Search

The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09?mg ml?1?Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of three-dimensional imaging of a 185??L simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi.

A thrombin-responsive closed-loop patch is developed for prolonged heparin delivery in a feedback-controlled manner. This microneedle-based patch can sense activated thrombin and subsequently releases heparin to prevent coagulation in the blood flow. This "smart" heparin patch can be transcutaneously inserted into skin without drug leakage and can sustainably regulate blood coagulation in response to thrombin.

Acoustic radiation force impulse (ARFI) imaging is an elastography technique that uses ultrasonic pulses to both displace and track tissue motion. Previous modeling studies have shown that ARFI displacements are susceptible to underestimation due to lateral and elevational shearing that occurs within the tracking resolution cell. In this study, optical tracking was utilized to experimentally measure the displacement underestimation achieved by acoustic tracking using a clinical ultrasound system. Two optically translucent phantoms of varying stiffness with embedded microspheres were created, and ARFI excitation pulses with F/1.5 or F/3 lateral focal configurations were transmitted from a standard linear array to induce phantom motion. Displacements were tracked using confocal optical and acoustic methods, with an acoustic tracking focal configuration of F/1.5 laterally. Acoustic displacement underestimation was observed for both excitation focal configurations; the maximum underestimation error was 51% of the optically measured displacement for the F/1.5 excitation pulse. This work experimentally demonstrates limitations of ARFI implemented on a clinical scanner using a standard linear array and sets up a framework for future displacement tracking validation studies.

Researchers have begun to investigate novel meniscus graft construction with donor cell replacement through decellularization and host stem cell seeding. In these techniques, there is an unmet need for a nondestructive mechanical testing platform that can monitor changing mechanical properties of the seeded graft over time. In this study, Monitored Steady-State Excitation and Recovery (MSSER) ultrasound, which exploits multiple successive acoustic radiation force excitations interspersed with tracking lines to mimic a materials creep test, was used to nondestructively test the mechanical stiffness of meniscus grafts. Four human meniscus samples were evaluated ex vivo using MSSER: two chemically decellularized samples and two intact samples. MSSER testing measured a median stiffness difference of 37% between intact and decellularized samples, which agreed well with the 35% difference measured by destructive compression testing. Volumetric MSSER scanning showed highly heterogeneous stiffness throughout the samples. This demonstration substantiates the use of MSSER as a relevant nondestructive testing tool in tissue engineering applications.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that is caused by a mutation in the gene for dystrophin leading to a loss of the dystrophin protein from the muscle cell (myofiber) membrane. Viscoelastic Strain Response (ViSR) ultrasound is a new, quantitative acoustic radiation force (ARF) based elastographic imaging method to calculate τ, the viscoelastic relaxation time constant for constant stress. We have investigated the use of ViSR imaging in human DMD. Imaging was performed in vivo on the right rectus femoris (RF), sartorius (SART), and gastrocnemius (GAST) muscles of two boys with DMD. The boys were 5- and 9-years-old at the time of imaging. ViSR results in the 5-year-old showed an average of 27.0%, 6.6%, and 18.2% fat/necrosis composition in the RF, SART, and GAST, respectively. In the 9-year old subject, ViSR showed an average fat/necrosis composition of 66.7% in the RF, 9.1% in the SART, and 37.2% in the GAST. These results are consistent with both the known phenotypic response of the three muscles and with functional testing results and point to ViSR's potential relevance as a novel outcome measure for diagnostics and clinical trials in DMD.

