Contrast-enhanced subharmonic aided pressure estimation for assessment of intracranial pressure in vivo.

Background: Intracranial pressure (ICP) monitoring in children currently requires invasive techniques. Subharmonic aided pressure estimation (SHAPE) uses contrast-enhanced ultrasound (CEUS) to measure intravascular and interstitial pressure, but utility in ICP measurements has yet to be explored.

Objective: The objective of this study was to investigate SHAPE as a novel tool for noninvasive ICP measurements in fetal lambs.

A Preliminary Study of Quantitative Ultrasound for Cancer-Risk Assessment of Thyroid Nodules.

Background: Gray-scale, B-mode ultrasound (US) imaging is part of the standard clinical procedure for evaluating thyroid nodules (TNs). It is limited by its instrument- and operator-dependence and inter-observer variability. In addition, the accepted high-risk B-mode US TN features are more specific for detecting classic papillary thyroid cancer rather than the follicular variant of papillary thyroid cancer or follicular thyroid cancer.

Toward 3-D Echocardiographic Determination of Regional Myofiber Structure.

As a step toward the goal of relating changes in underlying myocardial structure to observed altered cardiac function in the hearts of individual patients, this study addresses the feasibility of creating echocardiography-derived maps of regional myocardial fiber structure for entire, intact, excised sheep hearts. Backscatter data were obtained from apical echocardiographic images acquired with a clinical ultrasonic imaging system and used to determine local fiber orientations in each of seven hearts. Systematic acquisition across the entire heart volume provided information sufficient to give a complete map for each heart.

Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids.

Background: Low levels of HDL-C are an independent cardiovascular risk factor associated with increased premature cardiovascular death. However, HDL-C therapies historically have been limited by issues relating to immunogenicity, hepatotoxicity and scalability, and have been ineffective in clinical trials.

Objective: We examined the feasibility of using injectable acoustic microspheres to locally deliver human ApoA-I DNA plasmids in a pre-clinical model and quantify increased production of HDL-C in vivo.

4-D spatiotemporal analysis of ultrasound contrast agent dispersion for prostate cancer localization: a feasibility study.

Currently, nonradical treatment for prostate cancer is hampered by the lack of reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently shown great potential as a prostate cancer imaging technique. CUDI estimates the local dispersion of intravenously injected contrast agents, imaged by transrectal dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes related to tumor growth.

Use of smoothing splines for analysis of backscattered ultrasonic waveforms: application to monitoring of steroid treatment of dystrophic mice.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by progressive weakness and wasting of skeletal and cardiac muscle; boys present with weakness by the age of 5 years and, if left untreated, are unable to walk without assistance by the age of 10 years. Therapy for DMD has been primarily palliative, with oral steroids emerging as a first-line approach even though this treatment has serious side-effects. Consequently, low-cost imaging technology suitable for improved diagnosis and treatment monitoring of DMD would be of great value, especially in remote and underserved areas.

Simultaneous dual frequency 1H and 19F open coil imaging of arthritic rabbit knee at 3T.

The combination of sensitive magnetic resonance techniques with a selective site-targeted nanoparticle contrast agent has a demonstrated utility for molecular imaging studies. By detecting a unique signature of the contrast agent, this approach can be employed to identify specific bio-molecular markers and observe cellular-level processes within a large and complex organism (e.g.

Application of a real-time, calculable limiting form of the Renyi entropy for molecular imaging of tumors.

Previously, we reported new methods for ultrasound signal characterization using entropy, H(f); a generalized entropy, the Renyi entropy, I(f)(r); and a limiting form of Renyi entropy suitable for real-time calculation, I(f),(infinity). All of these quantities demonstrated significantly more sensitivity to subtle changes in scattering architecture than energy-based methods in certain settings. In this study, the real-time calculable limit of the Renyi entropy, I(f),(infinity), is applied for the imaging of angiogenic murine neovasculature in a breast cancer xenograft using a targeted contrast agent.

Fluidic measurement of electric field sensitivity of Ti-GaAs Schottky junction gated field effect biosensors.

We report the electric field and pH sensitivity of fluid gated metal-semiconductor hybrid (MSH) Schottky structures consisting of a Titanium layer on n-type GaAs. Compared to standard field-effect sensors, the MSH Schottky structures are 21 times more sensitive to electric field of -46.6 V/cm and show about six times larger resistance change as pH of the solution is decreased from 8.

Sensitive ultrasonic delineation of steroid treatment in living dystrophic mice with energy-based and entropy-based radio frequency signal processing.

