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

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

Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy

Using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy, we have developed an algorithm that successfully classifies normal breast tissue, fibrocystic change, fibroadenoma, and infiltrating ductal carcinoma in terms of physically meaningful parameters. We acquire 202 spectra from 104 sites in freshly excised breast biopsies from 17 patients within 30 min of surgical excision. The broadband diffuse reflectance and fluorescence spectra are collected via a portable clinical spectrometer and specially designed optical fiber probe. The diffuse reflectance spectra are fit using modified diffusion theory to extract absorption and scattering tissue parameters. Intrinsic fluorescence spectra are extracted from the combined fluorescence and diffuse reflectance spectra and analyzed using multivariate curve resolution. Spectroscopy results are compared to pathology diagnoses, and diagnostic algorithms are developed based on parameters obtained via logistic regression with cross-validation. The sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy (total efficiency) of the algorithm are 100, 96, 69, 100, and 91%, respectively. All invasive breast cancer specimens are correctly diagnosed. The combination of diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy yields promising results for discrimination of breast cancer from benign breast lesions and warrants a prospective clinical study.National Center for Research Resources (U.S.) (Grant No. P41-RR-02594)Pathology Associates of University Hospital