Tongue Volume Research Articles

0562 Differences in Upper Airway Soft Tissue Volumes Between African American and Caucasian Patients with Obstructive Sleep Apnea Using Magnetic Resonance Imaging

Abstract Introduction Research suggests greater obstructive sleep apnea (OSA) severity in African-Americans than Caucasians. However, the underlying mechanisms causing this ethnic disparity are unknown. To evaluate possible mechanisms, we compared the size of the tongue between African American and Caucasian OSA patients using magnetic resonance imaging (MRI), controlling for age, body mass index (BMI) and apnea-hypoxia index (AHI). Given prior evidence of more severe OSA in African Americans, we hypothesized these patients would have larger soft tissue volumes compared to Caucasians. Methods Upper airway soft tissue volumes, (total tongue, tongue fat, lateral walls, pterygoids, total soft tissue) were quantified using MRI and compared between Caucasian (n=133) and African American (n=175) patients with moderate OSA. Analyses were conducted using regression models controlling for age, sex, BMI and AHI. Results Among all OSA patients, African Americans had higher BMI than Caucasians (40.0±8.6 vs. 37.1±8.1 kg/m2, p=0.0024) and a higher proportion of females (66.3% vs. 36.1%; p<0.0001). There were no significant differences in age (p=0.143) or AHI (p=0.314). Controlling for these covariates, there were no differences between African American and Caucasian OSA patients in tongue fat volume (mean [95% confidence interval] difference = 479 [-3156, 4115] mm3; p=0.794). However, African Americans had a 13,286 (6,439, 20,132) mm3 larger total tongue volume compared to Caucasians (p=0.0002). Larger volumes in African Americans were also observed for the soft palate (p<0.0001), retropalatal lateral walls (p=0.003), pterygoid (p=0.034) and total soft tissue volume (p=0.0003). Conclusion African Americans were observed to have larger volumes of the tongue, soft palate, retropalatal lateral walls, pterygoids and total soft tissue volume compared to Caucasians, although there were no differences in AHI and tongue fat volume. The study contributes to the overall understanding of ethnic-specific pathology of OSA and can potentially influence how African Americans and Caucasians are diagnosed and treated specifically for the disease. Support

Preliminary study: evaluating the reliability of CBCT images for tongue space measurements in the field of orthodontics.

Accurately measuring tongue space is challenging, but this information can be useful to many dental specialties. This study was intended to estimate the reliability of using cone-beam computed tomography (CBCT) to measure tongue space, which includes tongue volume and the oral cavity air capacity. For this preliminary study, CBCT images from ten participants (five females and five males, mean age of 29.8 ± 3.3years) were available for evaluation. Each participant was radiographed two times (T0 and T1). The average time between T0 and T1 was 15.8 ± 3.7days. CBCT scans were standardized to reduce variability. Three-dimensional landmarks were established to identify tongue space and 3D image analysis software (SimPlant® 17 Pro; Materialise Dental, Leuven, Belgium) was used to measure the volume circumscribed by the landmarks. Two investigators independently calculated airway, tongue dimensions, and total tongue space for CBCT image T0 twice (day 1 and day 14), and T1 once. Intraclass correlation coefficients (ICCs) wereused to estimate intra-rater and inter-rater reliability. Bland-Altman charts were constructed to demonstrate agreement within and between raters. The intra-rater and inter-rater ICCs of the CBCT measurements at T0 were excellent (> 0.90). Measurements for T0 vs. T1 show good (0.75-0.90) intra-rater and excellent (> 0.90) inter-rater reliability. Bland-Altman charts show that 90-95% of the total measurements fall within the 95% limits of agreement for both intra- and inter-rater pairs CONCLUSIONS: The results of this preliminary study suggest that the landmarks chosen to measure the overall tongue space are reproducible and can be measured clearly using CBCT.

Effect of Mandibular Setback Surgery on Tongue Length and Height and Its Correlation with Upper Airway Dimensions.

