Lara Alina Schöllbauer

Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by four dry powder inhalers under realistic inhalation and exhalation conditions. To simulate patients undergoing inhalation therapy, the active respiratory system model (xPULM™) was used. A mechanical upper airway model was developed, manufactured, and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung, while particles with the size of (>0.5 μm) are least influenced by deposition mechanisms. The fraction of exhaled particles ranges from 2.13% (HandiHaler^®) over 2.94% (BreezHaler^®), and 6.22% (Turbohaler^®) to 10.24% (Ellipta^®). These values are comparable to previously published studies. Furthermore, the mechanical upper airway model increases the resistance of the overall system and acts as a filter for larger particles (>3 μm). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract regarding applicable deposition mechanisms. The model strives to support the reduction of animal experimentation in aerosol research and provides an alternative to experiments with human subjects.

Background: Whole-body PET images can be obtained by using the “step-and-shoot” (SaS) method (using multiple bed positions) or continuous bed motion (CBM). As transmission scans are not always feasible, an alternative method where attenuation data can be generated via emission-based attenuation correction (AC) maps is of interest. The aim of this preclinical study was to investigate the influence of the acquisition method and AC on the quantitation accuracy of [¹⁸F]FDG-PET. Methods: [¹⁸F]FDG-PET phantom images were acquired using either SaS or CBM. Transmission scans were recorded for the SaS method using a ⁵⁷Co-point source. Emission-based attenuation sinograms were obtained from the images after segmentation and inverse Fourier rebinning. PET images were reconstructed without AC, transmission based (TX-AC) and emission-based (EM-AC) attenuation correction. Moreover, [¹⁸F]FDG-PET scans of rats bearing mammary carcinomas acquired using either SaS or CBM were analyzed retrospectively and quantification in tissues was compared. Results: Phantom recovery coefficients (R_C) varied greatly, ranging from 0.49 ± 0.01 to 1.15 ± 0.07, dependent on acquisition method, reconstruction algorithm and AC method. In CBM acquired images, EM-AC improved quantification accuracy when compared to no-AC images in the phantom studies (R_C 0.79 ± 0.02 vs. 0.49 ± 0.01, respectively) and in tumors of rats (DMBA model: 1.16±0.42 SUV vs. 0.86±0.28 SUV, respectively). Conclusion: The method of AC has a strong influence on the quantification of [¹⁸F]FDG. Our data indicates that EM-AC improves quantification in images obtained by CBM and SaS. However, the obtained values were still underestimated when compared to TX-AC corrected images.