Assessing sinus aerosol deposition: Benefits of SPECT–CT imaging
Graphical abstract
Introduction
The treatment of nasal infections can be challenging (Baroody, 2007, Fokkens et al., 2012). Delivering antibiotics by aerosol straight through the site of infection is a common strategy (Costantino et al., 2007). Different regions are targeted for these pathologies: the middle meatus as the major site of drainage for sinuses, the maxillary and ethmoid sinuses and the superior and posterior region of the central nasal cavity (Laube, 2007).
Thanks to ongoing development of medical technology, medical imaging has been increasingly used in respiratory research. Deposition studies are essential in the field of aerosols. Nowadays, one of the main experimental methodologies proposed in the literature consist in using radioactive aerosol associated with 2-dimensional (2D) gamma-scintigraphy imaging (Möller et al., 2011, Vecellio et al., 2011). Indeed, nuclear medicine is commonly used to determine the aerosols deposition patterns. Gamma scintigraphy uses radiolabelled formulations with gamma-ray emitting radionucleides. Different ventilation markers can be used such as Diethylene-Triamine Penta-Acetic Acid (DTPA) labeled with Technetium 99m (99mTc), 81mKrypton gas or Technegas. The distribution of the radioactive aerosol is generally assessed by a single-head gamma scintigraphy. However, planar gamma camera imaging provides 2D nuclear data without any visualization of anatomical features such as maxillary sinuses (Möller et al., 2008, Möller et al., 2010a, Möller et al., 2010b, Moller et al., 2011, Vecellio et al., 2011).
Currently, SPECT is a 3D imaging modality routinely used in clinical nuclear medicine. The 3D information implement other methods in airway research by giving topographical information, visualization of functional or structural modifications, a sampling of the whole organ and potential for in vivo imaging in a repeated prospective nature. In research field, 3D imaging techniques (e.g. SPECT) have the potential to give more detailed data on regional aerosol deposition. Over the last few years combined SPECT–CT scanners have become available. The concomitant acquisition without moving the patient and on the same equipment improves the alignment. The combination of SPECT and CT enables us to assess regional function in relation to structural changes and so the action ways of drugs in airway diseases. Clinically, SPECT has considerably improved 2D measurement of radioactive aerosol deposition. The applications are very wide in the development of therapeutic aerosols and in the investigation of mucociliary clearance particularly for bronchiectasis or cystic fibrosis (Eberl et al., 2001, Eberl et al., 2006, Fleming et al., 2011, King, 2011).
In the first part, this paper presents an innovative 3D-imaging approach using SPECT–CT compared to 2D gamma-scintigraphy and radioactive quantification of maxillary sinus lavage. Experiments were performed using a ventilated realistic plastinated nasal cast and an air-jet nebulizer generating 2.8 μm airborne particle size to accurately determine the potential benefits provided by SPECT–CT compared to planar scintigraphy. In a second part, nasal and sinus deposition were described for different sizes of aerosols using SPECT–CT imaging. The combination to CT scans accurately relates 3D nuclear images to anatomy. Thus, the impact of aerosol size and then acoustic frequency on the regional depositions especially in the different sinusal compartments was accurately evaluated.
Section snippets
Plastinated nasal model and aerosol inhalation
Experiments were performed using a human plastinated nasal cast obtained by a specific plastination technique (Croce et al., 2006, Durand et al., 2001). The specimen has been obtained from a deceased man who donated his body to the Saint-Etienne Anatomy Laboratory in accordance with law and ethics committee. The obtained nasal casts do not present significant tissue retraction, the mucosa in particular is conserved. This specimen is dedicated to functional studies and has been anatomically and
Aerosol properties and experimental set-up
The different types of nebulizers used in this study lead to different mass median aerodynamic diameters, respectively expressed with their geometric standard deviation (±GSD): 2.8 ± 3.2 μm for the NL11/NL11S, 550 ± 2.1 for the Sidestream and 230 ± 1.6 nm for the Nanoneb. The nebulizer output rates were also assessed after 10 min of nebulization and expressed in percentage. Respectively 0.32 ± 0.03% for the Nanoneb, 1.11 ± 0.56% for the Sidestream and 10.28 ± 1.76% for the NL11S (7.71 ± 1.24 for the NL11). The
Discussion
This study clearly demonstrates the benefits of 3D imaging approach using SPECT/CT compared to planar gamma scintigraphy to assess aerosol sinus deposition in comparison to maxillary sinus lavage reference method. ROIs definition with the 2D methodology, based on anatomical means although inter-subject anatomical differences, appears unsatisfactory and the anatomical regions are not well-defined compared to CT datas available using the 3D approach. Finally results obtained with 2D imaging
Conclusion
SPECT/CT seems to be an efficient methodology for the prediction of sinusal deposition of an active substance by nebulization. Sensibility of the radioactivity detection and efficiency of the SPECT/CT imaging allow us to emphasize the aerosol size dependence of the deposition in different ENT regions. Compared to planar scintigraphy, benefits of SPECT/CT for the assessment of radiolabelled aerosol deposition in rhinology are clearly demonstrated. This 3D methodology should be preferentially
Authors contributions
JP, MD, LL contributed to the conception and the design of research.
LL, JP, NP, SLG, LV and MD materially participated in the research experiments analysis and interpretation of data.
LL and JP were involved with drafting article.
LL, JP, NP, LV, MD materially participated in article preparation.
LV, MC and MD and all others were involved with reviewing the article.
All authors have approved the final version of this article.
Conflict of interest
Marc Durand is a scientific consultant for DTF society.
Laurent Vecellio and Sandrine Le Guellec are employees of the DTF company.
Acknowledgements
The authors would like to acknowledge the financial support of the Regional French Association for Aid to Chronic Respiratory Failure Patients (ARAIR), Saint-Etienne Métropole and the Conseil Général de la Loire.
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