The changes in length and height of tongue following mandibular setback (MS) surgery may affect pharyngeal airway dimensions. There is limited literature correlating tongue dimensional changes with linear and volumetric airway changes following MS with bilateral sagittal split ramus osteotomy (BSSRO) in skeletal class III patients. Treatment records of 18 patients who underwent MS with BSSRO were evaluated for changes in tongue and linear airway dimensions, mean airway volume and area at T1 (1-week pre-surgery), T2 (6-month post-surgery) and T3 (2-year post-surgery). Amount of MS was recorded from case sheets of patients. Mean tongue length reduced, whereas mean tongue height increased at T2 compared to T1 (P value = 0.001 for both). Linear, area and volumetric airway parameters at T2 were significantly reduced (P value = 0.001). All parameters showed statistically nonsignificant increase from T2 to T3 (P value > 0.05). Correlation analysis showed that change in tongue length at T3 did not show statistically significant correlation with amount of MS, changes in linear, area and volumetric airway parameters (P value > 0.05). However, the change in tongue height at T3 showed a significant (P value < 0.05) negative correlation (r value = - 0.742) with change in posterior airway space (PAS). The appraisal of tongue length and height after MS surgery should be an integral part of diagnosis and treatment planning. The retro-positioning of tongue and increase in its height after MS surgery may compromise pharyngeal airway especially PAS. Additional options such as bi-jaw surgery, debulking of tongue volume and genioplasty should be explored to minimize adverse effects post-surgically.

Value Of Cephalometric And Volumetric Measurements Performed By Multi-Level Three-Dimensional Computed Tomography In Patients With Obstructive Sleep Apnea Syndrome

Objective: Upper airway narrowing plays an important role in obstructive sleep apnea syndrome (OSAS) etiology. Computed tomography (CT) provides a three-dimensional image and can be obtained in the supine body position. The main objectives of this study were to determine the correlation between the dimensions of upper airway structures and OSAS by reconstructing the nasal, pharyngeal and oropharyngeal airway using CT. Methods: The study was carried out on a total of 95 consecutive subjects with maxillofacial CT, including 59 OSAS patients and 36 healthy participants. CT data of the study subjects were obtained in the supine position with the Philips Ingeniuty Core 2017 model CT device. Volumetric and cross-sectional area measurements of upper airway were obtained in three dimensions. Results: Retrolingual area and retrouvulal area were significantly lower in the patient group (p <0.001 for two). The mean values of soft palate volume, tongue volume and concha volumes of both sides were found to be significantly higher in the patient group (p = 0.005 for lower right turbinate, p <0.001 for others). Total nasal passage volume averages were significantly lower in the patient group, however naso-pharyngeal volume averages were significantly lower in the control group (p<0,001, p=0,004 respectively). Both uvula thickness and soft palate length averages were significantly higher in the patient group (p <0.001 for both). Conclusion: Cephalometric analysis of patients with OSAS with CT scans provides objective evaluation of skeletal and soft tissue abnormalities. We believe that all surgical procedures should follow precise cephalometric measurements, including detailed measurements.

Influence of tongue volume, oral cavity volume and their ratio on upper airway: A cone beam computed tomography study

BackgroundOur study aimed to measure the tongue volume (TV), oral cavity volume (OCV), and their ratio (TV/OCV) and correlate with upper airway using cone-beam computed tomography (CBCT). MethodThe volume of oral cavity, tongue and upper airway were obtained by the manual process of segmentation of CBCT data of 15 subjects. The mean age of the sample was 21.86 years (range 15–33 years). Segmentation of the upper airway, tongue and oral cavity was performed manually using Mimics 11.0 (Materialise, Leuven, Belgium) software at different thresholds for air and the tongue. The Hounsfield units (HU) for airway volume of the different facial region ranged from −1024 to −500. For tongue volume, Hounsfield units (HU), ranging from −200 to 200 was calculated. ResultsA significant negative correlation between TV/OCV and oropharynx (r = − 0.51; P = 0.04), TV/OCV and oral cavity airway volume (r = − 0.74; P = 0.002) was found. There was a significant and a positive correlation with TV/OCV and tongue volume (r = 0.65; P = 0.009). ConclusionA significant negative correlation established between TV/OCV, oropharynx and oral cavity airway volume. This finding indicates an influence tongue volume, oral cavity volume and their ratio on patency of the oropharynx.

Decreased Tongue Volume Post Radiation.