Background Studies published in the 1970s by Mostafa S. Fahim and colleagues showed that a short treatment with ultrasound caused the depletion of germ cells and infertility. The goal of the current study was to determine if a commercially available therapeutic ultrasound generator and transducer could be used as the basis for a male contraceptive. Methods Sprague-Dawley rats were anesthetized and their testes were treated with 1 MHz or 3 MHz ultrasound while varying power, duration and temperature of treatment. Results We found that 3 MHz ultrasound delivered with 2.2 Watt per square cm power for fifteen minutes was necessary to deplete spermatocytes and spermatids from the testis and that this treatment significantly reduced epididymal sperm reserves. 3 MHz ultrasound treatment reduced total epididymal sperm count 10-fold lower than the wet-heat control and decreased motile sperm counts 1,000-fold lower than wet-heat alone. The current treatment regimen provided nominally more energy to the treatment chamber than Fahim's originally reported conditions of 1 MHz ultrasound delivered at 1 Watt per square cm for ten minutes. However, the true spatial average intensity, effective radiating area and power output of the transducers used by Fahim were not reported, making a direct comparison impossible. We found that germ cell depletion was most uniform and effective when we rotated the therapeutic transducer to mitigate non-uniformity of the beam field. The lowest sperm count was achieved when the coupling medium (3% saline) was held at 37 degrees C and two consecutive 15-minute treatments of 3 MHz ultrasound at 2.2 Watt per square cm were separated by 2 days. Conclusions The non-invasive nature of ultrasound and its efficacy in reducing sperm count make therapeutic ultrasound a promising candidate for a male contraceptive. However, further studies must be conducted to confirm its efficacy in providing a contraceptive effect, to test the result of repeated use, to verify that the contraceptive effect is reversible and to demonstrate that there are no detrimental, long-term effects from using ultrasound as a method of male contraception.

A validated method for assessing hemostasis in vivo is critical for testing the hemostatic efficacy of therapeutic agents designed for patients with bleeding disorders such as von Willebrand disease (VWD) and hemophilia A. We hypothesize that rate of bleeding and time to hemostasis can be monitored in vivo by acoustic radiation force impulse (ARFI) ultrasound. We performed ARFI imaging following 12-gauge needle puncture of hind limb muscle encompassing an ∼2 mm vein in six normal, eight naive hemophilia A before and after infusing canine factor VIII, three hemophilia A expressing canine factor VIIa following gene transfer, and two naive VWD dogs. Serial data sets were processed with custom software to (1) estimate the rate of hemorrhage and (2) estimate the time of hemostasis onset. The rate of hemorrhage during the first 30 min following puncture was markedly increased in the VWD dogs relative to normal but was not significantly different between normal, naive hemophilia A or hemophilia A expressing cFVIIa. ARFI-derived times to hemostasis were significantly longer in naive hemophilia A dogs than in normal dogs and were shortened by canine coagulation factors VIII and VIIa. These data support our hypothesis that rate of hemorrhage and time to hemostasis in vivo in response to a standardized hemostatic challenge can be detected by ARFI ultrasound in canine models of VWD and hemophilia. These data also suggest that the ARFI-monitored hemostatic challenge is relevant for in vivo testing of the hemostatic efficacy of therapeutic clotting factor replacement products used to treat inherited bleeding disorders.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that is caused by a mutation in the gene for dystrophin leading to a loss of the dystrophin protein from the muscle cell (myofiber) membrane. The golden retriever muscular dystrophy (GRMD) model also has a naturally-occurring dystrophin gene mutation and progressive phenotypic features analogous to those seen in DMD. We have investigated the use of Acoustic Radiation Force Impulse (ARFI) imaging in the GRMD canine model. Imaging was performed in vivo on the right rectus femoris (RF) and cranial sartorius (CS) muscles in both transverse and parallel planes. A cohort of 6 normal dogs and 4 GRMD dogs were imaged at 3, 6, and 12 months of age. Results showed significant differences in peak displacement in the RF for GRMD vs normal dog, but similar ARFI results in the CS. These results are consistent with known variations in disease progression in RF versus CS muscles in the dog model and suggest that ARFI could be relevant to monitoring therapy in affected individuals.

ARFI and SWEI have been demonstrated to be capable of detecting atherosclerotic plaques both ex vivo and in vivo. In order to ensure the best possible plaque detection capability, the most appropriate beam sequences must be used. A method for determining the performance of beam sequences is presented in the form of a reader evaluation study using trained readers to evaluate parametric image sets. Nine ARFI/SWEI beam sequences were applied in arterial mimicking phantoms with soft and hard inclusions, and 7 sequences were applied in 22 arterial segments from 6 pigs. The sequences consisted of 3 types of excitations: a single F/1.5 pulse, a single F/3 pulse, and two F/1.5 pulses, spaced 0.8 ms apart. These 3 excitation methods were combined with 3 types of tracking to generate the 9 total sequences: 1:1 Single A-line receive, 4:1 parallel receive and 4:1 parallel receive tracking lateral to the region of excitation (SWEI). Beam sequences that tracked in the region of excitation performed best in both phantoms and ex vivo arteries. The ranking of beam sequence performance was generally consistent in both phantom and ex vivo arteries.

