Permeability assessment of the focused ultrasound-induced blood-brain barrier opening using dynamic contrast-enhanced MRI.

Focused ultrasound (FUS) in conjunction with microbubbles has been shown to successfully open the blood-brain barrier (BBB) in the mouse brain. In this study, we compute the BBB permeability after opening in vivo. The spatial permeability of the BBB-opened region was assessed using dynamic contrast-enhanced MRI (DCE-MRI).

Simulation study of amplitude-modulated (AM) harmonic motion imaging (HMI) for stiffness contrast quantification with experimental validation.

The objective of this study is to show that Harmonic Motion Imaging (HMI) can be used as a reliable tumor-mapping technique based on the tumor's distinct stiffness at the early onset of disease. HMI is a radiation-force-based imaging method that generates a localized vibration deep inside the tissue to estimate the relative tissue stiffness based on the resulting displacement amplitude. In this paper, a finite-element model (FEM) study is presented, followed by an experimental validation in tissue-mimicking polyacrylamide gels and excised human breast tumors ex vivo.

A fast normalized cross-correlation calculation method for motion estimation.

High-precision motion estimation has become essential in ultrasound-based techniques such as time-domain Doppler and elastography. Normalized cross-correlation (NCC) has been shown as one of the best motion estimators. However, a significant drawback is its associated computational cost, especially when RF signals are used.

Identifying the inertial cavitation threshold and skull effects in a vessel phantom using focused ultrasound and microbubbles.

Focused ultrasound (FUS) in combination with microbubbles has been shown capable of delivering large molecules to the brain parenchyma through opening of the blood-brain barrier (BBB). However, the mechanism behind the opening remains unknown. To investigate the pressure threshold for inertial cavitation of preformed microbubbles during sonication, passive cavitation detection in conjunction with B-mode imaging was used.

In vivo characterization of the aortic wall stress-strain relationship.

Arterial stiffness has been shown to be a good indicator of arterial wall disease. However, a single parameter is insufficient to describe the complex stress-strain relationship of a multi-component, non-linear tissue such as the aorta. We therefore propose a new approach to measure the stress-strain relationship locally in vivo noninvasively, and present a clinically relevant parameter describing the mechanical interaction between aortic wall constituents.

Pulse wave imaging for noninvasive and quantitative measurement of arterial stiffness in vivo.

Background: Arterial stiffening is recognized to be associated with increased cardiovascular mortality and to be a major cause of several cardiovascular complications. Pulse wave velocity (PWV) has been widely accepted to be a reliable and robust measure of arterial stiffness. In this article, the novel ultrasound-based pulse wave imaging (PWI) method is hereby proposed for visualization of the pulse wave during its propagation and for calculation of the PWV.

An integrated motion capture system for evaluation of neuromuscular disease patients.

There currently exist a variety of methods for evaluating movement in patients suffering from neuromuscular diseases (NMD). These tests are primarily performed in the clinical setting and evaluated by highly trained individuals, rather than evaluating patient in their natural environments (i.e.

Key parameters for precise lateral displacement estimation in ultrasound elastography.

Complementary to axial, lateral and elevational displacement and strain can provide important information on the mechanical properties of biological soft tissues. In this paper, the effects of key parameters on the lateral displacement estimation were investigated in simulations and validated in phantom experiments. The performance of the lateral estimator was evaluated by measuring its associated bias, and jitter (i.

Characterization of the stress-strain relationship of the abdominal aortic wall in vivo.

We hereby propose a new method to determine the regionally passive, elastic, stress-strain relationship of the normal murine abdominal aorta in vivo. The circumferential stress-strain relationship was assessed through Laplace's law, a small deformation framework and a relationship between luminal pressure and diameter variation. The regional diameter variation of the murine abdominal aortas was obtained using a cross-correlation technique on radio-frequency (RF) signals at the extremely high frame rate of 8 kHz.

Design and evaluation of a hybrid passive and active gravity neutral orthosis (GNO).