To evaluate volume changes within the tongue post chemoradiation therapy (CRT). Retrospective review. Academic Medical Center. Subjects included 19 patients that received CRT as the primary treatment for tonsillar or hypopharynx squamous cell carcinoma. Tongue volumes were calculated by three raters from thin slice computed tomography images collected before treatment and up to 29 months post-CRT. Body mass index (BMI) was also collected at each time point. Inter-rater reliability was high with an ICC of 0.849 (95% CI = 0.773, 0.905). Linear mixed effects modeling showed a mean decrease of 0.45 cm3 (standard error of the mean [SEM] = 0.11) in tongue volume per month post-CRT (P < .001). However, the addition of BMI to the model was significant (χ2 (4) = 25.0, P < .001), indicating that BMI was a strong predictor of tongue volume, with a mean decrease of 1.75 cm3 (SEM = 0.49) in tongue volume per unit decrease in BMI (P < .001) and reducing the post-CRT effect on tongue volume decrease per month to 0.23 cm3 (P = .02). BMI significantly (P < .001) decreased by 0.11 units (SEM = 0.02) per month post radiation. Tongue dysfunction and decreased tongue strength are significant contributors to the dysphagia that patients experience after receiving CRT. In this study, both tongue volume and BMI decreased post-CRT; therefore, BMI could potentially be used as a predictor of tongue volume post-CRT.

Different 2D ultrasound calculation methods to evaluate tongue volume for prediction of difficult laryngoscopy.

Background and Aims:The aim of the study was to evaluate and compare three different ultrasonographic calculation methods for tongue volume in a real time 2D ultrasonography and correlate with Modified Cormack–Lehane grading observed under direct laryngoscopy.Methods:This prospective observational study was conducted in a tertiary care institute. Tongue volume was assessed ultrasonically in 50 adult patients using three techniques in all the patients undergoing surgery under general anesthesia and correlated with Modified Cormack–Lehane grading. In METHOD A, the tongue volume was calculated as multiplication of mid sagittal cross-sectional area and width in transverse plane; METHOD B, Cross-sectional area obtained in vertical plane was multiplied with the maximum width of tongue in transverse plane; METHOD C. the volume was calculated by multiplying length, width, and height in vertical, transverse, and mid-sagittal/oblique plane, respectively. The analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. Receiver operating characteristic (ROC) curve was used to find out cutoff point of different methods for predicting difficult laryngoscopy.Results:The specificity and sensitivity of three different methods were statistically compared and area under the receiver operating characteristic (ROC) curve for method A, B, and C was 0.562, 0.502, and 0.548, respectively.Conclusion:In our study, we found all three methods to calculate tongue volume to be equally good to assess difficult laryngoscopy.

The use of tumor-to-tongue thickness ratio to predict the need for microvascular flap reconstruction following glossectomy in carcinoma tongue

Background: Microvascular flap reconstruction (MFR) of medium–large tongue defects following ablative surgery is the standard of care. The decision for MFR is often made prior to surgery or intraoperatively depending on the extent of the defect and the volume of remnant tongue. However, there exists no objective technique to predict this requirement preoperatively. This knowledge is crucial for counseling and planning. We aimed to identify an objective magnetic resonance imaging (MRI) measurement tool to predict the need for MFR of tongue tumors. Materials and Methods: This was a retrospective analysis of patients undergoing surgery (with or without reconstruction) for squamous cell carcinoma of the tongue. Patients had a preoperative MRI as part of their assessment. As per our institution protocol, the decision for the requirement of MFR was made by a consensus of two experienced reconstructive surgeons intraoperatively. This decision was correlated with the ratio of tumor volume to the total tongue volume (tv) as observed in the MRI. Results: A total of 47 patients were identified. Twenty-eight patients underwent reconstruction, while 19 did not. The ratio of tumor thickness to tongue thickness (Tt/tt) was calculated, and a cutoff of >0.395 (sensitivity 89.3% and specificity 89.5%) was found to significantly correlate with the decision for MFR (P 4.2 (sensitivity 83.3 and specificity 90) was found to be correlated significantly with the decision for MFR (P

P3508A novel mouse model of sleep-disordered breathing is associated with contractile dysfunction and CaMKII overexpression

