Standardization of Techniques for Using Planar (2D) Imaging for Aerosol Deposition Assessment of Orally Inhaled Products

Abstract

Two-dimensional (2D or planar) imaging with (99m)Tc radiolabels enables quantification of whole-lung and regional lung depositions for orally inhaled drug products. This article recommends standardized methodology for 2D imaging studies. Simultaneous anterior and posterior imaging with a dual-headed gamma camera is preferred, but imaging with a single-headed gamma camera is also acceptable. Correction of raw data for the effects of gamma ray attenuation is considered essential for accurate quantification, for instance, using transmission scanning with a flood-field source of (99m)Tc or (57)Co. Evidence should be provided of the accuracy of the quantification method, for instance, by determining "mass balance." Lung deposition may be expressed as a percentage of ex-valve or ex-device dose, but should also be given as mass of drug when possible. Assessment of regional lung deposition requires delineation of the lung borders, using X-ray computed tomography, radioactive gas scans ((133)Xe or (81m)Kr), or transmission scans. When quantifying regional lung deposition, the lung should be divided into outer (O) and inner (I) zones. A penetration index should be calculated, as the O/I ratio for aerosol, normalized to that for a radioactive gas or transmission scan. A variety of methods can be used to assess lung deposition and distribution. Methodology and results should be documented in detail, so that data from different centers may be compared. The use of appropriate methodology will provide greater confidence in the results of 2D imaging studies, and should allay concerns that such studies are qualitative or semiquantitative in nature.

Effect of Drug Targeting Nebulization on Lung Deposition: A Randomized Crossover Scintigraphic Comparison Between Central and Peripheral Delivery

“…32 The choice of regions of interest was discussed in a recent recommendation. 24 Our results confirm that the Akita device offers a better method for drug administration to the peripheral lung compared with other modalities of nebulization, but they suggest that it is the device itself rather than the settings that are supposed to target differentially central or peripheral airways. Indeed, the bolus of air after drug delivery did not improve the deposition in this region, similar to the central targeted nebulization.…”

“…24 Images were acquired using a 128 ϫ 128 matrix for 1 or 2 min for the device (including the nebulizer and filter) and airways, respectively. The spatial resolution of this system is 5.3 mm at 10 cm.…”

“…3). 24 An I region with dimensions equal to half of the width of the whole-lung rectangle and half of its height was positioned on the interior boundary of the lung, centered by height. The I region is then 25% of the area of the whole-lung rectangle.…”

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

“…(67,68) In the previous validation study of Tian et al, (61) acceptable agreement was found between the in vivo results of Newman et al (62) and CFD computed airway predictions transferred to 2D planar images for the Novolizer inhaler, which was considered only at the PIFR of 99 LPM (fast inhalation), as well as a softmist inhaler also considered at a single flow rate. The methods established in the previous study of Tian et al (61) are repeated in the current study to evaluate the more challenging scenario of a single DPI evaluated at multiple flow rates generating different aerosol size distributions and tested in two separate airway geometries.…”

“…As described, the method used to segment the 2D planar image can influence the predictions of regional lung deposition, (67) and a newly recommend method for dividing planar images was described (68) after the publication of Newman et al (62) However, for validation purposes, the goal was to match the techniques used in the selected in vivo experiments as closely as possible. For the purpose of comparison, acceptable agreement between the CFD predictions and in vivo data will be determined based on the average relative error evaluated in the three regions of interest ( MT, C, and I+P) having a value of 15% or less.…”