Computed Tomography Imaging of the Larynx for Diagnosis of Vocal Cord Dysfunction.

BACKGROUND: Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO) is characterized by breathlessness and often mimics or accompanies severe asthma. The disorder occurs intermittently, and the diagnosis is established by using laryngoscopy. Dynamic computed tomography (CT) imaging of the larynx at low-radiation doses has the potential to provide an alternative method to make the diagnosis of VCD/ILO. METHODS: We report two case series: in series A, laryngoscopy (diagnostic standard) and CT imaging of the larynx were each performed within 1 hour of each other (n=31), and in series B, the procedures were performed on separate days 4 to 6 weeks apart (n=72). Diagnosis of VCD/ILO by laryngoscopy used conventional criteria, and diagnosis by CT imaging was based on vocal cord narrowing in excess of a validated normal threshold. In each series, we evaluated the accuracy of CT imaging of the larynx to establish a diagnosis of VCD/ILO compared with laryngoscopy. RESULTS: In series A, the sensitivity of CT imaging of the larynx was 53.8%, and specificity was 88.9%; in series B, the sensitivity of CT imaging of the larynx was 76.2%, and specificity was 93.3%. At a disease prevalence of 30% (which was known to be the case in our clinic), the positive predictive value was 67.5% in series A and 83% in series B. Negative predictive values were 81.8% and 90.1% in series A and B, respectively, and false-positive rates were 11.1% and 6.7%. CONCLUSIONS: When the population prevalence was assumed to be 30%, low-dose CT imaging of the larynx detected VCD/ILO with negative predictive values greater than 80% in both series settings and agreed with each other within 9 percentage points. Positive predictive values for laryngeal CT imaging varied substantially between the settings of the two case series. (Supported by Monash Lung and Sleep Institute and Grant APP ID 1198362 and others.)

A mathematical model for eph/ephrin-directed segregation of intermingled cells.

Eph receptors, the largest family of receptor tyrosine kinases, control cell-cell adhesion/de-adhesion, cell morphology and cell positioning through interaction with cell surface ephrin ligands. Bi-directional signalling from the Eph and ephrin complexes on interacting cells have a significant role in controlling normal tissue development and oncogenic tissue patterning. Eph-mediated tissue patterning is based on the fine-tuned balance of adhesion and de-adhesion reactions between distinct Eph- and ephrin-expressing cell populations, and adhesion within like populations (expressing either Eph or ephrin). Here we develop a stochastic, Lagrangian model that is based on Eph/ephrin biology: incorporating independent Brownian motion to describe cell movement and a deterministic term (the drift term) to represent repulsive and adhesive interactions between neighbouring cells. Comparison between the experimental and computer simulated Eph/ephrin cell patterning events shows that the model recapitulates the dynamics of cell-cell segregation and cell cluster formation. Moreover, by modulating the term for Eph/ephrin-mediated repulsion, the model can be tuned to match the actual behaviour of cells with different levels of Eph expression or activity. Together the results of our experiments and modelling suggest that the complexity of Eph/ephrin signalling mechanisms that control cell-cell interactions can be described well by a mathematical model with a single term balancing adhesion and de-adhesion between interacting cells. This model allows reliable prediction of Eph/ephrin-dependent control of cell patterning behaviour.

Abnormal vocal cord function in difficult-to-treat asthma.

RATIONALE: Upper airway dysfunction may complicate asthma but has been largely ignored as an etiological factor. Diagnosis using endoscopic evaluation of vocal cord function is difficult to quantify, with limited clinical application. OBJECTIVES: A novel imaging technique, dynamic 320-slice computerized tomography (CT), was used to examine laryngeal behavior in healthy individuals and individuals with asthma. METHODS: Vocal cord movement was imaged using 320-slice CT larynx. Healthy volunteers were studied to develop and validate an analysis algorithm for quantification of normal vocal cord function. Further studies were then conducted in 46 patients with difficult-to-treat asthma. MEASUREMENTS AND MAIN RESULTS: Vocal cord movement was quantified over the breathing cycle by CT using the ratio of vocal cord diameter to tracheal diameter. Normal limits were calculated, validated, and applied to evaluate difficult-to-treat asthma. Vocal cord movement was abnormal with excessive narrowing in 23 of 46 (50%) patients with asthma and severe in 9 (19%) patients (abnormal > 50% of inspiration or expiration time). Imaging also revealed that laryngeal dysfunction characterized the movement abnormality rather than isolated vocal cord dysfunction. CONCLUSIONS: Noninvasive quantification of laryngeal movement was achieved using CT larynx. Significant numbers of patients with difficult-to-treat asthma had excessive narrowing of the vocal cords. This new approach has identified frequent upper airway dysfunction in asthma with potential implications for disease control and treatment.