Diagnosing lung carcinomas with optical coherence tomography

Abstract

Rationale: Lung carcinoma diagnosis on tissue biopsy can be challenging because of insufficient tumor and lack of architectural information. Optical coherence tomography (OCT) is a high-resolution imaging modality that visualizes tissue microarchitecture in volumes orders of magnitude larger than biopsy. It has been proposed that OCT could potentially replace tissue biopsy.

Objectives: We aim to determine whether OCT could replace histology in diagnosing lung carcinomas. We develop and validate OCT interpretation criteria for common primary lung carcinomas: adenocarcinoma, squamous cell carcinoma (SCC), and poorly differentiated carcinoma.

Methods: A total of 82 ex vivo tumor samples were included in a blinded assessment with 3 independent readers. Readers were trained on the OCT criteria, and applied these criteria to diagnose adenocarcinoma, SCC, or poorly differentiated carcinoma in an OCT validation dataset. After a 7-month period, the readers repeated the training and validation dataset interpretation. An independent pathologist reviewed corresponding histology.

Measurements and main results: The average accuracy achieved by the readers was 82.6% (range, 73.7-94.7%). The sensitivity and specificity for adenocarcinoma were 80.3% (65.7-91.4%) and 88.6% (80.5-97.6%), respectively. The sensitivity and specificity for SCC were 83.3% (70.0-100.0%) and 87.0% (75.0-96.5%), respectively. The sensitivity and specificity for poorly differentiated carcinoma were 85.7% (81.0-95.2%) and 97.6% (92.9-100.0%), respectively.

Conclusions: Although these results are encouraging, they indicate that OCT cannot replace histology in the diagnosis of lung carcinomas. However, OCT has potential to aid in diagnosing lung carcinomas as a complement to tissue biopsy, particularly when insufficient tissue is available for pathology assessment.

Keywords: in vivo microscopy; lung cancer; optical biopsy guidance; optical frequency domain imaging; transbronchial fine needle aspiration guidance.

Figure 1.

Optical coherence tomography (OCT) of squamous cell carcinoma. (A) OCT of squamous cell carcinoma shows rounded or irregularly shaped, signal-intense nests (arrows) that display higher signal intensity than the surrounding tissues. Squamous cell carcinomas may contain variably sized, irregularly shaped signal-poor areas of necrosis either in the center of the nests (circled region) or admixed with the nests. (B) Corresponding histology stained with hematoxylin–eosin shows nests of malignant squamous cell carcinoma (arrows), some of which contain central necrosis (circled region). This example of squamous cell carcinoma was included in both OCT training sessions. Scale bars: 1 mm.

Figure 2.

Optical coherence tomography (OCT) of adenocarcinoma. (A) OCT of adenocarcinoma shows rounded or angulated signal-poor structures (arrows) and a lack of signal-intense nests. (B) Corresponding histology stained with hematoxylin–eosin confirms the presence of lung adenocarcinoma (arrows). This example of adenocarcinoma was included in both OCT training sessions. Scale bars: 1 mm.

Figure 3.

Optical coherence tomography (OCT) of poorly differentiated carcinoma. (A) OCT of poorly differentiated carcinoma lacks both signal-intense nests and small, round signal-poor structures. (B) Corresponding histology stained with hematoxylin–eosin. This example of poorly differentiated carcinoma was included in both the initial and second training sessions for the OCT readers. Scale bars: 0.5 mm.

Figure 4.

Optical coherence tomography (OCT) of lung carcinomas with fibrosis. Fibrosis appears as bright, signal-intense tissue on OCT. (A and B) OCT and corresponding histology of squamous cell carcinoma with dense fibrosis. The signal-intense nests (arrows) are more difficult to appreciate when intermixed with fibrosis. (C and D) OCT and corresponding histology of adenocarcinoma with fibrosis. Fibrosis makes the signal-void structures of adenocarcinoma (arrows) more difficult to visualize. Histology sections are stained with hematoxylin–eosin. Scale bars: 1 mm.

Figure 5.

Diagnostic algorithm flow chart. This diagnostic algorithm flow chart was provided to the optical coherence tomography (OCT) readers in the second validation assessment to help guide diagnostic decision-making.