Multi-modal spectroscopy of breast tissue

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.Includes bibliographical references (leaves 64-66).Breast cancer is the most common form of cancer afflicting women in the United States; one out of eight women will be diagnosed with breast cancer during her lifetime. Currently, screening is performed by a combination of annual clinical breast examinations and x-ray mammography. However, only 10 to 25 percent of suspicious lesions detected during mammography are diagnosed as malignant upon biopsy, which implies that a large number of biopsies can be avoided. Although mammography images anatomic changes, it is not sensitive to the underlying morphological and biochemical changes that distinguish benign and malignant breast lesions. Presently employed diagnostic procedures are invasive, time consuming, and expensive. Thus, there is a clinical need to develop new tools for the early diagnosis of malignancy in the breast. In recent years our laboratory has explored the use of Raman spectroscopy for diagnosing disease; one important area is the detection of breast cancer. Raman spectroscopy provides information about the morphological and biochemical make up of tissue and, with the aid of our diagnostic algorithm, has provided good results in distinguishing between malignant and benign breast lesions, with a sensitivity, specificity, and an overall accuracy of 90, 96, and 86 percent, respectively [Haka,2004].(cont.) Although these initial results are promising, we would like to improve the overall accuracy. Another promising spectroscopic technique developed in our laboratory is tri-modal spectroscopy (TMS), the combination of diffuse reflectance (DRS), intrinsic fluorescence (IFS), and light scattering spectroscopy (LSS). This technique has been successfully applied to the diagnosis of epithelial neoplastic tissue, leading to the interest in exploring its application to the diagnosis of lesions in breast tissue. Finally, the Raman and DRS/IFS modalities provide complementary information and the combination of this information into a single diagnostic algorithm may provide superior diagnostic capabilities. The central theme of this research is to investigate DRS/IFS as a useful technique for the diagnosis of breast cancer and to evaluate the effectiveness of its combination with Raman spectroscopy. Through this research, we hope to aid the medical community in early diagnosis, treatment, and prevention of breast cancer.by Zoya I. Volynskaya.S.M

Real-time diagnosis of breast cancer during core needle biopsy

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2010.Pages 1-36 (2nd group) has title: Raman clinical instrument manual, by Chae-Ryon Kong and Michael S. Feld; with contributions from Zoya Volynskaya and Luis Galindo. Cataloged from PDF version of thesis.Includes bibliographical references.Early detection of breast cancer is critical for improved survival. Currently, breast abnormalities are diagnosed based on a histopathological evaluation of tissue removed during core needle biopsy. Microcalcifications are used as targets to position biopsy devices, as they may indicate the presence of malignancy. Despite stereotactic guidance, needle biopsy fails to retrieve target microcalcifications in up to 15% of patients. Optical techniques may help clinicians accurately diagnose and treat patients by providing important diagnostic information in real time in a minimally invasive manner. This thesis describes the results of several studies we performed to evaluate the potential of Raman, reflectance, and intrinsic fluorescence spectroscopy to provide biochemical and morphological information for discriminating breast lesions. Each modality was evaluated individually, as well as in combination, using a technique known as multimodal spectroscopy (MMS). For the first part of this project we conducted a clinical study in which spectra were acquired from excised tissue in 99 patients and physically meaningful parameters were extracted by modeling the data. The goals of the study were as follows: 1) To prospectively validate previously developed diagnostic algorithms on the data from these patients; 2) To develop a new algorithm to evaluate additional histopathology diagnoses. Diffuse reflectance (DRS) spectra were modeled using diffusion theory and provided information about tissue absorbers and scatterers. Intrinsic fluorescence (IFS) spectra were extracted from the combined fluorescence and DRS spectra and analyzed using multivariate curve resolution. Raman spectroscopy data were fit using a linear combination of Raman active components (e.g. collagen, calcium, adipose) found in breast tissue. Prospective validation of Raman spectroscopy resulted in sensitivity and specificity and negative predictive value (NPV) of 78%, 98%, and 98%, respectively. An MMS system was developed to evaluate the benefit of combining information from all three spectroscopic modalities. We found that using new 3D Raman algorithm we could discriminate among 6 histopathology categories as compared to 4 categories previously diagnosed with Raman spectroscopy. For the second part of this project, we designed and developed a portable, miniature Raman clinical spectroscopy system to evaluate the potential of spectroscopy to guide the retrieval of microcalcifications during core needle biopsies. We focused specifically on the use of Raman spectroscopy for this application, as it is particularly sensitive to calcium-containing minerals. The system employs a side-viewing Raman probe that can be used in conjunction with commercial stereotactic needle biopsy devices. Prior to core needle excision, the Raman probe was inserted into the core needle biopsy device and spectra were acquired and analyzed in real time (<Is). The results from our work indicate that spectroscopy has the potential to accurately diagnose breast lesions and enable targeted biopsies of diseased tissue and retrieval of microcalcifications.by Zoya Volynskaya.Ph.D