Abstract Background Patients with sleep-disordered breathing (SDB) develop arrhythmias and contractile dysfunction, but the mechanisms are poorly understood, possibly due to the lack of mouse models that mimic airway obstruction in spontaneously sleeping mice. Interestingly, New Zealand obese mice have been shown to develop airway obstruction with inspiratory flow limitation resulting in apneas, but these mice also develop diabetes. Purpose We developed a novel mouse model of increased airway obstruction in spontaneously sleeping lean mice and investigated the impact on sleep-related apneas and contractile function. Methods and results Male C57BL6 mice at 8–12 weeks of age were subjected to polytetrafluoroethylene (PTFE) injection (100 μl) into the tongue. This resulted in an increased tongue volume and reduced pharyngeal luminal diameter. Conscious mice behave normal and there was no difference in body weight between PTFE injected mice and untreated littermates (control). Whole body plethysmography was used to monitor spontaneous breathing for 8h in a quiet environment. Interestingly, compared to control, mice with PTFE injection showed a significantly increased frequency of apneas (lasting &gt;1s, fig. A, * indicated P&lt;0.05, t-test). Echocardiographic analysis revealed that ejection fraction was significantly reduced in PTFE-treated mice 8 weeks after surgery (vs. control, fig. B). In accordance, the developed force of isolated papillary muscles from hearts of PTFE mice was significantly reduced compared to control (fig. C). Ca/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the development of heart failure. Intriguingly, compared to control, CaMKII expression was significantly increased in ventricular heart homogenates of PTFE-treated mice (fig. D). Moreover, the magnitude of CaMKII overexpression correlated significantly with the frequency of apneas (fig. E). Papillary muscle post-pause contractions can be used as measure of diastolic sarcoplasmic reticulum (SR) Ca leak, which is known to be enhanced by CaMKII. Compared to control, post-pause contraction amplitude was significantly smaller in PTFE-treated mice, indicating an increased SR Ca leak (fig. F). Figure 1 Conclusion PTFE injection in mice results in an increased frequency of spontaneous apneas. PTFE-treated mice develop mild contractile dysfunction, which is accompanied by CaMKII overexpression. This novel mouse model offers great opportunities for investigation of sleep-related breathing disorders. Acknowledgement/Funding This study was supported by the Medical Faculty of the University of Regensburg (ReForM programme).

The impact of tongue dimension on air volume in brachycephalic dogs

To compare the dimensions and density of the tongue in brachycephalic and mesaticephalic dog breeds and to document the relative extents of the nasopharyngeal and oropharyngeal airways occupied by the tongue and palatal tissues. Case control study. Sixteen brachycephalic dogs and 12 mesaticephalic dogs. The volume of the tongue was measured with computed tomography in all dogs. Cross-sectional areas of tongue, oropharynx, nasopharynx, and palatal soft tissue were evaluated at two levels, the caudal aspect of the hard palate and the level of the hamulae of the pterygoid. Density of the tongue and soft palate were measured. All variables were compared between brachycephalic and mesaticephalic dogs (P ≤ .05). Absolute tongue volumes did not differ between groups, the volume of the tongue was greater in brachycephalic dogs than in mesaticephalic dogs when expressed relative to (a) body weight (median 5650, interquartile range [IQR] 4833-6522 vs median 4454, IQR 4309-4743, respectively), (b) ratio between skull length/width (70 833, IQR 62490-126 209 vs 48 064, IQR 22984-64 279, respectively), and (c) skull length (689.93, IQR 618.55-970.61 vs 460.04, IQR 288.77-561.69, respectively). The proportion of air (oropharyngeal and nasopharyngeal)/soft tissue (tongue and palatal tissue) in brachycephalic dogs was decreased by approximately 60%, and the tongue was approximately 10 times denser in brachycephalic dogs than in mesaticephalic dogs. A relative macroglossia was detected in brachycephalic dogs along with reduced air volume in the upper airway. Tongues of brachycephalic dogs were denser than those of mesaticephalic dogs. The relative macroglossia in brachycephalic breeds may contribute to upper airway obstruction.

Development of a semi-customized tongue displacement device using a 3D printer for head and neck IMRT

PurposeTo reduce radiation doses to the tongue, a patient-specific semi-customized tongue displacement device (SCTDD) was developed using a 3D printer (3DP) for head and neck (H&N) radiation therapy (RT). Dosimetric characteristics of the SCTDD were compared with those of a standard mouthpiece (SMP).Materials and methodsThe SCTDD consists of three parts: a mouthpiece, connector with an immobilization mask, and tongue displacer, which can displace the tongue to the contralateral side of the planning target volume. Semi-customization was enabled by changing the thickness and length of the SCTDD. The instrument was printed using a 3DP with a biocompatible material. With the SCTDD and SMP, two sets of planning computed tomography (CT) and tomotherapy plans were obtained for seven H&N cancer patients. Dosimetric and geometric characteristics were compared.ResultsUsing the SCTDD, the tongue was effectively displaced from the planning target volume without significant tongue volume change compared to the SMP. The median tongue dose was significantly reduced (29.6 Gy vs. 34.3 Gy). The volumes of the tongue receiving a dose of 15 Gy, 30 Gy, 35 Gy, 45 Gy, and 60 Gy were significantly lower than using the SMP.ConclusionThe SCTDD significantly decreased the radiation dose to the tongue compared to the SMP, which may potentially reduce RT-related tongue toxicity.

