Dynamic Filtering of Adherent and Non-adherent Microbubble Signals Using Singular Value Thresholding and Normalized Singular Spectrum Area Techniques.

Ultrasound molecular imaging techniques rely on the separation and identification of three types of signals: static tissue, adherent microbubbles and non-adherent microbubbles. In this study, the image filtering techniques of singular value thresholding (SVT) and normalized singular spectrum area (NSSA) were combined to isolate and identify vascular endothelial growth factor receptor 2-targeted microbubbles in a mouse hindlimb tumor model (n = 24). By use of a Verasonics Vantage 256 imaging system with an L12-5 transducer, a custom-programmed pulse inversion sequence employing synthetic aperture virtual source element imaging was used to collect contrast images of mouse tumors perfused with microbubbles.

A Targeted Molecular Localization Imaging Method Applied to Tumor Microvasculature.

Objectives: Ultrasound contrast agents, consisting of gas-filled microbubbles (MBs), have been imaged using several techniques that include ultrasound localization microscopy and targeted molecular imaging. Each of these techniques aims to provide indicators of the disease state but has traditionally been performed independently without co-localization of molecular markers and super-resolved vessels. In this article, we present a new imaging technology: a targeted molecular localization (TML) approach, which uses a single imaging sequence and reconstruction approach to co-localize super-resolved vasculature with molecular imaging signature to provide simultaneous anatomic and biological information for potential multiscale disease evaluation.

Validation of Normalized Singular Spectrum Area as a Classifier for Molecularly Targeted Microbubble Adherence.

Ultrasound molecular imaging is a diagnostic technique wherein molecularly targeted microbubble contrast agents are imaged to reveal disease markers on the blood vessel endothelium. Currently, microbubble adhesion to affected tissue can be quantified using differential targeted enhancement (dTE), which measures the late enhancement of adherent microbubbles through administration of destructive ultrasound pressures. In this study, we investigated a statistical parameter called the normalized singular spectrum area (NSSA) as a means to detect microbubble adhesion without microbubble destruction.

Feasibility of Spinal Anesthesia Placement Using Automated Interpretation of Lumbar Ultrasound Images: A Prospective Randomized Controlled Trial.

Background: This study evaluated the efficacy of spinal anesthesia administration by resident physicians when using an ultrasound system with automated neuraxial landmark detection capabilities.

Methods: 150 patients were enrolled in this trial. Anesthesiology residents placed spinals in subjects undergoing scheduled cesarean delivery using one of three techniques to identify neuraxial landmarks: palpation, ultrasound, or combined palpation and ultrasound.

Ultrasound Molecular Imaging of Inflammation in Mouse Abdominal Aorta.

Objectives: The aim of this study was to demonstrate a new clinically translatable ultrasound molecular imaging approach, modulated acoustic radiation force-based imaging, which is capable of rapid and reliable detection of inflammation as validated in mouse abdominal aorta.

Materials And Methods: Animal studies were approved by the Institutional Animal Care and Use Committee at the University of Virginia. C57BL/6 mice stimulated with tumor necrosis factor α, or fed with a high-fat diet, were used as inflammation (MInflammation) and diet-induced obesity (DIO) (MDIO) models, respectively.

Imaging Performance of a Handheld Ultrasound System With Real-Time Computer-Aided Detection of Lumbar Spine Anatomy: A Feasibility Study.

Objectives: The aim of this study was to evaluate the imaging performance of a handheld ultrasound system and the accuracy of an automated lumbar spine computer-aided detection (CAD) algorithm in the spines of human subjects.

Materials And Methods: This study was approved by the institutional review board of the University of Virginia. The authors designed a handheld ultrasound system with enhanced bone image quality and fully automated CAD of lumbar spine anatomy.

Ultra-Low-Dose Ultrasound Molecular Imaging for the Detection of Angiogenesis in a Mouse Murine Tumor Model: How Little Can We See?

Objectives: The objective of this study was to evaluate the minimum microbubble dose for ultrasound molecular imaging to achieve statistically significant detection of angiogenesis in a mouse model.

