3D Quasi-Static Ultrasound Elastography With Plane Wave In Vivo

In biological tissue, an increase in elasticity is often a marker of abnormalities. Techniques such as quasi-static ultrasound elastography have been developed to assess the strain distribution in soft tissues in two dimensions using a quasi-static compression. However, as abnormalities can exhibit very heterogeneous shapes, a three dimensional approach would be necessary to accurately measure their volume and remove operator dependency. Acquisition of volumes at high rates is also critical to performing real-time imaging with a simple freehand compression. In this study, we developed for the first time a 3D quasi-static ultrasound elastography method with plane waves that estimates axial strain distribution in vivo in entire volumes at high volume rate. Acquisitions were performed with a 2D matrix array probe of 2.5MHz frequency and 256 elements. Plane waves were emitted at a volume rate of 100 volumes/s during a continuous motorized and freehand compression. 3D B-mode volumes and 3D cumulative axial strain volumes were successfully estimated in inclusion phantoms and in ex vivo canine liver before and after a high intensity focused ultrasound ablation. We also demonstrated the in vivo feasibility of the method using freehand compression on the calf muscle of a human volunteer and were able to retrieve 3D axial strain volume at a high volume rate depicting the differences in stiffness of the two muscles which compose the calf muscle. 3D ultrasound quasi-static elastography with plane waves could become an important technique for the imaging of the elasticity in human bodies in three dimensions using simple freehand scanning

Precision estimation and imaging of normal and shear components of the 3D strain tensor in elastography

Abstract. In elastography we have previously developed a tracking and correction method that estimates the axial and lateral strain components along and perpendicular to the compressor/scanning axis following an externally applied compression. However, the resulting motion is a three-dimensional problem. Therefore, in order to fully describe this motion we need to consider a 3D model and estimate all three principal strain components, i.e. axial, lateral and elevational (out-of-plane), for a full 3D tensor description. Since motion is coupled in all three dimensions, the three motion components have to be decoupled prior to their estimation. In this paper, we describe a method that estimates and corrects motion in three dimensions, which is an extension of the 2D motion tracking and correction method discussed before. In a similar way as in the 2D motion estimation, and by assuming that ultrasonic frames are available in more than one parallel elevational plane, we used methods of interpolation and cross-correlation between elevationally displaced RF echo segments to estimate the elevational displacement and strain. In addition, the axial, lateral and elevational displacements were used to estimate all three shear strain components that, together with the normal strain estimates, fully describe the full 3D normal strain tensor resulting from the uniform compression. Results of this method from three-dimensional finite-element simulations are shown

Getting ahead of Alzheimer’s disease: early intervention with focused ultrasound

The amyloid-β (Aβ) hypothesis implicates Aβ protein accumulation in Alzheimer’s disease (AD) onset and progression. However, therapies targeting Aβ have proven insufficient in achieving disease reversal, prompting a shift to focus on early intervention and alternative therapeutic targets. Focused ultrasound (FUS) paired with systemically-introduced microbubbles (μB) is a non-invasive technique for targeted and transient blood–brain barrier opening (BBBO), which has demonstrated Aβ and tau reduction, as well as memory improvement in models of late-stage AD. However, similar to drug treatments for AD, this approach is not sufficient for complete reversal of advanced, symptomatic AD. Here we aim to determine whether early intervention with FUS-BBBO in asymptomatic AD could delay disease onset. Thus, the objective of this study is to measure the protective effects of FUS-BBBO on anxiety, memory and AD-associated protein levels in female and male triple transgenic (3xTg) AD mice treated at an early age and disease state. Here we show that early, repeated intervention with FUS-BBBO decreased anxiety-associated behaviors in the open field test by 463.02 and 37.42% in male and female cohorts, respectively. FUS-BBBO preserved female aptitude for learning in the active place avoidance paradigm, reducing the shock quadrant time by 30.03 and 31.01% in the final long-term and reversal learning trials, respectively. Finally, FUS-BBBO reduced hippocampal accumulation of Aβ40, Aβ42, and total tau in females by 12.54, 13.05, and 3.57%, respectively, and reduced total tau in males by 18.98%. This demonstration of both cognitive and pathological protection could offer a solution for carriers of AD-associated mutations as a safe, non-invasive technique to delay the onset of the cognitive and pathological effects of AD

Texture-Driven Coronary Artery Plaque Characterization Using Wavelet Packet Signatures

High-frequency ultrasound transducers are being widely used to generate high resolution, real time, cross-sectional images of the coronary arteries. In this paper, we present a robust unsupervised texture-derived technique based on multi-channel wavelet frames to delineate atherosclerotic plaque compositions. The intravascular ultrasound (IVUS) signals were acquired from coronary arteries dissected from 32 diseased cadaver hearts employing 40 MHz mechanically rotating, single-element transducers. The wavelet packet representations were classified using a K- means clustering algorithm to generate IVUS-histology color maps (IV-HCMs) and categorize tissues in lipidic, fibrotic and calcified. Finally, two independent observers evaluated the results contrasting the histology images corresponding to the IV-HCMs. Our results show that the proposed algorithm may have great potential as an alternative to existing spectrum-based classification techniques

Automatic detection of blood versus non-blood regions on intravascular ultrasound (IVUS) images using wavelet packet signatures

