Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo

Abstract

Raman spectroscopy has the potential to provide real-time, in situ diagnosis of breast cancer during needle biopsy or surgery via an optical fiber probe. Understanding the chemical/morphological basis of the Raman spectrum of breast tissue is a necessary step in developing Raman spectroscopy as a tool for in situ breast cancer diagnosis. To understand the relationship between the Raman spectrum of a sample of breast tissue and its disease state, near-infrared Raman spectroscopic images of human breast tissue were acquired using a confocal microscope. These images were then compared with phase contrast and hematoxylinand eosin-stained images to develop a chemical/morphological model of breast tissue Raman spectra. This model fits macroscopic tissue spectra with a linear combination of basis spectra derived from spectra of the cell cytoplasm, cell nucleus, fat, b-carotene, collagen, calcium hydroxyapatite, calcium oxalate dihydrate, cholesterol-like lipid deposits and water. Each basis spectrum represents data acquired from multiple patients and, when appropriate, from a variety of normal and diseased states. The model explains the spectral features of a range of normal and diseased breast tissue samples, including breast cancer. It can be used to relate the Raman spectrum of a breast tissue sample to diagnostic parameters used by pathologists.

Raman active components of skin cancer

“…Some were commonly used in skin and non-skin models. For instance, collagen and triolein are known to be important contributors to the RS signal of breast, gastric, and artery tissues [17,19,20]. We demonstrated these two components also played an important role for fitting in vivo skin data.…”

“…Larger variance was observed in those bands between in situ ceramide and triolein. Triolein is not only abundant in skin lipid, but also in subcutaneous fat [20]. As triolein has a very strong Raman scattering cross-section, it contributes greatly to Raman spectrum of human skin.…”

“…The building blocks of our model are Raman active components extracted from skin in situ. Previous biophysical models used model components either measured directly from synthetic/purified chemicals [9,[15][16][17][18], or extracted from tissue sections in situ [19][20][21]. The advantage of using synthetic/purified chemicals as model components is that they can be easily measured without the need for Raman micro-imaging.…”

“…This concept has been applied successfully to a previous Raman model of excisional skin biopsies [9] and has given us some prior knowledge about skin composition. Other groups used in situ constituents to build biophysical models of other disease processes, such as coronary atherosclerosis [19], breast cancer [20], and brain tumor [21]. Here, we expand upon this approach by developing a biophysical human skin model using in situ skin constituents.…”

Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy

“…[1][2][3][4][5][6] These technologies have also been used for the early detection of cancer and biochemical changes in cells and tissues causing cancer. 7,8 Among these spectroscopic techniques, Raman spectroscopy has attracted considerable attention for medical diagnosis since it is nondestructive, does not require a sample preparation process, and provides detailed information about the molecular structure of normal and diseased tissues.…”