Progress toward optical biopsy: bringing the microscope to the patient.

The investigation of many lung diseases currently requires bronchoscopic or surgical histopathological tissue biopsy. This creates risks for patients and entails processing costs and delays in diagnosis. However, several mainly probe-based biophotonic techniques that can image solitary lesions and diffuse lung diseases are fuelling a paradigm shift toward real-time in vivo diagnosis. Optical coherence tomography (OCT) uses near-infrared light in a process analogous to ultrasonography to image the mucosal and submucosal tissue boundaries of the bronchial tree. With 15-μm resolution, early work suggests it can differentiate between neoplasia, carcinoma in situ, dysplasia, and metaplasia based around epithelial thickness and breaches in the basement membrane. Probe-based confocal laser endomicroscopy (pCLE) has superior resolution but less penetration than OCT and employs blue argon laser light to fluoresce the endogenous elastin of (1) the acinar scaffold of the peripheral lung and (2) the basement membrane lying under bronchial mucosa. Initial studies suggest that the regular fibre arrangement of the basement membrane is altered in the presence of overlying malignant epithelium. pCLE produces detailed representations of the alveolar septal walls, microvessels, and some inflammatory cells. A third device, the endocytoscope, is a contact microscope requiring contrast agent to provide subcellular resolution of bronchial mucosa. Further development of these "optical biopsy" techniques and evaluation of diagnostic sensitivity and specificity of the acquired images are needed before they can be considered effective methods for eliminating the need for, and thus risks of, pinch biopsy to enable real-time diagnosis to streamline management.