Sleep Apnea Multilevel Surgery (SAMS) trial protocol: a multicenter randomized clinical trial of upper airway surgery for patients with obstructive sleep apnea who have failed continuous positive airway pressure.

Obstructive sleep apnea (OSA) is a serious and costly public health problem. The main medical treatment, continuous positive airway pressure, is efficacious when used, but poorly tolerated in up to 50% of patients. Upper airway reconstructive surgery is available when medical treatments fail but randomized trial evidence supporting its use is limited. This protocol details a randomized controlled trial designed to assess the clinical effectiveness, safety, and cost-effectiveness of a multilevel upper airway surgical procedure for OSA. A prospective, parallel-group, open label, randomized, controlled, multicenter clinical trial in adults with moderate or severe OSA who have failed or refused medical therapies. Six clinical sites in Australia randomly allocated participants in a 1:1 ratio to receive either an upper airway surgical procedure consisting of a modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction, or to continue with ongoing medical management, and followed them for 6 months. Primary outcomes: difference between groups in baseline-adjusted 6 month OSA severity (apnea-hypopnea index) and subjective sleepiness (Epworth Sleepiness Scale). Secondary outcomes: other OSA symptoms (e.g. snoring and objective sleepiness), other polysomnography parameters (e.g. arousal index and 4% oxygen desaturation index), quality of life, 24 hr ambulatory blood pressure, adverse events, and adherence to ongoing medical therapies (medical group). The Sleep Apnea Multilevel Surgery (SAMS) trial is of global public health importance for testing the effectiveness and safety of a multilevel surgical procedure for patients with OSA who have failed medical treatment. Multilevel airway surgery in patients with moderate-severe Obstructive Sleep Apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366019&isReview=true Australian New Zealand Clinical Trials Registry ACTRN12614000338662, prospectively registered on 31 March 2014.

Comparing the Efficacy of Adeno‐associated Virus Serotype 9 (AAV9) Mediated Retrograde Transgene Delivery to Hypoglossal (XII) Motor Neurons (MNs) in Mouse Versus Rat Models

Previous work by our group shows that AAV9 can robustly transduce XII MNs following direct intralingual injection and subsequent retrograde transport along the XII nerve. The current experiments compared the effectiveness of this approach in commonly studied strains of mouse and rat. In the adult C57BL/6 mouse, delivery of AAV9‐CBA‐GFP (1.20e10vg/μL, 8.33μL) via a unilateral or bilateral injection to the base of the tongue both produced a robust transgene expression in XII MNs as determined by immunohistochemistry (tissues harvested 6 weeks post‐injection). The extent of XII MN transduction was similar with uni‐ or bilateral tongue injection, presumably owing to the small volume of the mouse tongue. In contrast to the murine data, following intralingual delivery of AAV9‐CMV‐mCherry in adult Sprague‐Dawley (SD) rats (1.42e10vg/μL, 1.5 μL or 7.0μL), transgene expression in XII MNs was not detected using either fluorescence microscopy or antibodies against mCherry. Intralingual delivery was repeated in 3 separate cohorts (N=28 total) and MN transduction was never detected. We next tried a direct unilateral injection of AAV9‐mCherry into the main trunk of the XII nerve of adult SD rats (1.42e10vg/μL, 1.5μL). The nerve was injected in the neck, proximal to the point where it bifurcates into medial and lateral branches. At 6 wks post‐injection, we observed clear expression of mCherry in XII MNs detected using immunochemistry. Unexpectedly, MN transgene expression was seen in both XII motor nuclei, despite the unilateral nature of the AAV delivery. We are unaware of any neuroanatomical evidence to suggest that retrograde transport along a single XII nerve would result in bilateral targeting of XII motoneurons, and ongoing experiments are aimed at determining the mechanisms underlying this result. Collectively, these results indicate that retrograde transport of AAV9 following intramuscular delivery may show species variability. Problems with intralingual delivery in the rat were circumvented by direct delivery of AAV9 to the XII nerve.Support or Funding InformationFunding: 1R01HL139708‐01A1 (DDF)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Relationships among tongue volume, hyoid position, airway volume and maxillofacial form in paediatric patients with Class-I, Class-II and Class-III malocclusions.

