This study demonstrates that rapid acquisition endoscopic OCT based on a swept source laser system and MEMS rotational motor, with a translational motorized stage for 3-D volumetric measurements, was able to detect significant in-vivo
airway changes following smoke exposure. Quantitative detection of changes in thickness of mucosal region in the airway, between epithelium and cartilage were sensitively detected and followed temporally after exposure to inhaled smoke and cyanide. Changes were evident using this technology within a few minutes following initial smoke exposure; much earlier than has been reported to be evident using standard methods [23
]. The ability to detect injury following smoke inhalation or other toxic exposures is needed for an approved diagnostics, prognostics (triage and intubation decisions), and will be important in developing and accurately assessing potential therapies.
We have previously shown that OCT is capable of detecting mucosal changes and following their progression after smoke inhalation injury and half mustard injury in vivo
in animal models [23
]. However, these previous reports utilized a time domain system with limited (two-dimensional) longitudinal images due to the slow acquisition capabilities of the time domain system. Two-dimensional imaging allows only highly selected portions of the airway to be imaged, leading to potential measurement variability and selection bias. Obviously, it is necessary to find same location within the airways for measurements of the airway thickness change. When only 2-D longitudinal image without a rotational scanning is obtained, it is generally difficult or impossible to reliably maintain exact position of the prior images. With 3-D acquisition, this problem is readily solved by reconstruction in any direction. Furthermore, thickness of the submucosal region with the two-dimensional longitudinal acquisition approach is susceptible to measurement error resulting from the incident angle of the probe versus airway wall as shown in and Media 2. To overcome these limitations, three-dimensional imaging with faster acquisition and the ability to reconstruct in any direction were developed for this study.
To demonstrate the capabilities for this system to detect smoke inhalation injury and followed temporally changes, we investigated three groups of animals; controls (no smoke injury), compared to animals exposed to smoke, and animals exposed to smoke and cyanide. Many smoke inhalation injury patients have concurrent cyanide exposure due to the presence of cyanide in the products of combustion. Thus, the model systems selected are relevant to human exposures, and should serve as the basis for future investigations into the effectiveness of therapeutic interventions.
Images were readily obtained in the animals using this system. Previously described algorithms were employed to eliminate cardiogenic motion artifact [25
]. High quality and contrast reconstructed longitudinal images obtained from the transverse image stacks readily allowed measurement of wall airway thickness, using cartilage surfaces as the objective end-point.
In this study, we found that the thickness change of the airway was increased due to smoke inhalation in both groups of animals exposed to smoke, without significant difference in airway change from the addition of cyanide. The airway thickness changes occurred very early, within 30 minutes, and appeared to peak and level off over the period from 1 to 6 hours. The pathophysiologic events occurring during early smoke inhalation injury have been described in previous studies [2
]. This is a cooled smoke injury animal model in which thermal effects have been eliminated. The acute injury responses are secondary to chemical/particulate injury and the immunologic responses that have been initiated. Our previous studies have shown that these early changes appear to be due to hyperemia and edema, and are clearly evident with three dimensional OCT imaging. Changes in edema and hyperemia are diminished or lost during histologic preparation, demonstrating potential value of noninvasive in vivo technologies such as optical coherence tomography to more clearly reflect events that cannot be seen with postmortem excised histologic preparations.
In this study, we did not see differences in the extent of airway changes following smoke inhalation exposure and animals receiving concurrent cyanide administration compared to smoke inhalation exposure alone. Such findings are expected, given the known initiating events in cold smoke airway injury. However, this is an important question to investigate, since many smoke inhalation injury victims are also exposed to cyanide, and studies have suggested that the cyanide blood levels correlate closely with mortality rates. One caveat to this study is that the cyanide was administered intravenously. It is possible that inhaled cyanide concurrent with inhaled smoke could produce different results. Future studies will be needed to further assess the role of local airway effects of cyanide in smoke inhalation injury.
This study illustrates the feasibility of three-dimensional airway OCT imaging based on rapid scanning swept source laser for inhalation injury assessment. This is the first report of a series of smoke inhalation exposures followed temporally using three-dimensional airway OCT with longitudinal image reconstruction.