Amy C. Sharma

A finite-element method model of soft tissue response to impulsive acoustic radiation force

Several groups are studying acoustic radiation force and its ability to image the mechanical properties of tissue. Acoustic radiation force impulse (ARFI) imaging is one modality using standard diagnostic ultrasound scanners to generate localized, impulsive, acoustic radiation forces in tissue. The dynamic response of tissue is measured via conventional ultrasonic speckle-tracking methods and provides information about the mechanical properties of tissue. A finite-element method (FEM) model has been developed that simulates the dynamic response of tissues, with and without spherical inclusions, to an impulsive acoustic radiation force excitation from a linear array transducer. These FEM models were validated with calibrated phantoms. Shear wave speed, and therefore elasticity, dictates tissue relaxation following ARFI excitation, but Poissons ratio and density do not significantly alter tissue relaxation rates. Increased acoustic attenuation in tissue increases the relative amount of tissue displacement in the near field compared with the focal depth, but relaxation rates are not altered. Applications of this model include improving image quality, and distilling material and structural information from tissues dynamic response to ARFI excitation. Future work on these models includes incorporation of viscous material properties and modeling the ultrasonic tracking of displaced scatterers.

Introduction to neutron stimulated emission computed tomography

Neutron stimulated emission computed tomography (NSECT) is presented as a new technique for in vivo tomographic spectroscopic imaging. A full implementation of NSECT is intended to provide an elemental spectrum of the body or part of the body being interrogated at each voxel of a three-dimensional computed tomographic image. An external neutron beam illuminates the sample and some of these neutrons scatter inelastically, producing characteristic gamma emission from the scattering nuclei. These characteristic gamma rays are acquired by a gamma spectrometer and the emitting nucleus is identified by the emitted gamma energy. The neutron beam is scanned over the body in a geometry that allows for tomographic reconstruction. Tomographic images of each element in the spectrum can be reconstructed to represent the spatial distribution of elements within the sample. Here we offer proof of concept for the NSECT method, present the first single projection spectra acquired from multi-element phantoms, and discuss potential biomedical applications.

Acoustic radiation force impulse imaging of in vivo breast masses

Acoustic radiation force impulse (ARFI) imaging utilizes brief, high energy, focused acoustic pulses to generate radiation force in tissue, and conventional ultrasonic correlation-based methods to track the resulting tissue displacements in order to image the relative mechanical properties of tissue. In an ongoing clinical study, ARFI datasets from in vivo breast masses are acquired prior to core biopsy. Matched B-mode and ARFI images are generated for each mass. Data sets are divided based upon biopsy results, and images are evaluated for differentiating features. The purpose of this study is to acquire in vivo ARFI datasets in real-time, and to identify differentiable features between benign and malignant breast masses in the ARFI images. A modified Siemens SONOLINE Antares/spl trade/ scanner and a VF10-5 probe were programmed to implement ARFI imaging in a multi-focal zone configuration. Under an IRB approved protocol. patients scheduled for breast core biopsy were recruited for participation. Data was acquired in real-time and processed offline. Matched B-mode and ARFI images were evaluated concurrently. To date, 27 masses have been imaged under this experimental protocol. In addition, single focal zone ARFI data acquired from 52 masses with a Siemens SONOLINE Elegra/spl trade/ scanner and a 75L40 transducer were evaluated for consistency of the differentiating features. Of the 27 masses interrogated via multi-focal-zone ARFI, 9 were malignant, 9 were benign fibroadenomas, 4 were cysts, and the rest were other benign masses (i.e. lymph nodes, fat necrosis, etc.) Structures in matched B-mode images are in good agreement with those in ARFI displacement images, with both modalities demonstrating comparable resolution. In general ARFI displacement images of malignant breast masses exhibit increased contrast and improved margin definition over matched B-mode images. Cancers displace less (i.e. they are stiffer) than the surrounding tissue, and generally appear larger than in matched B-mode images. In addition, some malignant masses exhibit a slower recovery time, which has not been observed with benign masses. The cysts and fibroadenomas, in general, exhibit less contrast in ARFI images than in matched B-mode images. In many cases, fibroadenomas are not clearly distinguished from the surrounding tissues in ARFI displacement images, and can appear either stiffer or softer than the surrounding tissue. Acoustic streaming is observed in cyst fluid in response to ARFI excitation. ARFI displacement images portray different, complementary information than matched B-mode images. Some possible differentiating features between malignant and benign breast masses have been identified by this pilot study. Promising features include: differences in B-mode and ARFI lesion size. displacement magnitude, recovery time, and image contrast. These results encourage further study of breast mass characterization using ARFI imaging.

