We have developed a realistic three-dimensional breast lesion phantom that can be computationally embedded in
physically-acquired background images of normal breast tissue. In order to develop new imaging techniques aimed at
the detection and diagnosis of breast lesions, a large number of lesions with varying physical characteristics must be
tested, especially if physical characteristics must be correlated with observed image features. The new tool presented
here, which incorporates three-dimensional tumor features, is potentially useful for testing imaging techniques such as
CT, tomosynthesis, and phase-sensitive X-ray imaging, as these require three-dimensional tissue models. The simulated
lesions improve significantly upon current methods, which lack the complexity and physical attributes of real tumors, by
incorporating a stochastic Gaussian random sphere model to simulate the central tumor mass and calcifications, and an
iterative fractal branching algorithm to model the complex spicula present in many tumors. Results show that userdefined
lesions with realistic features can be computationally embedded in mammographic background images and that
a wide range of physical properties can be modeled.
KEYWORDS: X-rays, Signal detection, Signal to noise ratio, X-ray imaging, Imaging systems, Tissues, Absorption, Detection theory, Radio propagation, Signal attenuation
Propagation-based X-ray phase-contrast imaging permits the visualization of tissues that have very similar X-ray absorption properties and may benefit a variety of biomedical imaging applications. Unlike conventional radiographic contrast that is related to the projected absorption properties of tissue, image contrast in phasecontrast radiographs contains contributions from absorption-contrast and phase-contrast. In this work, we
develop a general theoretical framework for assessing the contributions of these contrast mechanisms to signal
detectability measures in propagation-based X-ray phase-contrast imaging. Specifically, concepts from signal
detection theory are utilized to analyze the contributions of phase- and absorption-contrast to an ideal observer
figure of merit for a signal-known-exactly/background-known exactly detection task.
At diagnostic X-ray energies, variations in the real component of the refractive index of tissues are several orders of
magnitude larger than variations in the imaginary component, or equivalently, the X-ray attenuation coefficient.
Consequently, X-ray phase-contrast imaging may permit the visualization of tissues that have identical, or
very similar, X-ray absorption properties. Quantitative in-line
phase-contrast tomography methods seek to
reconstruct the three-dimensional (3D) complex X-ray refractive index distribution of tissue. Almost all existing
image reconstruction algorithms for quantitative phase-contrast tomography make physical assumptions that are
not consistent with benchtop or clinical implementations that employ an X-ray tube. Such assumptions include a
monochromatic plane-wave X-ray beam that possesses perfect coherence properties. In this work, we implement
and investigate a reconstruction theory for quantitative
phase-contrast tomography that is suitable for use with
polychromatic X-ray beams produced by a tube source. An image reconstruction algorithm is implemented that
requires, as input data, two intensity measurements at each tomographic view that correspond to incident X-ray
beams with distinct coherence properties. Computer-simulation studies that emulate polychromatic tube-based
imaging conditions are conducted to assess the effectiveness of the reconstruction method for characterizing soft
tissue structures.
It has been proposed that the sensitivity of breast lesion detection can be improved with phase-contrast mammographic
imaging. The recently introduced clinical system by Konica-Minolta, for example, reportedly yields enhanced lesion
detectability. We hypothesize that the use of an optimized x-ray spectrum will result in even better performance. To test
this hypothesis, we have performed a study of several clinical spectra from Mo and W sources over a broad spectral
range. In the study, we have incorporated established dose measurements from a simple breast phantom used in the
digital mammography literature, which has been updated to incorporate breast density properties in addition to
conventional attenuation information. Established phase-contrast imaging simulation techniques, which employed a
Fresnel propagator, were used to generate edge-enhanced radiographs for analysis. In addition, detector sensitivity and
tube loading parameters were incorporated into the analysis. The resulting mammography images were analyzed via
measurement of object edge-enhanced contrast.
Accurate models that describe the propagation of partially coherent wave fields and their interaction with refractive index inhomogeneities within a sample are required to optimally design X-ray phase-contrast imaging systems. Several methods have been proposed for the direct propagation of the second-order statistical properties of a wave field. One method, which has been demonstrated for x-ray microscopy, employs a single eikonal for propagation, approximating the phase by an average over the temporal Fourier components of the field. We have revisited this method by use of a
coherent mode model from classic coherence theory. Our analysis produces a variant of the transport of intensity equation for partially coherent wave fields.
Breast cancer continues to be one of the most widely diagnosed forms of cancer in women and the second leading type
of cancer deaths for women. The metastatic spread and staging of breast cancer is typically evaluated through the nodal
assessment of the regional lymphatic system, and often this is performed during the surgical resection of the tumor mass.
The recurrence rate of breast cancer is highly dependent on several factors including the complete removal of the
primary tumor during surgery, and the presence of cancer cells in involved lymph nodes. Hence, developing means to
more accurately resect tumor cells, along with the tumor mass, and ensure negative surgical margins, offers the potential
to impact outcomes of breast cancer. The use of diffuse optical tomography has been applied for screening optical
mammography applications as an alternative to standard x-ray mammography. The use of coherence ranging and
coherent optical imaging in breast tissue has also found numerous applications, including intra-operative assessment of
tumor margin status during lumpectomy procedures, assessment of lymph node changes for staging metastatic spread,
and for guiding needle-biopsy procedures. The development, pre-clinical testing, and translation of techniques such as
low-coherence interferometry (LCI) and optical coherence tomography (OCT) into clinical applications in breast cancer
is demonstrated in these feasibility studies.
