Kelly E. Michaelsen

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.

Sensitivity of MRI-guided near-infrared spectroscopy clinical breast exam data and its impact on diagnostic performance

In this study, data from breast MRI-guided near infrared spectroscopy (NIRS) exams delivered to 44 patients scheduled for surgical resection (ending in 16 benign and 28 malignant diagnoses) were analyzed using a spatial sensitivity metric to quantify the adequacy of the optical measurements for interrogating the tumor region of interest, as derived from the concurrent MRI scan. Along with positional sensitivity, the incorporation of spectral priors and the selection of an appropriate regularization parameter in the image reconstruction were considered, and found to influence the diagnostic accuracy of the recovered images. Once optimized, the MRI/NIRS data was able to differentiate the malignant from benign lesions through both total hemoglobin (p = 0.0037) and tissue optical index (p = 0.00019), but required the relative spatial sensitivity of the optical measurement data to each lesion to be above 1%. Spectral constraints implemented during the reconstruction were required to obtain statistically significant diagnostic information from images of H2O, lipids, and Tissue Optical Index (TOI). These results confirm the need for optical systems that have homogenous spatial coverage of the breast while still being able to accommodate the normal range of breast sizes.

Anthropomorphic breast phantoms with physiological water, lipid, and hemoglobin content for near-infrared spectral tomography

Abstract. Breast mimicking tissue optical phantoms with sufficient structural integrity to be deployed as stand-alone imaging targets are developed and successfully constructed with biologically relevant concentrations of water, lipid, and blood. The results show excellent material homogeneity and reproducibility with inter- and intraphantom variability of 3.5 and 3.8%, respectively, for water and lipid concentrations ranging from 15 to 85%. The phantoms were long-lasting and exhibited water and lipid fractions that were consistent to within 5% of their original content when measured 2 weeks after creation. A breast-shaped three-compartment model of adipose, fibroglandular, and malignant tissues was created with water content ranging from 30% for the adipose simulant to 80% for the tumor. Mean measured water content ranged from 30% in simulated adipose to 73% in simulated tumor with the higher water localized to the tumor-like material. This novel heterogeneous phantom design is composed of physiologically relevant concentrations of the major optical absorbers in the breast in the near-infrared wavelengths that should significantly improve imaging system characterization and optimization because the materials have stand-alone structural integrity and can be readily molded into the sizes and shapes of tissues commensurate with clinical breast imaging.

Near-infrared spectral tomography integrated with digital breast tomosynthesis: Effects of tissue scattering on optical data acquisition design

PURPOSE Design optimization and phantom validation of an integrated digital breast tomosynthesis (DBT) and near-infrared spectral tomography (NIRST) system targeting improvement in sensitivity and specificity of breast cancer detection is presented. Factors affecting instrumentation design include minimization of cost, complexity, and examination time while maintaining high fidelity NIRST measurements with sufficient information to recover accurate optical property maps. METHODS Reconstructed DBT slices from eight patients with abnormal mammograms provided anatomical information for the NIRST simulations. A limited frequency domain (FD) and extensive continuous wave (CW) NIRST system was modeled. The FD components provided tissue scattering estimations used in the reconstruction of the CW data. Scattering estimates were perturbed to study the effects on hemoglobin recovery. Breast mimicking agar phantoms with inclusions were imaged using the combined DBT/NIRST system for comparison with simulation results. RESULTS Patient simulations derived from DBT images show successful reconstruction of both normal and malignant lesions in the breast. They also demonstrate the importance of accurately quantifying tissue scattering. Specifically, 20% errors in optical scattering resulted in 22.6% or 35.1% error in quantification of total hemoglobin concentrations, depending on whether scattering was over- or underestimated, respectively. Limited frequency-domain optical signal sampling provided two regions scattering estimates (for fat and fibroglandular tissues) that led to hemoglobin concentrations that reduced the error in the tumor region by 31% relative to when a single estimate of optical scattering was used throughout the breast volume of interest. Acquiring frequency-domain data with six wavelengths instead of three did not significantly improve the hemoglobin concentration estimates. Simulation results were confirmed through experiments in two-region breast mimicking gelatin phantoms. CONCLUSIONS Accurate characterization of scattering is necessary for quantification of hemoglobin. Based on this study, a system design is described to optimally combine breast tomosynthesis with NIRST.PURPOSE Design optimization and phantom validation of an integrated digital breast tomosynthesis (DBT) and near-infrared spectral tomography (NIRST) system targeting improvement in sensitivity and specificity of breast cancer detection is presented. Factors affecting instrumentation design include minimization of cost, complexity, and examination time while maintaining high fidelity NIRST measurements with sufficient information to recover accurate optical property maps. METHODS Reconstructed DBT slices from eight patients with abnormal mammograms provided anatomical information for the NIRST simulations. A limited frequency domain (FD) and extensive continuous wave (CW) NIRST system was modeled. The FD components provided tissue scattering estimations used in the reconstruction of the CW data. Scattering estimates were perturbed to study the effects on hemoglobin recovery. Breast mimicking agar phantoms with inclusions were imaged using the combined DBT∕NIRST system for comparison with simulation results. RESULTS Patient simulations derived from DBT images show successful reconstruction of both normal and malignant lesions in the breast. They also demonstrate the importance of accurately quantifying tissue scattering. Specifically, 20% errors in optical scattering resulted in 22.6% or 35.1% error in quantification of total hemoglobin concentrations, depending on whether scattering was over- or underestimated, respectively. Limited frequency-domain optical signal sampling provided two regions scattering estimates (for fat and fibroglandular tissues) that led to hemoglobin concentrations that reduced the error in the tumor region by 31% relative to when a single estimate of optical scattering was used throughout the breast volume of interest. Acquiring frequency-domain data with six wavelengths instead of three did not significantly improve the hemoglobin concentration estimates. Simulation results were confirmed through experiments in two-region breast mimicking gelatin phantoms. CONCLUSIONS Accurate characterization of scattering is necessary for quantification of hemoglobin. Based on this study, a system design is described to optimally combine breast tomosynthesis with NIRST.