To clarify the associations among tongue volume, hyoid position, airway volume and maxillofacial form using cone beam computed tomography (CBCT) data for children with Class-I, Class-II and Class-III malocclusion. Sixty children (mean age, 9.2years) divided into Class-I, Class-II and Class-III malocclusion groups according to the A-nasion-B angle. Cone beam computed tomography was used for three-dimensional reconstruction of the maxillofacial region and airway. The hyoid position and the tongue, airway and oral cavity volumes were evaluated. Upper airway ventilation status was calculated using computational fluid dynamics. The groups were compared using analysis of variance and Kruskal-Wallis tests; relationships among the parameters were assessed using Pearson's and Spearman's rank correlation tests. The tongue volume was larger in Class-III patients (50.63cm3 ) than in Class-I patients (44.24cm3 ; P<0.05). The hyoid position was lower (49.44cm), and anatomical balance (AB; tongue volume/oral cavity volume; 85.06%) was greater in Class-II patients than in Class-I patients (46.06cm, 80.57%, respectively; P<0.05 for both). The hyoid height showed a positive correlation with AB (r=0.614; P<0.001). Children with Class-III malocclusion have large tongue volumes and small AB; the reverse is true for children with Class-II malocclusion. The hyoid position is closely associated with AB in children with malocclusion.

Trans-Oral Robotic Tongue Reduction for OSA: Does Lingual Anatomy Influence the Surgical Outcome?

To evaluate both the influence of the volume of the excised base of tongue (BOT) on the surgical outcome after robotic tongue reduction in patients affected by obstructive sleep apnea (OSA) and the role of the lymphatic or muscular predominance within the removed tissue. Fifty-one patients with OSA were included in this study. All patients were treated with a robotic tongue base reduction. Data registered for the analysis were: age, sex, preoperative body mass index, preoperative and postoperative apnea-hypopnea index (AHI), delta AHI (preoperative AHI - postoperative AHI), total volume of the excised BOT, total thickness of excised BOT, isolated lymphatic thickness and soft tissue thickness (including muscular component) of the excised BOT, and lymphatic/soft tissue ratio (lymphatic thickness / soft tissue thickness). A statistically significant reduction of AHI values was seen postoperatively, and a success rate of 74.5% was recorded. However, no significant correlations between delta AHI and tongue volume in cubic centimeters, lymphatic/soft tissue ratio, and total thickness were found. These findings reinforce the general opinion that OSA is not only influenced by anatomic factors but other phenomena may play a fundamental role in its genesis. A deeper understanding of OSA pathogenesis is needed in order to tailor an individual treatment strategy that could lead to a more effective therapy.

Influence of tongue composition change on tongue pressure in the elderly: A study using tongue MR imaging with Dixon

The mechanism of oral sarcopenia concerned with tongue muscle atrophy is imperfectly understood. We must pay careful attention whether the pathology of tongue muscle affects dysphagia in the elderly. The purpose of this study was to investigate the relationship between the decrease in tongue muscle volume and tongue weakness with magnetic resonance imaging (MRI) examination. Eleven elderly patients without stroke or neuromuscular disease participated (mean age: 72.6 ± 6.5). Tongue pressure was measured using a device (TPM-01, JMS, Hiroshima) equipped with a balloon probe. Tongue volume was evaluated with T1-weighted MR imaging. Tongue lean muscle mass was evaluated with Dixon MRI. The Pearson analysis was used to calculate coefficients between tongue pressure and tongue volume/lean tongue muscle mass. The mean tongue pressure, tongue volume and lean tongue muscle mass were 29.9 ± 8.1 kPa, 66.8 ± 12.3 cm 3 and 56.2 ± 10.4 cm 3 . Tongue pressure was significantly correlated with tongue volume and lean tongue muscle mass ( r = 0.60, P = 0.049 and r = 0.64, P = 0.035). To our knowledge, this is the first study to investigate tongue muscle mass, lean tongue muscle mass and tongue pressure using MRI images. Tongue muscle mass and lean tongue muscle mass was significantly associated with tongue pressure. Compared with previous studies for healthy young adults (Utanohara, 2008; Fabrice, 2010), tongue pressure was decrease in spite of tongue volume was similar. Bassler (1987) suggested that the tongue volume after muscular atrophy is compensated by metaplasia of fatty tissue. We speculated that adipose might be an important factor for reducing tongue pressure and dysphagia.

