(1/563) Focal hepatic lesions: contrast-enhancement patterns at pulse-inversion harmonic US using a microbubble contrast agent.

OBJECTIVE: To analyze the contrast-enhancement patterns obtained at pulse-inversion harmonic imaging (PIHI) of focal hepatic lesions, and to thus determine tumor vascularity and the acoustic emission effect. MATERIALS AND METHODS: We reviewed pulse-inversion images in 90 consecutive patients with focal hepatic lesions, namely hepatocellular carcinoma (HCC) (n=43), metastases (n=30), and hemangioma (n=17). Vascular and delayed phase images were obtained immediately and five minutes following the injection of a microbubble contrast agent. Tumoral vascularity at vascular phase imaging and the acoustic emission effect at delayed phase imaging were each classified as one of four patterns. RESULTS: Vascular phase images depicted internal vessels in 93% of HCCs, marginal vessels in 83% of metastases, and peripheral nodular enhancement in 71% of hemangiomas. Delayed phase images showed inhomogeneous enhancement in 86% of HCCs; hypoechoic, decreased enhancement in 93% of metastases; and hypoechoic and reversed echogenicity in 65% of hemangiomas. Vascular and delayed phase enhancement patterns were associated with a specificity of 91% or greater, and 92% or greater, respectively, and with positive predictive values of 71% or greater, and 85% or greater, respectively. CONCLUSION: Contrast-enhancement patterns depicting tumoral vascularity and the acoustic emission effect at PIHI can help differentiate focal hepatic lesions.  (+info)

(2/563) Leukocyte-targeted myocardial contrast echocardiography can assess the degree of acute allograft rejection in a rat cardiac transplantation model.

BACKGROUND: Repetitive endomyocardial biopsies are necessary to monitor the effects of immunosuppressants after cardiac transplantation. Contrast ultrasound with microbubble targeting of leukocytes detects acute leukocyte infiltration. We examined whether leukocyte-targeted myocardial contrast echocardiography (MCE) could provide for the quantitative assessment of acute cardiac rejection. METHODS AND RESULTS: Hearts from Brown Norway rats or Lewis rats were transplanted into other Brown Norway rats. Isografts and groups of allografts either untreated or treated with cyclosporin A (CsA) at a low dose (3 mg x kg(-1) x d(-1)) or high dose (10 mg x kg(-1) x d(-1)) from 3 days before transplantation were compared at posttransplantation day 3. Echocardiography-derived left ventricular wall thickening was comparable among the 4 groups. Myocardial blood flow assessed with MCE, relating pulsing intervals with signal intensity (SI), was slightly decreased only in untreated allografts. However, myocardial SI (in gray levels) obtained after a 10-minute period allowing microbubble-leukocyte interactions after contrast injection exhibited a clear gradient in these groups (12+/-2 in untreated allografts, 9+/-5 in allografts treated with low-dose CsA, 6+/-3 in allografts treated with high-dose CsA, and 2+/-1 in isografts, P<0.001). The pattern of difference in SI among the groups agreed well with that in ED-1-positive cell (macrophage) count (25+/-7, 12+/-4, 5+/-3, and 1+/-0 cells per high-power field, respectively, P<0.001), which correlated with CD3-positive cell (T lymphocyte) count (33+/-5, 22+/-5, 9+/-4, and 1+/-0 cells per high-power field, respectively, P<0.001). CONCLUSIONS: Leukocyte-targeted MCE can noninvasively assess the degree of rejection in transplanted hearts by directly revealing the magnitude of intramyocardial infiltration of macrophages and T lymphocytes.  (+info)

(3/563) Ultrasound microbubble destruction imaging in acute middle cerebral artery stroke.