Materials And Methods: The preburst minus postburst method was implemented on a Verasonics ultrasound research scanner using a multiframe compounding pulse inversion imaging sequence. Biotinylated lipid (distearoyl phosphatidylcholine-based) microbubbles that were conjugated with antivascular endothelial growth factor 2 (VEGFR2) antibody (MBVEGFR2) or isotype control antibody (MBControl) were injected into mice carrying adenocarcinoma xenografts.

The Use of Acoustic Radiation Force Decorrelation-Weighted Pulse Inversion for Enhanced Ultrasound Contrast Imaging.

Objectives: The use of ultrasound imaging for cancer diagnosis and screening can be enhanced with the use of molecularly targeted microbubbles. Nonlinear imaging strategies such as pulse inversion (PI) and "contrast pulse sequences" (CPS) can be used to differentiate microbubble signal, but often fail to suppress highly echogenic tissue interfaces. This failure results in false-positive detection and potential misdiagnosis.

Optical Verification of Microbubble Response to Acoustic Radiation Force in Large Vessels With In Vivo Results.

Objective: The objective of this study was to optically verify the dynamic behaviors of adherent microbubbles in large blood vessel environments in response to a new ultrasound technique using modulated acoustic radiation force.

Materials And Methods: Polydimethylsiloxane (PDMS) flow channels coated with streptavidin were used in targeted groups to mimic large blood vessels. The custom-modulated acoustic radiation force beam sequence was programmed on a Verasonics research scanner.

Ultrasound-based measurement of molecular marker concentration in large blood vessels: a feasibility study.

Ultrasound molecular imaging has demonstrated efficacy in pre-clinical studies for cancer and cardiovascular inflammation. However, these techniques often require lengthy protocols because of waiting periods or additional control microbubble injections. Moreover, they are not capable of quantifying molecular marker concentration in human tissue environments that exhibit variable attenuation and propagation path lengths.

Binding dynamics of targeted microbubbles in response to modulated acoustic radiation force.

Detection of molecular targeted microbubbles plays a foundational role in ultrasound-based molecular imaging and targeted gene or drug delivery. In this paper, an empirical model describing the binding dynamics of targeted microbubbles in response to modulated acoustic radiation forces in large vessels is presented and experimentally verified using tissue-mimicking flow phantoms. Higher flow velocity and microbubble concentration led to faster detaching rates for specifically bound microbubbles (p < 0.

Shear forces from flow are responsible for a distinct statistical signature of adherent microbubbles in large vessels.

Real-time ultrasound-based targeted molecular imaging in large blood vessels holds promise for early detection and diagnosis of stroke risk by identifying early markers for atherosclerosis prior to plaque formation. Singular spectrum-based targeted molecular (SiSTM) imaging is a recently proposed method that uses changes in statistical dimensionality-quantified by a normalized singular spectrum area (NSSA)-to image receptor-ligand-bound adherent microbubbles. However, the precise physical mechanism responsible for the distinct statistical signature was previously unknown.

Improved elevational and azimuthal motion tracking using sector scans.

Ultrasound data motion tracking is widely used to estimate relative tissue/transducer motion, for example in freehand 3-D imaging, in which successive 2-D ultrasound scan planes are registered in a 3-D volume. Speckle-tracking and decorrelation-based methods are used to estimate motion in the azimuthal and elevational planes. However, the performance of speckle-tracking is significantly degraded in sectorscan systems because of point-spread function rotation with lateral motion.

Real-time targeted molecular imaging using singular value spectra properties to isolate the adherent microbubble signal.

Ultrasound-based real-time molecular imaging in large blood vessels holds promise for early detection and diagnosis of various important and significant diseases, such as stroke, atherosclerosis, and cancer. Central to the success of this imaging technique is the isolation of ligand-receptor bound adherent microbubbles from free microbubbles and tissue structures. In this paper, we present a new approach, termed singular spectrum-based targeted molecular (SiSTM) imaging, which separates signal components using singular value spectra content over local regions of complex echo data.

Assessing and improving acoustic radiation force image quality using a 1.5-D transducer design.

