We present line scan reflectance diffuse optical tomography (LS-RDOT), a technique to generate quantitative cross-sectional images of hemoglobin concentration, tissue oxygen saturation, water content, and lipid content, for non-invasive bedside imaging of breast cancer. The LS-RDOT system is composed of a single-channel time-domain diffuse optical spectroscopy (TD-DOS) system measuring at wavelengths of 761, 802, 838, 908, 936, and 976 nm and hand-held probes with source–detector distances of 20, 30, and 40 mm. The line scans were performed by acquiring temporal point spread functions (TPSF) at 9 measurement points with a spacing of 5 mm linearly marked on the skin just above the breast lesion. The cross-sectional images were restored by an iterative image reconstruction method with an expression of the TPSF obtained from the photon diffusion equation using the Rytov approximation. A preliminary clinical measurement was conducted for a breast cancer patient with a tumor of approximately 10 mm in size. The reconstructed images captured changes in the physiological parameters of the breast cancer at the lesion location indicated by the ultrasonographic image. In addition, the results showed that LS-RDOT provides cross-sectional images of physiological parameters in a form that can be fused with structural images provided by ultrasonography
SignificanceThe water and lipid content of normal breast tissue showed mammary gland characteristics with less influence from the chest wall using six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) in a reflectance geometry.AimTo determine the depth sensitivity of a six-wavelength TD-DOS system and evaluate whether the optical parameters in normal breast tissue can distinguish dense breasts from non-dense breasts.ApproachMeasurements were performed in normal breast tissue of 37 breast cancer patients. We employed a six-wavelength TD-DOS system to measure the water and lipid content in addition to the hemoglobin concentration. The breast density in mammography and optical parameters were then compared.ResultsThe depth sensitivity of the system for water and lipid content was estimated to be ∼15 mm. Our findings suggest that the influence of the chest wall on the water content is weaker than that on the total hemoglobin concentration. In data with evaluation conditions, the water content was significantly higher (p < 0.001) and the lipid content was significantly lower (p < 0.001) in dense breast tissue. The water and lipid content exhibited a high sensitivity and specificity to distinguish dense from non-dense breasts in receiver-operating-characteristic curve analysis.ConclusionsWith less influence from the chest wall, the water and lipid content of normal breast tissue measured by a reflectance six-wavelength TD-DOS system, together with ultrasonography, can be applied to distinguish dense from non-dense breasts.
We report a time-domain reflectance diffuse optical tomography (TD-RDOT) system for providing three-dimensional images of hemoglobin concentration, tissue oxygen saturation, water and lipid contents of breast cancer from reflectance measurements. A scan area of 5 × 5 grid points with a 10-mm spacing is marked on the breast surface so that the tumor is just below the center of the area. The breast scan is performed by measuring the temporal profiles of six wavelengths at each grid point using a time-domain diffuse optical spectroscopy (TD-DOS) system and a hand-held probe. The TDDOS system that we developed is capable of measuring water and lipid contents and hemoglobin concentration. The hand-held probe is designed to measure the breast in reflectance mode with a source-to-detector separation of 20 mm. The three-dimensional distributions of the tissue parameters are restored using an iterative image reconstruction method. As a preliminary clinical demonstration, a breast cancer patient with a tumor size of approximately 20 mm was examined with the TD-RDOT. The reconstructed images show that the breast cancer had high hemoglobin concentration and water content, and low tissue oxygen saturation and lipid content. The results indicate that the TD-RDOT system has the potential to provide diagnostically relevant information on the tissue characteristics of the tumor at the bedside.
Time-domain (TD) near-infrared spectroscopy (NIRS) is an effective method of quantifying optical and biological properties, such as the mean optical path length, absorption coefficient, reduced scattering coefficient, and oxyhemoglobin and deoxy-hemoglobin concentrations of biological tissues. In addition to these parameters, water and lipid contents are important biological parameters expected to be useful information in clinical application. For our previous TD-NIRS systems, we used three wavelengths (760, 800, and 830 nm) that are sensitive to oxy- and deoxy-hemoglobin. To quantitatively measure water and lipid contents of biological tissues, we developed a new TD-NIRS system with three additional wavelengths (908, 936, and 976 nm) that are sensitive to water and lipids. The new six-wavelength TDNIRS system comprises six-wavelength pulsed light sources, two types of photomultiplier tubes (GaAs and InGaAs PMTs), a time-correlated single-photon counting unit, and optical fiber bundles. In this pilot study, we present the measurement results of oxy- and deoxy-hemoglobin concentrations, tissue oxygen saturation, and water and lipid contents at the calf, forearm, and abdomen of five healthy adult volunteers in a resting state using the six-wavelength TD-NIRS system. We thus confirmed that the fat thickness measured by ultrasonography and the water content measured by the six-wavelength TD-NIRS system were negatively correlated, whereas the fat thickness and lipid content were positively correlated. We expect that the six-wavelength TD-NIRS system will be used in clinical studies as a point-of-care testing device for the bedside monitoring of human subjects.
The purpose of this study was to evaluate the effects of the thickness and depth of tumors on hemoglobin measurements in breast cancer by optical spectroscopy and to demonstrate tissue oxygen saturation (SO2) and reduced scattering coefficient (μs′) in breast tissue and breast cancer in relation to the skin-to-chest wall distance. We examined 53 tumors from 44 patients. Total hemoglobin concentration (tHb), SO2, and μs′ were measured by time-resolved spectroscopy (TRS). The skin-to-chest wall distance and the size and depth of tumors were measured by ultrasonography. There was a positive correlation between tHb and tumor thickness, and a negative correlation between tHb and tumor depth. SO2 in breast tissue decreased when the skin-to-chest wall distance decreased, and SO2 in tumors tended to be lower than in breast tissue. In breast tissue, there was a negative correlation between μs′ and the skin-to-chest wall distance, and μs′ in tumors was higher than in breast tissue. Measurement of tHb in breast cancer by TRS was influenced by tumor thickness and depth. Although SO2 seemed lower and μs′ was higher in breast cancer than in breast tissue, the skin-to-chest wall distance may have affected the measurements.
We developed a time-resolved reflectance diffuse optical tomography (RDOT) system to measure tumor responses to chemotherapy in breast cancer patients at the bedside. This system irradiates the breast with a three-wavelength pulsed laser (760, 800, and 830 nm) through a source fiber specified by an optical switch. The light collected by detector fibers is guided to a detector unit consisting of variable attenuators and photomultiplier tubes. Thirteen irradiation and 12 detection points were set to a measurement area of 50 × 50 mm for a hand-held probe. The data acquisition time required to obtain the temporal profiles within the measurement area is about 2 minutes. The RDOT system generates topographic and tomographic images of tissue properties such as hemoglobin concentration and tissue oxygen saturation using two imaging methods. Topographic images are obtained from the optical properties determined for each source-detector pair using a curve-fitting method based on the photon diffusion theory, while tomographic images are reconstructed using an iterative image reconstruction method. In an experiment using a tissue-like solid phantom, a tumor-like cylindrical target (15 mm diameter, 15 mm high) embedded in a breast tissue-like background medium was successfully reconstructed. Preliminary clinical measurements indicated that the tumor in a breast cancer patient was detected as a region of high hemoglobin concentration. In addition, the total hemoglobin concentration decreased during chemotherapy. These results demonstrate the potential of RDOT for evaluating the effectiveness of chemotherapy in patients with breast cancer.
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