Dogs with hemophilia A and hemophilia B recapitulate the severe bleeding phenotype that occurs in humans with these disorders. We have investigated the use of Acoustic Radiation Force Impulse (ARFI) imaging as a method for assessing hemostasis in vivo in dogs with hemophilia A. ARFI imaging was performed in 6 normal, 7 hemophilia A, and 4 hemophilic dogs expressing canine factor FVIIa following gene transfer. Bleeding was induced by needle puncture in muscle and a 1–2 mm vein, and subcutaneous bleeding was monitored with ARFI for 100 minutes. Results showed delayed time to hemostasis in the hemophilia A dogs, consistent with the bleeding phenotype, but lower times to hemostasis in the FVIIa expressing dogs. These data suggest that ARFI imaging could be a relevant new hemostatic challenge for characterizing hemophilic phenotype.

Rehydrated, lyophilized platelets for hemostatic therapy are incorporated with commercial MRI iron oxide contrast agents. We demonstrate that magnetomotive OCT contrasts the platelets and propose this system for monitoring hemopathic sites targeted by platelets.

In ultrasound images, clutter is a noise artifact most easily observed in anechoic or hypoechoic regions. It appears as diffuse echoes overlying anatomical structures of diagnostic importance, obscuring tissue borders and reducing image contrast. A novel clutter reduction method for abdominal images is proposed, wherein the abdominal wall is displaced during successive-frame image acquisitions. A region of clutter distal to the abdominal wall was observed to move with the abdominal wall, and finite impulse response (FIR) and blind source separation (BSS) motion filters were implemented to reduce this clutter. The proposed clutter reduction method was tested in simulated and phantom data and applied to fundamental and harmonic in vivo bladder and liver images from 2 volunteers. Results show clutter reductions ranging from 0 to 18 dB in FIR-filtered images and 9 to 27 dB in BSS-filtered images. The contrast-to-noise ratio was improved by 21 to 68% and 44 to 108% in FIR- and BSS-filtered images, respectively. Improvements in contrast ranged from 4 to 12 dB. The method shows promise for reducing clutter in other abdominal images.

The world wide prevalence of cardiovascular disease leads to over seven million annual percutaneous coronary catheterization procedures, the majority of which exploit femoral artery access. Femoral puncture sites ('arteriotomies') can be associated with severe vessel complications after sheath removal if hemostasis is not properly achieved. Hemostasis onset is routinely determined by examination for bleeding at the skin puncture; however, clotting along the puncture path can obscure subcutaneous bleeding, and therefore hemostasis is blindly assessed. We hypothesize that hemostasis assessment can be un-blinded by Acoustic Radiation Force Impulse (ARFI) ultrasound. In this first of a two-part series, we present in vivo ARFI hemostasis imaging data obtained in relevant canine models of femoral artery puncture. Above arteriotomies, ARFI-induced displacements were large (3.5 to >5.0 microm) relative to surrounding soft tissue soon after needle removal, which was consistent with our expectation for pooled extravasated blood. ARFI-induced displacements above arteriotomies decreased in magnitude (to approximately 2 microm) some time after needle removal and suggested the onset of hemostasis. This preclinical investigation served as proof of concept and justification for a pilot human study, which is presented in part two of this series.

Noninvasively monitoring hemostasis at femoral artery puncture sites (arteriotomies) could reduce complications associated with percutaneous coronary artery catheterization and reduce medical cost, yet no diagnostic imaging method is proven for this application. In a pilot clinical investigation, ARFI imaging was performed at the femoral arteriotomies of 20 patient volunteers randomized to treatment with standard of care manual compression alone or to manual compression augmented by a hemostatic dressing to expedite time to hemostasis onset. Average ARFIderived times to hemostasis in patient volunteers treated with manual compression alone (n=10) and manual compression augmented by hemostatic dressing (n=9) were, respectively, 13.00 ± 1.56 and 9.44 ± 3.09 min (p ≤ 0.0065, Wilcoxon). ARFI-induced displacements were observed to be larger at arteriotomies and in extravasated blood pools. These data suggest that ARFI imaging is capable of noninvasively monitoring hemostasis onset at femoral arteriotomies.

