Browsing by Subject "Diffuse reflectance"
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Item Open Access Diffuse Reflectance Spectroscopy Characterization for Extraction of Tissue Physiological Parameters(2010) Phelps, Janelle EliseVariations in hemoglobin concentration can be indicative of a number of serious complications, including blood loss and anemia. Rapid, noninvasive measurements of hemoglobin are important in applications where blood status is reflective of patient well-being, such as in the emergency room, operating room, or the battlefield. Probe-based diffuse reflectance spectroscopy is capable of noninvasively quantifying tissue optical properties, including hemoglobin concentration. The quantification of hemoglobin concentration using optical methods is complicated by tissue scattering and the robustness of the algorithm and instrumentation used to interrogate the tissue. The sensing depth of diffuse reflectance spectroscopy can be tailored by the wavelengths of light and probe design used.
In this thesis, the accuracy and clinical viability of different diffuse reflectance spectroscopy implementations are presented. The robustness of an inverse Monte Carlo model, in which tissue optical properties are determined from measured reflectance using ultraviolet-visible (UV-VIS) wavelengths and a steady-state instrument, was tested using laboratory measurements. From the laboratory measurements, a set of references was identified which provided accurate absorption and scattering measurements, independent of the optical properties of the target. In addition, the ability to quantify hemoglobin concentration and saturation over large ranges and concentrations of multiple absorbers was established.
Following the laboratory measurements, a clinical study in which UV-VIS spectra were measured from the sublingual mucosa of patients undergoing surgeries was carried out. From this study, the correlations of extracted hemoglobin to expected blood hemoglobin were found to be improved when a simple ratiometric method based on isosbestic wavelengths of hemoglobin was used. During this study, the probe positioning in the mouth was found to be unwieldy, and so the transition to a more secure probe that could be taped to the hand was made.
In order to penetrate the overlying skin, near-infrared (NIR) wavelengths with a different probe geometry was explored. Further investigation of the inverse Monte Carlo model with NIR wavelengths was executed, and while in theory this combination should yield accurate optical property estimation, laboratory measurements indicated large errors, presumably due to the instrument or low magnitude and reduced spectral features of hemoglobin absorption in the NIR. Instead, the use of a well-established frequency-domain instrument coupled with diffusion approximation was implemented to measure spectra from the thenar eminence of volunteers undergoing induced hypovolemia and subsequent retransfusion. There were some moderate correlations with blood hemoglobin, but because both this method and the Monte Carlo method with mucosal probe placement showed higher variability with probe pressure than the isosbestic ratiometric method, further development of the ratiometric method was made.
The ratiometric method was developed using simulations and validated with phantoms and clinical data. Monte Carlo modeled reflectance was generated for a large range of biologically-relevant absorption and scattering values. The modeled reflectance was scaled by a calibration spectra obtained from a single laboratory phantom measurement so that linear regression equations relating hemoglobin concentration to ratios could be applied directly to clinical or laboratory measurements. Ratios which could best estimate hemoglobin concentration independent of saturation and scattering were determined through the simulation and laboratory measurements. Three isosbestic ratios - 545/390, 452/390, and 529/390 nm - were determined to best estimate hemoglobin concentration, and ratiometric-extracted hemoglobin was shown to correlate well to Monte Carlo-extracted hemoglobin in clinical measurements. Because only a single calibration measurement (which can be measured on a different day) is required per instrument and probe combination, this method can be implemented in near real-time and is thus appropriate for applications where hemoglobin concentration must be measured rapidly.
Item Open Access Exploiting Optical Contrasts for Cervical Precancer Diagnosis via Diffuse Reflectance Spectroscopy(2010) Chang, Vivide Tuan ChyanAmong women worldwide, cervical cancer is the third most common cancer with an incidence rate of 15.3 per 100,000 and a mortality rate of 7.8 per 100,000 women. This is largely attributed to the lack of infrastructure and resources in the developing countries to support the organized screening and diagnostic programs that are available to women in developed nations. Hence, there is a critical global need for a screening and diagnostic paradigm that is effective in low-resource settings. Various strategies are described to design an optical spectroscopic sensor capable of collecting reliable diffuse reflectance data to extract quantitative optical contrasts for cervical cancer screening and diagnosis.
A scalable Monte Carlo based optical toolbox can be used to extract absorption and scattering contrasts from diffuse reflectance acquired in the cervix in vivo. [Total Hb] was shown to increase significantly in high-grade cervical intraepithelial neoplasia (CIN 2+), clinically the most important tissue grade to identify, compared to normal and low-grade intraepithelial neoplasia (CIN 1). Scattering was not significantly decreased in CIN 2+ versus normal and CIN 1, but was significantly decreased in CIN relative to normal cervical tissues.
Immunohistochemistry via anti-CD34, which stains the endothelial cells that line blood vessels, was used to validate the observed absorption contrast. The concomitant increase in microvessel density and [total Hb] suggests that both are reactive to angiogenic forces from up-regulated expression of VEGF in CIN 2+. Masson's trichrome stain was used to assess collagen density changes associated with dysplastic transformation of the cervix, hypothesized as the dominant source of decreased scattering observed. Due to mismatch in optical and histological sampling, as well as the small sample size, collagen density and scattering did not change in a similar fashion with tissue grade. Dysplasia may also induce changes in cross-linking of collagen without altering the amount of collagen present. Further work would be required to elucidate the exact sources of scattering contrast observed.
