Steven P. Poplack

A clinical prototype for active microwave imaging of the breast

Despite its recognized value in detecting and characterizing breast disease, X-ray mammography has important limitations that motivate the quest for alternatives to augment the diagnostic tools that are currently available to the radiologist. The rationale for pursuing electromagnetic methods is strong given the data in the literature, which show that the electromagnetic properties of breast malignancy are significantly different than normal in the high megahertz to low gigahertz spectral range, microwave illumination can effectively penetrate the breast at these frequencies, and the breast is a small readily accessible tissue volume, making it an ideal site for deploying advanced near-field imaging concepts that exploit model-based image reconstruction methodology. In this paper a clinical prototype of a microwave imaging system, which actively illuminates the breast with a 16-element transceiving monopole antenna array in the 300-1000 MHz range, is reported. Microwave exams have been delivered to five women through a water-coupled interface to the pendant breast with the participant positioned prone on an examination table. This configuration has been found to be a practical, comfortable approach to microwave breast imaging. Sessions lasted 10-15 min per breast and included full tomographic data acquisition at seven different array heights beginning at the chest wall and moving anteriorly toward the nipple for seven different frequencies at each array position. This clinical experience appears to be the first report of active near-field microwave imaging of the breast and is certainly the first attempt to exploit model-based image reconstructions from in vivo breast data in order to convert the measured microwave signals into spatial maps of electrical permittivity and conductivity. While clearly preliminary, the results are encouraging and have supplied some interesting findings. Specifically, it appears that the average relative permittivity of the breast as a whole correlates with radiologic breast density categorization and may be considerably higher than previously published values, which have been based on ex vivo tissue specimens.

Digital Breast Tomosynthesis: Initial Experience in 98 Women with Abnormal Digital Screening Mammography

OBJECTIVE The purpose of our study was to compare the image quality of tomosynthesis with that of conventional mammography and to estimate the recall rate of screening when tomosynthesis is used in addition to mammography. MATERIALS AND METHODS Women with an abnormal screening mammography were recruited sequentially. Consenting women underwent tomosynthesis of the affected breast corresponding to the views obtained with diagnostic mammography. The study radiologist compared the image quality, including lesion conspicuity and feature analysis, of tomosynthesis with diagnostic film-screen mammography and assessed the need for recall when tomosynthesis was added to digital screening mammography. Screening recalls were considered unnecessary when tomosynthesis did not show a corresponding abnormality or allowed definitely benign lesion characterization. Fishers exact test was used to determine the association of equivalence and recall status with mammographic finding type. RESULTS There were 99 digital screening recalls in 98 women. The image quality of tomosynthesis was equivalent (n = 51) or superior (n = 37) to diagnostic mammography in 89% (88/99). Finding type was significantly (p < 0.001) associated with equivalence. Approximately half--52/99 (52%)--of the findings would not have been recalled when digital screening mammography was supplemented with tomosynthesis. When adjusting for confounding conditions, the recall reduction was 40% (37/92). The likelihood of recall was also dependent on finding type (p = 0.004). CONCLUSION Subjectively, tomosynthesis has comparable or superior image quality to that of film-screen mammography in the diagnostic setting, and it has the potential to decrease the recall rate when used adjunctively with digital screening mammography.

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.

Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography

Near-infrared spectroscopic tomography was used to measure the properties of 24 mammographically normal breasts to quantify whole-breast absorption and scattering spectra and to evaluate which tissue composition characteristics can be determined from these spectra. The absorption spectrum of breast tissue allows quantification of (i) total hemoglobin concentration, (ii) hemoglobin oxygen saturation, and (iii) water concentration, whereas the scattering spectrum provides information about the size and number density of cellular components and structural matrix elements. These property data were tested for correlation to demographic information, including subject age, body mass index, breast size, and radiographic density. Total hemoglobin concentration correlated inversely to body mass index, likely because lower body mass indicates proportionately less fat and more glandular tissue, and glandular tissue contains greater vascularity, hence, more total hemoglobin. Optical scattering was correlated to breast diameter, subject age, and radiographic density. In the radiographic density, fatty breasts had low scattering power and extremely dense breasts had higher values. This observation is consistent with low attenuation of conventional x-rays with fat and higher attenuation in glandular tissues. Optically, fatty tissues have large scatterers leading to a low scattering power, whereas glandular or fibrous tissues have more cellular and collagen-based structures that lead to high scattering power. The study presents correlative data supporting the hypothesis that optical measurements of absorption and scattering can provide physiologically relevant information about breast tissue composition. These breast constituents vary significantly between individuals and can be altered because of changes in breast physiology or pathological state.

