The ability of OCT to discern invasive cancer versus CIS or dysplasia was investigated [21]. Normal or hyperplasia is characterized by one or two cell layers above a highly scattering basement membrane and upper submucosa. As the epithelium changes from normal/hyperplasia to metaplasia, various grades of dysplasia, and CIS, the thickness of the epithelial layer increases; quantitative measurement of the epithelial thickness showed that invasive carcinoma is significantly thicker than carcinoma in situ (p = 0.004) and dysplasia is significantly thicker than metaplasia or hyperplasia (p = 0.002). The nuclei become more readily visible in high-grade dysplasia or CIS. The basement membrane is still intact in CIS but became discontinuous or no longer visible with invasive cancer [21]. Squamous cell carcinoma has different OCT features than adenocarcinoma [52, 53] (Fig. 16.4).

The morphology of the peripheral lung nodules has been characterized. Lung parenchyma can be identified by the presence of signal-void alveolar spaces that appear as a honeycomb-like structure. Pulmonary nodule is identified by replacement of alveoli with solid tissue [45, 58, 59]. Adenocarcinomas with lepidic growth pattern are recognized by their thickened alveolar walls [45] (Fig. 16.4). After OCT interpretation training sessions, clinicians can diagnose common primary lung cancers (adenocarcinoma, squamous cell carcinoma, and poorly differentiated carcinoma) with an average accuracy of 82.6% (range 73.7–94.7%) [60]. Although OCT cannot replace histology in the diagnosis of lung carcinoma, it has the potential to aid in diagnosing lung carcinomas as a complement to tissue biopsy, particularly when insufficient tissue is available for pathology assessment. OCT may be useful for confirming the nature of the lesion before taking a biopsy. Since OCT probes can be miniaturized, they can be inserted inside biopsy needles/catheters to guide biopsy under real time without removing the imaging probe from a guide sheath and reinserting the biopsy forceps or needle with the possibility of displacement or migration to a different airway [56].

It is known that asthma phenotypes are heterogeneous and influence the response to treatment. Bronchial thermoplasty (BT) is a non-pharmacologic method to treat patients with chronic persistent asthma [61]. Currently, there is no method to select patients who will benefit from BT. OCT imaging was performed in two patients with chronic persistent steroid-dependent asthma prior to and immediately after bronchial thermoplasty as well as at 3 weeks, 6 weeks, 6 months, and 2 years after bronchial thermoplasty. Prior to BT, distinct asthma phenotypes were observed between the patient (patient A) who had sustained benefit from BT for over 2 years and the one who did not (patient B) (Fig. 16.5) [62]. PS-OCT [36, 63, 64] that can define highly organized tissue layers such as smooth muscle and collagen may be a useful non-biopsy tool to study the effect of pharmacologic and non-pharmacologic therapies.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by both small airway and parenchymal abnormalities. There is increasing evidence to suggest that these two morphologic phenotypes, although related, may have different clinical presentations, prognosis, and therapeutic responses to medications. A recent ex vivo study using micro-CT showed that narrowing and disappearance of small conducting airways occur prior to the onset of emphysematous destruction and that these changes can explain the increased peripheral airways resistance reported in COPD [65]. Clinical CT using an acceptable dose of radiation provides airway images up to the fifth generation. Unfortunately, the resolution of CT is not adequate to image critical events that begin at the seventh branching generation nor can it measure morphological changes in different layers of the airway wall. OCT can overcome this limitation with small optical probes that can image airways as small as terminal bronchioles with high resolution [55, 65, 66]. Coxson et al. compared OCT measurements with CT scans and lung function in COPD patients [67]. In 44 current and former smokers, OCT imaging was used to measure the airway dimensions in specific bronchial segments. These data were compared with CT measurements of the exact same airway using a three-dimensional reconstruction of the airway tree (Pulmonary Workstation 2.0; VIDA Diagnostics, Inc., Iowa City, IA). A strong correlation between CT and OCT measurements of lumen and wall area was observed. The correlation between FEV₁%-predicted and CT- and OCT-measured wall area (as percentage of the total area) of fifth-generation airways was good for both imaging modalities, but the slope of the relationship was much steeper using OCT than using CT, indicating greater sensitivity of OCT in detecting changes in wall measurements that relate to FEV₁. They concluded that OCT is more sensitive for discriminating the changes in the more distal airways of subjects with a range of expiratory airflow obstruction compared with CT. In addition to airway wall remodeling, alveolar wall destruction in COPD can also be clearly visualized using OCT with the emphysematous alveoli appearing as large voids compared with the small alveoli seen in those with normal lung function [53] (Fig. 16.6).

Sex differences in airway remodeling in COPD have also been investigated using OCT to help understand why women have a 50% increased risk of COPD compared with men after adjustment for the amount of smoking. Female human smokers have significantly thicker airway walls compared to male human smokers similar to the changes in a mouse model of COPD [68].

Airway diameter measurement via bronchoscopy is not reliable due to optical distortion of the bronchoscope lens that varies among bronchoscopes and limited ability to gauge depth. Respiratory motions interfere with airway measurement. Airway measurement can be performed using CT scans. However, real-time examination is not always available, and radiation exposure is a concern. Using phantoms, excised pig airways, and in vivo human airways during bronchoscopy, Williamson et al. demonstrated that airway measurements using anatomic OCT are accurate and reliable and compare favorably with CT imaging [69]. OCT was used to measure airway diameter in patients with subglottic tracheal stenosis, main bronchial stenosis, and tracheomalacia. The real-time OCT information was found to be helpful for determining the length of the stenosis, extent of tumor involvement beyond the bronchoscopic view, and severity of the tracheomalacia or guide the choice of airway stent. The investigators conclude anatomic OCT with conventional bronchoscopy allows accurate real-time airway measurements and may assist bronchoscopic assessment [70].

Changing of the upper airway sizes during sleep is the key pathophysiologic change in patient with obstructive sleep apnea (OSA) . Reduction in pharyngeal size correlates with increased sleep disorder breathing and degree of nocturnal desaturation [71]. CT scan has been used to measure the upper airway size. However, measuring upper airway dimension during sleep and awake with CT is not practical plus concern with radiation exposure. Anatomic OCT offers a real-time quantitative measurement of the upper airway shape and size during sleep or awake comparable to CT scan [72]. Individuals with OSA were found to have a smaller velopharyngeal cross-sectional area than BMI-, gender-, and age-matched control volunteers, but comparable shape suggesting it is an abnormality in size rather than shape that is the more important anatomical predictor of OSA [73].