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Skin cancer is the most common form of cancer and it is on the rise. If skin cancer is diagnosed early enough, the survival rate is close to 90%. Oblique-incidence diffuse reflectance (OIR) spectroscopy offers a technology that may be used in the clinic to aid physicians in diagnosing both melanoma and non-melanoma skin cancers. The system includes a halogen light source, a fiber optic probe, an imaging spectrograph, a charge coupled device (CCD) camera, and a computer. Light is delivered to the skin surface via optical fibers in the probe. After interacting with the skin, the light is collected and sent to the spectrograph that generates optical spectra. Images and histopathological diagnoses were obtained from 250 lesions at the University of Texas M.D. Anderson Cancer Center (Melanoma and Skin Center). To classify OIR data, an image processing algorithm was developed and evaluated for both pigmented and non-pigmented lesions. The continuous wavelet transform and the genetic algorithm were employed to extract optimal classification features. Bayes decision rule was used to categorize spatiospectral images based on the selected classification features. The overall classification accuracy for pigmented melanomas and severely dysplastic nevi is 100%. The overall classification accuracy for non-pigmented skin cancers and severely dysplastic nevi is 93.33%. Oblique-incidence diffuse reflectance spectroscopy and the developed algorithms have high classification rates and may prove useful in the clinic as the process is fast, noninvasive and accurate.

Lung cancer is the leading cause of death from cancer in Canada and is typically treated with surgical resection of the tumor. To ensure good prognosis and limit metastases no cancer cells can be left behind during resection. This project uses time-resolved fluorescence and diffuse reflectance to differentiate cancerous and non-cancerous lung tissue. These differences could be used during surgical resection of tumor to ensure no positive margins are present. Using a bi-modal spectroscopy device, BEAR, optical properties were determined for 36 tumor, 36 fibrotic and 9 normal lung tissue samples. Most optical parameters showed statistically significant differences between tumor and other tissue types. Metabolic based optical parameters showed statistically significant differences between fibrotic and normal tissue while non-metabolic based parameters showed no difference. As surgical margins are likely to be between tumor and fibrotic tissue the results demonstrate success and promise for implementing this system. Future work using fresh samples would develop the system further and would be a step closer to in vivo use during surgery. / Thesis / Master of Science (MSc) / Lung cancer is the leading cause of death from cancer and is typically treated by surgically removing the tumor. To improve survival all cancer cells must be removed which can be challenging. This project uses light to extract properties that can differentiate cancerous and non-cancerous lung tissue. These differences could be used during surgery to ensure no cancer cells remain. The project tests this system on 36 tumor, 36 fibrotic and 9 normal lung tissue samples. Most parameters showed significant differences between tumor and other tissue types. Given that often times the surgical boundaries are between tumor and fibrotic tissue the results demonstrate promise in implementing this system. Future work using fresh samples would develop the system further and bring it one step closer to being used during surgery.

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Cancer is a class of diseases in which a group of cells grow uncontrollably, destroy surrounding tissue and eventually spread to other parts of the body, often leading to death. According to the American Cancer Society cancer causes accounts for 13% of all deaths. Much of the time cancer can be treated if diagnosed early. Considerable study is currently being undertaken to investigate tissue properties and their use in detecting cancer at an early stage through non invasive and non surgical methods. Oblique Incidence Diffuse Reflectance Spectrometry (OIDRS) is one such method. This thesis reports the design, fabrication and testing of a new miniaturized optical sensor probe with "side viewing" capability for oblique incidence diffuse reflectance spectrometry. The sensor probe consists of a lithographically patterned polymer waveguides chip and three micromachined positioning substrates and source/collection fibers to achieve 45 degree light incidence and collection of spatially resolved diffuse reflectance. The probe was tested at the Mayo Clinic in Rochester Minnesota. The test results show that the probe is capable of collecting data which can be analyzed to select image features to differentiate the cancerous tissue from non cancerous tissue. Using these probes, diffuse reflectance of human esophageal surface has been successfully measured for differentiation of cancerous tissues from normal ones.

This dissertation describes the design, fabrication and testing of an oblique incidence diffuse reflectance spectrometry (OIDRS) system for in-vivo and noninvasive detection of epithelial cancer. Two probes were fabricated using micromachining technology, which plays a significant role in the probe development by enabling device miniaturization, low-cost fabrication and precise assembly. The fist probe was developed and clinically tested for skin cancer detection. This probe consists of three source fibers, two linear array of collection fibers and four micromachined positioning devices for accurate alignment of the fibers. The spatially resolved diffuse reflectance spectra from 167 pigmented and 78 non-pigmented skin abnormalities were measured and used to design a set of classifiers to separate them into benign or malignant ones. These classifiers perform with an overall classification rate of 91%. The absorption and reduced scattering coefficient spectra were estimated to link the anatomic and physiologic properties of the lesions with the optical diagnosis. The melanoma cases presented larger average absorption and reduced scattering spectra than the dysplastic and benign ones. A second probe was designed to demonstrate the feasibility of a miniaturized ?side viewing? optical sensor probe for OIDRS. The sensor probe consists of a lithographically patterned polymer waveguides chip and two micromachined positioning substrates. This miniaturize probe was used to measure twenty ex-vivo esophageal samples. Two statistical classifiers were designed to separate the esophageal cases. The first one distinguishes benign and low dysplastic from high dysplastic and cancerous lesions. The second classifier separates benign lesions from low dysplastic ones. Both classifiers generated a classification rate of 100%.