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 microM or 13% of the background breast values was observed in the secretory phase relative to the follicular phase (p<0.0001), 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 microM, 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.

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.

Electrical impedance spectroscopy of the breast: clinical imaging results in 26 subjects

Electrical impedance spectroscopy (EIS) is a potential, noninvasive technique to image women for breast cancer. Studies have shown characteristic frequency dispersions in the electrical conductivity and permittivity of malignant versus normal tissue. Using a multifrequency EIS system, we imaged the breasts of 26 women. All patients had mammograms ranked using the American College of Radiology (ACR) BIRADS system. Of the 51 individual breasts imaged, 38 were ACR 1 negative, six had ACR 4-5 suspicious lesions, and seven had ACR 2 benign findings such as fibroadenomas or calcifications. A radially translatable circular array of 16 Ag/AgCl electrodes was placed around the breast while the patient lay prone. We applied trigonometric voltage patterns at ten frequencies between 10 and 950 kHz. Anatomically coronal images were reconstructed from this data using nonlinear partial differential equation methods. Typically, ACR 1-rated breasts were interrogated in a single central plane whereas ACR 2-5-rated breasts were imaged in multiple planes covering the region of suspicion. In general, a characteristic homogeneous image emerged for mammographically normal cases while focal inhomogeneities were observed in images from women with malignancies. Using a specific visual criterion, EIS images identified 83% of the ACR 4-5 lesions while 67% were detected using a numerical criterion. Overall, multifrequency electrical impedance imaging appears promising for detecting breast malignancies, but improvements must be made before the method reaches its full potential.

Image-guided optical spectroscopy provides molecular-specific information in vivo: MRI-guided spectroscopy of breast cancer hemoglobin, water, and scatterer size

A multimodality instrument that integrated optical or near-infrared spectroscopy into a magnetic resonance imaging (MRI) breast coil was used to perform a pilot study of image-guided spectroscopy on cancerous breast tissue. These results are believed to be the first multiwavelength spectroscopic images of breast cancer using MRI-guided constraints, and they show the cancer tumor to have high hemoglobin and water values, decreased oxygen saturation, and increased subcellular granularity. The use of frequency-domain diffuse tomography methods at many wavelengths provides the spectroscopy required for recovering maps of absorbers and scattering spectra, but the integration with MRI allows these data to be recovered on an image field that preserves high resolution and fuses the two data sets together. Integration of molecular spectroscopy into standard clinical MRI can be achieved with this approach to spectral tomography.

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.

Evaluation of Breast Tumor Response to Neoadjuvant Chemotherapy with Tomographic Diffuse Optical Spectroscopy: Case Studies of Tumor Region-of-Interest Changes

PURPOSE To evaluate two methods of summarizing tomographic diffuse optical spectroscopic (DOS) data through region-of-interest (ROI) analysis to differentiate complete from incomplete responses in patients with locally advanced breast cancer undergoing neoadjuvant treatment and to estimate the standard deviations of these methods for power analysis of larger study designs in the future. MATERIALS AND METHODS Subjects participating in the HIPAA-compliant imaging study, approved by the institutional review board, provided written informed consent and were compensated for their examination participation. Seven of 16 cases in women with complete study data were analyzed by using both fixed- and variable-size (full-width-at-half-maximum) ROI measures of the DOS total hemoglobin concentration (Hb(T)), blood oxygen saturation, water fraction, optical scattering amplitude, and scattering power in the ipsilateral and contralateral breasts. Postsurgical histopathologic analysis was used to categorize patients as having a complete or incomplete treatment response. RESULTS Average normalized change in Hb(T) was the only DOS parameter to show significant differences (P < or = .05) in the pathologic complete response (pCR) and pathologic incomplete response (pIR) outcomes in seven patients. Mean values of the changes for fixed-size ROIs were -64.2% +/- 50.8 (standard deviation) and 16.9% +/- 38.2 for the pCR and pIR groups, respectively, and those for variable-size ROIs were -96.7% +/- 91.8, and 14.1% +/- 26.7 for the pCR and pIR groups, respectively. CONCLUSION Tomographic DOS may provide findings predictive of therapeutic response, which could lead to superior individualized patient treatment. SUPPLEMENTAL MATERIAL http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1.