Jonathan Butler

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 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. Our results show strong tumor to normal tissue contrast in total hemoglobin concentration, water fraction, tissue hemoglobin oxygen saturation, S tO 2, and lipid fraction 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 while S tO 2 exceeded pretreatment levels. Approximately half of the hemoglobin and water changes occurred within 5 days of treatment. These data suggest that noninvasive, quantitative optical methods that characterize tumor physiology may be useful in assessing and optimizing individual response to neoadjuvant chemotherapy. © 2004 Society of Photo-Optical Instrumentation Engineers.

Near-infrared diffuse optical spectroscopy and, diffuse optical imaging show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration instrument. Wavelength-dependent absorption and reduced scattering parameters were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy- and deoxy- hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal women is approximately two-fold higher than for postmenopausal subjects at all positions. POST women have approximately 50% higher lipid content than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration, 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for μa and 5 to 12% for μs′. Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering within an individual. © 2004 Society of Photo-Optical Instrumentation Engineers.

Near-infrared diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR techniques are based on quantitative measurements of functional contrast between healthy and diseased tissue. In this study we measured the spectral dependence of tissue absorption and reduced scattering in the breasts of 30 healthy women and one woman with a fibroadenoma using a seven-wavelength frequency-domain photon migration probe. Subjects included pre- and postmenopausal women between the ages of 18 and 64. Multi-spectral measurements were used along with a four-component fit to determine the concentrations of de-oxy and oxyhemoglobin, water and lipids in breast. The scattering spectral shape was also quantified. Our measurements demonstrate that the measured concentrations of NIR analytes correlate well with known breast physiology. Although the tissue scattering at a single wavelength was found to have little value as a functional parameter, the dependence of the scattering on wavelength provided key insights into breast composition and physiology. Lipids and scattering spectra in the breast were found to increase and decrease, respectively, with increasing body mass index. Simple calculations are also provided to demonstrate potential penalties from ignoring the contributions of water and lipids in breast measurements. Finally, water is shown to be a possible indicator for detecting a fibroadenoma, whereas the hemoglobin saturation was found to be a poor indicator. Multi-spectral measurements, compared to measurements restricted to one or two wavelengths, provide additional information that may be useful in managing breast disease. © 2002 Society of Photo-Optical Instrumentation Engineers.

We describe an approach that combines clinical ultrasound and photon migration techniques to enhance the sensitivity and information content of diffuse optical tomography. Measurements were performed on a postmenopausal woman with a single 1.8×0.9 cm malignant ductal carcinoma in situ approximately 7.4 mm beneath the skin surface. The ultrasound-derived information about tumor geometry enabled us to segment the breast tissue into tumor and background regions. Optical data was obtained with a multifrequency, multiwavelength hand-held frequency-domain photon migration backscattering probe. The optical properties of the tumor and background were then computed using the ultrasound-derived geometrical constraints. An iterative perturbative approach, using parallel processing, provided quantitative information about scattering and absorption simultaneously with the ability to incorporate and resolve complex boundary conditions and geometries. A three to four fold increase in the tumor absorption coefficient and nearly 50% reduction in scattering coefficient relative to background was observed. Calculations of the mean physiological parameters reveal fourfold greater tumor total hemoglobin concentration [Hbtot] than normal breast and tumor hemoglobin oxygen saturation values of 63%. Comparison of semi-infinite to heterogeneous models shows superior tumor/background contrast for the latter in both absorption and scattering. Sensitivity studies assessing the impact of tumor size and refractive index assumptions, as well as scan direction, demonstrate modest effects on recovered properties.

Rationale and Objectives. Near-infrared diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR techniques are based on sensitive, quantitative measurements of functional contrast between healthy and diseased tissue. In this study, the authors quantified the origins of this contrast in healthy breasts. Materials and Methods. A seven-wavelength frequency-domain photon migration probe was used to perform noninvasive NIR measurements in the breasts of 28 healthy women, both pre- and postmenopausal, aged 18-64 years. A diffusive model of light transport quantified oxygenated and deoxygenated hemoglobin, water, and lipid by their absorption signatures. Changes in the measured light-scattering spectra were quantified by means of a "scatter power" parameter. Results. Substantial quantitative differences were observed in both absorption and scattering spectra of breast as a function of subject age. These physiologic changes were consistent with long-term hormone-dependent transformations that occur in breast. Instrument response was not adversely affected by subject age or menopausal status. Conclusion. These measurements provide new insight into endogenous optical absorption and scattering contrast mechanisms and have important implications for the development of optical mammography. NIR spectroscopy yields quantitative functional information that cannot be obtained with other noninvasive radiologic techniques.