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Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging.

ABSTRACT: To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system.The Administrative Institutional Panel on Laboratory Animal Care approved all experiments. A new motion correction algorithm measuring the sum of absolute differences in pixel displacements within a designated tracking box was implemented in a clinical ultrasound machine. In vivo angiogenesis measurements (expressed as percent contrast area) with and without motion compensated maximum intensity persistence (MIP) ultrasound imaging were analyzed in human colon cancer xenografts (n = 64) in mice. Differences in MIP ultrasound imaging signal with and without motion compensation were compared and correlated with displacements in x- and y-directions. The algorithm was tested in an additional twelve colon cancer xenograft-bearing mice with (n = 6) and without (n = 6) anti-vascular therapy (ASA-404). In vivo MIP percent contrast area measurements were quantitatively correlated with ex vivo microvessel density (MVD) analysis.MIP percent contrast area was significantly different (P < 0.001) with and without motion compensation. Differences in percent contrast area correlated significantly (P < 0.001) with x- and y-displacements. MIP percent contrast area measurements were more reproducible with motion compensation (ICC = 0.69) than without (ICC = 0.51) on two consecutive ultrasound scans. Following anti-vascular therapy, motion-compensated MIP percent contrast area significantly (P = 0.03) decreased by 39.4 ± 14.6 % compared to non-treated mice and correlated well with ex vivo MVD analysis (Rho = 0.70; P = 0.05).Real-time motion-compensated MIP ultrasound imaging allows reliable and accurate quantification and monitoring of angiogenesis in tumors exposed to breathing-induced motion artifacts.

SUBMITTER: Pysz MA

PROVIDER: S-EPMC4475587 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging.

Pysz Marybeth A MA Guracar Ismayil I Foygel Kira K Tian Lu L Willmann Jürgen K JK

Angiogenesis 20120426 3

<h4>Purpose</h4>To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system.<h4>Materials and methods</h4>The Administrative Institutional Panel on Laboratory Animal Care approved all experiments. A new motion correction algorithm measuring the sum of absolute differences in pixel displacements within a designated tracking box was implemented in a clinical ultrasound machine. In vivo angiogenesis mea ...[more]

PMID: 22535383

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Project description:PurposeDuring hepatic arterial interventions, catheter or guidewire position is determined by referencing or overlaying a previously acquired static vessel roadmap. Respiratory motion leads to significant discrepancies between the true position and configuration of the hepatic arteries and the roadmap, which makes navigation and accurate catheter placement more challenging and time consuming. The purpose of this work was to develop a dynamic respiratory motion compensated device guidance system and evaluate the accuracy and real-time performance in an in vivo porcine liver model.MethodsThe proposed device navigation system estimates a respiratory motion model for the hepatic vasculature from prenavigational X-ray image sequences acquired under free-breathing conditions with and without contrast enhancement. During device navigation, the respiratory state is tracked based on live fluoroscopic images and then used to estimate vessel deformation based on the previously determined motion model. Additionally, guidewires and catheters are segmented from the fluoroscopic images using a deep learning approach. The vessel and device information are combined and shown in a real-time display. Two different display modes are evaluated within this work: (1) a compensated roadmap display, where the vessel roadmap is shown moving with the respiratory motion; (2) an inverse compensated device display, where the device representation is compensated for respiratory motion and overlaid on a static roadmap. A porcine study including seven animals was performed to evaluate the accuracy and real-time performance of the system. In each pig, a guidewire and microcatheter with a radiopaque marker were navigated to distal branches of the hepatic arteries under fluoroscopic guidance. Motion compensated displays were generated showing real-time overlays of the vessel roadmap and intravascular devices. The accuracy of the motion model was estimated by comparing the estimated vessel motion to the motion of the X-ray visible marker.ResultsThe median (minimum, maximum) error across animals was 1.08 mm (0.92 mm, 1.87 mm). Across different respiratory states and vessel branch levels, the odds of the guidewire tip being shown in the correct vessel branch were significantly higher (odds ratio = 3.12, p < 0.0001) for motion compensated displays compared to a noncompensated display (median probabilities of 86 and 69%, respectively). The average processing time per frame was 17 ms.ConclusionsThe proposed respiratory motion compensated device guidance system increased the accuracy of the displayed device position relative to the hepatic vasculature. Additionally, the provided display modes combine both vessel and device information and do not require the mental integration of different displays by the physician. The processing times were well within the range of conventional clinical frame rates.

Project description:BACKGROUND:The uteroplacental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. OBJECTIVE:We demonstrate the feasibility of the use of contrast-enhanced ultrasound imaging to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. STUDY DESIGN:Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n = 6/group). Human subjects were recruited immediately before scheduled first-trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition with a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. RESULTS:In macaques, the rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and heat shock protein 70 as markers of apoptosis, nitrative, and oxidative stress, respectively, were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11 weeks gestation, and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast after first-trimester ultrasound studies. CONCLUSIONS:Use of contrast-enhanced ultrasound did not result in placental structural damage and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound imaging may offer a safe clinical tool for the identification of pregnancies that are at risk for vascular insufficiency; early recognition may facilitate intervention and improved pregnancy outcomes.

Project description:ObjectiveTo investigate the efficacy of contrast-enhanced ultrasound (CEUS) in quantitatively evaluating angiogenesis during patellar tendon healing in rats.MethodsA total of 40 Sprague-Dawley rats were used in this study. The patellar tendons of 30 rats (60 limbs) that underwent incision and suture were treated as the operation group and monitored after 7, 14, and 28 days. The normal patellar tendons of 10 rats (20 limbs) were treated as the control group and monitored on day 0. The ultrasound examination was used to evaluate the structure and blood perfusion of the patellar tendon. Immunohistochemistry was used to assess angiogenesis, and the biomechanical test was used to verify functional recovery of the patellar tendon.ResultsThe tendons in the operation group were significantly thickened compared with those in the control group (p < 0.01). The peak intensity (PI) in CEUS of the tendons showed a clear difference at each time point after the surgery (p < 0.01). PI increased in the operation group with a maximum on day 7, and then gradually decreased until day 28 when PI was close to the basic intensity (BI) in the control group (p > 0.05). It was consistent with the change of the CD31-positive staining areas representing angiogenesis of the injured patellar tendons. The PI was positively correlated with the CD31-positive staining area fraction (R = 0.849, p < 0.001). The failure load and tensile strength of the repaired patellar tendons in the operation group increased over time. The PI showed negative correlations with the failure load (R = -0.787, p < 0.001) and tensile strength (R = -0.714, p < 0.001).ConclusionThe PI in CEUS could quantitatively reflect the time-dependent change in the blood supply of the healing site, and the PI correlated with histologic and biomechanical properties of the healing tendon. Quantitative analysis of contrast-enhanced ultrasound could be a useful method to evaluate angiogenesis in healing tendons.

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Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging.

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Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging.

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