorly ventilated, and drug deposition simulation showed that some regions were undertreated. This patient underwent diaphragmatic plication to restore ventilation. In the second patient, all lobes were still ventilated. A conservative approach with regular follow-ups was chosen to wait for spontaneous recovery of the diaphragmatic function. Both patients improved subjectively and objectively. These cases demonstrate how novel medical imaging techniques such as FRI can be used to personalize respiratory treatment in patients with unilateral diaphragmatic paralysis.

Change in upper airway geometry between upright and supine position during tidal nasal breathing.

BACKGROUND: As the upper airway is the most important limiting factor for the deposition of inhalation medication in the lower airways, it is interesting to assess how its morphology varies between different postures. The goal of this study is to compare the upper airway morphology and functionality of healthy volunteers in the upright and supine positions during tidal nasal breathing and to search for baseline indicators for these changes. This is done by performing three-dimensional measurements on computed tomography (CT) and cone beam computed tomography (CBCT) scans. METHODS: This prospective study was approved by all relevant institutional review boards. All patients gave their signed informed consent. In this study, 20 healthy volunteers (mean age, 62 years; age range, 37-78 years; mean body mass index, 29.26; body mass index range, 21.63-42.17; 16 men, 4 women) underwent a supine low-dose CT scan and an upright CBCT scan of the upper airway. The (local) average (Savg) and minimal (Smin) cross-sectional area, the position of the latter, the concavity, and the airway resistance were examined to determine if they changed from the upright to the supine position. If changes were found, baseline parameters were sought that were indicators for these differences. RESULTS: There were five dropouts due to movement artifacts in the CBCT scans. Savg and Smin were 9.76% and 26.90% larger, respectively, in the CBCT scan than in the CT scan, whereas the resistance decreased by 26.15% in the upright position. The Savg of the region between the hard palate and the bottom of the uvula increased the most (49.85%). In people with a high body mass index, this value changed the least. The airway resistance in men decreased more than in women. CONCLUSIONS: This study demonstrated that there are differences in upper airway morphology and functionality between the supine and upright positions and that there are baseline indicators for these differences.

Validation of computational fluid dynamics in CT-based airway models with SPECT/CT.

PURPOSE: To compare the results obtained by using numerical flow simulations with the results of combined single photon emission computed tomography (SPECT) and computed tomography (CT) and to demonstrate the importance of correct boundary conditions for the numerical methods to account for the large amount of interpatient variability in airway geometry. MATERIALS AND METHODS: This study was approved by all relevant institutional review boards. All patients gave their signed informed consent. In this study, six patients with mild asthma (three men; three women; overall mean age, 46 years ± 17 [standard deviation]) underwent CT at functional residual capacity and total lung capacity, as well as SPECT/CT. CT data were used for segmentation and computational fluid dynamics (CFD) simulations. A comparison was made between airflow distribution, as derived with (a) SPECT/CT through tracer concentration analysis, (b) CT through lobar expansion measurement, and (c) CFD through flow computer simulation. Also, the heterogeneity of the ventilation was examined. RESULTS: Good agreement was found between SPECT/CT, CT, and CFD in terms of airflow distribution and hot spot detection. The average difference for the internal airflow distribution was less than 3% for CFD and CT versus SPECT/CT. Heterogeneity in ventilation patterns could be detected with SPECT/CT and CFD. CONCLUSION: This results of this study show that patient-specific computer simulations with appropriate boundary conditions yield information that is similar to that obtained with functional imaging tools, such as SPECT/CT. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100322/-/DC1.

Correlation between the severity of sleep apnea and upper airway morphology in pediatric and adult patients.

PURPOSE OF REVIEW: Recent advances in upper airway imaging allow a better analysis of the upper airway morphology. With the increased accuracy of computed tomography, MRI and other imaging techniques, it becomes possible to identify very local changes in bony structure, soft tissues and lumen of the pharyngeal airway. These advances are able to provide new insights into obstructive sleep apnea (OSA) evaluation and treatment. RECENT FINDINGS: The present review intends to capture the current status of the research on the correlation between OSA severity and upper airway morphology. Morphological abnormalities that are responsible for OSA differ with age. Therefore, correlations between morphology and OSA in children and adults and the effects of puberty are discussed in different chapters. Literature provides several anatomical correlates that correlate with the severity of OSA but are not able to differentiate healthy individuals from OSA patients. SUMMARY: As anatomical correlates are not able to identify OSA in an individual, their main importance might lie in the selection of the ideal treatment on a patient-specific basis. Several sources report promising results in this use of morphological biomarkers. These, in combination with the new insights gained by the advances in imaging, should be the bases for additional research in the domain of treatment selection and result prediction.

Study of the variability in upper and lower airway morphology in Sprague-Dawley rats using modern micro-CT scan-based segmentation techniques.

Animal models are being used extensively in pre-clinical and safety assessment studies to assess the effectiveness and safety of new chemical entities and delivery systems. Although never entirely replacing the need for animal testing, the use of computer simulations could eventually reduce the amount of animals needed for research purposes and refine the data acquired from the animal studies. Computational fluid dynamics is a powerful tool that makes it possible to simulate flow and particle behavior in animal or patient-specific respiratory models, for purposes of inhaled delivery. This tool requires an accurate representation of the respiratory system, respiration and dose delivery attributes. The aim of this study is to develop a representative airway model of the Sprague-Dawley rat using static and dynamic micro-CT scans. The entire respiratory tract was modeled, from the snout and nares down to the central airways at the point where no distinction could be made between intraluminal air and the surrounding tissue. For the selection of the representative model, variables such as upper airway movement, segmentation length, airway volume and size are taken into account. Dynamic scans of the nostril region were used to illustrate the characteristic morphology of this region in anaesthetized animals. It could be concluded from this study that it was possible to construct a highly detailed representative model of a Sprague-Dawley rat based on imaging modalities such as micro-CT scans.

Novel imaging techniques using computer methods for the evaluation of the upper airway in patients with sleep-disordered breathing: a comprehensive review.

Patients with sleep related breathing disorders (SRBD) can be treated with nasal continuous positive airway pressure (nCPAP) or with several upper airway (UA) interventions. While nCPAP is almost always effective when clinically well tolerated, the therapeutic outcome of UA surgery and UA devices is difficult to predict. The improvement of our capability to perform the latter predictions more accurately is of great clinical importance since it will prevent patients to be treated with ineffective, sometimes irreversible, techniques. In this review we describe the importance of new imaging methods in this respect. We first refer to the most important pathophysiological mechanisms known so far to play a role in SRBD, indicating that functional imaging could elucidate these mechanisms in a patient specific manner. Then we describe the new technologies that make UA imaging more functional referring to the data as they are presently available. Finally we summarise the studies that do indicate that the use of functional imaging of the UA in SRBD patients may significantly help to predict the clinical outcome after UA interventions.