Duchenne muscular dystrophy is a severe wasting disease, involving replacement of necrotic muscle tissue by fibrous material and fatty infiltrates. One primary animal model of this human disease is the X chromosome-linked mdx strain of mice. The goals of the present work were to validate and quantify the capability of both energy and entropy metrics of radio-frequency ultrasonic backscatter to differentiate among normal, dystrophic, and steroid-treated skeletal muscle in the mdx model.

Ultrasonic detection of the anisotropy of protein cross linking in myocardium at diagnostic frequencies.

Increased myocardial stiffness in aging and diabetes that may result in pathologies such as diastolic dysfunction has been attributed, in part, to an increase in cross linking of extracellular matrix proteins such as collagen. With the development of new approaches to cardiovascular therapy, it becomes increasingly important to develop noninvasive approaches for monitoring changes in myocardial cross linking. The objective of this study was to use ultrasound at frequencies used in clinical echocardiography to measure changes in myocardial attenuation resulting from increased cross linking as a function of angle of insonification over a complete rotation.

Regional variation in the measured apparent ultrasonic backscatter of mid-gestational fetal pig hearts.

The goal of this study was to characterize and compare regional backscatter properties of fetal hearts through measurements of the apparent integrated backscatter. Sixteen excised, formalin-fixed fetal pig hearts, representing an estimated 53 to 63 days of gestation, were investigated. Spatially localized measurements of integrated backscatter from these specimens were acquired using a 50 MHz single-element transducer.

Plane wave source with minimal harmonic distortion for investigating nonlinear acoustic properties.

The objective of this investigation is to introduce and validate a practical ultrasound source to be used in the investigation of the nonlinear material properties of liquids and soft tissues studied in vitro. Methods based on the progressive distortion of finite amplitude ultrasonic waves in the low megahertz frequency range are most easily implemented under the assumption of plane wave propagation. However, achieving an approximately planar ultrasonic field over substantial propagation distances can be challenging.

Sensitive ultrasonic detection of dystrophic skeletal muscle in patients with duchenne muscular dystrophy using an entropy-based signal receiver.

The dystrophinopathies comprise a group of X-linked genetic diseases that feature dystrophin deficiency. Duchenne and Becker muscular dystrophy are characterized by progressive weakness and wasting of skeletal, smooth, and/or cardiac muscle. Duchenne muscular dystrophy (DMD) is the most severe dystrophinopathy, with an incidence of 1:3500 male births.

Finite amplitude measurements of the nonlinear parameter B/A for liquid mixtures spanning a range relevant to tissue harmonic mode.

The objective of this investigation was to measure the nonlinear parameter B/A using an enhanced finite amplitude distortion technique, based on nonlinear propagation effects analogous to those associated with tissue harmonic imaging. These measurements validate an improved method for measuring the nonlinear parameter B/A, the small-signal speed of sound, and the attenuation coefficient from a single set of ultrasonic measurements. To test the method, measurements were performed on 11 different mixtures of isopropyl alcohol (isopropanol) and water that span the range of concentrations from 0% to 100% isopropanol.

Impact of propagation through an aberrating medium on the linear effective apodization of a nonlinearly generated second harmonic field.

Techniques based on the nonlinearly generated second harmonic signal (tissue harmonic imaging) have rapidly supplanted linear (fundamental) imaging methods as the standard in two-dimensional echocardiography. Enhancements to the compactness of the nonlinearly generated second harmonic (2f) field component with respect to the fundamental (1f) field component are widely considered to be among the factors contributing to the observed image quality improvements. The objective of this study was to measure the impact of phase and amplitude aberrations resulting from propagation through an inhomogeneous tissue, on the beamwidths associated with: the fundamental (1f); the nonlinearly generated second harmonic (2f); and the linearly propagated, effective apodization signal at the same (21) frequency.

Measurements of the anisotropy of ultrasonic attenuation in freshly excised myocardium.

Echocardiography requires imaging of the heart with sound propagating at varying angles relative to the predominant direction of the myofibers. The degree of anisotropy of attenuation can significantly influence ultrasonic imaging and tissue characterization measurements in vivo. This study quantifies the anisotropy of attenuation of freshly excised myocardium at frequencies typical of echocardiographic imaging.

The frequency dependence of ultrasonic velocity and the anisotropy of dispersion in both freshly excised and formalin-fixed myocardium.

