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 #
5R01CA075289-19
Application #
9071301
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Tandon, Pushpa
Project Start
1997-09-05
Project End
2019-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
19
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
Cahill, Lucas C; Giacomelli, Michael G; Yoshitake, Tadayuki et al. (2018) Rapid virtual hematoxylin and eosin histology of breast tissue specimens using a compact fluorescence nonlinear microscope. Lab Invest 98:150-160
Liang, Kaicheng; Wang, Zhao; Ahsen, Osman O et al. (2018) Cycloid scanning for wide field optical coherence tomography endomicroscopy and angiography in vivo. Optica 5:36-43
Yoshitake, Tadayuki; Giacomelli, Michael G; Quintana, Liza M et al. (2018) Rapid histopathological imaging of skin and breast cancer surgical specimens using immersion microscopy with ultraviolet surface excitation. Sci Rep 8:4476
Skalet, Alison H; Li, Yan; Lu, Chen D et al. (2017) Optical Coherence Tomography Angiography Characteristics of Iris Melanocytic Tumors. Ophthalmology 124:197-204
Lee, Hsiang-Chieh; Ahsen, Osman O; Liu, Jonathan J et al. (2017) Assessment of the radiofrequency ablation dynamics of esophageal tissue with optical coherence tomography. J Biomed Opt 22:76001
Liang, Kaicheng; Ahsen, Osman O; Wang, Zhao et al. (2017) Endoscopic forward-viewing optical coherence tomography and angiography with MHz swept source. Opt Lett 42:3193-3196
Lee, ByungKun; Novais, Eduardo A; Waheed, Nadia K et al. (2017) En Face Doppler Optical Coherence Tomography Measurement of Total Retinal Blood Flow in Diabetic Retinopathy and Diabetic Macular Edema. JAMA Ophthalmol 135:244-251
Moult, Eric M; Choi, WooJhon; Boas, David A et al. (2017) Evaluating anesthetic protocols for functional blood flow imaging in the rat eye. J Biomed Opt 22:16005
Choi, WooJhon; Waheed, Nadia K; Moult, Eric M et al. (2017) ULTRAHIGH SPEED SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL AND CHORIOCAPILLARIS ALTERATIONS IN DIABETIC PATIENTS WITH AND WITHOUT RETINOPATHY. Retina 37:11-21
Ahsen, Osman O; Lee, Hsiang-Chieh; Liang, Kaicheng et al. (2017) Ultrahigh-speed endoscopic optical coherence tomography and angiography enables delineation of lateral margins of endoscopic mucosal resection: a case report. Therap Adv Gastroenterol 10:931-936

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