Dataset Information

Short Acquisition Time Super-Resolution Ultrasound Microvessel Imaging via Microbubble Separation.

ABSTRACT: Super-resolution ultrasound localization microscopy (ULM), based on localization and tracking of individual microbubbles (MBs), offers unprecedented microvascular imaging resolution at clinically relevant penetration depths. However, ULM is currently limited by the requirement of dilute MB concentrations to ensure spatially sparse MB events for accurate localization and tracking. The corresponding long imaging acquisition times (tens of seconds or several minutes) to accumulate sufficient isolated MB events for full reconstruction of microvasculature preclude the clinical translation of the technique. To break this fundamental tradeoff between acquisition time and MB concentration, in this paper we propose to separate spatially overlapping MB events into sub-populations, each with sparser MB concentration, based on spatiotemporal differences in the flow dynamics (flow speeds and directions). MB localization and tracking are performed for each sub-population separately, permitting more robust ULM imaging of high-concentration MB injections. The superiority of the proposed MB separation technique over conventional ULM processing is demonstrated in flow channel phantom data, and in the chorioallantoic membrane of chicken embryos with optical imaging as an in vivo reference standard. Substantial improvement of ULM is further demonstrated on a chicken embryo tumor xenograft model and a chicken brain, showing both morphological and functional microvasculature details at super-resolution within a short acquisition time (several seconds). The proposed technique allows more robust MB localization and tracking at relatively high MB concentrations, alleviating the need for dilute MB injections, and thereby shortening the acquisition time of ULM imaging and showing great potential for clinical translation.

SUBMITTER: Huang C

PROVIDER: S-EPMC7138805 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Short Acquisition Time Super-Resolution Ultrasound Microvessel Imaging via Microbubble Separation.

Huang Chengwu C Lowerison Matthew R MR Trzasko Joshua D JD Manduca Armando A Bresler Yoram Y Tang Shanshan S Gong Ping P Lok U-Wai UW Song Pengfei P Chen Shigao S

Scientific reports 20200407 1

Super-resolution ultrasound localization microscopy (ULM), based on localization and tracking of individual microbubbles (MBs), offers unprecedented microvascular imaging resolution at clinically relevant penetration depths. However, ULM is currently limited by the requirement of dilute MB concentrations to ensure spatially sparse MB events for accurate localization and tracking. The corresponding long imaging acquisition times (tens of seconds or several minutes) to accumulate sufficient isolat ...[more]

PMID: 32265457

Similar Datasets

Project description:Ultrasound super-resolution (SR) microvessel imaging technologies are rapidly emerging and evolving. The unprecedented combination of imaging resolution and penetration promises a wide range of preclinical and clinical applications. This paper concerns spatial quantization error in SR imaging, a common issue that involves a majority of current SR imaging methods. While quantization error can be alleviated by the microbubble localization process (e.g., via upsampling or parametric fitting), it is unclear to what extent the localization process can suppress the spatial quantization error induced by discrete sampling. It is also unclear when low spatial sampling frequency will result in irreversible quantization errors that cannot be suppressed by the localization process. This paper had two goals: 1) to systematically investigate the effect of quantization in SR imaging and establish principles of adequate SR imaging spatial sampling that yield minimal quantization error with proper localization methods and 2) to compare the performance of various localization methods and study the level of tolerance of each method to quantization. We conducted experiments on a small wire target and on a microbubble flow phantom. We found that the Fourier analysis of an oversampled spatial profile of the microbubble signal could provide reliable guidance for selecting beamforming spatial sampling frequency. Among various localization methods, parametric Gaussian fitting and centroid-based localization on upsampled data had better microbubble localization performance and were less susceptible to quantization error than peak intensity-based localization methods. When spatial sampling resolution was low, parametric Gaussian fitting-based localization had the best performance in suppressing quantization error, and could produce acceptable SR microvessel imaging with no significant quantization artifacts. The findings from this paper can be used in practice to help intelligently determine the minimum requirement of spatial sampling for robust microbubble localization to avoid adding or even reduce the burden of computational cost and data storage that are commonly associated with SR imaging.

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.

Dataset Information

Short Acquisition Time Super-Resolution Ultrasound Microvessel Imaging via Microbubble Separation.

Publications

Short Acquisition Time Super-Resolution Ultrasound Microvessel Imaging via Microbubble Separation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure