This is a multidisciplinary collaboration between investigators at the Massachusetts Institute of Technology and the VA Boston Healthcare System integrating imaging technology research, clinical imaging studies, medical device development and animal imaging studies. Esophageal cancer is a lethal malignancy, with a five-year survival rate of 16%. Barrett's esophagus (BE) and dysplasia are precursors to esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) is becoming the standard of care as an effective treatment for dysplastic BE, greatly reducing progression to malignancy. However, RFA requires an average of >3 treatment sessions, and long term recurrence rates for BE are >25%. Optical coherence tomography (OCT) can perform high resolution, three-dimensional imaging of tissue morphology in situ and in real-time. The hypotheses are: 1. Endoscopic OCT can identify features associated with RFA treatment response, 2. Image guided ablation therapy can be developed for treatment planning and real time ablation monitoring, and 3. Image guidance can reduce sampling errors and increase yields for excisional biopsy diagnosis of dysplasia and early carcinoma.
Aim 1 : Endoscopic OCT markers for RFA treatment response. We will conduct a prospective, longitudinal study on patients with dysplastic BE being treated with RFA to identify structural features associated with RFA treatment response. Endoscopic OCT will be performed to volumetrically map markers including BE epithelium thickness, subsquamous intestinal metaplasia, and residual glandular structure due to insufficient ablation. We will evaluate the correlation of these features to RFA treatment efficacy/durability, including the total number of treatment sessions and recurrence of BE post treatment.
Aim 2 : Image guided esophageal ablation devices and techniques. OCT enables real time imaging of esophageal structure and ablation depth. We propose to develop and compare an OCT-guided multi-zone RFA ablation probe and OCT-guided laser ablation balloon. Studies will be performed on swine esophagus ex vivo to establish dosing parameters using OCT imaging and histological validation. An in vivo swine model will then be used to evaluate the ability to simpliy ablation protocols and to perform controlled depth and area ablations.
Aim 3 : Ultrahigh resolution endoscopic OCT for detecting dysplasia and early carcinoma. Detecting dysplasia and early carcinoma remains challenging and the standard diagnostic procedure relies on four quadrant biopsy sampling. We propose to develop ultrahigh speed swept source OCT and probe technologies for dysplasia and early carcinoma detection. Validation studies will be performed in patients with upper GI dysplasia and patients with lower GI endoscopic mucosal resection (EMR) to assess sensitivity and specificity of OCT imaging compared with standard histology. The proposed work will develop new imaging methods that could risk stratify RFA patients, enable future image guided clinical ablation devices, and increase sensitivity for dysplasia and early carcinoma diagnosis.

Public Health Relevance

Radiofrequency ablation (RFA) is the standard of care for dysplastic Barrett's esophagus, but requires multiple treatments and has a high recurrence rate. This goal of this program is to improve diagnosis and therapy. The program investigates endoscopic optical coherence tomography (OCT) imaging to identify markers for RFA treatment response, develops new image guided endoscopic ablation devices and methods to improve therapy, and develops ultrahigh resolution volumetric imaging to guide biopsy and reduce sampling error.

National Institute of Health (NIH)
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Biomedical Imaging Technology Study Section (BMIT)
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Tandon, Pushpa
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Massachusetts Institute of Technology
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Alasil, Tarek; Ferrara, Daniela; Adhi, Mehreen et al. (2015) En face imaging of the choroid in polypoidal choroidal vasculopathy using swept-source optical coherence tomography. Am J Ophthalmol 159:634-43
Ahsen, Osman O; Lee, Hsiang-Chieh; Giacomelli, Michael G et al. (2014) Correction of rotational distortion for catheter-based en face OCT and OCT angiography. Opt Lett 39:5973-6
Ferrara, Daniela; Mohler, Kathrin J; Waheed, Nadia et al. (2014) En face enhanced-depth swept-source optical coherence tomography features of chronic central serous chorioretinopathy. Ophthalmology 121:719-26
Tao, Yuankai K; Shen, Dejun; Sheikine, Yuri et al. (2014) Assessment of breast pathologies using nonlinear microscopy. Proc Natl Acad Sci U S A 111:15304-9
Liu, Jonathan J; Witkin, Andre J; Adhi, Mehreen et al. (2014) Enhanced vitreous imaging in healthy eyes using swept source optical coherence tomography. PLoS One 9:e102950
Zhang, Ning; Tsai, Tsung-Han; Ahsen, Osman O et al. (2014) Compact piezoelectric transducer fiber scanning probe for optical coherence tomography. Opt Lett 39:186-8
Choi, WooJhon; Potsaid, Benjamin; Jayaraman, Vijaysekhar et al. (2013) Phase-sensitive swept-source optical coherence tomography imaging of the human retina with a vertical cavity surface-emitting laser light source. Opt Lett 38:338-40
Ahsen, Osman O; Tao, Yuankai K; Potsaid, Benjamin M et al. (2013) Swept source optical coherence microscopy using a 1310 nm VCSEL light source. Opt Express 21:18021-33
Grulkowski, Ireneusz; Liu, Jonathan J; Potsaid, Benjamin et al. (2013) High-precision, high-accuracy ultralong-range swept-source optical coherence tomography using vertical cavity surface emitting laser light source. Opt Lett 38:673-5
Grulkowski, Ireneusz; Liu, Jonathan J; Zhang, Jason Y et al. (2013) Reproducibility of a long-range swept-source optical coherence tomography ocular biometry system and comparison with clinical biometers. Ophthalmology 120:2184-90

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