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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: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:Contrast-enhanced ultrasound (CEUS) cines of focal liver lesions (FLLs) can be quantitatively analyzed to measure tumor perfusion on a pixel-by-pixel basis for diagnostic indication. However, CEUS cines acquired freehand and during free breathing cause nonuniform in-plane and out-of-plane motion from frame to frame. These motions create fluctuations in the time-intensity curves (TICs), reducing the accuracy of quantitative measurements. Out-of-plane motion cannot be corrected by image registration in 2-dimensional CEUS and degrades the quality of in-plane motion correction (IPMC). A 2-tier IPMC strategy and adaptive out-of-plane motion filter (OPMF) are proposed to provide a stable correction of nonuniform motion to reduce the impact of motion on quantitative analyses.A total of 22 cines of FLLs were imaged with dual B-mode and contrast specific imaging to acquire a 3-minute TIC. B-mode images were analyzed for motion, and the motion correction was applied to both B-mode and contrast images. For IPMC, the main reference frame was automatically selected for each cine, and subreference frames were selected in each respiratory cycle and sequentially registered toward the main reference frame. All other frames were sequentially registered toward the local subreference frame. Four OPMFs were developed and tested: subsample normalized correlation (NC), subsample sum of absolute differences, mean frame NC, and histogram. The frames that were most dissimilar to the OPMF reference frame using 1 of the 4 above criteria in each respiratory cycle were adaptively removed by thresholding against the low-pass filter of the similarity curve. Out-of-plane motion filter was quantitatively evaluated by an out-of-plane motion metric (OPMM) that measured normalized variance in the high-pass filtered TIC within the tumor region-of-interest with low OPMM being the goal. Results for IPMC and OPMF were qualitatively evaluated by 2 blinded observers who ranked the motion in the cines before and after various combinations of motion correction steps.Quantitative measurements showed that 2-tier IPMC and OPMF improved imaging stability. With IPMC, the NC B-mode metric increased from 0.504 ± 0.149 to 0.585 ± 0.145 over all cines (P < 0.001). Two-tier IPMC also produced better fits on the contrast-specific TIC than industry standard IPMC techniques did (P < 0.02). In-plane motion correction and OPMF were shown to improve goodness of fit for pixel-by-pixel analysis (P < 0.001). Out-of-plane motion filter reduced variance in the contrast-specific signal as shown by a median decrease of 49.8% in the OPMM. Two-tier IPMC and OPMF were also shown to qualitatively reduce motion. Observers consistently ranked cines with IPMC higher than the same cine before IPMC (P < 0.001) as well as ranked cines with OPMF higher than when they were uncorrected.The 2-tier sequential IPMC and adaptive OPMF significantly reduced motion in 3-minute CEUS cines of FLLs, thereby overcoming the challenges of drift and irregular breathing motion in long cines. The 2-tier IPMC strategy provided stable motion correction tolerant of out-of-plane motion throughout the cine by sequentially registering subreference frames that bypassed the motion cycles, thereby overcoming the lack of a nearly stationary reference point in long cines. Out-of-plane motion filter reduced apparent motion by adaptively removing frames imaged off-plane from the automatically selected OPMF reference frame, thereby tolerating nonuniform breathing motion. Selection of the best OPMF by minimizing OPMM effectively reduced motion under a wide variety of motion patterns applicable to clinical CEUS. These semiautomated processes only required user input for region-of-interest selection and can improve the accuracy of quantitative perfusion measurements.

Project description:BackgroundThe aim of modern medicine is to safely classify diseases for successful therapy without invasive measures. Sonography, computed tomography (CT), and magnetic resonance imaging (MRI) are potent imaging techniques. However, without contrast medium, the informative value of the 3 native methods is limited. The advantages of sonography are: no radiation exposure or previously known physically harmful interactions with tissue, proportionate disappearance of a contrast agent risk, no (probably irreversible) contrast agent deposits, and no risk of renal insufficiency. But, is that enough to compete with of even exceed CT and MRI?SummaryIn this review, the state of the art of contrast-enhanced ultrasound (CEUS) in the abdominal cavity is presented. The remarkable diagnostic possibilities can unfortunately only be demonstrated here in a small number of impressive, typical case studies underpinned by the literature, so that, from one's own perspective, the full spectrum of CEUS can be used by oneself or initiated. Within the limits of physics, the real-time dynamics of CEUS enable conclusions to be drawn, so that with the current technology, sonography, including expansion by contrast, can be considered superior to other imaging methods. It is not uncommon for CEUS to have the value of a control and reference method.Key messagesSonography very often enables reliable diagnostics. The introduction of a contrast agent in sonography has led to a quantum leap similar to that of other imaging techniques. Already natively, the real-time representation of dynamic events leads to a certain superiority, i.e., complete observation of the inflow and outflow phases of the contrast medium and the resulting diagnostic; tissue-specific differentiation options provide a unique selling point. Further advantages of the first-choice imaging diagnostic method are: a lack of radiation exposure, repeatability of the examination at any time, local independence, a negligible allergy rate compared to the contrast agents of other methods, and a lack of kidney and thyroid exposure or excluded deposits.

Dataset Information

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

Publications

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

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