Diagnostic Accuracy of Aerodigestive Ultrasound for Predicting Swallowing Disorders
Diagnostic Accuracy of Aerodigestive Ultrasound for Predicting Swallowing Disorders
Swallowing disorders management requires an accurate recognition of implicated anatomical
 structures and pathways. The usual clinical assessment of swallowing disorders lacks
 reliability and accuracy. The gold standard remains the videofluoroscopy. However, this
 imaging technique lacks reliability and standardisation. Moreover, videofluoroscopy is not
 easily available, time and material consuming and exposes patients to ionisation. Ultrasound
 imaging, which can be performed at the patient's bedside, is a non-invasive tool. It allows
 the evaluation of the main structures involved in all the swallowing pathways and may be a
 promising tool to assess the swallowing disorders. An ultrasound predictive model has never
 been developed to diagnose swallowing disorders.

 The investigators aim to develop an ultrasound predictive model to diagnose swallowing
 disorders, and assess its reliability and accuracy.

 One hundred outpatients at risk of swallowing disorders (neck cancer, neurological diseases,
 previous ICU stay) will be enrolled in the Dysphagia Diagnostic Unit at the Forcilles'
 Hospital, during a 2-year period.

 All patients will undergo a clinical examination by a speech-language therapist, and a
 videofluoroscopy imaging in order to diagnose swallowing disorders. Then, an ultrasound
 examination will be performed by the ultrasonographer. The ultrasonographer will be blinded
 from the patient's status and previous clinical and imaging assessments. Severity of the
 swallowing disorder will be assessed by the Dysphagia Outcome and Severity Scale.

 The tongue kinetics and thickness, the laryngeal movement and the suprahyoid muscles
 thickness and echogenicity will be assessed by ultrasonography.

 Inter- and intra-reliability of ultrasound examination will be calculated. The threshold of
 each ultrasound measurement allowing the swallowing disorders will be estimated using the ROC
 curve analysis. Sensitivity and specificity of each ultrasound measurement will be estimated.
 A global ultrasound predictive model will be developed after selecting variables in logistic
 multivariable regression. Diagnostic accuracy of the global predictive model will also be
 assessed.

 The investigators hope a high reliability and accuracy of the ultrasound predictive model in
 the swallowing disorders diagnostic. As ultrasonography is easy-to-perform, rapidly
 available, non-invasive and inexpensive, it may be a valuable alternative to videofluoroscopy
 in swallowing disorder diagnostic.
Swallowing disorders management requires an accurate recognition of implicated anatomical
 structures and pathways. The usual clinical assessment of swallowing disorders lack of
 reliability and accuracy. The gold standard remains the videofluoroscopy. However, this
 imaging technique lacks reliability and standardisation. Moreover, videofluoroscopy not
 easily available is time and material consuming and implies ionisation. Ultrasound imaging,
 which can be performed at the patient's bedside, is a non-invasive tool. It allows the
 evaluation of the main structures involved in all the swallowing pathways and may be a
 promising tool for swallowing disorders assessment.

 The investigators aim to develop an ultrasound predictive model to diagnose swallowing
 disorders, and assess its reliability and accuracy.

 The investigators hope a high reliability and accuracy of the ultrasound predictive model in
 the swallowing disorders diagnostic. As ultrasonography is easy-to-perform, rapidly
 available, non-invasive and inexpensive, it may be a valuable alternative to videofluoroscopy
 in swallowing disorders diagnostic.

 1. Hypothesis The investigators hypothesise that a new ultrasound predictive model is valid
 and reliable to diagnose swallowing disorder.

 2. Objectives

 Primary objective:

 • To create a new ultrasound predictive model based on the most relevant ultrasound
 measurements of the swallowing structures.

 Secondary objectives:

 -  To assess the accuracy of the ultrasound predictive model in the swallowing
 disorders diagnostic;

 -  To assess the inter- and intra-reliability of the ultrasound measurements;

 -  To assess the accuracy of each ultrasound measurements.

 3. Study design:

 The prospective observational single-centre study will be performed per the ethical
 standards of the Declaration of Helsinki and will be reported according to the
 Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.

 4. Population:

 One hundred outpatients at risk of swallowing disorders (neck cancer, neurological
 diseases, previous ICU stay) will be enrolled in the Dysphagia Diagnostic Unit at the
 Forcilles' Hospital, during a 2-year period. All consecutive patients will be screened
 at hospital admission, and will be included if they satisfy the eligibility criteria.
 All patients will provide oral consent to participate, in accordance with the clinical
 research French laws. Duration of the patient's participation will take 3 hours.

 5. Data collection Data will be recorded using a local case report form. Demographic data,
 comorbidities, medical and surgical history, reason for swallowing assessment will be
 recorded at inclusion. Clinical, videofluoroscopy and ultrasound measurements will also
 be recorded. On-site monitoring is planned every month.

 Participants will first undergo an ultrasound examination, then the clinical examination
 and videofluoroscopy imaging.