Atherosclerotic risk stratification may be improved by identifying soft lipid-rich or necrotic plaque regions, fibrous caps, calcium deposits, and other plaque components with disparate mechanical impedances. Mechanical impedance interfaces reflect acoustic radiation force (ARF)-induced shear waves. For the purpose of detecting these shear wave reflections, we developed a novel method as an adjunct to conventional ARFI called reflected shear wave imaging (RSWI). RSWI identifies shear wave reflections in tissue as inflections in 1D axial displacement profiles measured in the ARF region of excitation. This technique generates parametric images of shear wave reflections (SWRs) using only conventional 2D ARFI data sets. RSWI was performed on three familial hypercholesterolemic (FH) porcine iliac arteries, two ex vivo and one in vivo. Our results suggest that RSWI improves identification of soft, lipid-rich or necrotic plaque regions near fibrous cap, calcium, and collagen deposits. RSWI supports shear wave velocity (SWV) estimation, which may be useful for quantitative ARF-based imaging.

In arterial ultrasound imaging, interpretation of plaque geometry may be distorted by reverberation artifacts in the lumen. Reverberation and arterial wall signals may be highly correlated, which precludes frequency domain or conventional regression filtering methods; however, decorrelation and rates vary. The variance of time derivatives in 1D axial cross-correlation (CC) and displacement (Disp) measures were exploited to reject the arterial lumen and reverberation artifact. Adaptively determined thresholds were applied to the variance of either individual or spatially clustered ARFI displacement profiles. The resulting binary masks were applied in vivo to six porcine arteries with varying degrees of reverberation artifact. Mask performance was measured as the percentage of the lumen rejected given at least 98% of each arterial wall remaining intact. The highest performing masks used the variance of the 2nd derivative of displacement or correlation with spatial clustering to preserve both arterial wall and soft tissue signals.

Seventy percent of cardiovascular disease (CVD) deaths are attributed to atherosclerosis. Despite their clinical significance, nonstenotic atherosclerotic plaques are not effectively detected by conventional atherosclerosis imaging methods. Moreover, conventional imaging methods are insufficient for describing plaque composition, which is relevant to cardiovascular risk assessment. Atherosclerosis imaging technologies capable of improving plaque detection and stratifying cardiovascular risk are needed. Acoustic radiation force impulse (ARFI) ultrasound, a novel imaging method for noninvasively differentiating the mechanical properties of tissue, is demonstrated for in vivo detection of nonstenotic plaques and plaque material assessment in this pilot investigation. In vivo ARFI imaging was performed on four iliac arteries: (1) of a normocholesterolemic pig with no atherosclerosis as a control, (2) of a familial hypercholesterolemic pig with diffuse atherosclerosis, (3) of a normocholesterolemic pig fed a high-fat diet with early atherosclerotic plaques and (4) of a familial hypercholesterolemic pig with diffuse atherosclerosis and a small, minimally occlusive plaque. ARFI results were compared with spatially matched immunohistochemistry, showing correlations between elastin and collagen content and ARFI-derived peak displacement and recovery time parameters. Faster recoveries from ARFI-induced peak displacements and smaller peak displacements were observed in areas of higher elastin and collagen content. Importantly, spatial correlations between tissue content and ARFI results were consistent and observable in large and highly evolved as well as small plaques. ARFI imaging successfully distinguished nonstenotic plaques, while conventional B-mode ultrasound did not. This work validates the potential relevance of ARFI imaging as a noninvasive imaging technology for in vivo detection and material assessment of atherosclerotic plaques.

