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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA075289-17
Application #
8694897
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Tandon, Pushpa
Project Start
1997-09-05
Project End
2019-04-30
Budget Start
2014-07-03
Budget End
2015-04-30
Support Year
17
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Moult, Eric M; Waheed, Nadia K; Novais, Eduardo A et al. (2016) SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS CHORIOCAPILLARIS ALTERATIONS IN EYES WITH NASCENT GEOGRAPHIC ATROPHY AND DRUSEN-ASSOCIATED GEOGRAPHIC ATROPHY. Retina 36 Suppl 1:S2-S11
Schottenhamml, Julia; Moult, Eric M; Ploner, Stefan et al. (2016) AN AUTOMATIC, INTERCAPILLARY AREA-BASED ALGORITHM FOR QUANTIFYING DIABETES-RELATED CAPILLARY DROPOUT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina 36 Suppl 1:S93-S101
Lee, Hsiang-Chieh; Ahsen, Osman Oguz; Liang, Kaicheng et al. (2016) Circumferential optical coherence tomography angiography imaging of the swine esophagus using a micromotor balloon catheter. Biomed Opt Express 7:2927-42
Minami, Yoshiyasu; Wang, Zhao; Aguirre, Aaron D et al. (2016) Quantitative analysis of the side-branch orifice after bifurcation stenting using en-face processing of OCT images: a comparison between Xience V and Resolute Integrity stents. Coron Artery Dis 27:19-28
Novais, Eduardo A; Adhi, Mehreen; Moult, Eric M et al. (2016) Choroidal Neovascularization Analyzed on Ultrahigh-Speed Swept-Source Optical Coherence Tomography Angiography Compared to Spectral-Domain Optical Coherence Tomography Angiography. Am J Ophthalmol 164:80-8
Schottenhamml, Julia; Moult, Eric M; Ploner, Stefan et al. (2016) AN AUTOMATIC, INTERCAPILLARY AREA-BASED ALGORITHM FOR QUANTIFYING DIABETES-RELATED CAPILLARY DROPOUT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina :
Moult, Eric M; Waheed, Nadia K; Novais, Eduardo A et al. (2016) SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS CHORIOCAPILLARIS ALTERATIONS IN EYES WITH NASCENT GEOGRAPHIC ATROPHY AND DRUSEN-ASSOCIATED GEOGRAPHIC ATROPHY. Retina :
Ploner, Stefan B; Moult, Eric M; Choi, WooJhon et al. (2016) TOWARD QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Visualizing Blood Flow Speeds in Ocular Pathology Using Variable Interscan Time Analysis. Retina :
Adhi, Mehreen; Badaro, Emmerson; Liu, Jonathan J et al. (2016) Three-Dimensional Enhanced Imaging of Vitreoretinal Interface in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography. Am J Ophthalmol 162:140-149.e1
Ploner, Stefan B; Moult, Eric M; Choi, WooJhon et al. (2016) TOWARD QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Visualizing Blood Flow Speeds in Ocular Pathology Using Variable Interscan Time Analysis. Retina 36 Suppl 1:S118-S126

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