Research of the Features of The Electricity Market

The article describes features of the electricity market, determined by the specificity of the circulating product. It is shown that electricity as a specific product, which is characterized by the demand inelasticity, continuity of the production and consumption processes, impossibility of accumulation and storage, standardized product range, etc., determines the basic characteristics of the electricity (power and capacity) market. Herewith, capacity can be considered as a related product. The level of competition in the electricity market is largely dependent on the presence of restrictions in the choice of markets; differentiation of the products; choice of fuel resources and their suppliers. In addition, an essential condition for the electricity market operation is the availability of a related infrastructure. The main electricity market models are described, which have been practically implemented in the world: the markets, in which only electric power is sold, the markets with capacity turnover, and the markets differentiation depending on the model of their organization. A brief description of the structure of the domestic market of the countries demonstrating the successful experience of the electricity market operation is provided. At the same time, a distinctive feature of the current Russian electricity market is the incompleteness of its architecture, difficulties in ensuring its competitiveness due to the allocation of a minimum number of price zones, which are characterized by a large number of suppliers and purchasers of electricity, a developed grid infrastructure. In addition, the so-called non-price zones, in which the prevailing conditions hinder organizing a full-fledged market economy, are highlighted. The conclusion about the need for further study of the electricity market operation in different regions in order to make use of the positive experience is made. DOI: 10.5901/mjss.2015.v6n4s4p19

A multimodal spectroscopy system for real-time disease diagnosis

The combination of reflectance, fluorescence, and Raman spectroscopy—termed multimodal spectroscopy (MMS)—provides complementary and depth-sensitive information about tissue composition. As such, MMS is a promising tool for disease diagnosis, particularly in atherosclerosis and breast cancer. We have developed an integrated MMS instrument and optical fiber spectral probe for simultaneous collection of all three modalities in a clinical setting. The MMS instrument multiplexes three excitation sources, a xenon flash lamp (370–740 nm), a nitrogen laser (337 nm), and a diode laser (830 nm), through the MMS probe to excite tissue and collect the spectra. The spectra are recorded on two spectrograph/charge-coupled device modules, one optimized for visible wavelengths (reflectance and fluorescence) and the other for the near-infrared (Raman), and processed to provide diagnostic parameters. We also describe the design and calibration of a unitary MMS optical fiber probe 2 mm in outer diameter, containing a single appropriately filtered excitation fiber and a ring of 15 collection fibers, with separate groups of appropriately filtered fibers for efficiently collecting reflectance, fluorescence, and Raman spectra from the same tissue location. A probe with this excitation/collection geometry has not been used previously to collect reflectance and fluorescence spectra, and thus physical tissue models (“phantoms”) are used to characterize the probe’s spectroscopic response. This calibration provides probe-specific modeling parameters that enable accurate extraction of spectral parameters. This clinical MMS system has been used recently to analyze artery and breast tissue in vivo and ex vivo.National Institutes of Health (U.S) ( Grant No. P41-RR-02594

Raman spectroscopy: a real-time tool for identifying microcalcifications during stereotactic breast core needle biopsies

Microcalcifications are an early mammographic sign of breast cancer and a target for stereotactic breast needle biopsy. We present here a Raman spectroscopic tool for detecting microcalcifications in breast tissue based on their chemical composition. We collected ex vivo Raman spectra from 159 tissue sites in fresh stereotactic breast needle biopsies from 33 patients, including 54 normal sites, 75 lesions with microcalcifications and 30 lesions without microcalcifications. Application of our Raman technique resulted in a positive predictive value of 97% for detecting microcalcifications. This study shows that Raman spectroscopy has the potential to detect microcalcifications during stereotactic breast core biopsies and provide real-time feedback to radiologists, thus reducing non-diagnostic and false negative biopsies