Neutron Stimulated Emission Computed Tomography for Diagnosis of Breast Cancer

Neutron stimulated emission computed tomography (NSECT) is being developed as a non-invasive spectroscopic imaging technique to determine element concentrations in the human body. NSECT uses a beam of fast neutrons that scatter inelastically from atomic nuclei in tissue, causing them to emit characteristic gamma photons that are detected and identified using an energy-sensitive gamma detector. By measuring the energy and number of emitted gamma photons, the system can determine the elemental composition of the target tissue. Such determination is useful in detecting several disorders in the human body that are characterized by changes in element concentration, such as breast cancer. In this paper we describe our experimental implementation of a prototype NSECT system for the diagnosis of breast cancer and present experimental results from sensitivity studies using this prototype. Results are shown from three sets of samples: (a) excised breast tissue samples with unknown element concentrations, (b) a multi-element calibration sample used for sensitivity studies, and (c) a small-animal specimen, to demonstrate detection ability from in-vivo tissue. Preliminary results show that NSECT has the potential to detect elements in breast tissue. Several elements were identified common to both benign and malignant samples, which were confirmed through neutron activation analysis (NAA). Statistically significant differences were seen for peaks at energies corresponding to 37Cl, 56Fe, 58Ni, 59Co, 79Br and 87Rb. The spectrum from the small animal specimen showed the presence of 12C from tissue, from bone, and elements 39K, 27Al, 37Cl, 56Fe, 68Zn and 25Mg. Threshold sensitivity for the four elements analyzed was found to range from 0.3 grams to 1 gram, which is higher than the microgram sensitivity required for cancer detection. Patient dose levels from NSECT were found to be comparable to those of screening mammography.

Breast cancer detection using neutron stimulated emission computed tomography: prominent elements and dose requirements.

Neutron stimulated emission computed tomography (NSECT) is being developed to noninvasively determine concentrations of trace elements in biological tissue. Studies have shown prominent differences in the trace element concentration of normal and malignant breast tissue. NSECT has the potential to detect these differences and diagnose malignancy with high accuracy with dose comparable to that of a single mammogram. In this study, NSECT imaging was simulated for normal and malignant human breast tissue samples to determine the significance of individual elements in determining malignancy. The normal and malignant models were designed with different elemental compositions, and each was scanned spectroscopically using a simulated 2.5 MeV neutron beam. The number of incident neutrons was varied from 0.5 million to 10 million neutrons. The resulting gamma spectra were evaluated through receiver operating characteristic (ROC) analysis to determine which trace elements were prominent enough to be considered markers for breast cancer detection. Four elemental isotopes (133Cs, 81Br, 79Br, and 87Rb) at five energy levels were shown to be promising features for breast cancer detection with an area under the ROC curve (A(Z)) above 0.85. One of these elements--87Rb at 1338 keV--achieved perfect classification at 10 million incident neutrons and could be detected with as low as 3 million incident neutrons. Patient dose was calculated for each gamma spectrum obtained and was found to range from between 0.05 and 0.112 mSv depending on the number of neutrons. This simulation demonstrates that NSECT has the potential to noninvasively detect breast cancer through five prominent trace element energy levels, at dose levels comparable to other breast cancer screening techniques.

Neutron stimulated emission computed tomography: a Monte Carlo simulation approach

A Monte Carlo simulation has been developed for neutron stimulated emission computed tomography (NSECT) using the GEANT4 toolkit. NSECT is a new approach to biomedical imaging that allows spectral analysis of the elements present within the sample. In NSECT, a beam of high-energy neutrons interrogates a sample and the nuclei in the sample are stimulated to an excited state by inelastic scattering of the neutrons. The characteristic gammas emitted by the excited nuclei are captured in a spectrometer to form multi-energy spectra. Currently, a tomographic image is formed using a collimated neutron beam to define the line integral paths for the tomographic projections. These projection data are reconstructed to form a representation of the distribution of individual elements in the sample. To facilitate the development of this technique, a Monte Carlo simulation model has been constructed from the GEANT4 toolkit. This simulation includes modeling of the neutron beam source and collimation, the samples, the neutron interactions within the samples, the emission of characteristic gammas, and the detection of these gammas in a Germanium crystal. In addition, the model allows the absorbed radiation dose to be calculated for internal components of the sample. NSECT presents challenges not typically addressed in Monte Carlo modeling of high-energy physics applications. In order to address issues critical to the clinical development of NSECT, this paper will describe the GEANT4 simulation environment and three separate simulations performed to accomplish three specific aims. First, comparison of a simulation to a tomographic experiment will verify the accuracy of both the gamma energy spectra produced and the positioning of the beam relative to the sample. Second, parametric analysis of simulations performed with different user-defined variables will determine the best way to effectively model low energy neutrons in tissue, which is a concern with the high hydrogen content in biological tissue. Third, determination of the energy absorbed in tissue during neutron interrogation in order to estimate the dose. Results from these three simulation experiments demonstrate that GEANT4 is an effective simulation platform that can be used to facilitate the future development and optimization of NSECT.

