Browsing by Subject "Optical properties"
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Item Open Access Exploring Optical Contrast in Ex-Vivo Breast Tissue Using Diffuse Reflectance Spectroscopy and Tissue Morphology(2012) Kennedy, Stephanie AnnIn 2011, an estimated 230,480 new cases of invasive breast cancer were diagnosed among women, as well as an estimated 57,650 additional cases of in situ breast cancer [1]. Breast conserving surgery (BCS) is a recommended surgical choice for women with early stage breast cancer (stages 0, I, II) and for those with Stage II-III disease who undergo successful neo-adjuvant treatment to reduce their tumor burden [2, 3]. Cancer within 2mm of a margin following BCS increases the risk of local recurrence and mortality [4-6]. Margin assessment presents an unmet clinical need. Breast tissue is markedly heterogeneous which makes identifying cancer foci within benign tissue challenging. Optical spectroscopy can provide surgeons with intra-operative diagnostic tools. Here, ex-vivo breast tissue is evaluated to determine which sources of optical contrast have the potential to detect malignancy at the margins in women of differing breast composition. Then, H&E images of ex-vivo breast tissue sites are quantified to further deconstruct the relationship between optical scattering and the underlying tissue morphology.
Diffuse reflectance spectra were measured from benign and malignant sites from the margins of lumpectomy specimens. Benign and malignant sites were compared and then stratified by tissue type and depth. The median and median absolute deviance (MAD) was calculated for each category. The frequencies of the benign tissue types were separated by menopausal status and compared to the corresponding optical properties.
H&E images were then taken of the malignant and benign sites and quantified to describe the % adipose, % collagen and % glands. Adipose sites, images at 10x, were predominantly fatty and quantified according to adipocyte morphology. H&E-stained adipose tissue sections were analyzed with an automated image processing algorithm to extract average cell area and cell density. Non-adipose sites were imaged with a 2.5x objective. Grids of 200µm boxes corresponding to the 3mm x 2mm area were overlaid on each non-adipose image. The non-adipose images were classified as the following: adipose and collagen (fibroadipose); collagen and glands (fibroglandular); adipose, collagen and glands (mixed); and malignant sites. Correlations between <&mus′> and % collagen in were determined in benign sites. Age, BMI, and MBD were then correlated to <&mus′> in the adipose and non-adipose sites. Variability in <&mus′> was determined to be related to collagen and not adipose content. In order to further investigate this relationship, the importance of age, BMI and MBD was analyzed after adjusting for the % collagen. Lastly, the relationship between % collagen and % glands was analyzed to determine the relative contributions of % collagen and % glands <&mus′>. Statistics were calculated using Wilcoxon rank-sum tests, Pearson correlation coefficients and linear fits in R.
The diagnostic ability of the optical parameters was linked to the distance of tumor from the margin as well as menopausal status. [THb] showed statistical differences from <&mus′> between malignant (<&mus′>: 8.96cm-1±2.24MAD, [THb]: 42.70&muM±29.31MAD) compared to benign sites (<&mus′>: 7.29cm-1±2.15MAD, [THb]: 32.09&muM±16.73MAD) (p<0.05). Fibroglandular (FG) sites exhibited increased <&mus′> while adipose sites showed increased [&beta-carotene] within benign tissues. Scattering differentiated between ductal carcinoma in situ (DCIS) (9.46cm-1±1.06MAD) and invasive ductal carcinoma (IDC) (8.00cm-1±1.81MAD), versus adipose sites (6.50cm-1±1.95MAD). [&beta-carotene] showed marginal differences between DCIS (19.00&muM±6.93MAD, and FG (15.30&muM±5.64MAD). [THb] exhibited statistical differences between positive sites (92.57&muM±18.46MAD) and FG (34.12&muM±22.77MAD), FA (28.63&muM±14.19MAD), and A (30.36&muM±14.86MAD). Due to decreased fibrous content and increased adipose content, benign sites in post-menopausal patients exhibited lower <&mus′>, but higher [&beta-carotene] than pre-menopausal patients.
Further deconstructing the relationship between optical scattering and tissue morphology resulted in a positive relationship between <&mus′> and % collagen (r=0.28, p=0.00034). Increased variability was observed in sites with a higher percentage of collagen. In adipose tissues MBD was negatively correlated with age (r=-0.19, p=0.006), BMI (r=-0.33, p=2.3e-6) and average cell area (r=-0.15, p=0.032) but positively related to the log of the average cell density (r=0.17, p=0.12). In addition, BMI was positively correlated to average cell area (r=0.31, p=1.2e-5) and negatively related to log of the cell density (r=-0.28, p=7.6e-5). In non-adipose sites, age was negatively correlated to <&mus′> in benign (r=-0.32, p=4.7e-5) and malignant (r=-0.32, p=1.4e-5) sites and this correlation varied significantly by the collagen level (r=-0.40 vs. -0.13). BMI was negatively correlated to <&mus′> in benign (r=-0.32, p=4e-5) and malignant (r=-0.31, p=2.8e-5) sites but this relationship did not vary by collagen level. MBD was positively correlated to <&mus′> in benign (r=0.22, p=0.01) and malignant (r=0.21, p=4.6e-3) sites. Optical scattering was shown to be tied to patient demographics. Lastly, the analysis of collagen vs. glands was narrowed to investigate sites with glands between 0-40% (the dynamic range of the data), the linear model reflected an equivalent relationship to scattering from % glands and the % collagen in benign sites (r=0.18 vs. r=0.17). In addition, the malignant sites showed a stronger positive relationship (r=0.64, p=0.005) to <&mus′> compared to the benign sites (r=0.52, p=0.03).
