Multimodal Imaging of Upper Airway Anatomy, Airflow, and Dry Powder Deposition in Inhaler Therapy.

The efficacy of inhaler therapy is intricately linked to the interaction between drug particle dynamics and upper airway anatomy. Inhaled medications navigate a complex pathway where factors like airflow patterns, airway geometry, and individual characteristics—particularly Body Mass Index (BMI)—influence drug transport and deposition. Increased BMI is often associated with a reduction in airway calibre, especially in the oropharynx, creating higher resistance and turbulence that alter where particles settle. Mouthpiece design and inhalation technique are also critical; appropriately sized mouthpieces enhance aerosol direction and velocity, improving particle reach in lower respiratory regions. Conversely, suboptimal designs or techniques can lead to unwanted deposition in the upper airway, diminishing therapeutic impact and possibly causing side effects. However, a comprehensive understanding of airflow and particle behavior in the upper airway remains limited, as traditional methods typically rely on simplified models that overlook anatomical complexity. This thesis addresses these gaps by integrating Magnetic Resonance Imaging (MRI), Particle Image Velocimetry (PIV), and Swept-Source Optical Coherence Tomography (SS-OCT) to analyze the interplay between airway anatomy, airflow dynamics, and drug particle deposition. This combined approach provides detailed insights into how individual airway variations and inhalation profiles affect drug delivery efficiency, offering guidance for designing personalized inhalers. The first study utilizes MRI to examine the effects of BMI and mouthpiece size on upper airway geometry, identifying significant correlations between BMI and cross-sectional area (CSA) changes. Notably, the anterior-posterior length of the oropharynx shows marked increases with BMI, while larger mouthpieces yield greater CSA at the epiglottis in individuals with elevated BMI, suggesting that adjusting mouthpiece size could enhance delivery efficacy in these populations. The second study uses PIV to explore how respiratory rates influence airflow patterns in a realistic airway model, showing that higher respiratory rates create more uniform airflow in the latter stages of inhalation and exhalation. At higher rates, peak velocity is reduced near the soft palate, with downstream homogenization due to airway collapse, highlighting respiratory rate’s role in achieving efficient particle transport. The third study employs SS-OCT for high-resolution imaging of drug particle deposition across various airway regions. Results reveal significant regional variation, with the oropharynx exhibiting substantial powder thickness at high flow rates, underscoring inspiratory flow rate's critical impact on deposition. Less deposition in the laryngeal regions indicates that airflow complexity and anatomical features like curvature significantly influence particle impaction. By combining anatomical imaging with flow visualization and deposition mapping, this research offers a comprehensive perspective on the factors influencing inhaled drug delivery. Results suggest that tailoring inhaler designs to match individual anatomy and flow profiles could enhance drug delivery by up to 30%. This thesis lays the groundwork for developing patient-specific inhalers that more effectively target medications to the intended areas, advancing therapeutic outcomes for respiratory patients.<p></p>