Semi-automated segmentation and classification of digital breast tomosynthesis reconstructed images

Digital breast tomosynthesis (DBT) is a limited-angle tomographic x-ray imaging technique that reduces the effect of tissue superposition observed in planar mammography. An integrated imaging platform that combines DBT with near infrared spectroscopy (NIRS) to provide co-registered anatomical and functional imaging is under development. Incorporation of anatomic priors can benefit NIRS reconstruction. In this work, we provide a segmentation and classification method to extract potential lesions, as well as adipose, fibroglandular, muscle and skin tissue in reconstructed DBT images that serve as anatomic priors during NIRS reconstruction. The method may also be adaptable for estimating tumor volume, breast glandular content, and for extracting lesion features for potential application to computer aided detection and diagnosis.

Digital breast tomosynthesis guided near infrared spectroscopy: volumetric estimates of fibroglandular fraction and breast density from tomosynthesis reconstructions

A multimodality system combining a clinical prototype digital breast tomosynthesis with its imaging geometry modified to facilitate near-infrared spectroscopic imaging has been developed. The accuracy of parameters recovered from near-infrared spectroscopy is dependent on fibroglandular tissue content. Hence, in this study, volumetric estimates of fibroglandular tissue from tomosynthesis reconstructions were determined. A kernel-based fuzzy c-means algorithm was implemented to segment tomosynthesis reconstructed slices in order to estimate fibroglandular content and to provide anatomic priors for near-infrared spectroscopy. This algorithm was used to determine volumetric breast density (VBD), defined as the ratio of fibroglandular tissue volume to the total breast volume, expressed as percentage, from 62 tomosynthesis reconstructions of 34 study participants. For a subset of study participants who subsequently underwent mammography, VBD from mammography matched for subject, breast laterality and mammographic view was quantified using commercial software and statistically analyzed to determine if it differed from tomosynthesis. Summary statistics of the VBD from all study participants were compared with prior independent studies. The fibroglandular volume from tomosynthesis and mammography were not statistically different (p=0.211, paired t-test). After accounting for the compressed breast thickness, which were different between tomosynthesis and mammography, the VBD from tomosynthesis was correlated with (r =0.809, p<0.001), did not statistically differ from (p>0.99, paired t-test), and was linearly related to, the VBD from mammography. Summary statistics of the VBD from tomosynthesis were not statistically different from prior studies using high-resolution dedicated breast computed tomography. The observation of correlation and linear association in VBD between mammography and tomosynthesis suggests that breast density associated risk measures determined for mammography are translatable to tomosynthesis. Accounting for compressed breast thickness is important when it differs between the two modalities. The fibroglandular volume from tomosynthesis reconstructions is similar to mammography indicating suitability for use during near-infrared spectroscopy.

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 patients 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 μM vs. 9.5 μM). Tools developed improved imaging system characterization and optimization of signal quality, which will ultimately improve patient selection and subsequent clinical trial results.

Pilot study assessment of dynamic vascular changes in breast cancer with near-infrared tomography from prospectively targeted manipulations of inspired end-tidal partial pressure of oxygen and carbon dioxide

Abstract. The dynamic vascular changes in the breast resulting from manipulation of both inspired end-tidal partial pressure of oxygen and carbon dioxide were imaged using a 30 s per frame frequency-domain near-infrared spectral (NIRS) tomography system. By analyzing the images from five subjects with asymptomatic mammography under different inspired gas stimulation sequences, the mixture that maximized tissue vascular and oxygenation changes was established. These results indicate maximum changes in deoxy-hemoglobin, oxygen saturation, and total hemoglobin of 21, 9, and 3%, respectively. Using this inspired gas manipulation sequence, an individual case study of a subject with locally advanced breast cancer undergoing neoadjuvant chemotherapy (NAC) was analyzed. Dynamic NIRS imaging was performed at different time points during treatment. The maximum tumor dynamic changes in deoxy-hemoglobin increased from less than 7% at cycle 1, day 5 (C1, D5) to 17% at (C1, D28), which indicated a complete response to NAC early during treatment and was subsequently confirmed pathologically at the time of surgery.

Characterization of materials for optimal near-infrared and x-ray imaging of the breast

Development of a detector case for complete co-registration of images in a non-fiber-based combined near-infrared spectral tomography and digital breast tomosynthesis, required analysis to find materials that could support a breast under full mammographic compression without affecting the x-ray images or the quality of the near infrared measurements. Several possible solutions were considered, and many types of plastics were tested in the development of the detector case. Light channeling within the detector case changed the data obtained in resin and agarose phantoms, lowering recovered absorption values. Additional developments focusing on blocking stray light were successful and permitted a normal subject imaging exam.

Digital Breast Tomosynthesis Guided Near-Infrared Spectral Tomography: Early Clinical Results

A cohort of 34 normal, benign and malignant breasts were imaged using a combined NIR tomography and breast tomosynthesis unit with two views and compression levels, recovering region based estimates of hemoglobin, oxygen saturation, water and lipids.