SBIR-STTR Award

Newton Laboratories, Inc. (NLI) will design a prototype instrument for use by gastroenterologists performing endoscopic surveillance of patients with Barrett's esophagus (BE). The instrument will identify dysplastic changes in real-time using an innovative spectroscopic technique called Light Scattering Spectroscopy (LSS). LSS Measures the size distribution and density of cell nuclei in the surface of esophageal mucosa by analyzing light scattered from those nuclei. A recent clinical study has shown that LSS can accurately detect both high grade and low grade dysplasia in patients with BE. The instrument used in this study was a laboratory device designed to test the scientific principle in a clinical setting. In this Phase I program, NLI will design a clinical instrument, to be constructed and clinically tested in Phase II, which is easy to use and commercially practical. The instrument will incorporate improved methods for removing the background and extracting the clinical information, so that information can he provided in an automated fashion in real time. The new design will be tested on tissue phantoms to establish that it meets performance goals. If successful, this project will lead to an important new tool for routine use by gastroenterologists for detecting and diagnosing this serious condition. PROPOSED COMMERCIAL APPLICATIONS: The LSS technique has significant advantages over current biopsy- dependent surveillance methods, It is minimally invasive, provides diagnoses in real-time, allows a much greater number of sites to be sampled and has proven to he highly reliable in its initial clinical trials, compared to both the average and consensus diagnoses of pathologists. As such it will find a ready market in hospitals and clinics which perform these surveillance procedures

Barrett's esophagus (BE) is an acquired condition of the lower esophagus in which the normal squamous tissue is replaced by a metaplastic columnar mucosa. BE itself is not malignant, but it is the primary risk factor for esophageal adenocarcinoma, and a significant number of patients with BE will have adenocarcinoma at the time of first endoscopy. Currently, examination for dysplasia requires numerous random biopsy samples. This work will complete the development and clinically test an optical instrument for detecting and grading Barrett's dysplasia. Light scattering spectroscopy (LSS) has already been shown to differentiate between normal and diseased tissue conditions in BE patients, but the analysis is complex so the data is analyzed after the procedure is over. The instrument developed by this work will be based on white light LSS, but it will use a special probe design and data reduction algorithm, developed by NLI, enabling real-time results. The probe design makes use of the properties of light scattering by cell nuclei and other tissue components to enable the separation and subtraction of interfering effects, and the characterization of the nuclei, based on using spectral, angular, and polarization characteristics of the scattering processes. The tissue characterization follows from the instrument's quantitative determination of the nuclear size and number density for the surface mucosal cells - two properties commonly used by pathologists. Specifically, NLI will (i) produce the probe, (it) calculate the data base for the real-time algorithm, (iii) produce the instrument with light source, spectrometer, and embedded computer (suitable for interface with a standard clinical video endoscope), (iv) verify the instrument operation in the laboratory using standard scattering materials, (v) verify the background subtraction properties by using normal and diseased resected colon tissue, and (vi) conduct clinical studies on patients with Barrett's Esophagus