Interventional Bronchoscopy from Bench to Bedside: New Techniques for Early Lung Cancer Detection

Rationale for early detection

Lung cancer is a leading cause of cancer-related death in the world, and it accounts for more deaths than breast, colon, and prostate cancer combined in the United States.¹ Most patients present with advanced disease, and the overall 5-year survival is approximately 15%.² From a historical perspective, the premise behind early lung cancer detection strategy is that if early treatment of lung cancer improves outcome, than early lung cancer detection is justified. Although initially the quest for

Autofluorescence bronchoscopy

Fluorescence bronchoscopy is based on the premise that differences in epithelial thickness, blood flow, and tissue fluorophore concentration cause preinvasive and neoplastic tissues to have diminished red fluorescence and substantially diminished green fluorescence compared with normal tissues when exposed to blue-light excitation of 440 to 480 nm wavelength.¹⁰ Normally, when a surface is illuminated by light, the light can be reflected, backscattered, or absorbed. In addition, light also

High-magnification bronchoscopy

Although the only abnormality of WLB seen in dysplasia is swelling and redness at bronchial bifurcations, histologically there is neovascularization or increased mucosal microvascular growth.18, 19 Furthermore, mucosal blood flow is thought to be influenced by vascular and airway pressures, inspired air conditions, and anatomic neurotransmitters.¹⁸ High-magnification bronchoscopy (HMB) enables observation of vascular networks to identify potential areas of increased vascularity in the bronchial

Narrowband imaging

Microvascular structures are further observed if a new narrowband filter is used instead of the conventional red/green/blue broadband filter. This narrowband imaging (NBI) technique uses a 415-nm blue light, which is absorbed by hemoglobin contained in the capillary network on the mucosal surface and a 540-nm green light that is absorbed by blood vessels located a bit deeper below the capillary layer.¹¹ Compared with WLB, NBI was shown to increase the rate of detection of dysplasia or

Multimodality fluorescein imaging

Researchers are investigating a multimodality technique whereby fluorescein imaging, analogous to that used in ophthalmology, in conjunction with high-resolution computed tomography (CT) scanning, bronchoscopy, and four-dimensional spatial reconstructions allow detailed examination of the bronchial microcirculatory system.24, 25, 26 The idea is to develop a macro-optical technique that would allow large field visibility of alterations in blood flow to identify focused regions of interest for

Endobronchial ultrasonography

Ultrasound and Doppler ultrasound image tissue structure and blood flow, but are limited in spatial resolution to approximately 50 to 200 μm because of their relatively long acoustic wavelengths (Fig. 1A, B). Endobronchial ultrasound (EBUS), however, has been used to accurately measure the depth of tumor invasion beyond the cartilaginous layer and to identify the structural layers of the airway wall that are important in defining and understanding various central airway disorders, such as

OCT

The search for a rapid acquisition, high-spatial resolution, and noninvasive technique for endoscopic imaging of in vivo tissue structure and function has resulted in the development of OCT systems. OCT resembles ultrasound but uses light rather than acoustic waves. In ultrasound, the imaging is obtained by measuring the delay time (echo delay) for an incident ultrasonic pulse to be reflected back from structures within tissues (Fig. 1C, D). Because the velocity of sound is relatively slow,

Confocal endoscopy

Another major area of optical technology advances for endoscopic imaging is confocal endoscopy/endomicroscopy. Confocal endoscopy/endomicroscopy has the capabilities for submicrometer-level resolution imaging but has even further limitations in depth of penetration (approximately 0.5 mm compared with approximately 2–3 mm with OCT) (see Fig. 2). Confocal endoscopy uses principles that are analogous to confocal microscopy, where the source light is focused through a pinhole to localize the

Summary

Studies increasingly demonstrate the importance of structural wall changes, angiogenesis, cellular proliferation, and genetic alterations in the pathogenesis of benign and malignant airway abnormalities. Angiogenesis in malignancy, airway remodeling in asthma, and destruction of the airway cartilage by cancer or in malacia can already be explored in vivo using bronchoscopic optical technologies.

New optical technologies such as those presented in this article allow dynamic study of these