Gregory Boverman

Combined Optical and X-ray Tomosynthesis Breast Imaging

PURPOSE To explore the optical and physiologic properties of normal and lesion-bearing breasts by using a combined optical and digital breast tomosynthesis (DBT) imaging system. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained for this HIPAA-compliant study. Combined optical and tomosynthesis imaging analysis was performed in 189 breasts from 125 subjects (mean age, 56 years ± 13 [standard deviation]), including 138 breasts with negative findings and 51 breasts with lesions. Three-dimensional (3D) maps of total hemoglobin concentration (Hb(T)), oxygen saturation (So(2)), and tissue reduced scattering coefficients were interpreted by using the coregistered DBT images. Paired and unpaired t tests were performed between various tissue types to identify significant differences. RESULTS The estimated average bulk Hb(T) from 138 normal breasts was 19.2 μmol/L. The corresponding mean So(2) was 0.73, within the range of values in the literature. A linear correlation (R = 0.57, P < .0001) was found between Hb(T) and the fibroglandular volume fraction derived from the 3D DBT scans. Optical reconstructions of normal breasts revealed structures corresponding to chest-wall muscle, fibroglandular, and adipose tissues in the Hb(T), So(2), and scattering images. In 26 malignant tumors of 0.6-2.5 cm in size, Hb(T) was significantly greater than that in the fibroglandular tissue of the same breast (P = .0062). Solid benign lesions (n = 17) and cysts (n = 8) had significantly lower Hb(T) contrast than did the malignant lesions (P = .025 and P = .0033, respectively). CONCLUSION The optical and DBT images were structurally consistent. The malignant tumors and benign lesions demonstrated different Hb(T) and scattering contrasts, which can potentially be exploited to reduce the false-positive rate of conventional mammography and unnecessary biopsies.

Combined Optical Imaging and Mammography of the Healthy Breast: Optical Contrast Derived From Breast Structure and Compression

In this paper, we report new progress in developing the instrument and software platform of a combined X-ray mammography/diffuse optical breast imaging system. Particularly, we focus on system validation using a series of balloon phantom experiments and the optical image analysis of 49 healthy patients. Using the finite-element method for forward modeling and a regularized Gauss-Newton method for parameter reconstruction, we recovered the inclusions inside the phantom and the hemoglobin images of the human breasts. An enhanced coupling coefficient estimation scheme was also incorporated to improve the accuracy and robustness of the reconstructions. The recovered average total hemoglobin concentration (HbT) and oxygen saturation (SO₂) from 68 breast measurements are 16.2 mum and 71%, respectively, where the HbT presents a linear trend with breast density. The low HbT value compared to literature is likely due to the associated mammographic compression. From the spatially co-registered optical/X-ray images, we can identify the chest-wall muscle, fatty tissue, and fibroglandular regions with an average HbT of 20.1plusmn6.1 &nbsp;mum for fibroglandular tissue, 15.4plusmn5.0&nbsp;mum for adipose, and 22.2plusmn7.3&nbsp;mum for muscle tissue. The differences between fibroglandular tissue and the orresponding adipose tissue are significant. At the same time, we recognize that the optical images are influenced, to a certain extent, by mammographical compression. The optical images from a subset of patients show composite features from both tissue structure and pressure distribution. We present mechanical simulations which further confirm this hypothesis.

Time resolved fluorescence tomography of turbid media based on lifetime contrast

A general linear model for time domain (TD) fluorescence tomography is presented that allows a lifetime-based analysis of the entire temporal fluorescence response from a turbid medium. Simulations are used to show that TD fluorescence tomography is optimally performed using two complementary approaches: A direct TD analysis of a few time points near the peak of the temporal response, which provides superior resolution; and an asymptotic multi-exponential analysis based tomography of the decay portion of the temporal response, which provides accurate localization of yield distributions for various lifetime components present in the imaging medium. These results indicate the potential of TD technology for biomedical imaging with lifetime sensitive targeted probes, and provide useful guidelines for an optimal approach to fluorescence tomography with TD data.

Spatio-temporal imaging of the hemoglobin in the compressed breast with diffuse optical tomography

We develop algorithms for imaging the time-varying optical absorption within the breast given diffuse optical tomographic data collected over a time span that is long compared to the dynamics of the medium. Multispectral measurements allow for the determination of the time-varying total hemoglobin concentration and of oxygen saturation. To facilitate the image reconstruction, we decompose the hemodynamics in time into a linear combination of spatio-temporal basis functions, the coefficients of which are estimated using all of the data simultaneously, making use of a Newton-based nonlinear optimization algorithm. The solution of the extremely large least-squares problem which arises in computing the Newton update is obtained iteratively using the LSQR algorithm. A Laplacian spatial regularization operator is applied, and, in addition, we make use of temporal regularization which tends to encourage similarity between the images of the spatio-temporal coefficients. Results are shown for an extensive simulation, in which we are able to image and quantify localized changes in both total hemoglobin concentration and oxygen saturation. Finally, a breast compression study has been performed for a normal breast cancer screening subject, using an instrument which allows for highly accurate co-registration of multispectral diffuse optical measurements with an x-ray tomosynthesis image of the breast. We are able to quantify the global return of blood to the breast following compression, and, in addition, localized changes are observed which correspond to the glandular region of the breast.