The data indicate that the ability of an optical parameter to differentiate benign from malignant breast tissues is dictated by patient demographics. Scattering differentiated between malignant and adipose sites and would be most effective in post-menopausal women. [&beta-carotene] or [THb] may be more applicable in pre-menopausal women to differentiate malignant from fibrous sites. Patient demographics are therefore an important component to incorporate into optical characterization of breast specimens. Through the subsequent stepwise analysis of tissue morphology, <&mus′> was positively correlated to collagen and negatively correlated to age and BMI. Increased variability of <&mus′> with collagen level was not dependent on the adipose contribution. A stronger correlation between age and <&mus′> was seen in high collagen sites compared to low collagen sites. Contributions from collagen and glands to <&mus′> were independent and equivalent in benign sites; glands showed a stronger correlation to <&mus′> in malignant sites than collagen. This information will help develop improved scattering models and additional technologies from separating fibroglandular sites from malignant sites and ultimately improve margin assessment.
Item Open Access First-Principles Studies of Electronic, Optical and Defect Properties of Photovoltaic Materials(2019) Zhu, TongThe development of the technology depends heavily on the development of materials. However, how to select the best materials for a specific purpose — i.e. materials selection, is a tricky problem in academia, industry, and our daily lives. Recently, because of the rapid development of computers, ab initio theoretical calculations can be used to aid in materials selection. However, since many approximations in the theoretical calculations exist, choosing appropriate approximations to obtain accurate and predictable materials properties is still difficult. This is the main focus of this thesis. More specifically, we will focus on the materials selection for photovoltaics, which plays a significant role in the energy field today. While modern commercial thin-film PV cells, e.g., based on metal chalcogenide zinc-blende-type materials (Cu(In,Ga)(S,Se)2 (CIGSSe), CdTe) suffer from problems like relying on elements that are either toxic or rare in the earth’s crust, a recent alternative candidate based on kesterite Cu2ZnSn(S,Se)4 (CZTS) peaked at relatively low efficiencies (12.6%) due to the limited open circuit voltage (Voc) caused by the prevalent anti-site structure disorder (e.g. Cu on Zn, Zn on Cu). A possible path forward to reduce this antisite disorder is to pursue materials in which the Cu/Zn combination is replaced by elements that are chemically less similar but that retain the same valence. Recently, Cu2 BaSnS4 ́x Sex (CBTSSe) materials with a trigonal structure (space group P31 ) and composed of only earth abundant metals have been proposed and demonstrated as emerging PV absorbers to address the above issues of CZTSSe. Results obtained as part of this thesis elucidated the band structure and electronic properties of the CBTSSe alloys. A recent device prepared from the Cu2BaSnS4 ́xSex (x « 3) has now been demonstrated with power conversion efficiency (PCE) exceeding 5%. Starting from this early prototype, many avenues remain to optimize the materials, including the underlying chemical positions, the electronic, optical and defect properties of specific compounds. In this thesis, we expand on the CBTSSe paradigm by exploring 16 related compounds, denoted I2-II-IV-VI4 (I=Cu,Ag; II=Sr,Ba; IV=Ge,Sn; VI=S,Se), and some of their alloys for their possible utility as thin-film PV absorbers.
A main methodological result of this thesis concerns the appropriate approximations we can use to obtain accurate and predictable structure, electronic, optical and defect properties for photovoltaic materials. Specifically, structure optimization using computationally expensive hybrid density functional theory is more appropriate than the normally used (semi)local functional (PBE, LDA) and can lead to reasonable and predictable structure and electronic properties. Furthermore, a detailed approach to obtain accurate carrier effective masses is pursued. For the optical properties, the effect of different broadening functions on the onset of absorption coefficients is discussed, and the correct onset behavior can be obtained using Gaussian broadening. At last, a validation of the infinite-size limit of charged defect formation energies calculated by supercell approach is given based on a benchmark study for the gallium vacancy (within charge state q = 0, -1, -2, -3) in GaAs. In general, the bare supercell approach, a supercell approach developed earlier by Freysoldt and coworkers, and a cluster approach can lead to the same infinite-size limit for the charged defect formation energies. Then, based on the appropriate approximations mentioned above, a study of materials properties is described in the I2-II-IV-VI4 (I=Cu,Ag; II=Sr,Ba; IV=Ge,Sn; VI=S,Se) 16 compound systems based on the theoretical structure, electronic and optical properties. Four compounds (Cu2BaSnS4, Cu2BaSnSe4, Cu2BaGeSe4, Cu2SrSnSe4) are identified as potential PV candidates based on their appropriate electronic, and optical properties. Then, two further re- finements are pursued for the Cu2BaSnS4 and Cu2BaGeSe4 compounds. The specific alloys Cu2BaGe1 ́xSnxSe4 (x « 3/4) and Cu2BaSnS4 ́xSex (x « 3) prove to be the best candidates for photovoltaics absorbers among the alloys of these two compounds.