Abstract 4498: Lysyl oxidase like-2 mediates tumor to stromal cell communication in oral cancer

Abstract Introduction: The lysyl oxidase family consists of 5 members and oxidizes specific lysine residues in biosynthetic collagen and elastin maturation. Lysyl oxidase like-2 (LOXL2) is elevated in oral cancer and promotes metastasis and correlates with poor prognosis. The objective of this study is to determine the mechanism by which LOXL2 promotes the progression and invasiveness of oral squamous cell carcinoma. Methods: In vitro: To investigate functions of LOXL2 in oral cancer, the effects of LOXL2 inhibitor (PXS-S1C) on human gingival fibroblasts treated with tumor cell conditioned medium (CM) were investigated. Cell proliferation assays, signaling arrays and western blots were used to evaluate the effect of PXS-S1C on CM-treated fibroblasts. The effect of PXS-S1C on cancer cells expression of LOXL2 and proliferation was determined. To find potential LOXL2 substrates in gingival fibroblasts treated with CM +/- PXS-S1C, carbonyl-containing proteins were purified by affinity chromatography and identified by MS and western blot. In vivo: The effect of PXS-S1C on cancer growth and metastasis in vivo was investigated using an orthotopic oral tongue cancer mouse model in both immunodeficient and immunocompetent mice. PXS-S1C at 10 mg/kg and 30 mg/kg was injected immediately following tumor cell injections. Tumors were monitored by caliper measurements, and by in vivo imaging (IVIS). The mice were sacrificed and their organs were subjected to immunohistochemistry staining for proliferation markers. Results: PXS-S1C significantly inhibited gingival fibroblast proliferation triggered by tumor cell CM and attenuated phosphorylation of PDGFRβ Y771 and P-PDGFRβ Y857, but not PDGFRβ Y751 in response to CM. PXS-S1C inhibited ERK1/2-signaling in fibroblasts and not AKT in response to CM. PDGFR activation by oral tumor cells was mimicked by PDGF-AB, but not PDGF-BB. PXS-S1C decreased the expression of LOXL2 by 5-fold in HSC3 oral cancer cells in vitro, suggesting a positive autoregulatory loop. Assessing for direct LOXL2 substrates in fibroblasts with functional consequences identified both PDGFR and integrin αV. Caliper measurements, IVIS, and immunohistochemistry demonstrated that inhibition of LOXL2 significantly decreases oral cancer progression and metastasis in vivo. Mice without PXS-S1C treatment developed larger tongue volumes (p&amp;lt;0.05), and more mice developed larger lymph nodes (3 out 12) compared to the PXS-S1C-treated mice (1 out of 12). IVIS imaging revealed inhibition of metastasis by PXS-S1C treatment. The expression of proliferation marker (Ki-67) and LOXL2 was lower in tongue tumors treated with PXS-S1C (p&amp;lt;0.05). Conclusions: LOXL2 secreted by cancer cells stimulates fibroblasts by enhancing PDGFR signaling and proliferation, and by stimulating αV integrin function and cell adhesion. Inhibition of LOXL2 could provide therapeutic strategies to address oral cancer. Citation Format: Faranak Mahjour, Philip C. Trackman. Lysyl oxidase like-2 mediates tumor to stromal cell communication in oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4498.

