The results shown here demonstrate in vivo 3D-OCT endomicroscopy analysis of normal and pathologic tissue in the human colon. Although larger-scale clinical studies are needed to definitively establish the utility of this technique for specific applications, the pilot study described here illustrates several potential avenues for future investigation. First, 3D-OCT can be used to distinguish normal from abnormal tissue for applications involving the detection of pathology. In addition, it can be used as an adjunct to endoscopic therapies by assisting in treatment planning, monitoring, and follow-up assessment.
The majority of previous endoscopic OCT studies in the GI tract have focused on detecting pathology, with special emphasis on detecting dysplasia in Barrett's esophagus [6
]. Because 2D-OCT is constrained to image individual cross-sections of several mm to cm length, it remains prone to random sampling errors also common in pinch biopsy. Furthermore, subtle dysplastic lesions obscured by diffuse inflammatory processes have proven difficult to detect using single cross-sectional images. This may be partially due to a lack of contextual awareness from analyzing 2D views of 3D tissue microstructure. 3D-OCT endomicroscopy could enhance pathology detection by providing a larger field of view, 3D visualization of tissue structure, and higher dimensional information for use in automated tissue classification algorithms. 3D-OCT may also be valuable for detecting early-stage cancers in the colon, where inflammatory conditions such as UC and Crohn's disease can mask the subtle subsurface features associated with dysplasia. This is an analogous situation to the detection of dysplasia in BE, where 3D-OCT endomicroscopy could also find utility.
3D-OCT endomicroscopy can also be a valuable tool for use with endoscopic therapies. Previous investigations of OCT as a therapeutic monitoring tool have been relatively limited, although some studies have been performed using endoscopic 2D-OCT to monitor photodynamic therapy (PDT) [39
]. OCT may be used in conjunction with a wide variety of other therapies including argon plasma coagulation, laser ablation, radiofrequency ablation, EMR, band ligation and snare resection. 3D-OCT has the potential to significantly expand and enhance applications such as this by enabling 3D microstructural analysis of the entire target site. Prior to treatment, the lesion can be assessed for transverse extent, axial penetration, vascularization and structural makeup. During a therapy such as PDT, radiofrequency ablation, or laser coagulation, 3D-OCT could monitor the treatment site to assess when complete destruction of the lesion is achieved. This could be useful to prevent overexposure and unnecessary collateral damage to surrounding healthy tissue. The concept of monitoring the response of tissue to thermal therapy has been demonstrated ex vivo
using pig tissue [41
] and could be applied in vivo
using 3D-OCT endomicroscopy. Following therapy, 3D-OCT can be used during follow-up visits to assess healing and check for disease recurrence. The ability to precisely co-register cross-sectional images to anatomic landmarks or other en face
features could be valuable when imaging the same patient at multiple time points, since it enables the same tissue region to be imaged with greatly improved registration.
Perhaps the most significant current limitation in 3D-OCT is the availability and performance of scanning imaging probes suitable for endoscopic use. The ability to resolve microstructural features in three dimensions requires precise and reproducible two dimensional beam scanning at the distal end of an endoscope. In this study, we used a proximally actuated spiral-scanning probe because it can be readily introduced into the working port of an endoscope and enables long regions of the lumen to be imaged. However the ability to resolve very small features in three dimensions was limited by rotational uniformity of the distal optics. Although frame-to-frame positional jitter was < 10 μm for the majority of frames in a typical 3D dataset, approximately 20% of the frames showed visible motion artifacts when viewed at extremely high magnification. For these frames, sequential rotational images had a maximum jitter in position on the order of 10 – 18 milliradians, corresponding to a 15 – 25 um maximum rotational frame variation measured ~200 μm beneath the tissue surface. Rotational uniformity degrades as the probe length is extended, rotational speed is increased, or if sharp bends are present in the catheter. There were also occasional larger discontinuities which produced artifacts in the 3D data sets and en face views. The rotational uniformity can be improved in the future by redesigning the torque cable and sheath material used in the imaging probe.
Other groups have performed studies using spiral-scanning probes with balloon stabilization in the pig [17
] and human esophagus [18
] and using a spiral-scanning MEMS micro-motor probe in the human airway [19
]. The balloon design is well-suited for use in the esophagus, where heartbeat- and respiration-induced motion artifacts can significantly degrade image quality. The balloon design centers the optical fiber in the middle of the esophageal lumen, which increases the working distance and limits the minimum spot size to ~15 μm [17
]. The design has the advantage of enabling large areas to be imaged, however variation between sequential rotational frames is expected to be high, owing to the large circumference of the balloon. The highest precision two dimensional scanning approaches will probably require the use of distal actuators. However, the design and packaging of these micro-scanning systems is challenging due to the miniaturization required for use in the working channels of standard endoscopes. The MEMS design reported in [19
] uses a micro-motor at the distal tip of the probe to produce high speed rotational motion and an external linear stage to produce a slow pullback. The MEMS device can be miniaturized to an outer diameter of 2.2 mm, making it suitable for use in the working channel of an endoscope. However the rigid length of the probe must also be minimized in order to enable it to be inserted into the curved introducer portion of endoscopes.
From the viewpoint of OCT technology itself, as data acquisition and signal processing continues to improve, 3D-OCT endomicroscopy should be possible at even higher axial line rates of 250 – 500 kHz supported by advanced FDML lasers. This will enable increased spatial sampling densities for improved resolution, decreased motion artifacts for improved image quality, and still-larger fields of view for reduced sampling errors. All of these advances will improve the ability of 3D-OCT to detect subtle changes associated with early GI disease and to assist in endoscopic therapies, potentially leading to more effective interventions and decreased morbidity and mortality.