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Biomedical Optics & Medical Imaging

3D imaging for faster diagnosis of esophageal disease

A tethered capsule that is swallowed by the patient offers a quick and pain-free method of screening and diagnosing gastrointestinal diseases.
7 May 2013, SPIE Newsroom. DOI: 10.1117/2.1201304.004813

Diagnosing gastrointestinal (GI) diseases usually involves endoscopy, combining an invasive probe and video imaging or other optical methods. While effective, this method often causes patient discomfort and typically requires anesthesia, making it costly and time-consuming. Here we describe a new option for screening using a swallowable optomechanically engineered pill that rapidly provides 3D microscopic images of the gastrointestinal tract. The process is pain-free, so there is no need for anesthesia, and enables quick diagnosis of esophageal diseases.

Figure 1. A tethered-capsule endomicroscope. (A) Photograph of the capsule with its flexible tether. (B) Close-up showing the capsule portion adjacent to a penny for scale.

Barrett's esophagus (BE) is a condition where the normal squamous epithelium (the surface layer of cells) in the esophagus is replaced with glandular epithelium. An important factor in this change is reflux of stomach acid to the esophagus, known as gastroesophageal reflux disease (GERD). Patients with BE are 35–120 times more likely to develop adenocarcinoma (cancer of the epithelial tissue), which if detected early can be completely cured. However, as many as 40% of BE patients do not present with any symptoms of GERD, and therefore it is imperative that asymptomatic persons suffering from GERD and other risk factors be screened regularly for BE.1

Endoscopy diagnoses upper gastrointestinal tract diseases using a 1cm-diameter flexible video imaging probe to visualize superficial structures of the mucous membranes. The images alone may not be sufficient for diagnosis, and are used alongside biopsy samples examined by a pathologist. Endoscopy can be used for visualization and tool delivery, and is justified for treating GI diseases where patients need to be sedated anyway. But, with its limitations, it is inconvenient and may be impractical for screening a large population.

Optical coherence tomography (OCT) is an optical diagnostic method that allows imaging of tissue structures in a non-invasive way. The technology is widely used in ophthalmic applications, and can provide microscopic information needed to diagnose BE. However, using a catheter design, it requires endoscopy, leaving unanswered the problem of finding a low-cost and optimal screening method.

Figure 2. (A) Tethered-capsule endomicroscopy cross-sectional image of the normal esophagus obtained in vivo. (B) An expanded view of (A): the normal layered esophageal wall architectural morphology. (C) Barrett's esophagus with an irregular luminal surface, heterogeneous backscattering, and glands within the mucosa. (D) A 3D image of the normal esophagus.

We developed a tethered, swallowable capsule (see Figure 1) that uses a second-generation OCT technique called optical frequency-domain imaging (OFDI).2 Once swallowed, this pill-shaped device allows 3D microscopic imaging of the esophagus in a quick procedure without sedation or endoscopic assistance. The device comprises a clear capsule connected to a flexible stringlike tether. Within the capsule are optics that focus a beam of near-IR light to the side of the capsule and onto the tissue to be imaged. The 1.6m tether houses an optical fiber, which transceives the light from an OFDI system to the capsule and back. Rotating the optical fiber enables 2D imaging of the circumferential cross-section of the esophageal wall with 30μm (lateral) × 7μm (axial) resolution (see Figure 2A). The capsule progresses down the lumen with the natural propulsion of peristalsis or can be pulled up using the tether. As the capsule traverses the GI tract, we can compile multiple cross-sectional images to obtain a 3D microscopic image of the whole length of the esophagus (see Figure 2).

We have successfully imaged and analyzed 13 subjects using this device.3 Subjects included seven healthy volunteers and six with BE. We found that the total imaging time from swallowing the pill to its removal was approximately six minutes, which included four imaging acquisition passes: two while the capsule moved up and two down. Imaging ∼15cm of esophagus took about 60s. We completed the procedures without complications, and all but one of the subjects said they would prefer to have capsule endomicroscopy instead of regular endoscopy. This study is active and approved by the Partners HealthCare Institutional Review Board (IRB) under study number 2011-P-002619.

Because the tethered capsule passes down the gastrointestinal tract independently of any visual guidance, minimal training is required to perform the procedure. It can be completed with ease and comfort, making the device suitable for use in basic healthcare settings such as a primary care physician's office. The capsule can be retrieved, sterilized, and used many times, making it inexpensive and therefore highly accessible to the general population.

Tethered-capsule endomicroscopy has potential for use in widespread screening and diagnosis of gastrointestinal diseases due to its ease of use for both medical personnel and patients. In future, we aim to reduce the cost and size of the imaging system, and will modify the capsule device to enable diagnosis in the stomach and small intestine.

Author disclosure: Tearney and Nishioka have the rights to receive royalty payments from Ninepoint Medical. Tearney is a consultant for and obtains sponsored research support from Ninepoint Medical.

Amna Soomro, Michalina Gora, Robert Carruth, Weina Lu, Drew Carlton
The Wellman Center for Photomedicine
Massachusetts General Hospital
Boston, MA
Jenny Sauk, Norman Nishioka
Department of Gastroenterology
Massachusetts General Hospital
Boston, MA
Gary Tearney
The Wellman Center for Photomedicine
Department of Pathology
Massachussetts General Hospital
Boston, MA

1. K. K. Wang, R. E. Sampliner, Updated guidelines for 2008 for the diagnosis, surveillance and therapy of Barrett's Esophagus, Am. J. Gastroenterol. 103, p. 788-797, 2008.
2. S. H. Yun, G. J. Tearney, J. F. de Boer, N. Iftimia, B. E. Bouma, High-speed optical frequency-domain imaging, Opt. Express 11, p. 2953-2963, 2003.
3. M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure, Nat. Med. 19, p. 238-240, 2013. doi:10.1038/nm3052