Weina Lu

Imaging the upper gastrointestinal tract in unsedated patients using tethered capsule endomicroscopy.

Endoscopic examination of the upper gastrointestinal tract is costly, inconvenient, and typically requires that the patient be sedated.1 Standard video endoscopy only provides macroscopic information so small, focal biopsies are excised in order to obtain a microscopic tissue diagnosis. Because there are few reliable visible cues for Barrett’s esophagus and dysplasia, crucial diagnostic regions can be missed. In order to overcome these limitations of endoscopy, we have integrated a microscopic imaging technology into a tethered capsule that can be swallowed. This new method, which we term tethered capsule endomicroscopy, provides microscopic information from the entire esophagus as the pill passes through the GI tract.

Tethered capsule endomicroscopy: from bench to bedside at a primary care practice

Abstract. Due to the relatively high cost and inconvenience of upper endoscopic biopsy and the rising incidence of esophageal adenocarcinoma, there is currently a need for an improved method for screening for Barrett’s esophagus. Ideally, such a test would be applied in the primary care setting and patients referred to endoscopy if the result is suspicious for Barrett’s. Tethered capsule endomicroscopy (TCE) is a recently developed technology that rapidly acquires microscopic images of the entire esophagus in unsedated subjects. Here, we present our first experience with clinical translation and feasibility of TCE in a primary care practice. The acceptance of the TCE device by the primary care clinical staff and patients shows the potential of this device to be useful as a screening tool for a broader population.

Tethered capsule OCT endomicroscopy for upper gastrointestinal tract imaging by using ball lens probe (Conference Presentation)

While endoscopy is the most commonly used modality for diagnosing upper GI tract disease, this procedure usually requires patient sedation that increases cost and mandates its operation in specialized settings. In addition, endoscopy only visualizes tissue superfically at the macroscopic scale, which is problematic for many diseases that manifest below the surface at a microscopic scale. Our lab has previously developed technology termed tethered capsule OCT endomicroscopy (TCE) to overcome these diagnostic limitations of endoscopy. The TCE device is a swallowable capsule that contains optomechanical components that circumferentially scan the OCT beam inside the body as the pill traverses the organ via peristalsis. While we have successfully imaged ~100 patients with the TCE device, the optics of our current device have many elements and are complex, comprising a glass ferrule, optical fiber, glass spacer, GRIN lens and prism. As we scale up manufacturing of this device for clinical translation, we must decrease the cost and improve the manufacturability of the capsule’s optical configuration. In this abstract, we report on the design and development of simplificed TCE optics that replace the GRIN lens-based configuration with an angle-polished ball lens design. The new optics include a single mode optical fiber, a glass spacer and an angle polished ball lens, that are all fusion spliced together. The ball lens capsule has resolutions that are comparable with those of our previous GRIN lens configuration (30µm (lateral) × 7 µm (axial)). Results in human subjects show that OCT-based TCE using the ball lens not only provides rapid, high quality microstructural images of upper GI tract, but also makes it possible to implement this technology inexpensively and on a larger scale.

SECM half-inch tethered endoscopic capsule (HITEC) for esophageal imaging (Conference Presentation)

Spectrally encoded confocal microscopy (SECM) is a high-speed confocal endomicroscopy technology that can image extremely large regions of human tissue at cellular resolution within a short imaging time. Previously, we have developed a 7-mm-diameter SECM endoscopic capsule and successfully demonstrated imaging of human esophagus in vivo. Even though we were able to successfully capture images with the previous capsule, it suffered from two limitations: (1) the capsule had a small diameter, which provided a limited contact between SECM capsule and esophagus; and (2) speckle noise in SECM images made it challenging to appreciate cellular features. In this paper, we present a new SECM capsule, termed SECM half-inch tethered endoscopic capsule (HITEC), which addresses the two aforementioned technical challenges. With the SECM HITEC, a dual-clad fiber was used to reduce the speckle noise. Miniature GRIN optics was used to increase the NA of the fiber from 0.09 to 0.25, which made it possible to build a SECM capsule with large diameter (12.7 mm) while maintaining a short rigid length (22 mm). A water-immersion objective lens was custom designed and manufactured to provide high NA of 0.7. We have manufactured the SECM HITEC catheter and tested its optical and mechanical performance. Lateral and axial resolution was measured as 1.2 µm and 13 µm, respectively. We have imaged swine esophageal tissues ex vivo, and SECM images clearly visualized cell nuclei. Non-uniform rotational distortion (NURD) was small, less than 5%. Preliminary results suggest that SECM HITEC provides sufficient optical and mechanical performance for tissue imaging. In a future clinical study, we will test the feasibility of utilizing SECM HITEC for improved cellular imaging human of the human esophagus in vivo.

Clinical experience using the tethered capsule-based spectrally encoded confocal microendoscopy for diagnosis of eosinophilic esophagitis(Conference Presentation)

Eosinophilic Esophagitis (EoE) is caused by food allergies, and defined by histological presence of eosinophil cells in the esophagus. The current gold standard for EoE diagnosis is endoscopy with pinch biopsy to detect more than 15 eosinophils/ High power field (HPF). Biopsy examinations are expensive, time consuming and are difficult to tolerate for patients. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology capable of imaging individual eosinophils as highly scattering cells (diameter between 8 µm to 15 µm) in the epithelium. Our lab has developed a tethered SECM capsule that can be swallowed by unsedated patients. The capsule acquires large area confocal images, equivalent to more than 30,000 HPFs, as it traverses through the esophagus. In this paper, we present the outcome of a clinical study using the tethered SECM capsule for diagnosing EoE. To date, 32 subjects have been enrolled in this study. 88% of the subjects swallowed the capsules without difficulty and of those who swallowed the capsule, 95% preferred the tethered capsule imaging procedure to sedated endoscopic biopsy. Each imaging session took about 12 ± 2.4 minutes during which 8 images each spanning of 24 ± 5 cm2 of the esophagus were acquired. SECM images acquired from EoE patients showed abundant eosinophils as highly scattering cells in squamous epithelium. Results from this study suggest that the SECM capsule has the potential to become a less-invasive, cost-effective tool for diagnosing EoE and monitoring the response of this disease to therapy.