The objectives of this study were to measure the frequency dependence of the ultrasonic velocity in myocardium and to quantify the frequency dependence of phase velocity as a function of the insonification angle relative to the predominant direction of the myofibers. Broadband phase spectroscopy data were acquired, spanning a frequency range of 3 to 8 MHz. Measurements were made on 36 tissue specimens cored from 12 freshly excised lamb hearts and were repeated after fixation with formalin.

Elastic stiffness coefficients (c11, C33, and C13) for freshly excised and formalin-fixed myocardium from ultrasonic velocity measurements.

The goal of this study was to measure elastic stiffness coefficients of freshly excised and subsequently formalin-fixed myocardial tissue. Our approach was to measure the angle-dependent phase velocities associated with the propagation of a longitudinal ultrasonic wave (3-8 MHz) in ovine myocardium using phase spectroscopy techniques and to interpret the results in the context of orthotropic and transversely isotropic models describing the elastic properties of myocardium. The phase velocity results together with density measurements were used to obtain the elastic stiffness coefficients c11, c33, and c13 for both symmetries.

Anisotropy of apparent backscatter in the short-axis view of mouse hearts.

The goals of this investigation were to measure the anisotropy of backscattered ultrasound observed in the short-axis view of mouse hearts in systole and diastole and to compare these measurements with predictions from a computer simulation. Measurements of midmyocardial apparent backscatter were obtained from analyses of the hearts of seven wild-type mice using a clinical imaging system utilizing a linear array with a nominal center frequency of 13 MHz. A computer model simulating the short-axis view was implemented based on previous measurements of the angle of insonification dependence of myocardial backscatter and attenuation.

Measurements of the anisotropy of ultrasonic velocity in freshly excised and formalin-fixed myocardial tissue.

The objective of this study was to quantify the anisotropy of ultrasonic velocity in freshly excised myocardial tissue and to examine the effects of formalin-fixation. Through-transmission radio-frequency-based measurements were performed on ovine and bovine myocardial specimens from 24 different hearts. A total of 81 specimens were obtained from specific locations within each heart to investigate the possibility of regional differences in anisotropy of velocity in the left ventricular wall and septum.

On the stability of the effective apodization of the nonlinearly generated second harmonic with respect to range.

The concept of an effective apodization was introduced to describe the field pattern for the nonlinearly generated second harmonic (2f) within the focal zone using a linear propagation model. Our objective in this study was to investigate the validity of the concept of an effective apodization at 2f as an approach to approximating the field of the second harmonic over a wide range of depths. Two experimental setups were employed: a vascular imaging array with a water path and an adult cardiac imaging array with an attenuating liver path.

Influence of bright intramural echoes on estimates of ultrasonic attenuation from backscattered ultrasound in excised myocardium.

The purpose of this study was to quantitate the influence of bright intramural echoes on estimates of myocardial attenuation from analyses of backscattered ultrasound. To achieve this, M-mode image-based measurements of the inherent anisotropic properties of myocardial attenuation were performed on rotating myocardial specimens. The approach was to use a commercially-available ultrasonic imaging system to acquire M-mode images of 24 excised cylindrical specimens from six formalin-fixed lamb hearts for data analysis using a video signal analysis technique.

Estimating myocardial attenuation from M-mode ultrasonic backscatter.

The objective of this investigation was to determine whether measurements of myocardial attenuation can be obtained from analyses of M-mode images. We exploited the inherent anisotropy of myocardial properties as a means of systematically varying the attenuation to evaluate this M-mode image-based method for myocardial tissue characterization. A commercially available ultrasonic imaging system was used to acquire M-mode images of 24 excised cylindrical specimens from six formalin-fixed sheep hearts that were analyzed using video signal analysis.

Potential relationships among myocardial stiffness, the measured level of myocardial backscatter ("image brightness"), and the magnitude of the systematic variation of backscatter (cyclic variation) over the heart cycle.

Background: In a number of recently published studies comparing measurements from patients with those from control subjects, a decreased magnitude of the systematic variation of backscattered energy over the heart cycle (cyclic variation) is accompanied by an increased level of overall myocardial backscatter (calibrated myocardial image brightness) when measured at a specific phase of the heart cycle (eg, end systole or end diastole). The goal of this study was to investigate whether this observation is consistent with predictions based on a model of the mechanisms of cyclic variation incorporating changes in relative intracellular and extracellular acoustic impedance over the heart cycle.

Methods: A previously described 3-component Maxwell-type model of muscle mechanics representing cardiac cell mechanical behavior was utilized to predict the systematic variation in the relative acoustic impedance differences between intracellular and extracellular elastic properties over the heart cycle and hence the observed magnitude of cyclic variation and overall myocardial scattering level.