Noninvasive functional optical spectroscopy of human breast tissue

Abstract

Near infrared diffuse optical spectroscopy and diffuse optical imaging are promising methods that eventually may enhance or replace existing technologies for breast cancer screening and diagnosis. These techniques are based on highly sensitive, quantitative measurements of optical and functional contrast between healthy and diseased tissue. In this study, we examine whether changes in breast physiology caused by exogenous hormones, aging, and fluctuations during the menstrual cycle result in significant alterations in breast tissue optical contrast. A noninvasive quantitative diffuse optical spectroscopy technique, frequency-domain photon migration, was used. Measurements were performed on 14 volunteer subjects by using a hand-held probe. Intrinsic tissue absorption and reduced scattering parameters were calculated from frequency-domain photon migration data. Wavelength-dependent absorption (at 674, 803, 849, and 956 nm) was used to determine tissue concentration of oxyhemoglobin, deoxyhemoglobin, total hemoglobin, tissue hemoglobin oxygen saturation, and bulk water content. Results show significant and dramatic differences in optical properties between menopausal states. Average premenopausal intrinsic tissue absorption and reduced scattering values at each wavelength are 2.5- to 3-fold higher and 16-28 % greater, respectively, than absorption and scattering for postmenopausal subjects. Absorption and scattering properties for women using hormone replacement therapy are intermediate between premenopausal and postmenopausal populations. Physiological properties show differences in mean total hemoglobin (7.0 microM, 11.8 microM, and 19.2 microM) and water concentration relative to pure water (10.9 %, 15.3 %, and 27.3 %) for postmenopausal, hormone replacement therapy, and premenopausal subjects, respectively. Because of their unique, quantitative information content, diffuse optical methods may play an important role in breast diagnostics and improving our understanding of breast disease.

Figure 1

Schematic drawing of FDPM instrument, hand-held probe, and measurement map of healthy subjects. The components of the instrument are: diode lasers (box 1), avalanche photodiode (box 2), network analyzer (box 3), DC current source (box 4), bias T (box 5), and optical switch (box 6). See text for detailed description. The breast is divided into four quadrants: upper outer (a), upper inner (b), lower outer (c), and lower inner (d). FDPM measurements are made in each quadrant, on the areolar border (e), and on the glandular tail (f) that extends into the axilla.

Figure 2

FDPM measurements of phase lag (a) and amplitude vs. modulation frequency (b) for Pre 1 and Post 1. Source-detector separation, 2.5 cm; wavelength, 849 nm. Solid lines represent best diffusion-model function fits to phase and amplitude data for each subject. Error bars are on the order of the marker size.

Figure 3

μ_a vs. μ_s′ for six pre- and three postmenopausal subjects at all wavelengths. Values are calculated from best diffusion-model fits to phase and amplitude data

Figure 4

μ_s′ vs. wavelength for three subjects of varied hormonal and menopausal status. Some values at 980 nm represent values extrapolated from Aλ^−B linear regression analysis of the data.

Figure 5

μ_s′ at 674 nm vs. age for all subjects. Pre 6 (age 18) is represented as an average of two points corresponding to two separate measurement dates.

Figure 6

Mean Hb concentrations [μM, HbO₂, deoxy, and total (THC)] and water (H₂O) concentration relative to pure water (%) for each subject group. Values are determined from wavelength-dependent absorption values at 674, 803, 849, and 956 or 980 nm. Error bars represent the normalized standard deviation to the mean for six premenopausal, five HRT, and three postmenopausal subjects. Confidence values are ≈99% for Hb, HbO₂, THC, and H₂O.

Figure 7

Total Hb concentration vs. age for all subjects. Pre 6 (age 18) is represented as an average of two points corresponding to two separate measurement dates.