Conventional sonography, which performs well in dense breast tissue and is comfortable and radiation-free, is
not practical for screening because of its operator dependence and the time needed to scan the whole breast.
While magnetic resonance imaging (MRI) can significantly improve on these limitations, it is also not
practical because it has long been prohibitively expensive for routine use. There is therefore a need for an
alternative breast imaging method that obviates the constraints of these standard imaging modalities. The
lack of such an alternative is a barrier to dramatically impacting mortality (about 45,000 women in the US per
year) and morbidity from breast cancer because, currently, there is a trade-off between the cost effectiveness
of mammography and sonography on the one hand and the imaging accuracy of MRI on the other. This paper
presents a progress report on our long term goal to eliminate this trade-off and thereby improve breast cancer
survival rates and decrease unnecessary biopsies through the introduction of safe, cost-effective, operatorindependent
sonography that can rival MRI in accuracy.
The objective of the study described in this paper was to design and build an improved ultrasound
tomography (UST) scanner in support of our goals. To that end, we report on a design that builds on our
current research prototype. The design of the new scanner is based on a comparison of the capabilities of our
existing prototype and the performance needed for clinical efficacy. The performance gap was quantified by
using clinical studies to establish the baseline performance of the research prototype, and using known MRI
capabilities to establish the required performance. Simulation software was used to determine the basic
operating characteristics of an improved scanner that would provide the necessary performance. Design
elements focused on transducer geometry, which in turn drove the data acquisition system and the image
reconstruction engine specifications. The feasibility of UST established by our earlier work and that of other
groups, forms the rationale for developing a UST system that has the potential to become a practical, low-cost
device for breast cancer screening and diagnosis.
The objective of this study is to present imaging parameters and display thresholds of an ultrasound tomography (UST)
prototype in order to demonstrate analogous visualization of overall breast anatomy and lesions relative to magnetic
resonance (MR). Thirty-six women were imaged with MR and our UST prototype. The UST scan generated sound
speed, attenuation, and reflection images and were subjected to variable thresholds then fused together into a single UST
image. Qualitative and quantitative comparisons of MR and UST images were utilized to identify anatomical similarities
and mass characteristics. Overall, UST demonstrated the ability to visualize and characterize breast tissues in a manner
comparable to MR without the use of IV contrast. For optimal visualization, fused images utilized thresholds of 1.46±0.1
km/s for sound speed to represent architectural features of the breast including parenchyma. An arithmetic combination
of images using the logical .AND. and .OR. operators, along with thresholds of 1.52±0.03 km/s for sound speed and
0.16±0.04 dB/cm for attenuation, allowed for mass detection and characterization similar to MR.
Breast ultrasound tomography is a rapidly developing imaging modality that has the potential to impact breast
cancer screening and diagnosis. Double difference (DD) tomography utilizes more accurate differential time-of-flight
(ToF) data to reconstruct the sound speed structure of the breast. It can produce more precise and better
resolution sound speed images than standard tomography that uses absolute ToF data. We apply DD tomography to
phantom data and excised mouse mammary glands data. DD tomograms demonstrate sharper sound speed contrast
than the standard tomograms.
The purpose of this study was to investigate the performance of an ultrasound tomography (UST) prototype relative to
magnetic resonance (MR) for imaging overall breast anatomy and accentuating tumors relative to background tissue.
The study was HIPAA compliant, approved by the Institutional Review Board, and performed after obtaining the
requisite informed consent. Twenty-three patients were imaged with MR and the UST prototype. T<sub>1</sub> weighted images
with fat saturation, with and without gadolinium enhancement, were used to examine anatomical structures and tumors,
while T<sub>2</sub> weighted images were used to identify cysts. The UST scans generated sound speed, attenuation, and reflection
images. A qualitative visual comparison of the MRI and UST images was then used to identify anatomical similarities. A
more focused approach that involved a comparison of reported masses, lesion volumes, and breast density was used to
quantify the findings from the visual assessment. Our acoustic tomography prototype imaged distributions of fibrous
stroma, parenchyma, fatty tissues, and lesions in patterns similar to those seen in the MR images. The range of
thresholds required to establish tumor volume equivalency between MRI and UST suggested that a universal threshold for isolating masses relative to background tissue is feasible with UST. UST has demonstrated the ability to visualize and characterize breast tissues in a manner comparable to MRI. Thresholding techniques accentuate masses relative to background anatomy, which may prove clinically useful for early cancer detection.