BACKGROUND AND PURPOSE: Cerebral perfusion imaging in acute stroke assists in determining the subtype and the severity of ischemia. Recent studies in perfusion models and in healthy volunteers have shown that ultrasound perfusion imaging based on microbubble destruction can be used to assess tissue perfusion. We applied ultrasound microbubble destruction imaging (MDI) to identify perfusion deficits in patients with acute middle cerebral artery (MCA) territory stroke. METHODS: Fifteen acute MCA stroke patients with sufficient transtemporal bone windows were investigated with ultrasound MDI and perfusion-weighted MRI (PWI). MDI was performed using power pulse-inversion contrast harmonic imaging. Thirty seconds after a bolus injection of the echo contrast agent SonoVue, microbubbles were destroyed using a series of high-energy pulses. Local perfusion status was analyzed in selected regions of interest by destruction curves and acoustic intensity differences (DeltaI) before and after microbubble destruction. Local perfusion status was then compared with perfusion compromise as identified on PWI. RESULTS: The mean differences of acoustic intensity from the ischemic MCA territory were significantly diminished compared with the normal hemisphere (DeltaI=2.52+/-1.75 versus DeltaI=13.79+/-7.31; P<0.001), resulting in lower slopes of microbubble destruction. PWI confirmed perfusion changes in the selected anatomical regions on time-to-peak maps in all 15 patients. CONCLUSIONS: MDI is a qualitative method that can rapidly detect perfusion changes in acute stroke. When combined with other ultrasound techniques and PWI, it may well be valuable in the care of stroke unit patients, eg, as a screening method and for follow-up assessments of perfusion deficits.  (+info)

(4/563) Microbubbles and ultrasound: from diagnosis to therapy.

The development of ultrasound contrast agents, containing encapsulated microbubbles, has increased the possibilities for diagnostic imaging. Ultrasound contrast agents are currently used to enhance left ventricular opacification, increase Doppler signal intensity, and in myocardial perfusion imaging. Diagnostic imaging with contrast agents is performed with low acoustic pressure using non-linear reflection of ultrasound waves by microbubbles. Ultrasound causes bubble destruction, which lowers the threshold for cavitation, resulting in microstreaming and increased permeability of cell membranes. Interestingly, this mechanism can be used for delivery of drugs or genes into tissue. Microbubbles have been shown to be capable of carrying drugs and genes, and destruction of the bubbles will result in local release of their contents. Recent studies demonstrated the potential of microbubbles and ultrasound in thrombolysis. In this article, we will review the recent advances of microbubbles as a vehicle for delivery of drugs and genes, and discuss possible therapeutic applications in thrombolysis.  (+info)

(5/563) The powerful microbubble: from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond.

This review discusses the development, current applications, and therapeutic potential of ultrasound contrast agents. Microbubbles containing gases act as true, intravascular indicators, permitting a noninvasive, quantitative analysis of the spatial and temporal heterogeneity of blood flow and volumes within the microvasculature. These shelled microbubbles are near-perfect reflectors of acoustic ultrasound energy and, when injected intravenously into the bloodstream, reflect ultrasound waves within the capillaries without disrupting the local environment. Accordingly, microbubble ultrasound contrast agents are clinically useful in enhancing ultrasound images and improving the accuracy of diagnoses. More recently, ultrasound contrast agents have been used to directly visualize the vasa vasorum and neovascularization of atherosclerotic carotid artery plaques, thus suggesting a new paradigm for diagnosis and treatment of atherosclerosis. Future applications of these microscopic agents include the deliver of site-specific therapy to targeted organs in the body. Medical therapies may use these microbubbles as carriers for newer therapeutic options.  (+info)

(6/563) Validation of the depletion kinetic in semiquantitative ultrasonographic cerebral perfusion imaging using 2 different techniques of data acquisition.