A 1.5-D transducer array was proposed to improve acoustic radiation force impulse (ARFI) imaging signal-to-noise ratio (SNRARFI) and image contrast relative to a conventional 1-D array. To predict performance gains from the proposed 1.

The effects of transducer geometry on artifacts common to diagnostic bone imaging with conventional medical ultrasound.

The portability, low cost, and non-ionizing radiation associated with medical ultrasound suggest that it has potential as a superior alternative to X-ray for bone imaging. However, when conventional ultrasound imaging systems are used for bone imaging, clinical acceptance is frequently limited by artifacts derived from reflections occurring away from the main axis of the acoustic beam. In this paper, the physical source of off-axis artifacts and the effect of transducer geometry on these artifacts are investigated in simulation and experimental studies.

The singular value filter: a general filter design strategy for PCA-based signal separation in medical ultrasound imaging.

A general filtering method, called the singular value filter (SVF), is presented as a framework for principal component analysis (PCA) based filter design in medical ultrasound imaging. The SVF approach operates by projecting the original data onto a new set of bases determined from PCA using singular value decomposition (SVD). The shape of the SVF weighting function, which relates the singular value spectrum of the input data to the filtering coefficients assigned to each basis function, is designed in accordance with a signal model and statistical assumptions regarding the underlying source signals.

Complex principal components for robust motion estimation.

Bias and variance errors in motion estimation result from electronic noise, decorrelation, aliasing, and inherent algorithm limitations. Unlike most error sources, decorrelation is coherent over time and has the same power spectrum as the signal. Thus, reducing decorrelation is impossible through frequency domain filtering or simple averaging and must be achieved through other methods.

Adaptive force sonorheometry for assessment of whole blood coagulation.

Background: Viscoelastic diagnostics that monitor the hemostatic function of whole blood (WB), such as thromboelastography, have been developed with demonstrated clinical utility. By measuring the cumulative effects of all components of hemostasis, viscoelastic diagnostics have circumvented many of the challenges associated with more common tests of blood coagulation.

Methods: We describe a new technology, called sonorheometry, that adaptively applies acoustic radiation force to assess coagulation function in WB.

A novel ultrasound-based method to evaluate hemostatic function of whole blood.

Background: Unregulated hemostasis represents a leading cause of mortality and morbidity in the developed world. Being able to recognize and quantify defects of the hemostatic process is critical to reduce mortality and implement appropriate treatment.

Methods: We describe a novel ultrasound-based technology, named sonorheometry, which can assess hemostasis function from a small sample of blood.

Reduction of echo decorrelation via complex principal component filtering.

Ultrasound motion estimation is a fundamental component of clinical and research techniques that include color flow Doppler, spectral Doppler, radiation force imaging and ultrasound-based elasticity estimation. In each of these applications, motion estimates are corrupted by signal decorrelation that originates from nonuniform target motion across the acoustic beam. In this article, complex principal component filtering (PCF) is demonstrated as a filtering technique for dramatically reducing echo decorrelation in blood flow estimation and radiation force imaging.

Monitored steady-state excitation and recovery (MSSER) radiation force imaging using viscoelastic models.

Acoustic radiation force imaging methods distinguish tissue structure and composition by monitoring tissue responses to applied radiation force excitations. Although these responses are a complex, multidimensional function of the geometric and viscoelastic nature of tissue, simplified discrete biomechanical models offer meaningful insight to the physical phenomena that govern induced tissue motion. Applying Voigt and standard linear viscoelastic tissue models, we present a new radiation force technique - monitored steady-state excitation and recovery (MSSER) imaging - that tracks both steady-state displacement during prolonged force application and transient response following force cessation to estimate tissue mechanical properties such as elasticity and viscosity.

Robust principal component analysis and clustering methods for automated classification of tissue response to ARFI excitation.

We introduce a new method for automatic classification of acoustic radiation force impulse (ARFI) displacement profiles using what have been termed "robust" methods for principal component analysis (PCA) and clustering. Unlike classical approaches, the robust methods are less sensitive to high variance outlier profiles and require no a priori information regarding expected tissue response to ARFI excitation. We first validate our methods using synthetic data with additive noise and/or outlier curves.