Neuromuscular diseases (NMD), including Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD), result in progressive muscular weakness that often leaves patients functionally dependent on caregivers for many activities of daily living (ADL) such as eating, bathing, grooming (touching the face and head), reaching (grabbing for objects), and dressing. In severe cases, patients are unable to perform even the simplest of activities from exploring their 3D space to touching their own face. The ability to move and initiate age appropriate tasks, such as playing and exploration, are considered to be of vital importance to both their physical and cognitive development.

Fundamental performance assessment of 2-D myocardial elastography in a phased-array configuration.

Two-dimensional myocardial elastography, an RF-based, speckle-tracking technique, uses 1-D cross-correlation and recorrelation methods in a 2-D search, and can estimate and image the 2-D transmural motion and deformation of the myocardium so as to characterize the cardiac function. Based on a 3-D finite-element (FE) canine left-ventricular model, a theoretical framework was previously developed by our group to evaluate the estimation quality of 2-D myocardial elastography using a linear array. In this paper, an ultrasound simulation program, Field II, was used to generate the RF signals of a model of the heart in a phased-array configuration and under 3-D motion conditions; thus simulating a standard echocardiography exam.

Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo.

Focused ultrasound (FUS) is hereby shown to noninvasively and selectively deliver compounds at pharmacologically relevant molecular weights through the opened blood-brain barrier (BBB). A complete examination on the size of the FUS-induced BBB opening, the spatial distribution of the delivered agents and its dependence on the agent's molecular weight were imaged and quantified using fluorescence microscopy. BBB opening in mice (n=13) was achieved in vivo after systemic administration of microbubbles and subsequent application of pulsed FUS (frequency: 1.

Noninvasive electromechanical wave imaging and conduction-relevant velocity estimation in vivo.

Electromechanical wave imaging is a novel technique for the noninvasive mapping of conduction waves in the left ventricle through the combination of ECG gating, high frame rate ultrasound imaging and radio-frequency (RF)-based displacement estimation techniques. In this paper, we describe this new technique and characterize the origin and velocity of the wave under distinct pacing schemes. First, in vivo imaging (30 MHz) was performed on anesthetized, wild-type mice (n=12) at high frame rates in order to take advantage of the transient electromechanical coupling occurring in the myocardium.

Microbubble-size dependence of focused ultrasound-induced blood-brain barrier opening in mice in vivo.

The therapeutic efficacy of neurological agents is severely limited, because large compounds do not cross the blood-brain barrier (BBB). Focused ultrasound (FUS) sonication in the presence of microbubbles has been shown to temporarily open the BBB, allowing systemically administered agents into the brain. Until now, polydispersed microbubbles (1-10 microm in diameter) were used, and, therefore, the bubble sizes better suited for inducing the opening remain unknown.

Electromechanical wave imaging of normal and ischemic hearts in vivo.

Electromechanical wave imaging (EWI) has recently been introduced as a noninvasive, ultrasound-based imaging modality, which could map the electrical activation of the heart in various echocardiographic planes in mice, dogs, and humans in vivo. By acquiring radio-frequency (RF) frames at very high frame rates (390-520 Hz), the onset of small, localized, transient deformations resulting from the electrical activation of the heart, i.e.

In vivo feasibility of real-time monitoring of focused ultrasound surgery (FUS) using harmonic motion imaging (HMI).

In this study, the Harmonic Motion Imaging for Focused Ultrasound (HMIFU) technique is applied to monitor changes in mechanical properties of tissues during thermal therapy in a transgenic breast cancer mouse model in vivo. An HMIFU system, composed of a 4.5-MHz focused ultrasound (FUS) and a 3.

Effects of various parameters on lateral displacement estimation in ultrasound elastography.

Complementary to axial, lateral displacement and strain can provide important information on the biological soft tissues. In this paper, the effects of key parameters (i.e.

Quantitative viscoelastic parameters measured by harmonic motion imaging.

