Nicola Balestreri

Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy.

Breast density is a recognized strong and independent risk factor for breast cancer. We propose the use of time-resolved transmittance spectroscopy to estimate breast tissue density and potentially provide even more direct information on breast cancer risk. Time-resolved optical mammography at seven wavelengths (635 to 1060 nm) is performed on 49 subjects. Average information on breast tissue of each subject is obtained on oxy- and deoxyhemoglobin, water, lipids, and collagen content, as well as scattering amplitude and power. All parameters, except for blood volume and oxygenation, correlate with mammographic breast density, even if not to the same extent. A synthetic optical index proves to be quite effective in separating different breast density categories. Finally, the estimate of collagen content as a more direct means for the assessment of breast cancer risk is discussed.

Estimate of tissue composition in malignant and benign breast lesions by time-domain optical mammography.

The optical characterization of malignant and benign breast lesions is presented. Time-resolved transmittance measurements were performed in the 630-1060 nm range by means of a 7-wavelength optical mammograph, providing both imaging and spectroscopy information. A total of 62 lesions were analyzed, including 33 malignant and 29 benign lesions. The characterization of breast lesions was performed applying a perturbation model based on the high-order calculation of the pathlength of photons inside the lesion, which led to the assessment of oxy- and deoxy-hemoglobin, lipids, water and collagen concentrations. Significant variations between tumor and healthy tissue were observed in terms of both absorption properties and constituents concentration. In particular, benign lesions and tumors show a statistically significant discrimination in terms of absorption at several wavelengths and also in terms of oxy-hemoglobin and collagen content.

Optical Identification of Subjects at High Risk for Developing Breast Cancer

Abstract. A time-domain multiwavelength (635 to 1060 nm) optical mammography was performed on 147 subjects with recent x-ray mammograms available, and average breast tissue composition (water, lipid, collagen, oxy- and deoxyhemoglobin) and scattering parameters (amplitude a and slope b) were estimated. Correlation was observed between optically derived parameters and mammographic density [Breast Imaging and Reporting Data System (BI-RADS) categories], which is a strong risk factor for breast cancer. A regression logistic model was obtained to best identify high-risk (BI-RADS 4) subjects, based on collagen content and scattering parameters. The model presents a total misclassification error of 12.3%, sensitivity of 69%, specificity of 94%, and simple kappa of 0.84, which compares favorably even with intraradiologist assignments of BI-RADS categories.

Breast Tissue Composition and Its Dependence on Demographic Risk Factors for Breast Cancer: Non-Invasive Assessment by Time Domain Diffuse Optical Spectroscopy

Background Breast tissue composition is recognized as a strong and independent risk factor for breast cancer. It is a heritable feature, but is also significantly affected by several other elements (e.g., age, menopause). Nowadays it is quantified by mammographic density, thus requiring the use of ionizing radiation. Optical techniques are absolutely non-invasive and have already proved effective in the investigation of biological tissues, as they are sensitive to tissue composition and structure. Methods Time domain diffuse optical spectroscopy was performed at 7 wavelengths (635-1060 nm) on 200 subjects to derive their breast tissue composition (in terms of water, lipid and collagen content), blood parameters (total hemoglobin content and oxygen saturation level), and information on the microscopic structure (scattering amplitude and power). The dependence of all optically-derived parameters on age, menopausal status, body mass index, and use of oral contraceptives, and the correlation with mammographic density were investigated. Results Younger age, premenopausal status, lower body mass index values, and use of oral contraceptives all correspond to significantly higher water, collagen and total hemoglobin content, and lower lipid content (always p < 0.05 and often p < 10-4), while oxygen saturation level and scattering parameters show significant dependence only on some conditions. Even when age-adjusted groups of subjects are compared, several optically derived parameters (and in particular always collagen and total hemoglobin content) remain significantly different. Conclusions Time domain diffuse optical spectroscopy can probe non-invasively breast tissue composition and physiologic blood parameters, and provide information on tissue structure. The measurement is suitable for in vivo studies and monitoring of changes in breast tissue (e.g., with age, lifestyle, chemotherapy, etc.) and to gain insight into related processes, like the origin of cancer risk associated with breast density.

Effects of tissue heterogeneity on the optical estimate of breast density.

Breast density is a recognized strong and independent risk factor for developing breast cancer. At present, breast density is assessed based on the radiological appearance of breast tissue, thus relying on the use of ionizing radiation. We have previously obtained encouraging preliminary results with our portable instrument for time domain optical mammography performed at 7 wavelengths (635–1060 nm). In that case, information was averaged over four images (cranio-caudal and oblique views of both breasts) available for each subject. In the present work, we tested the effectiveness of just one or few point measurements, to investigate if tissue heterogeneity significantly affects the correlation between optically derived parameters and mammographic density. Data show that parameters estimated through a single optical measurement correlate strongly with mammographic density estimated by using BIRADS categories. A central position is optimal for the measurement, but its exact location is not critical.

Collagen content as a risk factor in breast cancer? A pilot clinical study

A retrospective pilot clinical study on time domain multi-wavelength (635 to 1060 nm) optical mammography was exploited to assess collagen as a breast-cancer risk factor on a total of 109 subjects (53 healthy and 56 with malignant lesions). An increased cancer occurrence is observed on the 15% subset of patients with higher age-matched collagen content. Further, a similar clustering based on the percentage breast density leads to a different set of patients, possibly indicating collagen as a new independent breast cancer risk factor. If confirmed statistically and on larger numbers, these results could have huge impact on personalized diagnostics, health care systems, as well as on basic research.

Breast density assessment by means of time domain optical mammography at 635-1060 nm

Breast density is a major risk factor for developing breast cancer. Non-invasive assessment of breast density was performed by means of time-resolved 7-wavelength (635-1060 nm) optical mammography. Good correlation was achieved between mammographic density and optically derived indexes in a clinical study that is presently ongoing and that has involved 63 subjects up to now.

Optical study on the dependence of breast tissue composition and structure on subject anamnesis

Time domain multi-wavelength (635 to 1060 nm) optical mammography was performed on 200 subjects to estimate their average breast tissue composition in terms of oxy- and deoxy-hemoglobin, water, lipid and collagen, and structural information, as provided by scattering parameters (amplitude and power). Significant (and often marked) dependence of tissue composition and structure on age, menopausal status, body mass index, and use of oral contraceptives was demonstrated.

Optical Characterization of Benign and Malignant Breast Lesions by Perturbative Model

The characterization of benign and malignant breast lesions was performed by the use of a perturbative model. Concentrations of blood, lipid, water and collagen were obtained. Differences between lesions and healthy tissue were observed.

Correlation between Optically-derived Tissue Parameters and Percentage Mammographic Density

Strong correlation is observed between percentage mammographic density and optically-derived tissue parameters (especially water, lipids, scattering power and collagen index) that could be used for the non-invasive assessment of breast density.