Acoustic Radiation Force Impulse (ARFI) has been demonstrated for differentiating mechanical properties in a variety of tissues. To fully maximize the potential of ARFI imaging in the context of material characterization of atherosclerosis it is important to understand the benefits and drawbacks of various radiation force excitation and tracking methods. We investigated the impact of five excitation methods and two tracking methods of radiation force beam sequences in a pig model of hypercholesterolemic atherosclerosis. The pigs were either familial hypercholesterolemic (FH) or dietary hypercholesterolemic (DH). First, we compared two methods of A-line receiving: single receive (SRX) and parallel receive (ParRX) in a FH female pig. Second, ARFI excitations with varying F/#'s of F/1, F/1.5, F/2, and F/3, were examined in another FH female. Lastly, to compare the utility of multiple ARFI excitations, both single excitation pulse ARFI (SP) and double excitation pulse ARFI (DP) were compared in a DH female. Comparing A-line receiving methods, SP-ParRX was observed to have lower spatial sensitivity to local variation of mechanical property than SP-SRX. Large excitation pulse F/#'s were observed to yield more variability in measured ARFI parameters in the location of a large calcification and better differentiation of local variations in material content. DP ARFI provided useful insights that were supplemental to those provided by SP ARFI alone.

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. Second, the robust techniques are applied to classifying ARFI displacement profiles acquired in an atherosclerotic familial hypercholesterolemic (FH) pig iliac artery in vivo. The in-vivo classification results are compared with parametric ARFI images showing peak induced displacement and time to 67% recovery and to spatially correlated immunohistochemistry. Our results support that robust techniques outperform conventional PCA and clustering approaches to classification when ARFI data are inclusive of low to relatively high noise levels (up to 5 dB average signal-to-noise [SNR] to amplitude) but no outliers: for example, 99.53% correct for robust techniques vs. 97.75% correct for the classical approach. The robust techniques also perform better than conventional approaches when ARFI data are inclusive of moderately high noise levels (10 dB average SNR to amplitude) in addition to a high concentration of outlier displacement profiles (10% outlier content): for example, 99.87% correct for robust techniques vs. 33.33% correct for the classical approach. This work suggests that automatic identification of tissue structures exhibiting similar displacement responses to ARFI excitation is possible, even in the context of outlier profiles. Moreover, this work represents an important first step toward automatic correlation of ARFI data to spatially matched immunohistochemistry.

Physiologic motion corrupts measurements of induced tissue displacements and obscures tissue mechanical properties in radiation force ultrasound. Wall dilation and contraction with cardiac pulsation is especially disruptive to radiation force imaging the arterial system. We hypothesize that exploiting a rigid arterial wall model, which assumes long wavelength arterial pulse waves, will improve physiologic motion rejection in arterial radiation force imaging. Three rigid wall assuming filters (polynomial regression, principal component regression, and FIR high-pass filters) were compared to four filters that did not assume a rigid arterial wall (linear regression, quadratic regression, principal component regression, and FIR high-pass filters). The filters were tested using Field II generated data inclusive of simulated arterial wall motion combined with experimental acoustic radiation force impulse (ARFI) or shear wave elastography imaging (SWEI) displacement profiles. Performance metrics were sum of absolute differences (SAD) between original and filtered ARFI or SWEI displacement profiles in terms of total profile error, measured peak displacement error, measured recovery time error, and time-to-peak displacement error. Rigid wall assuming polynomial and principal component regression filters yielded the lowest SAD scores. The filters were also qualitatively compared on in vivo ARFI and SWEI data acquired in healthy pig iliac arteries.

Acoustic radiation force imaging methods distinguish tissue structure and composition by monitoring tissue responses to applied radiation force excitations. Applying Voigt and Kelvin 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. In concert with shear wave elasticity imaging (SWEI) estimates for Young's modulus, MSSER methods are useful for estimating tissue mechanical properties independent of the applied force magnitude. We test our methods in gelatin phantoms and excised pig muscle, with confirmation through mechanical property measurement using the BOSE EnduraTEC ELF 3200. Our results measured 10.6 kPa, 14.7 kPa, 17.1 kPa, (gelatin) and 122.4 kPa (pig muscle) with less than 10% error. This work demonstrates the feasibility of MSSER imaging and supports the merit of further efforts to incorporate relevant mechanical tissue models into the development of novel radiation force imaging techniques.

