Chapter 4 - Imaging Aerosol Deposition and Mucociliary Clearance
This chapter includes following sub-chapters:
Chapter 4.1 - Radiolabeling methods
Myrna B. Dolovich, B. Eng., P. Eng
In vivo measurements of the deposition of an inhaled radiolabeled pharmaceutic have provided useful information related to the inhaler efficiency for depositing drug in the lung. A number of labeling techniques have been developed and applied to pharmaceutical aerosols delivered by pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs) and nebulizers; the choice of radiotracer depends on the type of imaging study being performed and the equipment used to image the lung. Preparation, validation and calibration of the radiolabeled pharmaceutical product is key to successful interpretation of the imaging study.
Chapter 4.2 - Design of in vivo Deposition and Clearance Experiments
William D. Bennett, PhD
Experiments designed to image in vivo deposition of radiolabel-drug mixtures are useful for estimating inhaled drug delivery and for assessing bioequivalence of delivery devices. Validation of the radiolabel-drug mixture is vital to ensure that subsequent imaging is reflective of drug deposition. Application of gamma attenuation corrections allows both total and regional lung deposition of drug to be estimated by two-dimensional (2D) imaging. Imaging methods are also useful for measuring in vivo mucociliary clearance (MC) function. Such measures allow assessment of the efficacy of drugs designed to improve clearance of airway secretions in airway disease. MC rates can be measured by controlled inhalation and gamma camera monitoring of radiolabeled aerosols containing non-permeating tracers.
Chapter 4.3 - Imaging Aerosol Deposition with Two- Dimensional Gamma Scintigraphy
Beth L. Laube, PhD
Several imaging modalities have been employed to quantify lung dose and the distribution of the dose of orally inhaled aerosols in vivo. Two-dimensional (2D, or planar) imaging using gamma scintigraphy is the most widely used of these modalities. Two-dimensional gamma scintigraphy studies are accomplished using a single- or dual-headed gamma camera. The formulation to be tested is admixed with the gamma emitting radioisotope 99mtechnetium, which serves as a surrogate for the drug. This article provides details as to how 2D gamma scintigraphy images should be acquired and analyzed using recently standardized methods.
Chapter 4.4 - Single Photon Emission Computed Tomography (SPECT)
John S. Fleming, PhD
Imaging of radiolabeled aerosols provides useful in vivo data on both the initial site of deposition and its subsequent transport by mucociliary clearance and epithelial permeability. Single Photon Emission Computed Tomography (SPECT) uses a gamma camera with multiple rotating heads to produce three-dimensional (3D) images of inhaled radioaerosol labeled with technetium-99m. This enables total lung deposition and its 3D regional distribution to be quantified. Aligned 3D images of lung structure allow deposition data to be related to lung anatomy. Mucociliary clearance or epithelial permeability can be assessed from a time series of SPECT aerosol images. SPECT is slightly superior to planar imaging for measuring total lung deposition.
Chapter 4.5 - Measuring Anatomical Distributions of Ventilation and Aerosol Deposition with ET-CT
Jose G. Venegas, PhD
heterogeneity is relevant to aerosol medicine and for quantifying mucociliary clearance from different parts of the lung. In this chapter, we describe positron emission tomography (PET) imaging methods to quantitatively assess the deposition of aerosol and ventilation distribution within the lung. The anatomical information from computed tomography (CT) combined with the PET- deposition data allows estimates of airway surface concentration and peripheral tissue dosing in bronchoconstricted asthmatic subjects.
