Comprehensive volumetric confocal microscopy with adaptive focusing.

Comprehensive microscopy of distal esophagus could greatly improve the screening and surveillance of esophageal diseases such as Barrett's esophagus by providing histomorphologic information over the entire region at risk. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that can be configured to image the entire distal esophagus by helically scanning the beam using optics within a balloon-centering probe. It is challenging to image the human esophagus in vivo with balloon-based SECM, however, because patient motion and anatomic tissue surface irregularities decenter the optics, making it difficult to keep the focus at a predetermined location within the tissue as the beam is scanned. In this paper, we present a SECM probe equipped with an adaptive focusing mechanism that can compensate for tissue surface irregularity and dynamic focal variation. A tilted arrangement of the objective lens is employed in the SECM probe to provide feedback signals to an adaptive focusing mechanism. The tilted configuration also allows the probe to obtain reflectance confocal data from multiple depth levels, enabling the acquisition of three-dimensional volumetric data during a single scan of the probe. A tissue phantom with a surface area of 12.6 cm(2) was imaged using the new SECM probe, and 8 large-area reflectance confocal microscopy images were acquired over the depth range of 56 µm in 20 minutes. Large-area SECM images of excised swine small intestine tissue were also acquired, enabling the visualization of villous architecture, epithelium, and lamina propria. The adaptive focusing mechanism was demonstrated to enable acquisition of in-focus images even when the probe was not centered and the tissue surface was irregular.

Image-guided biopsy in the esophagus through comprehensive optical frequency domain imaging and laser marking: a study in living swine.

BACKGROUND: Random biopsy esophageal surveillance can be subject to sampling errors, resulting in diagnostic uncertainty. Optical frequency domain imaging (OFDI) is a high-speed, 3-dimensional endoscopic microscopy technique. When deployed through a balloon-centering catheter, OFDI can automatically image the entire distal esophagus (6.0 cm length) in approximately 2 minutes. OBJECTIVE: To test a new platform for guided biopsy that allows the operator to select target regions of interest on an OFDI dataset, and then use a laser to mark the esophagus at corresponding locations. The specific goals include determining the optimal laser parameters, testing the accuracy of the laser marking process, evaluating the endoscopic visibility of the laser marks, and assessing the amount of mucosal damage produced by the laser. DESIGN: Experimental study conducted in 5 swine in vivo. SETTING: Massachusetts General Hospital. MAIN OUTCOME MEASUREMENTS: Success rate, including endoscopic visibility of laser marks and accuracy of the laser marking process for selected target sites, and extent of the thermal damage caused by the laser marks. RESULTS: All of the laser-induced marks were visible by endoscopy. Target locations were correctly marked with a success rate of 97.07% (95% confidence interval, 89.8%-99.7%). Thermal damage was limited to the superficial layers of the mucosa and was observed to partially heal within 2 days. LIMITATIONS: An animal study with artificially placed targets to simulate pathology. CONCLUSIONS: The study demonstrates that laser marking of esophageal sites identified in comprehensive OFDI datasets is feasible and can be performed with sufficient accuracy, precision, and visibility to guide biopsy in vivo.

Miniature swept source for point of care optical frequency domain imaging.

Point of care (POC) medical technologies require portable, small, robust instrumentation for practical implementation. In their current embodiment, optical frequency domain imaging (OFDI) systems employ large form-factor wavelength-swept lasers, making them impractical in the POC environment. Here, we describe a first step toward a POC OFDI system by demonstrating a miniaturized swept-wavelength source. The laser is based on a tunable optical filter using a reflection grating and a miniature resonant scanning mirror. The laser achieves 75 nm of bandwidth centered at 1340 nm, a 0.24 nm instantaneous line width, a 15.3 kHz repetition rate with 12 mW peak output power, and a 30.4 kHz A-line rate when utilizing forward and backward sweeps. The entire laser system is approximately the size of a deck of cards and can operate on battery power for at least one hour.