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Ultrasound molecular imaging: insights into cardiovascular pathology.

ABSTRACT: Similar to what has already occurred in cancer medicine, the management of cardiovascular conditions will likely be improved by non-invasive molecular imaging technologies that can provide earlier or more accurate diagnosis. These techniques are already having a positive impact in pre-clinical research by providing insight into pathophysiology or efficacy of new therapies. Contrast enhanced ultrasound (CEU) molecular imaging is a technique that relies on the ultrasound detection of targeted microbubble contrast agents to examine molecular or cellular events that occur at the blood pool-endothelial interface. CEU molecular imaging techniques have been developed that are able to provide unique information on atherosclerosis, ischemia reperfusion injury, angiogenesis, vascular inflammation, and thrombus formation. Accordingly, CEU has the potential to be used in a wide variety of circumstances to detect disease early or at the bedside, and to guide appropriate therapy based on vascular phenotype. This review will describe the physical basis for CEU molecular imaging, and the specific disease processes for the pre-clinical translational research experience.

SUBMITTER: Ozawa K

PROVIDER: S-EPMC7244457 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Ultrasound molecular imaging: insights into cardiovascular pathology.

Ozawa Koya K Lindner Jonathan R JR

Journal of echocardiography 20200213 2

Similar to what has already occurred in cancer medicine, the management of cardiovascular conditions will likely be improved by non-invasive molecular imaging technologies that can provide earlier or more accurate diagnosis. These techniques are already having a positive impact in pre-clinical research by providing insight into pathophysiology or efficacy of new therapies. Contrast enhanced ultrasound (CEU) molecular imaging is a technique that relies on the ultrasound detection of targeted micr ...[more]

PMID: 32056137

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Project description:RationaleMicrobubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld.ObjectiveTo develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging.Methods and resultsMicrobubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab')2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification.ConclusionsTargeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)-(iii) desired for clinical applications.

Project description:Aim:To develop a standardised ultrasound imaging (USI)-based criteria for the diagnosis of tendinopathy that aligns with the continuum model of tendon pathology. Secondary aims were to assess both the intra-rater and inter-rater reliability of the criteria. Methods:A criteria was developed following a face validity assessment and a total of 31 Achilles tendon ultrasound images were analysed. Intra-rater and inter-rater reliability were assessed for overall tendinopathy stage (normal, reactive/early dysrepair or late dysrepair/degenerative) as well as for individual parameters (thickness, echogenicity and vascularity). Quadratic weighted kappa (kw) was used to report on reliability. Results:Intra-rater reliability was 'substantial' for overall tendinopathy staging (kw rater A; 0.77, 95%?CI 0.59 to 0.94, rater B; 0.70, 95%?CI 0.52 to 0.89) and ranged from 'substantial' to 'almost perfect' for thickness (kw rater A; 0.75, 95%?CI 0.59 to 0.90, rater B; 0.84, 95%?CI 0.71 to 0.98), echogenicity (kw rater A; 0.78, 95%?CI 0.62 to 0.95, rater B; 0.73, 95%?CI 0.58 to 0.89) and vascularity (kw rater A; 0.86, 95%?CI 0.74 to 0.98, rater B; 0.89, 95%?CI 0.79 to 0.99). Inter-rater reliability ranged from 'substantial' to 'almost perfect' for overall tendinopathy staging (kw round 1; 0.75, 95%?CI 0.58 to 0.91, round 2; 0.81, 95%?CI 0.63 to 0.99), thickness (kw round 1; 0.65, 95%?CI 0.48 to 0.83, round 2; 0.77, 95%?CI 0.60 to 0.93), echogenicity (kw round 1; 0.70, 95%?CI 0.54 to 0.85, round 2; 0.76, 95%?CI 0.58 to 0.94) and vascularity (kw round 1; 0.89, 95%?CI 0.79 to 0.99, round 2; 0.86, 95%?CI 0.74 to 0.98). Inter-rater reliability increased from 'substantial' in round 1 (kw 0.75, 95%?CI 0.58 to 0.91) to 'almost perfect' in round 2 (0.81, 95%?CI 0.63 to 0.99). Conclusion:Intra-rater and inter-rater reliability were 'substantial' to 'almost perfect' when utilising an USI-based criteria to diagnose Achilles tendinopathy. This is the first study to use the continuum model of tendon pathology to develop an USI-based criteria to diagnose tendinopathy.

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Ultrasound molecular imaging: insights into cardiovascular pathology.

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Ultrasound molecular imaging: insights into cardiovascular pathology.

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