Osseous Loading by a Volume-Reduced Tongue During Muscle Contractions

To investigate how tongue volume reduction affects loads on surrounding bone surfaces produced by neuromuscular stimulation of the tongue. Of each pair of same-gender minipig siblings, 1 received tongue reduction and 1 underwent sham surgery. Either immediately (acute, 6 pairs) or 1month (chronic, 5 pairs) after surgery, bone surface and/or suture strains and pressures were recorded from the following locations when the hypoglossal nerve trunk, hypoglossal nerve medial branch, hypoglossal nerve lateral branch, genioglossus, and styloglossus (SG) were electrically stimulated: 1) three rosette strain gauges on the premaxillary palatal surface (premaxilla [PM]) and lingual surfaces of the mandibular alveolus at anterior (mandibular incisor [MI]) and posterior (mandibular molar [MM]) locations; 2) two single-element strain gauges over the palatal surface of the premaxillary-maxillary suture and the lingual surface of the mandibular symphysis; and 3) two pressure transducers on the palatal surface of the maxilla (palatal process) and the lingual surface of the mandibular alveolus (mandibular corpus). Compared with the sham animals in the acute study, reduction animals showed significantly decreased PM and MI strains, as well as palatal process pressure.With muscle contractions, mandibular symphysis and MM strains were enhanced significantly with a more dorsal orientation.In the chronic study, reduction animals showed decreased PM and increased MM strains. On comparison of chronic versus acute studies, PM, MI, and MM strains under SG stimulation were significantly smaller whereas MM strain was significantly larger under hypoglossal nerve trunk, hypoglossal nerve lateral branch, and SG stimulations. Muscle contractions from a volume-reduced tongue produce lower and higher loads in the anterior and posterior mouth, respectively.However, although the effects on reducing loads in the anterior mouth are persisting over time, compensatory load enhancement in the posterior mouth diminishes owing to surgical healing.

Evaluation of the pharyngeal airway using computational fluid dynamics in patients with acromegaly.

ObjectivesPerioperative airway management may be particularly challenging in patients with acromegaly undergoing trans‐sphenoidal pituitary surgery (TSS). Management for airway obstruction is required prior to pituitary surgery to minimize perioperative hypoxia. The purpose of this retrospective study was to evaluate airway obstruction by simulation of computational fluid dynamics (CFD) using computed tomography (CT) images in patients who had undergone TSS.MethodsCT images of the nasopharyngeal airways of patients with acromegaly (n = 5) or nonfunctional pituitary adenoma (n = 6) undergoing TSS from April 2012 to January 2017 were used to construct these airways in three dimensions. Estimated airflow pressure and velocity in the retropalatal airway (RA), oropharyngeal airway (OA), and hypopharyngeal airway (HA) were simulated using CFD.ResultsEstimated pharyngeal airflow pressure in the HA, OA, and RA was significantly greater in patients with acromegaly than in those with nonfunctional pituitary adenomas whereas the estimated pharyngeal airflow velocity was significantly impaired only in the RA of patients with acromegaly. Minimum postoperative SpO2 both within 3 hours and from 3 to 12 hours after the end of anesthesia was significantly lower in the patients with acromegaly. Additionally, estimated volume of tongue and pharyngeal airflow pressure in the HA, OA, and RA correlated with minimum postoperative SpO2.ConclusionPharyngeal airflow pressure estimated from CT images is high in patients with acromegaly, and these values correlate with postoperative minimum values for SpO2. Preoperative evaluation of CT images by CFD can predict difficulty in airway management and perioperative hypoxia.Level of Evidence4.

3D computer simulation analysis of the flap volume change in total tongue reconstruction flaps

BackgroundA decreased flap volume can be an obstacle to proper phonation and swallowing. In this study we verified the proportion of volume decrease using 3D reconstructed images and identified the contributors to flap volume loss. MethodsWe retrospectively analyzed all patients who underwent radical excision of tongue cancer and reconstructive surgery in our institution from January 2003 to October 2016. Segmentation of the DICOM images, 3D rendering of the neotongue flap, and analysis of the reconstructed images were performed using SPlanner V1® software. ResultsThe first postoperative imaging work-up was performed within an average of 22 days (T1). The last follow-up images were taken at an average of 6.25 months (T2). The mean flap volume at T2 was reduced to 82.99 per cent compared with T1, and flap height was reduced to 91.85 per cent, giving mean volume and height decreases of 17.01 per cent and 8.15 per cent, respectively. Neither the volume/height difference between T1 and T2 nor the flap volume/height discrepancy compared with the preoperative tongue affected speech or feeding function. The difference between the flap and preoperative tongue volumes was significantly related to the presence of complications (p = 0.0153). Initial flap volume was significantly related to the flap volume reduction (p = 0.0159). ConclusionsThe mean flap volume reduction is the only factor significantly related to initial flap volume. Our realistic 3D reconstructed image and novel software enables us to more precisely predict the flap volume of the postoperative state and preoperatively evaluate the required flap size for covering defects.