Development of a Wide Field Diffuse Reflectance Spectral Imaging System for Breast Tumor Margin Assessment
Breast conserving surgery (BCS) is a common treatment option for breast cancer patients. The goal of BCS is to remove the entire tumor from the breast while preserving as much normal tissue as possible for a better cosmetic outcome after surgery. Specifically, the excised specimen must have at least 2 mm of normal tissue surrounding the diseased mass. Unfortunately, a staggering 20-70% of patients undergoing BCS require repeated surgeries due to the incomplete removal of the tumor diagnosed post-operatively. Due to these high re-excision rates as well as limited post-operative histopathological sampling of the tumor specimen, there is an unmet clinical need for margin assessment. Quantitative diffuse reflectance spectral imaging has previously been explored as a promising, method for providing real-time visual maps of tissue composition to help surgeons determine breast tumor margins to ensure the complete removal of the disease during breast conserving surgery. We have leveraged the underlying sources of contrast in breast tissue, specifically total hemoglobin content, beta-carotene content, and tissue scattering, and developed various fiber optics based spectral imaging systems for this clinical application. Combined with a fast inverse Monte Carlo model of reflectance, previous studies have shown that this technology may be able to decrease re-excision rates for BCS. However, these systems, which all consist of a broadband source, fiber optics probes, an imaging spectrograph and a CCD, have severe limitations in system footprint, tumor area coverage, and speed for acquisition and analysis. The fiber based spectral imaging systems are not scalable to smaller designs that cover a large surveillance area at a very fast speed, which ultimately makes them impractical for use in the clinical environment. The objective of this dissertation was to design, develop, test, and show clinical feasibility of a novel wide field spectral imaging system that utilizes the same scientific principles of previously developed fiber optics based imaging systems, but improves upon the technical issues, such as size, complexity, and speed,to meet the demands of the intra-operative setting.
First, our simple re-design of the system completely eliminated the need for an imaging spectrograph and CCD by replacing them with an array of custom annular photodiodes. The geometry of the photodiodes were designed with the goal of minimizing optical crosstalk, maximizing SNR, and achieving the appropriate tissue sensing depth of up to 2 mm for tumor margin assessment. Without the imaging spectrograph and CCD, the system requires discrete wavelengths of light to launch into the tissue sample. A wavelength selection method that combines an inverse Monte Carlo model and a genetic algorithm was developed in order to optimize the wavelength choices specifically for the underlying breast tissue optical contrast. The final system design consisted of a broadband source with an 8-slot filter wheel containing the optimized set of wavelength choices, an optical light guide and quartz light delivery tube to send the 8 wavelengths of light in free space through the back apertures of each annular photodiode in the imaging array, an 8-channel integrating transimpedance amplifier circuit with a switch box and data acquisition card to collect the reflectance signal, and a laptop computer that controls all the components and analyzes the data.
This newly designed wide field spectral imaging system was tested in tissue-mimicking liquid phantoms and achieved comparable performance to previous clinically-validated fiber optics based systems in its ability to extract optical properties with high accuracy. The system was also tested in various biological samples, including a murine tumor model, porcine tissue, and human breast tissue, for the direct comparison with its fiber optics based counterparts. The photodiode based imaging system achieved comparable or better SNR, comparable extractions of optical properties extractions for all tissue types, and feasible improvements in speed and coverage for future iterations. We show proof of concept in performing fast, wide field spectral imaging with a simple, inexpensive design. With a reduction in size, cost, number of wavelengths used, and overall complexity, the system described by this dissertation allows for a more seamless scaling to higher pixel number and density in future iterations of the technology, which will help make this a clinically translatable tool for breast tumor margin assessment.
diffuse reflectance spectroscopy
tissue spectral imaging
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