Cardiovascular disease (CVD) is the leading cause of death in the United States, with coronary artery disease and stroke alone accounting for 70% of CVD mortalities. Given this tremendous human impact, imaging technologies that enhance CVD outcomes by enabling earlier disease detection, monitoring the effects of therapeutic interventions, and delineating disease progression or regression are in critical need. We hypothesize that Acoustic Radiation Force Impulse (ARFI) ultrasound is efficacious for noninvasive characterization of atherosclerotic plaque and arterial walls in CVD assessment. To test this hypothesis, we performed ARFI imaging in three iliac arteries: 1) an excised familial hypercholesterolemic (FH) pig iliac with a raised focal atherosclerotic plaque, 2) an in vivo FH pig iliac with diffuse atherosclerosis, and 3) an in vivo control pig iliac with no known disease. In all three cases, our ARFI results were compared to matched immunohistochemistry, which showed a spatial correlation between collagen and elastin content and tissue mechanical property. This work supports the merit of additional investigations into ARFI imaging as a noninvasive, in vivo imaging technology for characterizing atherosclerotic plaque and arteries

Blind source separation (BSS) is a time domain method for signal decomposition previously demonstrated in medical ultrasound for adaptive regression filtering. Just as BSS is relevant to clutter rejection by differentiating RF signals from moving blood versus arterial wall tissue, BSS is useful for distinguishing displacement profiles measured in tissue exhibiting different mechanical responses to radiation force. In concert with K-means clustering, an algorithm for partitioning N data points into K subsets, BSS can be employed for automated image segmentation via mechanical property in acoustic radiation force impulse (ARFI) ultrasound. We present BSS-based ARFI image segmentation in application to the peripheral vasculature. First, our segmentation method is validated using a synthetic data set with additive noise. Second, our method is demonstrated in an excised atherosclerotic familial hypercholesterolemic (FH) pig iliac artery with confirmation by matched immunohistochemistry. Finally, the method is applied to segmenting in vivo ARFI images in an atherosclerotic FH pig iliac artery as well as a human popliteal vein with no known disease. This work substantiates additional applications of BSS-based ARFI image segmentation

Complex blind source separation (CBSS) is presented in an application to adaptive clutter filtering for acoustic radiation force impulse (ARFI) imaging in the peripheral vasculature, in vivo. In addition to the conventional challenges of wall filtering for Doppler imaging in peripheral vessels, ARFI imaging introduces the complication of isolating ARFI-induced blood motion from ARFI-induced vessel wall and surrounding elastic tissue motion. Raw RF data was collected using ARFI M-mode imaging sequences from a pulsatile flow vessel phantom, the jugular vein of a male volunteer performing the Valsalva maneuver, and the carotid artery of a female volunteer. The imaginary component of the RF data was computed via the Hilbert transform, and CBSS clutter filtering was performed on the isolated blood signal. Following CBSS filtering, phase-shift estimation reveals radiation force-induced axial blood velocities that peak at 10-25 cm/s. These results demonstrate that CBSS sufficiently rejects elastic tissue and vessel wall signal components to allow for measurement of ARFI-induced axial blood velocities in both phantom and clinical investigation.

In the context of complex tissue motion patterns including physiological and acoustic radiation force impulse (ARFI) -induced tissue, blood, and cyst fluid motion, the same adaptive blind source separation (BSS)-based filtering method is effective for four diverse applications: 1) clutter filtering prior to blood velocity estimation, 2) extracting axial velocity components from noisy velocity measurements given large flow angles, 3) reducing noise in measured ARFI displacement profiles, and 4) complex phase clutter filtering to measure ARFI-induced cyst streaming. RF data was collected using ARFI imaging beam sequences from the carotid arteries of healthy volunteers and from female subjects (recruited under IRB guidance), each presenting one breast lesion. Biopsy determined that one lesion was a fluid-filled cyst and the other was a malignant mass. In the examined arteries, velocity profiles are parabolic in shape, with nearly zero axial velocity beyond the vessel lumen following BSS clutter filtering and BSS extraction of small axial velocity components. The method maintains peak displacement (1.81 to 21.5/spl mu/ m) and time to 63% recovery (1.38 to 2.20 ms) parameters after BSS noise reduction in ARFI displacement profiles. Colorflow images generated after BSS complex phase clutter rejection reveal ARFI-induced streaming in the fluid-filled cyst but no streaming in the malignant lesion. Successful filtering for four diverse purposes illustrates the breadth of applications for BSS adaptive filtering in the clinical imaging environment.

