Dorota Jakubowski

Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study

Presurgical chemotherapy is widely used in the treatment of locally advanced breast cancer. Monitoring the response to therapy can improve survival and reduce morbidity. We employ a noninvasive, near-infrared method based on diffuse optical spectroscopy (DOS) to quantitatively monitor tumor response to neoadjuvant chemotherapy. DOS was used to monitor tumor response in one patient with locally advanced breast cancer throughout the course of her therapy. Measurements were performed prior to doxorubicin-cyclophosphamide therapy and at several time points over the course of three treatment cycles (68 days). Our results show strong tumor to normal (T/N) tissue contrast in total hemoglobin concentration (T/N=2.4), water fraction (T/N=6.9), tissue hemoglobin oxygen saturation, S(t)O(2) (T/N=0.9), and lipid fraction (T/N=0.7) prior to treatment. Over a 10-week period, the peak total hemoglobin and water dropped 56 and 67%, respectively. Lipid content nearly returned to baseline (T/N =0.9) while S(t)O(2) exceeded pretreatment levels (T/N =1.5). Approximately half of the hemoglobin and water changes occurred within 5 days of treatment (26 and 37%, respectively). These data suggest that noninvasive, quantitative optical methods that characterize tumor physiology may be useful in assessing and optimizing individual response to neoadjuvant chemotherapy.

The Role of Diffuse Optical Spectroscopy in the Clinical Management of Breast Cancer

Diffuse optical spectroscopy (DOS) of breast tissue provides quantitative, functional information based on optical absorption and scattering properties that cannot be obtained with other radiographic methods. DOS-measured absorption spectra are used to determine the tissue concentrations of deoxyhemoglobin (Hb-R), oxyhemoglobin (Hb-O2), lipid, and water (H2O), as well as to provide an index of tissue hemoglobin oxygen saturation (StO2). Tissue-scattering spectra provide insight into epithelial, collagen, and lipid contributions to breast density. Clinical studies of women with malignant tumors show that DOS is sensitive to processes such as increased tissue vascularization, hypoxia, and edema. In studies of healthy women, DOS detects variations in breast physiology associated with menopausal status, menstrual cycle changes, and hormone replacement. Current research involves using DOS to monitor tumor response to therapy and the co-registration of DOS with magnetic resonance imaging. By correlating DOS-derived parameters with lesion pathology and specific molecular markers, we anticipate that composite “tissue optical indices” can be developed that non-invasively characterize both tumor and normal breast-tissue function.

Superficial tissue optical property determination using spatially resolved measurements close to the source: comparison with frequency-domain photon migration measurements

Local and superficial optical property characterization of biological tissues can be performed by measuring spatially-resolved diffuse reflectance at small source-detector separations. Monte Carlo simulations and experiments were performed to assess the performance of a spatially-resolved reflectance probe, employing multiple detector fibers (0.3 to 1.4 mm from the source). Under these conditions, the inverse problem, i.e. calculating the absorption and reduced scattering coefficients, is necessarily sensitive to the phase function. This effect must be taken into account by considering a new parameter of the phase function, which depends on the first and second moments of the phase function. Probe performance is compared to another technique for quantitatively measuring optical coefficients, based on the analysis of photon density waves (Frequency Domain Photon Migration). The two techniques are found to be in reasonable agreement. However, the spatially resolved probe shows optimum measurement sensitivity in the volume immediately beneath the probe, while FDPM typically samples much larger regions of tissues. Measurements on human brain in vivo are reported using both methods.

Functional diffuse optical spectroscopy of human breast tissue

We describe a method for obtaining broad wavelength (650 nm-1000 nm) quantitative optical property data with deep tissue penetration. The wavelength-dependence of absorption (/spl mu/a) and scattering (/spl mu/s) parameters is used to provide fundamental information on tissue biochemistry and structure.

The effects of water and lipids on NIR optical breast measurements

Near infrared diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR spectroscopy yields quantitative functional information that cannot be obtained with other non-invasive radiological techniques. In this study we focused upon the origins of this contrast in healthy breast, especially from water and lipids.