A Digital X-Ray Tomosynthesis Coupled Near Infrared Spectral Tomography System for Dual-Modality Breast Imaging

A Near Infrared Spectral Tomography (NIRST) system has been developed and integrated into a commercial Digital Breast Tomosynthesis (DBT) scanner to allow structural and functional imaging of breast in vivo. The NIRST instrument uses an 8-wavelength continuous wave (CW) laser-based scanning source assembly and a 75-element silicon photodiode solid-state detector panel to produce dense spectral and spatial projection data from which spectrally constrained 3D tomographic images of tissue chromophores are produced. Integration of the optical imaging system into the DBT scanner allows direct co-registration of the optical and DBT images, while also facilitating the synergistic use of x-ray contrast as anatomical priors in optical image reconstruction. Currently, the total scan time for a combined NIRST-DBT exam is ~50s with data collection from 8 wavelengths in the optical scan requiring ~42s to complete. The system was tested in breast simulating phantoms constructed using intralipid and blood in an agarose matrix with a 3 cm x 2 cm cylindrical inclusion at 1 cm depth from the surface. Diffuse image reconstruction of total hemoglobin (HbT) concentration resulted in accurate recovery of the lateral size and position of the inclusion to within 6% and 8%, respectively. Use of DBT structural priors in the NIRST reconstruction process improved the quantitative accuracy of the HbT recovery, and led to linear changes in imaged versus actual contrast, underscoring the advantages of dual-modality optical imaging approaches. The quantitative accuracy of the system can be further improved with independent measurements of scattering properties through integration of frequency or time domain data

Near-Infrared Characterization of Breast Tumors In Vivo using Spectrally-Constrained Reconstruction

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six cases were malignant (infiltrating ductal carcinomas) and showed higher hemoglobin (34–86% increase), a reduction in oxygen saturation, an increase in water content as well as scatter changes relative to surrounding normal tissue. Three of six cases were benign, two of which were diagnosed with fibrocystic disease and showed a dominant contrast in water, consistent with fluid filled cysts. Scatter amplitude was the main source of contrast in the volunteer with the benign condition fibrosis, which typically contains denser collagen tissue. The changes monitored correspond to physiological changes associated with angiogenesis, hypoxia and cell proliferation anticipated in cancers. These changes represent potential diagnostic indicators, which can be assessed to characterize breast tumors

Characterization of Hemoglobin, Water, and NIR Scattering in Breast Tissue: Analysis of Intersubject Variability and Menstrual Cycle Changes

Near-infrared imaging was used to quantify typical values of hemoglobin concentration, oxygen saturation, water fraction, scattering power, and scattering amplitude within the breast tissue of volunteer subjects. A systematic study of the menstrual variations in these parameters was carried out by measuring a group of seven premenopausal normal women (aged 41 to 47 years) in the follicular (days 7 to 14 of the cycle) and secretory phases (days 21 to 28) of the cycle, for two complete menstrual cycles. An average increase in hemoglobin concentration of 2.6 μM or 13% of the background breast values was observed in the secretory phase relative to the follicular phase (p\u3c0.0001), but no other average near-infrared parameter changes were significant. While repeatable and systematic changes were observed in all parameters for individual subjects, large intersubject variations were present in all parameters. In a survey of thirty-nine normal subjects, the total hemoglobin varied from 9 to 45 μM, with a systematic correlation observed between total hemoglobin concentration and breast radiographic density. Scattering power and scattering amplitude were also correlated with radiographic density, but oxygen saturation and water fraction were not. Images of breast lesions indicate that total hemoglobin-based contrast can be up to 200% relative to the background in the same breast. Yet, since the background hemoglobin values vary considerably among breasts, the maximum hemoglobin concentrations observed in cancer tumors may vary considerably as well. In light of these observations, it may be important to use hemoglobin contrast values relative to the background for a given breast, rather than absolute hemoglobin contrast when trying to compare the features of breast lesions among subjects

Multiwavelength three-dimensional near-infrared tomography of the breast:Initial simulation, phantom, and clinical results

Three-dimensional (3D), multiwavelength near-infrared tomography has the potential to provide new physiological information about biological tissue function and pathological transformation. Fast and reliable measurements of multiwavelength data from multiple planes over a region of interest, together with adequate model-based nonlinear image reconstruction, form the major components of successful estimation of internal optical properties of the region. These images can then be used to examine the concentration of chromophores such as hemoglobin, deoxyhemoglobin, water, and lipids that in turn can serve to identify and characterize abnormalities located deep within the domain. We introduce and discuss a 3D modeling method and image reconstruction algorithm that is currently in place. Reconstructed images of optical properties are presented from simulated data, measured phantoms, and clinical data acquired from a breast cancer patient. It is shown that, with a relatively fast 3D inversion algorithm, useful images of optical absorption and scatter can be calculated with good separation and localization in all cases. It is also shown that, by use of the calculated optical absorption over a range of wavelengths, the oxygen saturation distribution of a tissue under investigation can be deduced from oxygenated and deoxygenated hemoglobin maps. With this method the reconstructed tumor from the breast cancer patient was found to have a higher oxy-deoxy hemoglobin concentration and also a higher oxygen saturation level than the background, indicating a ductal carcinoma that corresponds well to histology findings.</p