We present a novel, two-dimensional tissue motion estimation method using blind source separation (BSS), which accurately measures both axial and lateral blood velocity components in the common carotid artery. Ensembles (packet length=20) of raw RF data were decomposed via BSS into orthogonal basis functions generally spanning vessel wall, blood, and noise signal subspaces separately. The depth and time projections corresponding to each basis function were computed. Employing knowledge of the imaging system's axial and lateral spatial frequencies, two-dimensional blood velocity is calculated from the basis function time projections. The BSS technique is verified using field II pulsatile flow simulations at 45/spl deg/, 60/spl deg/, 70/spl deg/, 80/spl deg/, and 90/spl deg/ flow angles. The method, blind source separation-based velocity estimation (BSSVE), is demonstrated for clinical application and compared to speckle tracking methods using raw RF data collected from the carotid artery of a volunteer. BSSVE velocity and angle measurements in the simulated data are consistently below 10% error. The BSSVE clinical velocity and angle measurements are within 10% of the values computed with speckle tracking. Simulation results indicate that the method successfully measures axial and lateral flow components. Clinical results affirm the efficacy of BSS for two-dimensional in vivo tissue velocity estimation.

A method for adaptive clutter rejection via blind signal separation (BSS) is presented in application to angle-independent blood velocity measurement in the carotid artery. Clutter filtering via frequency domain-based approaches is ineffective given short ensemble lengths and/or overlapping axial wall and lateral blood frequency spectra. Rather than operating in the frequency domain, BSS decomposes the input data ensemble into source signals in time. The method is demonstrated using Field II simulated and clinical examples of flow in the common carotid artery. In addition to clutter rejection, the BSS technique is presented for detection of small axial flow components and filtering acoustic radiation force impulse (ARFI) displacement profiles.

Blind source separation (BSS) for adaptive filtering is presented in application to imaging both physiological and acoustic radiation force impulse (ARFI)-induced tissue and blood motion in the common carotid artery. The collected raw radiofrequency (RF) data includes vessel wall motion, blood flow and ARFI-induced motion. In the context of these complex motion patterns, the same BSS adaptive filtering method was employed for three diverse applications: 1. clutter filtering ensembles prior to blood velocity estimation, 2. extracting small axial velocity components from noisy velocity measurements given large flow angles and 3. reducing noise in measured ARFI-induced tissue displacement profiles to enhance differentiation of local tissue structures. The filter separated physiological vessel wall motion from axial blood flow and ARFI-induced motion; successful filter performance is demonstrated in velocity estimates, color flow images and ARFI displacement profiles. The results demonstrate the breadth of applications for BSS adaptive filtering in the clinical imaging environment.

We have developed a new method of imaging the mechanical properties of tissues based on very brief (

A method for adaptive clutter rejection via blind source separation (BSS) using principal and independent component analyses is presented in application to blood velocity measurement in the carotid artery. In particular, the filtering method's efficacy for eliminating clutter and preserving lateral blood flow signal components is presented. The performance of IIR filters is compromised by shorth data ensembles (10 to 20 temporal samples) as implemented for color-flow and high frame-rate imaging due to initialization requirements. Further, the ultrasonic imaging system's transfer function maps axial wall and lateral blood motion to overlapping spectra. As such, frequency domain-based approaches to wall filtering are ineffective for distinguishing wall from blood motion signals. Rather than operating in the frequency domain, BSS performs clutter rejection by decomposing the input data ensemble into N constitutive source signals in time, where N is the ensemble length. Source signal energy coupled with respective signal depth and time course profiles reveal which source signals correspond to blood, noise and clutter components. Clutter components may then be removed without disruption of lateral blood flow information needed for two-dimensional blood velocity measurement. A simplistic data simulation is employed to offer an intuitive understanding of BSS methods for signal separation. The adaptive BSS filter is further demonstrated using a Field II simulation of blood flow through the carotid artery including tissue motion. BSS clutter filter performance is compared to the performance of FIR, IIR and polynomial regression clutter filters. Finally, the filter is employed for clinical application using a Siemens Elegra scanner, carotid artery data with lateral blood flow collected from healthy volunteers, and Speckle Tracking; velocity magnitude and angle profiles are shown. Once again, the BSS clutter filter is contrasted to FIR, IIR and polynomial regression clutter filters using clinical examples. Velocities computed with Speckle Tracking after BSS wall filtering are highest in the center of the artery and diminish to low velocities near the vessel walls, with velocity magnitudes consistent with physiological expectations. These results demonstrate that the BSS adaptive filter sufficiently suppresses wall motion signal for clinical lateral blood velocity measurement using data ensembles suitable for color-flow and high frame-rate imaging.