Experimental detection of iron overload in liver through neutron stimulated emission spectroscopy

Iron overload disorders have been the focus of several quantification studies involving non-invasive imaging modalities. Neutron spectroscopic techniques have demonstrated great potential in detecting iron concentrations within biological tissue. We are developing a neutron spectroscopic technique called neutron stimulated emission computed tomography (NSECT), which has the potential to diagnose iron overload in the liver at clinically acceptable patient dose levels through a non-invasive scan. The technique uses inelastic scatter interactions between atomic nuclei in the sample and incoming fast neutrons to non-invasively determine the concentration of elements in the sample. This paper discusses a non-tomographic application of NSECT investigating the feasibility of detecting elevated iron concentrations in the liver. A model of iron overload in the human body was created using bovine liver tissue housed inside a human torso phantom and was scanned with a 5 MeV pulsed beam using single-position spectroscopy. Spectra were reconstructed and analyzed with algorithms designed specifically for NSECT. Results from spectroscopic quantification indicate that NSECT can currently detect liver iron concentrations of 6 mg g(-1) or higher and has the potential to detect lower concentrations by optimizing the acquisition geometry to scan a larger volume of tissue. The experiment described in this paper has two important outcomes: (i) it demonstrates that NSECT has the potential to detect clinically relevant concentrations of iron in the human body through a non-invasive scan and (ii) it provides a comparative standard to guide the design of iron overload phantoms for future NSECT liver iron quantification studies.

Design and Development of a High-Energy Gamma Camera for Use With NSECT Imaging: Feasibility for Breast Imaging

A new spectroscopic imaging technique, neutron stimulated emission computed tomography (NSECT), is currently being developed to non-invasively and non-destructively measure and image elemental concentrations within the body. NSECT has potential for use in breast imaging as several studies have shown a link between elemental concentration and tumor status. In NSECT, a region of interest is illuminated with a high-energy (3-5 MeV) beam of neutrons that scatter inelastically with elemental nuclei within the body. The characteristic gamma rays that are emitted as the excited nuclei relax allow the identification of elements and the formation of elemental composition images. This imaging technique requires high-resolution and high-energy gamma spectroscopy; thereby eliminating current scintillation crystal based position sensitive gamma cameras. Instead, we propose to adapt high-energy gamma imaging techniques used in space-based imaging. A high purity germanium (HPGe) detector provides high-resolution energy spectra while a rotating modulation collimator (RMC) placed in front of the detector modulates the incoming signal to provide spatial information. Counting the number of gamma events at each collimator rotation angle allows for reconstruction of images. Herein we report on the design and testing of a prototype RMC, a Monte Carlo simulation of this camera, and the use of this simulation tool to access the feasibility of imaging a breast with such a camera. The prototype RMC was tested with a 22Na point source and verified that the RMC modulates the gamma rays in a predictable manner. The Monte Carlo simulation accurately modeled this behavior. Other simulations were used to accurately reconstruct images of a point source located within a 10 cm cube, suggesting NSECTs potential as a breast imaging method.

Neutron-stimulated emission computed tomography of a multi-element phantom

This paper describes the implementation of neutron-stimulated emission computed tomography (NSECT) for non-invasive imaging and reconstruction of a multi-element phantom. The experimental apparatus and process for acquisition of multi-spectral projection data are described along with the reconstruction algorithm and images of the two elements in the phantom. Independent tomographic reconstruction of each element of the multi-element phantom was performed successfully. This reconstruction result is the first of its kind and provides encouraging proof of concept for proposed subsequent spectroscopic tomography of biological samples using NSECT.

Near-field high-energy spectroscopic gamma imaging using a rotation modulation collimator

Certain trace elements are vital to the body and elemental imbalances can be indicators of certain diseases including cancer and liver diseases. Neutron Stimulated Emission Computed Tomography (NSECT) is being developed as spectroscopic imaging technique to non-invasively and non-destructively measure and image elemental concentrations within the body. A region of interest is illuminated via a high-energy beam of neutrons that scatter inelastically with elemental nuclei within the body. The excited nuclei then relax by emitting characteristic gamma rays. Acquiring the gamma spectrum in a tomographic manner allows not only the identification of elements, but also the formation of images representing spatial distributions of specific elements. We are developing a high-energy position-sensitive gamma camera that allows full illumination of the entire region of interest. Because current scintillation crystal based position-sensitive gamma cameras operate in too low of an energy range, we are adapting high-energy gamma imaging techniques used in space-based imaging. A High Purity Germanium (HPGe) detector provides high-resolution energy spectra while a rotating modulation collimator (RMC) placed in front of the detector modulates the incoming signal to provide spatial information. The purpose of this manuscript is to describe the near-field RMC geometry, which varies greatly from the infinite-focus space-based applications, and how it modulates the incident gamma flux. A simple geometric model is presented and then used to reconstruct two-dimensional planar images of both simulated point sources and extended sources.