Effects of Breast Density and Compression on Normal Breast Tissue Hemodynamics through Breast Tomosynthesis Guided Near-Infrared Spectral Tomography

Optically derived tissue properties across a range of breast densities and the effects of breast compression on estimates of hemoglobin, oxygen metabolism, and water and lipid concentrations were obtained from a coregistered imaging system that integrates near-infrared spectral tomography (NIRST) with digital breast tomosynthesis (DBT). Image data were analyzed from 27 women who underwent four IRB approved NIRST/DBT exams that included fully and mildly compressed breast acquisitions in two projections—craniocaudal (CC) and mediolateral-oblique (MLO)—and generated four data sets per patient (full and moderate compression in CC and MLO views). Breast density was correlated with HbT (r=0.64, p=0.001), water (r=0.62, p=0.003), and lipid concentrations (r=?0.74, p\u3c0.001), but not oxygen saturation. CC and MLO views were correlated for individual subjects and demonstrated no statistically significant differences in grouped analysis. Comparison of compressed and uncompressed imaging demonstrated a significant decrease in oxygen saturation under compression (58% versus 50%, p=0.04). Mammographic breast density categorization was correlated with measured optically derived properties

Hemoglobin Oxygen Saturation Tomography:Calibration in Phantom Studies and Patient Data Analysis

Oxygen saturation imaging has been calibrated relative to the measured pO2 values in tissue phantoms of Intralipid and blood. These calibration results are used to interpret the oxygen saturation of patient tumors and normal tissues.</p

Hemoglobin Oxygen Saturation Tomography:Calibration in Phantom Studies and Patient Data Analysis

Oxygen saturation imaging has been calibrated relative to the measured pO2 values in tissue phantoms of Intralipid and blood. These calibration results are used to interpret the oxygen saturation of patient tumors and normal tissues.</p

Combining near-infrared tomography and magnetic resonance imaging to study in vivo breast tissue:Implementation of a Laplacian-type regularization to incorporate magnetic resonance structure

An imaging system that simultaneously performs near infrared (NIR) tomography and magnetic resonance imaging (MRI) is used to study breast tissue phantoms and a healthy woman in vivo. An NIR image reconstruction that exploits the combined data set is presented that implements the MR structure as a soft-constraint in the NIR property estimation. The algorithm incorporates the MR spatially segmented regions into a regularization matrix that links locations with similar MR properties, and applies a Laplacian-type filter to minimize variation within each region. When prior knowledge of the structure of phantoms is used to guide NIR property estimation, root mean square (rms) image error decreases from 26 to 58%. For a representative in vivo case, images of hemoglobin concentration, oxygen saturation, water fraction, scattering power, and scattering amplitude are derived and the properties of adipose and fibroglandular breast tissue types, identified from MRI, are quantified. Fibroglandular tissue is observed to have more than four times as much water content as adipose tissue, almost twice as much blood volume, and slightly reduced oxygen saturation. This approach is expected to improve recovery of abnormalities within the breast, as the inclusion of structural information increases the accuracy of recovery of embedded heterogeneities, at least in phantom studies.</p

Calibration and optimization of 3D digital breast tomosynthesis guided near infrared spectral tomography

Calibration of a three-dimensional multimodal digital breast tomosynthesis (DBT) x-ray and non-fiber based near infrared spectral tomography (NIRST) system is challenging but essential for clinical studies. Phantom imaging results yielded linear contrast recovery of total hemoglobin (HbT) concentration for cylindrical inclusions of 15 mm, 10 mm and 7 mm with a 3.5% decrease in the HbT estimate for each 1 cm increase in inclusion depth. A clinical exam of a patient\u27s breast containing both benign and malignant lesions was successfully imaged, with greater HbT was found in the malignancy relative to the benign abnormality and fibroglandular regions (11 muM vs. 9.5 muM). Tools developed improved imaging system characterization and optimization of signal quality, which will ultimately improve patient selection and subsequent clinical trial results

Spectral priors improve near-infrared diffuse tomography more than spatial priors

We compare the benefits of spatial and spectral priors in near-infrared diffuse tomography image reconstruction. Although previous studies that incorporated anatomical spatial priors have shown improvement in algorithm convergence and resolution, our results indicate that functional parameter quantification by this approach can be suboptimal. The incorporation of a priori spectral information significantly improves the accuracy observed in recovered images. Specifically, phantom results show that the maximum total hemoglobin concentration ([HbT]) in a region of heterogeneity reached 91% of the true value compared to 63% using spatial priors. The combination of both priors produced results accurate to 98% of the true [HbT]. When both spatial and spectral priors were applied in a healthy volunteer, glandular tissue showed a higher [HbT], water fraction, and scattering power compared to adipose tissue.</p