Caterina M. Gallippi

ARFI imaging for noninvasive material characterization of atherosclerosis. Part II: toward in vivo characterization.

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.

Adaptive clutter filtering via blind source separation for two-dimensional ultrasonic blood velocity measurement.

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 methods 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 systems 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.

A motion-based approach to abdominal clutter reduction

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.

Non-invasive in vivo characterization of human carotid plaques with acoustic radiation force impulse ultrasound: comparison with histology after endarterectomy.

Ischemic stroke from thromboembolic sources is linked to carotid artery atherosclerotic disease with a trend toward medical management in asymptomatic patients. Extent of disease is currently diagnosed by non-invasive imaging techniques that measure luminal stenosis, but it has been suggested that a better biomarker for determining risk of future thromboembolic events is plaque morphology and composition. Specifically, plaques that are composed of mechanically soft lipid/necrotic regions covered by thin fibrous caps are the most vulnerable to rupture. An ultrasound technique that non-invasively interrogates the mechanical properties of soft tissue, called acoustic radiation force impulse (ARFI) imaging, has been developed as a new modality for atherosclerotic plaque characterization using phantoms and atherosclerotic pigs, but the technique has yet to be validated in vivo in humans. In this preliminary study, in vivo ARFI imaging is presented in a case study format for four patients undergoing clinically indicated carotid endarterectomy and compared with histology. In two type Va plaques, characterized by lipid/necrotic cores covered by fibrous caps, mean ARFI displacements in focal regions were high relative to the surrounding plaque material, suggesting soft features were covered by stiffer layers within the plaques. In two type Vb plaques, characterized by heavy calcification, mean ARFI peak displacements were low relative to the surrounding plaque and arterial wall, suggesting stiff tissue. This pilot study illustrates the feasibility and challenges of transcutaneous ARFI for characterizing the material and structural composition of carotid atherosclerotic plaques via mechanical properties, in humans, in vivo.

Viscoelastic response (VisR) imaging for assessment of viscoelasticity in voigt materials

Viscoelastic response (VisR) imaging is presented as a new acoustic radiation force (ARF)-based elastographic imaging method. Exploiting the Voigt model, VisR imaging estimates displacement in only the ARF region of excitation from one or two successive ARF impulses to estimate τσ, the relaxation time for constant stress. Double-push VisR τσ estimates were not statistically significantly different (p <; 0.02) from those of shearwave dispersion ultrasound vibrometry (SDUV) or monitored steady-state excitation recovery (MSSER) ultrasound in six homogeneous viscoelastic tissue mimicking phantoms with elastic moduli ranging from 3.92 to 15.34 kPa and coefficients of viscosity ranging from 0.87 to 14.06 Pa·s. In two-dimensional imaging, double-push VisR τσ images discriminated a viscous spherical inclusion in a structured phantom with higher CNR over a larger axial range than single-push VisR or conventional acoustic radiation force impulse (ARFI) ultrasound. Finally, 2-D in vivo double-push VisR images in normal canine semitendinosus muscle were compared with spatially matched histochemistry to corroborate lower double-push VisR τσ values in highly collagenated connective tissue than in muscle, suggesting double-push VisRs in vivo relevance to diagnostic imaging, particularly in muscle. The key advantages and disadvantages to VisR, including lack of compensation for inertial terms, are discussed.

Acoustic radiation force beam sequence performance for detection and material characterization of atherosclerotic plaques: preclinical, ex vivo results

This work presents preclinical data demonstrating performance of acoustic radiation force (ARF)-based elasticity imaging with five different beam sequences for atherosclerotic plaque detection and material characterization. Twelve trained, blinded readers evaluated parametric images taken ex vivo under simulated in vivo conditions of 22 porcine femoral arterial segments. Receiver operating characteristic (ROC) curve analysis was carried out to quantify reader performance using spatially-matched immunohistochemistry for validation. The beam sequences employed had high sensitivity (sens) and specificity (spec) for detecting Type III+ plaques (sens: 85%, spec: 79%), lipid pools (sens: 80%, spec: 86%), fibrous caps (sens: 86%, spec: 82%), calcium (sens: 96%, spec: 85%), collagen (sens: 78%, spec: 77%), and disrupted internal elastic lamina (sens: 92%, spec: 75%). 1:1 single-receive tracking yielded the highest median areas under the ROC curve (AUC), but was not statistically significantly higher than 4:1 parallel-receive tracking. Excitation focal configuration did not result in statistically different AUCs. Overall, these results suggest ARF-based imaging is relevant to detecting and characterizing plaques and support its use for diagnosing and monitoring atherosclerosis.

Fully Automated Registration and Warping of Contrast-Enhanced First-Pass Perfusion Images

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 (P < 0.0001). 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 (P < 0.001). 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.

Therapeutic ultrasound as a potential male contraceptive: power, frequency and temperature required to deplete rat testes of meiotic cells and epididymides of sperm determined using a commercially available system

BackgroundStudies 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.MethodsSprague-Dawley rats were anesthetized and their testes were treated with 1 MHz or 3 MHz ultrasound while varying power, duration and temperature of treatment.ResultsWe 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 Fahims 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.ConclusionsThe 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.

Automatic Image Registration for MR and Ultrasound Cardiac Images

The Statistics Based Image Registration (SBR) method for automatic image registration is presented with application to magnetic resonance (MR)and ultrasound (US) cardiac time series images. SBR is demonstrated for MR myocardial perfusion assessment and US myocardial kinetics studies. The utility of the method for a range of other clinical applications is discussed.

Experimental Validation of Displacement Underestimation in ARFI Ultrasound

Acoustic radiation force impulse (ARFI) imaging is an elastography technique that uses ultrasonic pulses to 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. Three optically translucent phantoms of varying stiffness were created, embedded with subwavelength diameter microspheres, 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. As predicted by earlier finite element method studies, significant acoustic displacement underestimation was observed for both excitation focal configurations; the maximum underestimation error was 35% of the optically measured displacement for the F/1.5 excitation pulse in the softest phantom. Using higher F/#, less tightly focused beams in the lateral dimension improved accuracy of displacements by approximately 10 percentage points. 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.