Common confounding variables that limit the accuracy and clinical acceptability of optical spectroscopic systems are calibration requirements and variable probe-tissue contact pressures. Our results suggest that using a real-time self-calibration channel, as opposed to conventional post-experiment diffuse reflectance standard calibration measurements, significantly improved data integrity for the extraction of scattering contrast. Extracted [total Hb] and scattering were also significantly associated with applied contact probe pressure in colposcopically normal sites. Hence, future contact probe spectroscopy or imaging systems should incorporate a self-calibration channel and ensure spectral acquisition at a consistent contact pressure to collect reliable data with enhanced absorption and scattering contrasts.
Another method to enhance optical contrast is to selectively interrogate different depths in the dysplastic cervix. For instance, scattering has been shown to increase in the epithelium (increase in nuclear-to-cytoplasmic ratio) while decrease in the stroma (re-organization of the extra-cellular matrix and changes in of collagen fiber cross-links). A fiber-optic probe with 45° illumination and collection fibers with a separation distance of 330 μm was designed and constructed to selectively interrogate the cervical epithelium. Mean extraction errors from liquid phantoms with optical properties mimicking the cervical epithelium for μa and μs' were 11.3 % and 12.7 %, respectively. Diffuse reflectance spectra from 9 sites in four loop electrosurgical excision procedure (LEEP) patients were analyzed. Preliminary data demonstrate the utility of the oblique fiber geometry in extracting scattering contrast in the cervical epithelium. Further work is needed to study the systematic error in optical property extraction and to incorporate simultaneous extraction of epithelial and stromal contrasts using both flat and oblique illumination and collection fibers.
Various strategies, namely self-calibration, consistent contact pressure, and the incorporation of depth-selective sensing, have been proposed to improve the data integrity of an optical spectroscopic system for maximal contrast. In addition to addressing field operation requirements (such as power and operator training requirement), these improvements should enable the collection of reliable spectral data to aid in the adoption of optical smart sensors in the screening and diagnosis of cervical precancer, especially in a global health setting.
Item Open Access Systems and Methods for Quantitative Functional Imaging of Breast Tumor Margin Morphology(2016) Nichols, Brandon Scott\abstract
Among women, breast cancer has the highest incidence rate worldwide and remains the leading cause of cancer-related deaths in developed countries. Women with stage I or II breast cancer are eligible for a surgical procedure known as breast conserving surgery (BCS) which seeks to optimize the amount of tissue removed.BCS involves removing the tumor and a minimally thin peripheral layer, or margin of disease-free tissue surrounding the tumor. While the procedure dramatically minimizes the amount of tissue removed, an unfortunate concomitant reality is that a significant percentage (around 25$\%$) of patients will be advised to return for a second surgery due to the discovery of malignant cells at the tissue margin edge, suggesting that it is likely not all of the malignant cells were removed in the initial procedure. The fact that margins are analyzed in histopathology post-operatively (in most cases) presents a substantial clinical burden that could be reduced if the surgeon was able to reliably assess suspicious areas intra-operatively.
The primary challenge in addressing this need stems from the need to resolve microscopic cellular morphology within a relatively tremendous amount of benign breast tissue. Many investigative optical tools seek to address this challenge, as the wavelength-dependent nature of light propagation within tissue can be used to assign optical signatures to tissue types derived from the relative tissue constituents.
Among the numerous techniques, quantitative diffuse reflectance spectroscopy (QDRS) is a well-established, comparatively simple technique that has been extensively validated in simulation, tissue-simulating phantoms, and various clinical contexts to robustly provide feature-specific optical signatures related to tissue morphology. We have leveraged QDRS in an evolution of several system formats to describe the morphological state of excised breast tissue based on the endogenous optical chromophores and scatterers within the breast, specifically, the amount of hemoglobin from blood, \betac~ in fat, as well as the size distribution and number density of scatterers.
We have employed multiple hardware embodiments of this technique related to the context of use. Each device leverages the same physical principles: The diffuse reflectance spectrum is measured using an imaging probe with multiple optical channels and is analyzed with a feature extraction algorithm based on a fast, scalable \mc~ model to quantitatively determine the absorption spectrum (\mualam) and reduced scattering spectrum (\musplam). The technology detects varying amounts of malignancy in the presence of benign tissue by quantifying the margin “landscape” as a cumulative distribution function (CDF) of the ratio of \betac~ concentration (absorber) and the wavelength averaged tissue scattering (\bscat), derived from \oprop, respectively. We have established through histopathological validation that the \bscat~ reports on the relative amount of adipose to collagen, glands, and fibrous content; decreased ratios are strongly associated with the presence of residual disease.
Local recurrence in BCS has a compelling association with residual disease, suggesting that QDRS could be used to reduce re-excision rates. The work presented here demonstrates a systematic approach in the development of a pragmatic and clinically viable QDRS imaging system. Two approaches are employed: a robust, research-grade 49-channel system is used to validate previous clinical findings and determine the optimal sampling resolution, and secondly, a low-cost, portable, miniature system based on annular photodiodes is developed and shown to be diagnostically comparable. These systems are accompanied by the development of a unique imaging platform that provides robust quality control and improved resolution, further improving the diagnostic capability. The diagnostic utility of the \bscat parameter is explored in a 100-patient clinical study. The potential for commercialization of the miniature system is informed through deployment of a replica system at a remote institution. Accessibility is improved through the design of a generic, object oriented software package that abstracts the individual hardware components.
The portability, accuracy, and manufacturability provide a realistically translatable path for integration into the clinical standard of care.