OBJECTIVE: To validate the potential of ultrasonographic depletion imaging for semiquantitatively visualizing cerebral parenchymal perfusion with contrast burst depletion imaging (CODIM) in comparison with phase inversion harmonic depletion imaging (PIDIM) in healthy volunteers. METHODS: Thirteen healthy adults were examined with both CODIM and PIDIM in accordance with previously described criteria. In addition to the perfusion coefficient, the time to decrease image intensity to 10% above equilibrium intensity from the initial value and the relative error (deviation of measured data from the fitted model) were evaluated to compare the reliability of both techniques in 3 different regions of interest. RESULTS: Perfusion coefficient values did not show significantly differing values in both groups (1.57-1.64 * 10(-2) s(-1) for CODIM and 1.42-1.58 * 10(-2) s(-1) for PIDIM). The relative error was significantly smaller in the PIDIM group (0.38-0.53 for CODIM and 0.18-0.25 for PIDIM; P < .002). CONCLUSIONS: Phase inversion harmonic depletion imaging proved to be more reliable than CODIM because values of the relative error were significantly lower in PIDIM even in this relatively small cohort. This is of interest because the underlying technique, phase inversion harmonic imaging, is more widely available than contrast burst imaging.  (+info)

(7/563) Ultrasonic analysis of peptide- and antibody-targeted microbubble contrast agents for molecular imaging of alphavbeta3-expressing cells.

The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. In this manuscript, three distinct contrast agents targeted to the alphavbeta3 integrin are examined. The alphavbeta3 integrin has been shown to be highly expressed on metastatic tumors and endothelial cells during neovascularization, and its expression has been shown to correlate with tumor grade. Specific adhesion of these contrast agents to alphavbeta3-expressing cell monolayers is demonstrated in vitro, and compared with that of nontargeted agents. Acoustic studies illustrate a backscatter amplitude increase from monolayers exposed to the targeted contrast agents of up to 13-fold (22 dB) relative to enhancement due to control bubbles. A linear dependence between the echo amplitude and bubble concentration was observed for bound agents. The decorrelation of the echo from adherent targeted agents is observed over successive pulses as a function of acoustic pressure and bubble density. Frequency-domain analysis demonstrates that adherent targeted bubbles exhibit high-amplitude narrowband echo components, in contrast to the primarily wideband response from free microbubbles. Results suggest that adherent targeted contrast agents are differentiable from free-floating microbubbles, that targeted contrast agents provide higher sensitivity in the detection of angiogenesis, and that conventional ultrasound imaging techniques such as signal subtraction or decorrelation detection can be used to detect integrin-expressing vasculature with sufficient signal-to-noise.  (+info)

(8/563) Microvascular remodeling and accelerated hyperemia blood flow restoration in arterially occluded skeletal muscle exposed to ultrasonic microbubble destruction.

We showed previously that microbubble destruction with pulsed 1-MHz ultrasound creates a bioeffect that stimulates arteriogenesis and a chronic increase in hyperemia blood flow in normal rat muscle. Here we tested whether ultrasonic microbubble destruction can be used to create a microvascular remodeling response that restores hyperemia blood flow to rat skeletal muscle affected by arterial occlusion. Pulsed ultrasound (1 MHz) was applied to gracilis muscles in which the lateral feed artery was occluded but the medial feed artery was left intact. Control muscles were similarly occluded but did not receive ultrasound, microbubbles, or both. Hyperemia blood flow and number of smooth muscle (SM) alpha-actin-positive vessels, >30-mum arterioles, and capillaries per fiber were determined 7, 14, and 28 days after treatment. In ultrasound-microbubble-treated muscles, lateral region hyperemia blood flow was increased at all time points and restored to normal at day 28. The number of SM alpha-actin vessels per fiber was increased over control in this region at days 7 and 14 but decreased by day 28, when larger-diameter arterioles became more prevalent in the medial region. The number of capillaries per fiber was increased over control only at day 7 in the lateral region and only at days 7 and 14 in the medial region, indicating that the angiogenesis response was transient and likely did not contribute significantly to flow restoration at day 28. We conclude that ultrasonic microbubble destruction can be tailored to stimulate an arteriogenesis response that restores hyperemia blood flow to skeletal muscle in a rat model of arterial occlusion.  (+info)