The purpose of this study was to correlate changes in biomechanical properties of breast cancer lesions in response to
neoadjuvant chemotherapy. Nine patients were examined repeatedly throughout their treatment, using an experimental
prototype based on the principles of ultrasound tomography. The study was HIPAA compliant, approved by the
Institutional Review Board, and performed after obtaining the requisite informed consent. Images of reflection, sound
speed and attenuation, representing the entire volume of the breast, were reconstructed from the exam data and analyzed
for time-dependent changes during the treatment period. It was found that changes in tumor properties could be
measured in all cases. Furthermore, changes in sound speed were found to vary strongly from patient to patient. A
comparison of the sound speed response curves with pathological findings suggests that complete responders exhibit
distinctly different responses as measured by sound speed. These preliminary results were used to define a cut-point for
predicting response. Subsequently, a prospective prediction of the treatment response of a new patient was made
correctly. We hypothesize that changes in the biomechanical properties of breast cancers, as measured by sound speed,
can predict response. Future studies will focus on testing this hypothesis and defining and quantifying markers of response.
Since a 1976 study by Wolfe, high breast density has gained recognition as a factor strongly correlating with an
increased incidence of breast cancer. These observations have led to mammographic density being designated a "risk
factor" for breast cancer. Clinically, the exclusive reliance on mammography for breast density measurement has
forestalled the inclusion of breast density into statistical risk models. This exclusion has in large part been due to the
ionizing radiation associated with the method. Additionally, the use of mammography as valid tool for measuring a three
dimensional characteristic (breast density) has been criticized for its prima facie incongruity. These shortfalls have
prompted MRI studies of breast density as an alternative three-dimensional method of assessing breast density.
Although, MRI is safe and can be used to measure volumetric density, its cost has prohibited its use in screening. Here,
we report that sound speed measurements using a prototype ultrasound tomography device have potential for use as surrogates for breast density measurement. Accordingly, we report a strong positive linear correlation between volume-averaged sound speed of the breast and percent glandular tissue volume as assessed by MR.
Our laboratory has focused on the development of ultrasound tomography (UST) for breast imaging. To that end we
have been developing and testing a clinical prototype in the Karmanos Cancer Institute's (KCI) breast center. The
development of our prototype has been guided by clinical feedback from data accumulated from over 300 patients
recruited over the last 4 years. Our techniques generate whole breast reflection images as well as images of the acoustic
parameters of sound speed and attenuation. The combination of these images reveals major breast anatomy, including
fat, parenchyma, fibrous stroma and masses. Fusion imaging, utilizing thresholding, is shown to visualize mass
characterization and facilitates separation of cancer from benign masses. These results indicate that operator-independent
whole-breast imaging and the detection and characterization of cancerous breast masses are feasible using acoustic
Analyses of the prototype images suggests that we can detect the variety of mass attributes noted by current ultrasound-BIRADS criteria, such as mass shape, acoustic mass properties and architecture of the tumor environment. These
attributes help quantify current BIRADS criteria (e.g. "shadowing" or high attenuation) and provide greater possibilities
for defining a unique signature of cancer. The potential for UST to detect and characterize breast masses was quantified
using UST measurements of 86 masses from the most recent cohort of patients imaged with the latest version of our prototype. Our preliminary results suggest that the development of a formal predictive model, in support of larger future trials, is warranted.
We report on a continuing assessment of the in-vivo performance of an operator independent breast imaging device
based on the principles of acoustic tomography. This study highlights the feasibility of mass characterization using
criteria derived from reflection, sound speed and attenuation imaging. The data were collected with a clinical prototype
at the Karmanos Cancer Institute in Detroit MI from patients recruited at our breast center. Tomographic sets of images
were constructed from the data and used to form 3-D image stacks corresponding to the volume of the breast. Masses
were identified independently by either ultrasound or biopsy and their locations determined from conventional
mammography and ultrasound exams. The nature of the mass and its location were used to assess the feasibility of our
prototype to detect and characterize masses in a case-following scenario.