Since its introduction, optical coherence tomography (OCT) technology has advanced from the laboratory bench to the clinic and back again. Arising from the fields of low coherence interferometry and optical time- and frequency-domain reflectometry, OCT was initially demonstrated for retinal imaging and followed a unique path to commercialization for clinical use. Concurrently, significant technological advances were brought about from within the research community, including improved laser sources, beam delivery instruments, and detection schemes. While many of these technologies improved retinal imaging, they also allowed for the application of OCT to many new clinical areas. As a result, OCT has been clinically demonstrated in a diverse set of medical and surgical specialties, including gastroenterology, dermatology, cardiology, and oncology, among others. The lessons learned in the clinic are currently spurring a new set of advances in the laboratory that will again expand the clinical use of OCT by adding molecular sensitivity, improving image quality, and increasing acquisition speeds. This continuous cycle of laboratory development and clinical application has allowed the OCT technology to grow at a rapid rate and represents a unique model for the translation of biomedical optics to the patient bedside. This work presents a brief history of OCT development, reviews current clinical applications, discusses some clinical translation challenges, and reviews laboratory developments poised for future clinical application.
KEYWORDS: Optical coherence tomography, Tissues, Tumors, Lymphatic system, Breast cancer, Cancer, Surgery, Imaging systems, Breast, Signal to noise ratio
Breast cancer continues to be one of the most widely diagnosed forms of cancer amongst women and the second leading
type of cancer deaths amongst women. The recurrence rate of breast cancer is highly dependent on several factors
including the complete removal of the primary tumor and the presence of cancer cells in involved lymph nodes. The
metastatic spread and staging of breast cancer is also evaluated through the nodal assessment of the regional lymphatic
system. A portable real-time spectral domain optical coherence tomography system is being presented as a clinical
diagnostic tool in the intraoperative delineation of tumor margins as well as for real time lymph node assessment. The
system employs a super luminescent diode centered at 1310 nm with a bandwidth of 92 nm. Using a spectral domain
detection system, the data is acquired at a rate of 5 KHz / axial scan. The sample arm is a galvanometer scanning
telecentric probe with an objective lens (f = 60 mm, confocal parameter = 1.5 mm) yielding an axial resolution of 8.3 &mgr;m
and a transverse resolution of 35.0 &mgr;m. Images of tumor margins are acquired in the operating room ex vivo on freshly
excised human tissue specimen. This data shows the potential of the use of OCT in defining the structural tumor margins
in breast cancer. Images taken from ex-vivo samples on the bench system clearly delineate the differences between
clusters of tumor cells and nearby adipose cells. In addition, the data shows the potential for OCT as a diagnostic tool in
the staging of cancer metastasis through locoregional lymph node assessment.
Needle-based devices, which are in wide clinical use for needle biopsy procedures, may be augmented by
suitable optical techniques for the localization and diagnosis of diseased tissue. Tissue refractive index is
one optical contrast mechanism with diagnostic potential. In the case of mammary tissue, for example,
recent research indicates that refractive index variations between tissue types may be useful for the
identification of cancerous tissue. While many coherence-based forward-sensing devices have been
developed to detect scattering changes, none have demonstrated refractive index measurement capabilities.
We present a novel needle-based device that is capable of simultaneously measuring refractive index and
scattering. Coupled to the sample arm of an optical coherence tomography system, the needle device
detects the scattering response and optical pathlength through tissue residing in a fixed-width channel.
Near-infrared measurements of tissues and materials with known optical properties using a prototype
device will be presented. This work demonstrates the feasibility of integrated in vivo measurement of
refractive index and scattering in conjunction with existing clinical needle-based devices.
Optical coherence tomography (OCT) has been demonstrated as a promising means of identifying the boundaries between normal and diseased breast tissue. This capability has yielded promise for the development of OCT techniques for biopsy guidance, surgical margin assessment, and minimally invasive evaluation of disease states. We present methods for the assessment of human breast tissue based on spatial and Fourier-domain analysis. Derived from preliminary OCT data, these methods are aimed at the development of automated diagnostic tools that will aid in the translation of this technology into the clinical environment.
Projected index computed tomography (PICT) is a newly developed technique that uses the measured optical path length from multiple optical coherence tomography (OCT) scans through a semitransparent sample to computationally reconstruct tomographic images based on the spatial variations of the refractive index. Since the index of refraction of most samples is not constant, a depth-wise distortion due to the varying index of the sample is evident. Using a highly reflective reference surface placed behind the sample, optical path length measurements yield an aggregate index value for each beampath through the sample. Rotating the sample allows a data set to be formed for multiple beam angles. These data can be understood as the projections of the object index, i.e. the Radon tranform of the index of the object. Using filtered backprojection algorithms set of projection data were used to reconstruct PICT images. The resulting images are free from the spatial distortions found in standard OCT. Experimental results show that PICT images correspond well with the dimensional characteristics of specific samples.
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