SBIR-STTR Award

The long term objective is a practical clinical Raman instrument with a fiberoptic probe, for use with a bronchoscope, for characterizing bronchial tissue with respect to precancerous conditions. The system will be especially effective with a new generation of bronchoscopes that have their screening efficacy enhanced by use of auto-fluorescence or other spectroscopic imaging methods. Since lung cancer is the second most common cancer in humans, is the most common cause of cancer deaths in the world, and has a very low (14%) five year survival rate, an instrument that can be easily utilized with normal bronchoscopy procedures will add clinical medical value by enabling real time examination of suspicious sights, with enhanced sensitivity relative to white light bronchoscopy alone. This will enable greater yield of "positives" from those sites that are chosen for biopsy. The Specific Aims for Phase I are: (1) The acquisition of Raman spectra at an excitation wavelength of 830 nm from in-vitro samples of normal, dysplastic and cancerous lung tissue, using free-space propagating beams. (2) The production and testing of a small-diameter, filtered, fiberoptic Raman probe, suitable for insertion through the biopsy channel of a bronchoscope. (3) The development of real-time data analysis algorithms which can indicate the state of the observed tissue on the basis of characteristic signatures described in the literature. Basic Raman data will be obtained on in vitro bronchial tissue to assist probe design and algorithm development. Probes will be designed, fabricated and used with a Raman prototype instrument on in vitro bronchial tissue samples to compare with modeling calculations and demonstrate feasibility of a real-time in vivo instrument for use in conjunction with a bronchoscope in clinical examinations

The goal of this program is to improve the diagnostic sensitivity and especially the specificity of autofluorescence endoscopes by examining additional information on the molecular constituents of the tissue being observed as determined by a fiberoptic Raman probe. The combined instrument will first use autofluorescence imaging to quickly identify areas of tissue which are likely to be dysplastic or cancerous. In a standard bronchoscopy procedure a small sample of tissue from this area would be taken with forceps passed through the narrow biopsy channel of the endoscope. In this program, a fiberoptic Raman probe will first be passed through this biopsy channel and pressed lightly against the suspect area of tissue. A 1-second pulse of narrowband, 830 nm light will be directed onto the tissue through a central fiber and lens assembly at the distal tip of the probe. A long-pass filter in the tip of the probe will block the backscattered 830 nm excitation wavelength but pass the longer wavelength tissue fluorescence and Raman-shifted light into a ring of collection fibers. These collection fibers will carry the scattered light back to a spectrometer which will disperse it into a characteristic Raman "fingerprint" spectrum. This spectrum contains many individual peaks corresponding to the concentration of specific molecules in the tissue. The standard biopsy will then be taken from the tissue site and sent to a pathology lab to be examined for evidence of dysplasia or cancer. This program will catalog the measured spectra and correlate them with the results of pathology. Once the catalog of spectra contains samples of normal, dysplastic and cancerous tissue fingerprints it will be possible to begin to predict, in real-time, what the results of pathology will be. A large number of spectra will need to be collected, however, from many different stages of discovered cancers before the predicted results are likely to be reliable. The use of autofluorescence imaging during bronchoscopy procedures has been shown to improve the sensitivity of cancer diagnosis over that which can be achieved by white light observation alone. This means there are few instances where a truly cancerous or dysplastic area of tissue is seen to be normal (a false negative determination of cancer). On the other hand, the method often classifies normal tissue as cancerous (a false positive determination) which leads to an additional risk to the patient from unnecessary biopsies, wasted time during the procedure and additional costs. The additional information from the Raman probe is expected to be able to identify many of these false positive sites as truly normal, increasing the specificity of the tissue characterization. Once the method is proven to be effective it will reduce patient risk, reduce the time required for procedures and reduce the cost of unnecessary biopsies.

Thesaurus Terms:
Raman spectrometry, biomedical equipment development, bronchoscopy, bronchus neoplasm, clinical biomedical equipment, fiber optics, lung neoplasm, neoplasm /cancer diagnosis, preneoplastic state, respiratory imaging /visualization computer assisted diagnosis, computer program /software, diagnosis quality /standard, fluorescence, miniature biomedical equipment bioengineering /biomedical engineering, bioimaging /biomedical imaging, clinical research, human subject, human tissue