Our techniques generated whole breast reflection images as well as images of the acoustic parameters of sound speed
and attenuation. The combination of these images reveals major breast anatomy, including fat, parenchyma, fibrous
stroma and masses. The three types of images are intrinsically co-registered because the reconstructions are performed
using a common data set acquired by the prototype. Fusion imaging, utilizing thresholding, is shown to visualize mass
characterization and facilitates separation of cancer from benign masses. These initial results indicate that operatorindependent
whole-breast imaging and the detection and a characterization of cancerous breast masses are feasible using
acoustic tomography techniques.
The objective of this study is to investigate a potential low-cost-alternative to MRI, based on acoustic tomography.
Using MRI as the gold standard, our goals are to assess the performance of acoustic tomography in (i) depicting normal
breast anatomy, (ii) imaging cancerous lesions and (iii) accentuating lesions relative to background tissue using
thresholding techniques. Fifteen patients were imaged with MRI and with an acoustic tomography prototype. A
qualitative visual comparison of the MRI and prototype images was used to verify anatomical similarities. These
similarities suggest that the prototype can image fibrous stroma, parenchyma and fatty tissues, with similar sensitivity to
MRI. The prototype was also shown to be able to image masses but equivalency in mass sensitivity with MRI could not
be established because of the small numbers of patients and the prototype's limited scanning range. The range of
thresholds required to establish tumor volume equivalency suggests that a universal threshold for isolating masses
relative to background tissue is possible with acoustic tomography. Thresholding techniques promise to accentuate
masses relative to background anatomy which may prove clinically useful in potential screening applications. Future
work will utilize larger trials to verify these preliminary conclusions.
As part of an ongoing assessment of the in-vivo performance of a operator independent breast imaging device, based on
acoustic tomography, we report on new results obtained with patients undergoing neoadjuvant chemotherapy. Five
patients were examined with the prototype on multiple occasions corresponding in time to their chemotherapy sessions.
Images of reflection, sound speed and attenuation, representing the entire volume of the breast, were reconstructed from
the exam data and analyzed for time-dependent changes during the treatment period. It was found that changes in
acoustic properties of the tumors could be measured directly from the images. The measured properties include
reflectivity, sound speed and attenuation, leading to measurable changes in the volume, shape and internal attributes of
the tumors. These measurements were used to monitor the response of the tumors to the therapy with the long term goal
of correlating results with pathological and clinical outcomes. Comparisons with tumor size changes based on traditional
US and MRI indicates potential for accurate, quantifiable tracking of tumor volume. Furthermore, our tentative results
also show declines in internal properties of the tumors, possibly relating to a reduction in tissue stiffness and/or density.
Future work will include an expansion of the study to a larger cohort of patients for determining the statistical
significance of our findings.
A major limitation of thermal therapies is the lack of detailed thermal information needed to monitor the
therapy. Temperatures are routinely measured invasively with thermocouples, but only sparse measurements
can be made. Ultrasound tomography is an attractive modality for temperature monitoring because it is noninvasive,
non-ionizing, convenient and inexpensive. It capitalizes on the fact that the changes in temperature
cause the changes in sound speed. In this work we investigate the possibility of monitoring large temperature
changes, in the interval from body temperature to -40°C. The ability to estimate temperature in this interval is
of a great importance in cryosurgery, where freezing is used to destroy abnormal tissue. In our experiment, we
freeze locally a tissue-mimicking phantom using a combination of one, two or three cryoprobes. The estimation of
sound speed is a difficult task because, first, the sound is highly attenuated when traversing the frozen tissue; and
second, the sound speed to be reconstructed has a high spatial bandwidth, due to the dramatic change in speed
between the frozen and unfrozen tissue. We show that the first problem can be overcome using a beamforming
technique. As the classical reconstruction algorithms inherently smooth the reconstruction, we propose to solve
the second problem by applying reconstruction techniques based on sparsity.