Effect of bile absorption coefficients on the estimation of liver tissue optical properties and related implications in discriminating healthy and tumorous samples

We investigated differences between healthy tissue and metastatic tumor from ex vivo human partial liver resections using diffuse optical spectroscopy with a fiber optic probe. We extracted various physiological and morphological parameters from the spectra. During evaluation of the residual between the measurements and a fit model based on diffusion theory, we found that bile is an additional chromophore absorbing in the visible wavelength range that was missing in our model. Consistency of the residual with the absorption spectrum of bile was noticed. An accurate measurement of the absorption coefficient of bile from various human bile samples was performed and implemented into the fit model. Having the absorption coefficient of bile as a priori knowledge in the model showed a clear improvement in terms of reducing the fitting discrepancies. The addition of this chromophore yields significantly different estimates of the amount of blood. Furthermore, the estimated bile volume fraction and reduced scattering amplitude turned out to be two main relevant discriminators between normal and metastatic liver tissues

Analysis of causes of perinatal transmission of HIV infection in the group of children born in 2008-2010 years in Sverdlovsk region

The results of epidemiological investigations and medical histories of 246 HIV-infected children born in Sverdlovsk region in 2008-2010 years were analyzed in order to identify the causes of perinatal transmission of HIV infection. Measures for decreasing of HIV transmission from mother to a child were developed.Проанализированы результаты эпидемиологических расследований и историй болезни 246 ВИЧ-инфицированных детей, родившихся в Свердловской области в 2008-2010 гг., с целью выявления причин перинатальной передачи ВИЧ-инфекции. Разработан комплекс мероприятий, направленных на снижение передачи ВИЧ-инфекции от матери к ребёнку

Portable Optical Fiber Probe-Based Spectroscopic Scanner for Rapid Cancer Diagnosis: A New Tool for Intraoperative Margin Assessment

There continues to be a significant clinical need for rapid and reliable intraoperative margin assessment during cancer surgery. Here we describe a portable, quantitative, optical fiber probe-based, spectroscopic tissue scanner designed for intraoperative diagnostic imaging of surgical margins, which we tested in a proof of concept study in human tissue for breast cancer diagnosis. The tissue scanner combines both diffuse reflectance spectroscopy (DRS) and intrinsic fluorescence spectroscopy (IFS), and has hyperspectral imaging capability, acquiring full DRS and IFS spectra for each scanned image pixel. Modeling of the DRS and IFS spectra yields quantitative parameters that reflect the metabolic, biochemical and morphological state of tissue, which are translated into disease diagnosis. The tissue scanner has high spatial resolution (0.25 mm) over a wide field of view (10 cm×10 cm), and both high spectral resolution (2 nm) and high spectral contrast, readily distinguishing tissues with widely varying optical properties (bone, skeletal muscle, fat and connective tissue). Tissue-simulating phantom experiments confirm that the tissue scanner can quantitatively measure spectral parameters, such as hemoglobin concentration, in a physiologically relevant range with a high degree of accuracy (<5% error). Finally, studies using human breast tissues showed that the tissue scanner can detect small foci of breast cancer in a background of normal breast tissue. This tissue scanner is simpler in design, images a larger field of view at higher resolution and provides a more physically meaningful tissue diagnosis than other spectroscopic imaging systems currently reported in literatures. We believe this spectroscopic tissue scanner can provide real-time, comprehensive diagnostic imaging of surgical margins in excised tissues, overcoming the sampling limitation in current histopathology margin assessment. As such it is a significant step in the development of a platform technology for intraoperative management of cancer, a clinical problem that has been inadequately addressed to date.Case Comprehensive Cancer Center. Tissue Procurement, Histology and Immunohistochemistry Core Facility (P30 CA43703)National Cancer Institute (U.S.) (R01-CA140288)National Cancer Institute (U.S.) (R01-CA97966)National Center for Research Resources (U.S.) (S10-RR031845)National Center for Research Resources (U.S.) (P41-RR02594