Respiratory motion during acquisition of first-pass myocardial perfusion images results in translation, distortion from out-of-plane motion, and changes in left ventricular geometry. Together these effects make visual image analysis more difficult and limit methods of quantitative analysis of contrast kinetics. We present a fully automated registration and warping algorithm for correcting translation and geometric distortions using a statistically based image registration method. Twelve patients (mean age 51 +/- 12 years) were studied 3 +/- 1 days after reperfused first myocardial infarction. Perfusion images were acquired during bolus administration of nonionic Gd-DTPA. Pixel intensity statistics were computed for each image in the neighborhood of high spatial frequencies. These statistics were then used to register and warp each target image (image to be registered and warped) to a common template image. Average image-to-image vertical translation was 2.6 +/- 0.8 pixels (3.4 +/- 1.0 mm) prior to processing and 0.9 +/- 0.3 pixels (1.2 +/- 0.4 mm) post-processing (P0.0001). Mean image-to-image horizontal translation was 1.7 +/- 1.2 pixels (1.8 +/- 1.2 mm) before and 1.3 +/- 0.7 pixels (1.4 +/- 0.7 mm) after processing (P = 0.05). Left ventricular endocardial area varied an average of 105 +/- 55 pixels (140.7 +/- 53.7 mm2) between images prior to processing vs. 51 +/- 15 pixels (68.3 +/- 20.1 mm2) after processing (P0.001). Thus automated, statistically based registration and warping of perfusion images is effective in reducing image-to-image translation. This method may permit more sensitive qualitative and quantitative evaluation of myocardial contrast-enhanced first-pass images.

A method for measurement of lateral blood velocity in the carotid artery is presented. Conventional Doppler methods are not capable of measuring lateral velocities since they quantify only the axial component of blood flow. 2D Speckle Tracking methods measure both axial and lateral velocity components, and recent advances in Speckle Tracking enhance its ability to calculate lateral flow velocities in vivo. Specifically, adaptive wall filtering and the implementation of nine disparate transmit beams, each with 2 parallel receive beams, are presented with application to imaging with a Siemens Elegra scanner. Phantom measurements verify the calibration and performance of the data acquisition system and flow tracking algorithm. The methods are demonstrated for flow in the common carotid arteries of five volunteers; velocity magnitude and angle profiles from the nine transmit locations are shown. Velocities computed with Speckle Tracking are highest in the center of the artery and diminish to low velocities near the vessel walls, with velocity magnitudes consistent with physiological expectations.

Optical coherence tomography (OCT) provides 3D tissue imaging by contrasting light backscattering. OCT also senses nanoscale motions from optical phase shifts. We employ temporally modulated magnetic field gradients to mechanically displace superparamagnetic iron oxide nanoparticles (SPIOs). By locking in to the modulation frequency, SPIOs are contrasted in OCT, dubbed magnetomotive OCT (MMOCT).Rehydrated lyophilized human platelets (“RL platelets”), are chemically stabilized infusion hemostatic agents retaining viability. We investigate similar dried platelets with intracellular SPIOs (“SPIO platelets”) as imaging therapeutics. SPIOs are uptaken into the surface connected open canalicular system of platelets where they form clusters. Platelets are then stabilized and dried with the same methods as RL platelets. These SPIO platelets retain the primary hemostatic functions of RL and fresh platelets.We found that MMOCT provides highly specific contrast to SPIO platelets at 1.5e6/μL in 1% agarose scaffolding (see figure). Furthermore, by sweeping the modulation frequency, a mechanical frequency spectrum is obtained, and resonance peaks are associated with the sample elasticity. This has potential for imaging sites of vascular damage and monitoring the local mechanical microenvironment to provide more detailed information about vascular pathologies.View Large Image | View Hi-Res Image | Download PowerPoint Slide