 6. Ultrasound examination:

 Ultrasonography will be performed using a Sonosite E2 Expert ultrasound device (Digital
 Color Doppler Ultrasound System; Sonoscape medical corp. China) with a 7-10 MHz linear
 and a 3-5 MHz probes. Detailed information for ultrasound procedure is described in the
 research protocol. Ultrasonography will be performed with the patients in near-to-supine
 position (30°).

 The hyoid bone movement, tongue kinetics and geniohyoid muscle measurement will be
 performed in a sagittal plane with the curvilinear probe. The probe will be placed
 between the posterior border of the symphysis and the anterior margin of the hyoid bone.

 The anterior belly of digastric and geniohyoid muscles evaluation will be performed in a
 frontal plane with the linear probe. The probe will be placed in the submandibular area,
 behind the symphysis.

 Ultrasonographer will be blinded from all patients' status and previous examination.
 Reliability will be assessed in the first twenty participants. All ultrasound
 measurements will be repeated twice by the first ultrasonographer to assess the
 intra-operator reliability. A second ultrasound operator will perform all the ultrasound
 measurement, allowing the inter-operator reliability evaluation.

 7. Videofluoroscopy (VFSS):

 VFSS is a radiographic procedure that provides a direct, dynamic view of oral,
 pharyngeal, and upper oesophageal function during swallowing. The radiologist and SLP
 work as a team to follow a standard protocol for conducting this examination.

 During this procedure, the speech-language therapist presents food and fluid mixed with
 barium. The barium is necessary to view structures via videofluoroscopy during the
 swallow. The following procedure will be followed: 5 ml of thin fluid; 5 ml of
 ultra-thick liquid; 5 ml of solid aliment, then 30 ml of thin fluid.

 The VFSS allow the assessment of the characteristics of the swallow and the patterns of
 bolus movement, including initiation of the swallow, nasopharyngeal reflux, pharyngeal
 clearance, and laryngeal penetration and aspiration.

 At any time, the radiologist may not initiate or stop the examination if it may be
 harmful to the patient. The reason to stop the test will be recorded.

 In case of penetration or aspiration, the speech language therapist will use the
 'Penetration-Aspiration Scale'.

 8. Statistical plan:

 Continuous variables will be expressed as the mean (± standard deviation) and compared
 using the Student's t test if the null hypothesis is not rejected by the Shapiro-Wilk
 test. Continuous variables will be expressed as the median (interquartile range) and
 compared with the Mann-Whitney U or Kruskal-Wallis test if the null hypothesis is
 rejected by the Shapiro-Wilk test. For categorical variables, the proportions of
 patients in each category will be calculated. Then the groups will be compared using Chi
 squared test.

 Continuous ultrasound variables will be dichotomised or grouped by class, depending on
 the linear relation between the logit of the swallowing disorder diagnostic and the
 ultrasound variable. The threshold for continuous ultrasound variables will be
 calculated with the ROC curve analysis.

 A multivariate logistic regression model will be carried out to assess the relation
 between swallowing disorders and ultrasound measures associated in univariate analyses.
 All statistically significant ultrasound variables will be included in the model.
 Variable selection will be stepwise, based on Akaike Information Criterion. To check
 multicollinearity between independent variables, the variance inflation factor will be
 calculated before performing multivariate logistic regression. Multicollinearity will be
 regarded as present when the variance inflation factor is > 5. Goodness of fit will be
 assessed by Hosmer-Lemeshow method.

 The outcome of each ultrasound variable from the multivariable logistic regression will
 be used to weight it in the global ultrasound predictive model.

 Intra- and inter-operator reliability will be assessed using the kappa coefficient for
 categorical variables or intra-class coefficients for continuous variables.

 For all tests, a p-value ≤ 0.05 will be considered statistically significant. All
 statistical analysis will be made using R software (version 3.6.1, www.R-project.org).

 9. Sample size calculation:

 The investigators based the sample size calculation on the number of independent variables
 which will be included in the logistic multivariable regression model. The investigators use
 the criterion of one variable per 10 events for binary logistic regression analysis. The
 investigators plan to include the 8 most relevant ultrasound measures in the model. As
 prevalence of swallowing disorders in our unit is estimated at 0.8, the investigators plan a
 sample size of 100 patients.

 Reliability will be assessed on the first 20 patients. With an 80% predicted kappa, a minimal
 value of the kappa of 50%, 2 observations, a 95% certainty and a 80% power, 20 patients will
 be required.
Inclusion Criteria:

 -  Outpatients refered to swallowing assessment at the Forcilles' hospital;

 -  Medical indication to perform a videofluoroscopy;

 -  Ultrasonographer available;

 -  Age > 18 years old;

 -  Membership of a social insurance sheme;

 -  Patient provides consent.

 Exclusion Criteria:

 -  Previous laryngectomy surgery;

 -  Refusal to participate in the study;

 -  Known pregnancy;

 -  Person subject to judicial health protection;

 -  Cognitive disorder incompatible with the understanding of instructions;

 -  Patient under guardianship or curatorship.