Quantifying the mechanical properties of soft tissues remains a challenging objective in the field of elasticity imaging. In this work, we propose an ultrasound-based method for quantitatively estimating viscoelastic properties, using the amplitude-modulated harmonic motion imaging (HMI) technique. In HMI, an oscillating acoustic radiation force is generated inside the medium by using focused ultrasound and the resulting displacements are measured using an imaging transducer.

Pulse wave imaging of normal and aneurysmal abdominal aortas in vivo.

The abdominal aortic aneurysm (AAA) is a common vascular disease. The current clinical criterion for treating AAAs is an increased diameter above a critical value. However, the maximum diameter does not correlate well with aortic rupture, the main cause of death from AAA disease.

Noninvasive and transient blood-brain barrier opening in the hippocampus of Alzheimer's double transgenic mice using focused ultrasound.

The spatio-temporal nature of focused ultrasound-induced blood-brain barrier (BBB) opening as a brain drug delivery method was investigated in Alzheimer's disease model mice. The left hippocampus of transgenic (APP/PS1, n = 3) and nontransgenic (n = 3) mice was sonicated (frequency: 1.525 MHz, peak-negative pressure: 600 kPa, pulse length: 20 ms, duty cycle: 20%, duration: 1 min) in vivo, through their intact skin and skull, after intravenous injection of microbubbles (SonoVue; 25 microl).

A composite high-frame-rate system for clinical cardiovascular imaging.

High frame-rate ultrasound RF data acquisition has been proved to be critical for novel cardiovascular imaging techniques, such as high-precision myocardial elastography, pulse wave imaging (PWI), and electromechanical wave imaging (EWI). To overcome the frame-rate limitations on standard clinical ultrasound systems, we developed an automated method for multi-sector ultrasound imaging through retrospective electrocardiogram (ECG) gating on a clinically used open architecture system. The method achieved both high spatial (64 beam density) and high temporal resolution (frame rate of 481 Hz) at an imaging depth up to 11 cm and a 100% field of view in a single breath-hold duration.

Preliminary validation of angle-independent myocardial elastography using MR tagging in a clinical setting.

Myocardial elastography (ME), a radio-frequency (RF) based speckle tracking technique, was employed in order to image the entire two-dimensional (2D) transmural deformation field in full echocardiographic views and was validated against tagged magnetic resonance imaging (tMRI) in normal as well as reperfused (i.e., treated myocardial infarction [MI]) human left ventricles.

Angle-independent and multi-dimensional myocardial elastography--from theory to clinical validation.

The angle-independent myocardial elastography, which shows good performance in our proposed theoretical framework using a three-dimensional, ultrasonic image formation model based on well-established, 3D finite-element, canine, left-ventricular models in both normal and left-circumflex ischemic cases, is employed as well as validated in vivo to assess the contractility of normal and pathological myocardia. Angle-independent myocardial elastography consists of: (1) iterative estimation of in-plane and out-of-plane cumulative displacements during systole using 1D cross-correlation and recorrelation techniques in a 2D search; (2) calculation of in-plane finite strains from the in-plane cumulative motion; and (3) computation of in-plane principal strains from the finite strains by eigen decomposition with a classification strategy. The in vivo raw data of healthy and pathological human left ventricles were acquired at 136 fps in a short-axis echocardiographic view.

Challenges in atherosclerotic plaque characterization with intravascular ultrasound (IVUS): from data collection to classification.

In vivo plaque characterization is an important research field in interventional cardiology. We will study the realistic challenges to this goal by deploying 40 MHz single-element, mechanically rotating transducers. The intrinsic variability among the transducers' spectral parameters as well as tissue signals will be demonstrated.

A mechanical model to compute elastic modulus of tissues for harmonic motion imaging.

Numerous experimental and computational methods have been developed to estimate tissue elasticity. The existing testing techniques are generally classified into in vitro, invasive in vivo and non-invasive in vivo. For each experimental method, a computational scheme is accordingly proposed to calculate mechanical properties of soft biological tissues.