Intravascular ultrasound (IVUS) has been proven a reliable imaging modality that is widely employed in cardiac interventional procedures. It can provide morphologic as well as pathologic information on the occluded plaques in the coronary arteries. In this paper, we present a new technique using wavelet packet analysis that differentiates between blood and non-blood regions on the IVUS images. We utilized the multi-channel texture segmentation algorithm based on the discrete wavelet packet frames (DWPF). A k-mean clustering algorithm was deployed to partition the extracted textural features into blood and non-blood in an unsupervised fashion. Finally, the geometric and statistical information of the segmented regions was used to estimate the closest set of pixels to the lumen border and a spline curve was fitted to the set. The presented algorithm may be helpful in delineating the lumen border automatically and more reliably prior to the process of plaque characterization, especially with 40 MHz transducers, where appearance of the red blood cells renders the border detection more challenging, even manually. Experimental results are shown and they are quantitatively compared with manually traced borders by an expert. It is concluded that our two dimensional (2-D) algorithm, which is independent of the cardiac and catheter motions performs well in both in-vivo and in-vitro cases

In Vivo Feasibility of Real-Time Monitoring of Focused Ultrasound Surgery (FUS) Using Harmonic Motion Imaging (HMI)

Abstract-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 3.3-MHz phased-array imaging transducer, was mechanically moved to image and ablate the entire tumor. The FUS transducer was driven by an amplitude-modulated (AM) signal at 15 Hz. The acoustic intensity (I sp ta ) was equal to 1050 W/cm 2 at the focus. A digital low-pass filter was used to filter out the spectrum of the FUS beam and its harmonics prior to displacement estimation. The resulting axial displacement was estimated using 1-D crosscorrelation on the acquired RF signals. Results from two mice with eight lesions formed in each mouse (16 lesions total) showed that the average peak-to-peak displacement amplitude before and after lesion formation was respectively equal to 17.34 ± 1.34 µm and 10.98 ± 1.82 µm (p < 0.001). Cell death was also confirmed by hematoxylin and eosin histology. HMI displacement can be used to monitor the relative tissue stiffness changes in real time during heating so that the treatment procedure can be performed in a timeefficient manner. The HMIFU system may, therefore, constitute a cost-efficient and reliable alternative for real-time monitoring of thermal ablation. Index Terms-Acoustic radiation force, breast cancer, focused ultrasound surgery (FUS), harmonic motion imaging, highintensity focused ultrasound (HIFU), in vivo, monitoring, noninvasive estimation, tissue ablation, ultrasound

Assessment of regional myocardial strain using cardiac elastography: Distinguishing infarcted from non-infarcted myocardium,”

Abstract -Estimation of the regional mechanical properties of the cardiac muscle has been shown to play a crucial role in the detection of cardiovascular disease. Current echocardiography-based cardiac motion estimation techniques, such as Doppler Myocardial Imaging (DMI), are limited due to angle dependence. By contrast, elastography, a method designed and used for the detection of tumors, measures displacement and strain by comparing echoes before and aper (not during) a deformation and thus is not angle-dependent. Therefore, the feasibility of cardiac elastography to provide reliable and reproducible displacement and strain estimates from multiple sonographic views was recently demonstrated utilizing RF data from a normal human heart in vivo [ 11. In this paper, we demonstrate this technique utilizing 2D B-scan data in a patient with a known myocardial infarction. Envelopedetected sonographic data was used to estimate regional wall motion and deformation. Displacement and strain estimates were obtained in both non-infarcted, normally contracting and infarcted regions. By obtaining cine-loop and M-Mode elastograms from both regions, the ischemic regions could be identified. In conclusion, elastography may be a clinically viable method for detection of abnormalities of regional wall motion throughout the cardiac cycle

Noninvasive Blood-Brain Barrier Opening in Live Mice

Abstract. Most therapeutic agents cannot be delivered to the brain because of brain′s natural defense: the Blood-Brain Barrier (BBB). It has recently been shown that Focused Ultrasound (FUS) can produce reversible and localized BBB opening in the brain when applied in the presence of ultrasound contrast agents post-craniotomy in rabbits [1]. However, a major limitation of ultrasound in the brain is the strong phase aberration and attenuation of the skull bone, and, as a result, no study of trans-cranial ultrasound-targeted drug treatment in the brain in vivo has been reported as of yet. In this study, the feasibility of BBB opening in the hippocampus of wildtype mice using FUS through the intact skull and skin was investigated. In order to investigate the effect of the skull, simulations of ultrasound wave propagation (1.5 MHz) through the skull using µCT data, and needle hydrophone measurements through an exvivo skull were made. The pressure field showed minimal attenuation (18% of the pressure amplitude) and a well-focused pattern through the left and right halves of the parietal bone. In experiments in vivo, the brains of four mice were sonicated through intact skull and skin. Ultrasound sonications (burst length: 20 ms; duty cycle: 20%; acoustic pressure range: 2.0 to 2.7 MPa) was applied 5 times for 30 s per shot with a 30 s delay between shots. Prior to sonication, ultrasound contrast agents (Optison; 10 µL) were injected intravenously. Contrast material enhanced high resolution MR Imaging (9.4 Tesla) was able to distinguish opening of large vessels in the region of the hippocampus. These results demonstrate the feasibility of locally opening the BBB in the mouse hippocampus using focused ultrasound through intact skull and skin. Future investigations will deal with optimization and reproducibility of the technique as well as application on Alzheimer's-model mice