Quantitative spectroscopic diffuse optical tomography of the breast guided by imperfect a priori structural information

Spectroscopic diffuse optical tomography (DOT) can directly image the concentrations of physiologically significant chromophores in the body. This information may be of importance in characterizing breast tumours and distinguishing them from benign structures. This paper studies the accuracy with which lesions can be characterized given a physiologically realistic situation in which the background architecture of the breast is heterogeneous yet highly structured. Specifically, in simulation studies, we assume that the breast is segmented into distinct glandular and adipose regions. Imaging with a high-resolution imaging modality, such as magnetic resonance imaging, in conjunction with a segmentation by a clinical expert, allows the glandular/adipose boundary to be determined. We then apply a two-step approach in which the background chromophore concentrations of each region are estimated in a nonlinear fashion, and a more localized lesion is subsequently estimated using a linear perturbational approach. In addition, we examine the consequences which errors in the breast segmentation have on estimating both the background and inhomogeneity chromophore concentrations.

Robust Linearized Image Reconstruction for Multifrequency EIT of the Breast

Electrical impedance tomography (EIT) is a developing imaging modality that is beginning to show promise for detecting and characterizing tumors in the breast. At Rensselaer Polytechnic Institute, we have developed a combined EIT-tomosynthesis system that allows for the coregistered and simultaneous analysis of the breast using EIT and X-ray imaging. A significant challenge in EIT is the design of computationally efficient image reconstruction algorithms which are robust to various forms of model mismatch. Specifically, we have implemented a scaling procedure that is robust to the presence of a thin highly-resistive layer of skin at the boundary of the breast and we have developed an algorithm to detect and exclude from the image reconstruction electrodes that are in poor contact with the breast. In our initial clinical studies, it has been difficult to ensure that all electrodes make adequate contact with the breast, and thus procedures for the use of data sets containing poorly contacting electrodes are particularly important. We also present a novel, efficient method to compute the Jacobian matrix for our linearized image reconstruction algorithm by reducing the computation of the sensitivity for each voxel to a quadratic form. Initial clinical results are presented, showing the potential of our algorithms to detect and localize breast tumors.

Methods for Compensating for Variable Electrode Contact in EIT

Electrical impedance tomography (EIT) is an imaging modality that currently shows promise for the detection and characterization of breast cancer. A very significant problem in EIT imaging is the proper modeling of the interface between the body and the electrodes. We have found empirically that it is very difficult, in a clinical setting, to assure that all electrodes make satisfactory contact with the body. In addition, we have observed a capacitive effect at the skin/electrode boundary that is spatially heterogeneous. To compensate for these problems, we have developed a hybrid nonlinear-linear reconstruction algorithm using the complete electrode model in which we first estimate electrode surface impedances, by means of a Levenberg-Marquardt iterative optimization procedure with an analytically computed Jacobian matrix. We, subsequently, use a linearized algorithm to perform a 3-D reconstruction of perturbations in both contact impedances, and in the spatial distributions of conductivity and permittivity. Results show that, with this procedure, artifacts due to electrodes making poor contact can be greatly reduced. If the experimental apparatus physically applies voltages and measures currents, we show that it is preferable to compute the reconstruction with respect to the Dirichlet-to-Neumann map rather than the Neumann-to-Dirichlet map if there is a significant possibility that electrodes will be fully disconnected. Finally, we test our electrode compensation algorithms for a set of clinical data, showing that we can significantly improve the fit of our model to the measurements by allowing the electrode surface impedances to vary.

The complete electrode model for EIT in a mammography geometry.

We have developed an EIT system for simultaneous use in a mammography examination, allowing for highly accurate co-registration between the two modalities. In this pre-clinical study, we investigate the importance of properly modeling the interface between the electrodes and the medium being imaged. We have implemented the complete electrode model for a parallel-plane mammography geometry, in which currents are injected into the medium through two planar sets of electrodes above and below the medium. We make use of the ACT4 device to conduct saline-tank experiments showing the improvement of the complete model over an ave-gap model, which ignores both the conductivity of the electrodes and the surface impedance. The experimental results show an improvement in both forward modeling accuracy and in the quality of the resulting reconstructed images using the complete electrode model, as compared to the ave-gap model.

An Implementation of CalderÓn's Method for 3-D Limited-View EIT

Mathematical interest in electrical impedance tomography has been strong since the publication of Calderons foundational paper. This paper introduced the idea of applying external voltage patterns to a medium such that, assuming that the medium is sufficiently close to a constant admittivity, the reconstruction can be accomplished directly by inverse Fourier transform. Motivated by Calderons method, we have developed a variant of the algorithm which is applicable to the case of measurement on only a part of the boundary and on discrete electrodes. Here we determine voltage or current patterns to apply to the electrodes which optimally approximate Calderons special functions in the interior. Furthermore, in three dimensions and higher, Calderons method allows each point in Fourier space to be computed in a multiplicity of ways. We show that by making use of the inherent redundancy in our measurements, we can significantly improve the quality of the static images produced by our algorithm.

A two-layered forward model of tissue for electrical impedance tomography

Electrical impedance tomography is being explored as a technique to detect breast cancer, exploiting the differences in admittivity between normal tissue and tumors. In this paper, the geometry is modeled as an infinite half space under a hand-held probe. A forward solution and a reconstruction algorithm for this geometry were developed previously by Mueller et al (1999 IEEE Trans. Biomed. Eng. 46 1379). In this paper, we present a different approach which uses the decomposition of the forward solution into its Fourier components to obtain the forward solution and the reconstructions. The two approaches are compared in terms of the forward solutions and the reconstructions of experimental tank data. We also introduce a two-layered model to incorporate the presence of the skin that surrounds the body area being imaged. We demonstrate an improvement in the reconstruction of a target in a layered medium using this layered model with finite difference simulated data. We then extend the application of our layered model to human subject data and estimate the skin and the tissue admittivities for data collected on the human abdomen using an ultrasound-like hand-held EIT probe. Lastly, we show that for this set of human subject data, the layered model yields an improvement in predicting the measured voltages of around 81% for the lowest temporal frequency (3 kHz) and around 61% for the highest temporal frequency (1 MHz) applied when compared to the homogeneous model.