Clinical studies (Table 21.1) using these devices have generally demonstrated improved sensitivity of AF (1.3–6.4 times) over WLB for the detection of preinvasive lesions, also in patients with abnormal sputum cytology. AF appears to be better at defining tumor margins and may add useful information in preoperative surgical planning as well as in targeting the area for endoscopic treatment (Fig. 21.2).

With the advent of the video bronchoscope that has a miniature charge couple device built in its tip which delivers clearer images, sensitivity for premalignant lesions has correspondingly improved without compromising its specificity. Chhajed et al. showed that the addition of video bronchoscopy to LIFE could better select sites for biopsy. However, the procedure required a change of scopes and represented a source of discomfort to the patient and inconvenience to the bronchoscopist. AFI is a video bronchoscope that displays a composite image by integrating three signals: autofluorescence caused by excitation light (395–445 nm), green and red light signals by respective green (550 nm), and red (610 nm) wavelengths. Since hemoglobin absorbs green and minimal red light, in areas with high hemoglobin due to increased vascularity, a feature of dysplasia rather than bronchitis, Chiyo and coworkers showed that AFI was superior to LIFE in discriminating preinvasive and malignant lesions from bronchitis or hyperplasia where LIFE would otherwise indicate as abnormal. Although switching from WLB to AFI involves hitting the button on the bronchoscope, simultaneous comparison of the video-endoscopic and AF images cannot be achieved (Fig. 21.2).

Dual real-time display of video-endoscopic and AF images is recently made possible with SAFE 3000 (Pentax, Tokyo, Japan). SAFE 3000 is a video bronchoscope that uses xenon lamp for WLB and allows real-time color image transmission using the miniature charge couple device that is built into its tip. The AF mode utilizes a diode laser that delivers excitation light to the target from the tip of the scope, and fluorescence from the target is captured by filtering out the wavelength of excitation light with the objective lens. Since both light sources are available, dual real-time display of video and AF bronchoscopic images of the target is achieved. Our study showed that dual real-time display of video-bronchoscopic and AFB images was not only sensitive for detecting preneoplastic lesions (0.86), it was highly specific (0.94) as it provided both functional and anatomic information of the lesion simultaneously (Fig. 21.3). By doing so, it allowed targeted biopsy that led to shorter procedural time, better patient comfort, and safety. Good correlation between visual classification (normal, abnormal, suspicious) and pathology was achieved particularly in identifying previous biopsy site, bronchitis, and airway fibrosis following endobronchial therapy (Fig. 21.4).

The newly developed Onco-LIFE device uses both reflectance and fluorescence light for imaging. Blue light (395–445 nm) and small amount of red light (675–720 nm) from a filtered mercury arc lamp are used for illumination. A red-reflectance image together with the green-autofluorescence image is captured by nonimage-intensified charge-coupled device which further enhances the contrast between preinvasive/malignant from normal tissues. By using reflected infrared red light as a reference, it has an advantage over reflected blue or green light as it is less absorbed by hemoglobin and may be less influenced by changes in vascularity associated with airway inflammation, thereby reducing its false-positivity. Red light is also uniformly scattered within the tissue and serves as a reference signal from which differences in light intensities due to changes in angle and distance of the bronchoscope from the bronchial surface are corrected (Fig. 21.5). In addition, Onco-LIFE allows quantitative analysis of the fluorescence image by providing a numeric representation (R/G ratio) of the combined colors in the central portion of the displayed image. R/G ratio of the 16  ×  16 pixel square target defined within the displayed brackets is calculated by dividing the average red reflectance with green fluorescence signals captured by the camera (Fig. 21.6). We performed a study correlating pathology of 3,362 biopsies with their corresponding R/G ratios. R/G ratio 0.54 and greater conferred 85% sensitivity and 80% specificity for the detection of high-grade and moderate dysplasia. When visual score (normal, abnormal, suspicious) was combined with R/G ratio, specificity in diagnosing moderate dysplasia or worse was further improved to 88% suggesting that color fluorescence ratio could objectively guide the bronchoscopist in selecting sites for biopsy with good pathological correlation.