Fabrizia Bevilacqua

We describe the development of a rapid, noncontact imaging method, modulated imaging, for quantitative, wide-field characterization of optical absorption and scattering properties of turbid media. MI utilizes principles of frequency-domain sampling and model-based analysis of the spatial modulation transfer function. We present and compare analytic diffusion and probabilistic Monte Carlo models of diffuse reflectance in the spatial frequency domain. Next, we perform MI measurements on tissue-simulating phantoms exhibiting a wide range of l * values and ratios, reporting an overall accuracy of approximately 6% and 3% in absorption and reduced scattering parameters, respectively. Sampling of only two spatial frequencies, achieved with only three camera images, is found to be sufficient for accurate determination of the optical properties. We then perform MI measurements in an in vivo tissue system, demonstrating spatial mapping of the absorption and scattering optical contrast in a human forearm and dynamic measurements of a forearm during venous occlusion. Last, metrics of spatial resolution are assessed through both simulations and measurements of spatially heterogeneous phantoms. © 2009 Society of Photo-Optical Instrumentation Engineers.

We report coregistration of near-infrared diffuse optical spectroscopy and magnetic resonance imaging for the study of animal model tumors. A combined broadband steady-state and frequency-domain apparatus was used to determine tissue oxyhemoglobin, deoxyhemoglobin, and water concentration locally in tumors. Simultaneous MRI coregistration provided structural and contrast-enhanced images of the tumor that were correlated with the optical measurements. By use of Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, showing precisely which tissue structure was probed optically. DOS and MRI coregistration measurements were performed on seven rats over 20 days and were separated into three tumor tissue classifications: viable, edematous, and necrotic. A ratio of water concentration to total hemoglobin concentration, as measured optically, was performed for each tissue type and showed values for edematous tissue to be greater than viable tissue. Tissue hemoglobin oxygen saturation also showed a large variation between tissue types: viable tissue had an optically measured StO2 value of 61 ± 5%, whereas StO2 determined for necrotic tissue was 43 ± 6%. © 2003 Optical Society of America.

We present a study of the dynamics of optical contrast agents indocyanine green and methylene blue in an adenocarcinoma rat tumor model. Measurements are conducted with a combined frequency-domain and steady-state optical technique that facilitates rapid measurement of tissue absorption in the 650–1000-nm spectral region. Tumors were also imaged by use of contrast-enhanced magnetic resonance imaging and coregistered with the location of the optical probe. The absolute concentrations of contrast agent, oxyhemoglobin, deoxyhemoglobin, and water are measured simultaneously each second for approximately 10 min. The differing tissue uptake kinetics of ICG and MB in these late-stage tumors arise from differences in their effective molecular weights. ICG, because of its binding to plasma proteins, behaves as a macromolecular contrast agent with a low vascular permeability. A compartmental model describing ICG dynamics is used to quantify physiologic parameters related to capillary permeability. In contrast, MB behaves as a small-molecular-weight contrast agent that leaks rapidly from the vasculature into the extravascular, extracellular space, and is sensitive to blood flow and the arterial input function. © 2003 Optical Society of America.

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.

We present a combined near-infrared diffuse optical spectroscopy and Magnetic Resonance Imaging system for the study of animal model tumors. A combined broad-band steady-state and frequency domain optical spectroscopy apparatus was integrated with the MRI. The physiological properties of tissue rendered by MRI, including vascular volume fraction and water, were compared with chromophore concentrations as determined from the parameters obtained by optical measurements. DOS measurements provided oxyhemoglobin, deoxy-hemoglobin, and water concentration locally in tumors. A method for coregistration of the information obtained by both modalities was developed. Using Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, illustrating which tissue structure was probed optically. Finally, two optical contrast agents, indocyanine green and methylene blue, were employed and their kinetics were measured by DOS system from different locations on the tumor and compared with Gd-DTPA enhancement maps obtained from MRI.

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.

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.

We introduce a novel and efficient method to provide solutions to inverse photon migration problems in heterogeneous turbid media. The method extracts derivative information from a single Monte Carlo simulation to permit the rapid determination of rates of change in the detected photon signal with respect to perturbations in background tissue optical properties. We then feed this derivative information to a nonlinear optimization algorithm to determine the optical properties of the tissue heterogeneity under examination. We demonstrate the use of this approach to solve rapidly a two-region inverse problem of photon migration in the transport regime, for which diffusion-approximation-based approaches are not applicable. © 2001 Optical Society of America.

Absorption and reduced scattering spectra of turbid media were quantified with a noncontact imaging approach based on a Fourier-transform interferometric imaging system. The FTIIS was used to collect hyperspectral images of the steady-state diffuse reflectance from turbid media. Spatially resolved reflectance data from Monte Carlo simulations were fitted to the recorded hyperspectral images to quantify ma and m9s spectra in the 550-850-nm region. A simple and effective calibration approach was introduced to account for the instrument response. With reflectance data that were close to and far from the source, μa and μ‘s of homogeneous, semi-infinite turbid phantoms with optical property ranges comparable with those of tissues were determined with an accuracy of ±7% and ±3%, respectively. Prediction accuracy for μa and μ‘s degraded to ±12% and ±4%, respectively, when only reflectance data close to the source were used. Results indicate that reflectance data close to and far from the source are necessary for optimal quantification of μa and μ‘s. The spectral properties of μa and μ‘s values were used to determine the concentrations of absorbers and scatterers, respectively. Absorber and scatterer concentrations of two-chromophore turbid media were determined with an accuracy of ±5% and ±3%, respectively. © 2000 Optical Society of America.

Local and superficial near-infrared optical-property characterization of turbid biological tissues can be achieved by measurement of spatially resolved diffuse reflectance at small source-detector separations. However, in these conditions the inverse problem, i.e., calculation of localized absorption and the reduced scattering coefficients, is necessarily sensitive to the scattering phase function. This effect can be minimized if a new parameter of the phase function g, which depends on the first and the second moments of the phase function, is known. Ifγis unknown, an estimation of this parameter can be obtained by the measurement, but the uncertainty of the absorption coefficient is increased. A spatially resolved reflectance probe employing multiple detector fibers is described. Monte Carlo simulations are used to determine γ, the reduced scattering and absorption coefficients from reflectance data. Probe performance is assessed by measurements on phantoms, the optical properties of which were measured by other techniques [frequency domain photon migration and spatially resolved transmittance]. Our results show that changes in the absorption coefficient, the reduced scattering coefficient, andγcan be measured to within ±0.005 mm−1, ±0.05 mm−1, and ±0.2, respectively. In vivo measurements performed intraoperatively on a human skull and brain are reported for four NIR wavelengths when the spatially resolved probe and FDPM are used. The spatially resolved probe shows optimum measurement sensitivity in the measurement volume immediately beneath the probe, whereas FDPM typically samples larger regions of tissues. Optical-property values for human skull, white matter, scar tissue, optic nerve, and tumors are reported that show distinct absorption and scattering differences between structures and a dependence on the phase-function parameter γ. © 1999 Optical Society of America.