<p>The visible wavelength range has proven to be a useful spectral window for observing biophotonic events such as absorption in materials (oxy-hemoglobin and deoxy-hemoglobin), light scattering in biological tissue, and biochemical and fluorescence reactions. Diffuse reflectance spectroscopy (DRS) is a technique that utilizes the diffuse reflectance spectra from turbid media (e.g. biological tissue) to quantify the optical properties (e.g. absorption and scattering) of those media. DRS in the visible wavelength range can be utilized to optically differentiate between healthy and cancerous tissue, and thus has applications in intra-operative tumor margin assessment. </p><p>The footprint of conventional DRS systems used for intra-operative tissue margin assessment prohibits their widespread use inside the surgical suite, where space is at a premium. Conventional quantitative DRS imaging systems utilize unwieldy fiber probes, cooled CCD cameras, and imaging spectrographs for imaging tissue margins. These system components not only increase system size, limiting their use inside the surgical suite, but also limit imaging resolution, imaging speed, and increase overall system cost. </p><p>Silicon is an attractive candidate for the development of compact, customized photodetector elements for biophotonic imaging applications such as intra-operative tumor margin assessment using DRS. This thesis deals with the design and development of a customized DRS imaging probe composed of custom silicon imaging arrays for intra-operative breast tumor margin assessment. The first generation of the customized imaging probe consisted of a 4x4 array of annular epitaxial Si pn junction photodiodes (PDs) with a measured responsivity of 0.28 A/W - 0.37 A/W for &#955;= 470 nm - 600 nm, and a measured dark current density of 1.456 nA/cm2 - 4.48 nA/cm2. The imaging array was used to detect diffuse reflectance when placed in direct contact with tissue. A quartz light delivery tube coupled to a xenon lamp was optimized to deliver light to the tissue through the holes of the annular imaging array across a 256 mm2 imaging area. The pixel-to-pixel spacing in the imaging array was 4.5 mm, the highest resolution reported to date for a multi-pixel DRS probe. This resolution was limited by pixel-to-pixel optical crosstalk, which was theoretically calculated and experimentally characterized, to validate the theoretical model for future designs. This first generation probe was successfully tested on diffuse reflectance standards, tissue-mimicking phantoms, animal tissue, and human breast tissue, and yielded an SNR of 30 dB - 55 dB on all measured specimens. </p><p>The next generation of the customized imaging probe consisted of a 4x4 array of annular thin-film Si pn junction PDs heterogeneously bonded to a transparent Pyrex substrate, to enable integration with a guided wave light delivery system. The 4x4 thin-film PD array design and development was prototyped using a 1x2 thin-film PD array heterogeneously bonded to a Pyrex substrate. The responsivity and dark current of the thin-film PDs in the 1x2 array were measured to be 0.19 A/W - 0.34 A/W for &#955;= 470 nm - 600 nm and 0.63 nA/cm2, respectively. The process for the 1x2 thin-film PD array was scaled to fabricate a 4x4 array of thin-film PDs for DRS, and the 4x4 array was optically and electrically characterized. These heterogeneously bonded thin-film single crystal Si PDs have the highest uncooled responsivity to dark current density ratio (greater than 0.30 - 0.54 cm2/nW for &#955;= 470 nm - 600 nm) reported to date, to the best of our knowledge. The 1x2 array of thin-film PDs were also heterogeneously bonded to a flexible substrate without any degradation in PD optical and electrical characteristics, opening the door towards conformal tissue imaging.</p> / Dissertation

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Optical biopsy is a medical technique that uses light to perform non-invasive analysis of tissue in-situ. This technology has many applications in the medical profession, opening up exciting new possibilities for surgical guidance and diagnosis of malignancies and other conditions. Optical biopsy allows a medical professional to perform near instantaneous, real time analysis of tissue composition without the need to physically remove tissue from the body, as required in traditional biopsy. A technique frequently used for this purpose is diffuse reflectance spectroscopy (DRS): collection and analysis of the spectrum of light reflected from a material. Another technique frequently used for optical biopsy is laser induced fluorescence spectroscopy (LIFS): analysis of the fluorescence spectrum returned by a material when illuminated at a specific wavelength. This thesis discusses the design and construction of a spatially resolved DRS system intended for use in a dual modality DRS and time resolved LIFS optical biopsy instrument for clinical analysis of brain tissue. This instrument is specifically intended for use in the surgical removal of malignant gliomas: infiltrating tumours associated with a poor patient prognosis. Theoretical simulation based studies were used to optimize the design of a compact, dual modality fibre optic probe for use in the system and a novel algorithm was developed to allow recovery of the optical properties of tissue from reflectance spectra obtained with this probe. This probe was manufactured and a corresponding spectrometer based system was created for the acquisition of diffuse reflectance spectra. Components were designed to allow sterilization and thus clinical use in an operating room environment. A laboratory trial of this system demonstrated its range and ability to recover the optical properties of lipid emulsion optical phantoms. / Thesis / Doctor of Philosophy (PhD)

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