Molecular Imaging Using Ultrasound and Targeted Microbubbles

使用超声波和靶向微泡的分子成像

• 批准号: EP/G038163/1
• 负责人: Mengxing Tang
• 金额: $ 70.9万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG038163%2F1
• 关键词: Molecular; Imaging; Using; Ultrasound; Targeted

This project investigates the use of ultrasound and microbubbles for molecular imaging. Molecular imaging, sometimes referred to as targeted imaging, is a variation of the normal anatomical imaging familiar to most people. In molecular imaging, the aim is to reveal the physiological function of the tissues under investigation at a cellular or molecular level. This is done by using a marker designed to target specific cells and molecules. The technique has widespread potential for the diagnosis of diseases such as cancer, and neurological and cardiovascular diseases. It also has a role to play in improving treatment of many disorders by enabling detailed pre-clinical and clinical tests of new medication. Traditional ultrasound imaging is one of the most frequently used clinical imaging modalities. The primary advantages of the technique are the practicality of the technique, the very low risk to patients, the real-time nature, and the relatively low cost. A recent advance in ultrasound imaging is the development of microbubble contrast agents. The microbubbles are injected into the blood stream of the patient. They act to increase the scattered ultrasound signals, making the blood appear more clearly on the ultrasound image. Ultrasound imaging with microbubbles is gaining acceptance in clinical practice. The microbubbles consist of a gas core that is encapsulated by a thin shell, typically constructed of a lipid monolayer or cross-linked albumin and are typically the same size as the red blood cells that circulate within our blood. The microbubbles have acoustic properties very different from the patient's blood in which they are suspended. Even a single bubble can create significant and specific ultrasound echoes. Ultrasound contrast enhanced imaging exploits these differences and emerging clinical applications include diagnosis of myocardial perfusion and angiogenesis in malignant tumours. By incorporating active biological markers into the microbubble shells, they can be targeted to specific molecules within the body. These molecules only exist at certain sites within the body and under specific physiological or pathological conditions. For example, the microbubbles can be designed to stick to molecules that only exist in areas of inflammation on vessel walls. The stuck microbubbles can then be detected using ultrasound. This new approach is provoking worldwide interest in the research community from both basic scientists and clinical researchers.There are two major challenges that we aim to address through this research: Firstly to make the microbubbles stick effectively and only to the targets of interest, and for them to remain stable for a sufficient length of time once stuck. Secondly to improve the specificity of the ultrasound imaging so that the stuck microbubbles can be differentiated from those still flowing freely in the ultrasound images that are used to detect them.In this project, we aim to improve both the microbubbles and the ultrasound technique used to detect them. We will develop methodology for fabrication and evaluation of novel targeted microbubbles. The performance of these microbubbles will be optimised in terms of the efficiency and strength of their binding to the target and their visibility under ultrasound. At the same time, we will develop a combined acoustic and optical experimental system and thoroughly investigate the physical properties of these targeted microbubbles. This will enable more detailed optimisation of the microbubble fabrication process and help us identify and understand how their behaviour differs once they are attached to the target. This understanding will allow us to develop new and more effective molecular image approaches. Based on these we will develop novel techniques for selective imaging of targeted microbubbles and address the confounding issue of tissue motion.

这个项目研究了超声波和微泡在分子成像中的应用。分子成像，有时被称为靶向成像，是大多数人熟悉的正常解剖成像的变体。在分子成像中，目的是在细胞或分子水平上揭示被研究组织的生理功能。这是通过使用专门针对特定细胞和分子的标记来完成的。这项技术在诊断癌症、神经和心血管疾病等疾病方面具有广泛的潜力。它还可以通过对新药进行详细的临床前和临床测试，在改善许多疾病的治疗方面发挥作用。传统的超声成像是临床上最常用的成像方式之一。该技术的主要优点是技术的实用性、对患者的极低风险、实时性和相对较低的成本。超声成像的最新进展是微泡造影剂的发展。这些微泡被注入患者的血液中。它们的作用是增加散射的超声信号，使血液在超声图像上显示得更清楚。微泡超声成像在临床上得到了越来越多的认可。微泡由一个被薄壳包裹的气体核心组成，薄壳通常由脂类单层或交联白蛋白组成，通常与在我们血液中循环的红细胞大小相同。微泡的声学特性与患者血液中悬浮的微泡非常不同。即使是一个单独的气泡也能产生显著和特定的超声回声。超声增强成像利用了这些差异，新出现的临床应用包括诊断恶性肿瘤的心肌灌注和血管生成。通过在微泡外壳中加入活性生物标记，它们可以针对体内的特定分子。这些分子只存在于体内的某些部位，并在特定的生理或病理条件下存在。例如，微泡可以被设计成附着在只存在于血管壁炎症区域的分子上。然后，可以使用超声波检测粘连的微泡。这一新方法引起了基础科学家和临床研究人员对研究界的广泛兴趣。通过这项研究，我们旨在解决两个主要挑战：第一，使微泡有效地并仅粘在感兴趣的目标上，以及一旦粘住，它们将在足够长的时间内保持稳定。其次，为了提高超声成像的特异性，以便在用于检测微泡的超声图像中区分粘连的微泡和仍然自由流动的微泡。在本项目中，我们的目标是改进微泡和用于检测微泡的超声技术。我们将开发新的靶向微泡的制备和评估方法。这些微泡的性能将根据它们与目标结合的效率和强度以及它们在超声波下的可见性而得到优化。同时，我们将开发声光联合实验系统，深入研究这些靶向微泡的物理性质。这将使我们能够更详细地优化微泡制造过程，并帮助我们识别和了解它们在连接到靶标后的行为有何不同。这一认识将使我们能够开发新的、更有效的分子成像方法。在此基础上，我们将开发选择性成像靶向微泡的新技术，并解决令人困惑的组织运动问题。

项目成果

The assessment of microvascular flow and tissue perfusion using ultrasound imaging.

使用超声成像评估微血管血流和组织灌注。

• DOI: 10.1243/09544119jeim621
• 发表时间: 2010
• 期刊: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine
• 作者: Sboros V

Dynamics of targeted microbubble adhesion under pulsatile compared with steady flow.

脉动流与稳态流下目标微泡粘附的动力学比较。

• DOI: 10.1016/j.ultrasmedbio.2014.03.015
• 发表时间: 2014
• 期刊: Ultrasound in medicine & biology
• 影响因子: 2.9
• 作者: Sennoga CA

Effect of ultrasound on adherent microbubble contrast agents.

超声对粘附微泡造影剂的影响。

• DOI: 10.1088/0031-9155/57/21/6999
• 发表时间: 2012
• 期刊: Physics in medicine and biology
• 影响因子: 3.5
• 作者: Loughran J

Modeling non-spherical oscillations and stability of acoustically driven shelled microbubbles.

模拟声驱动带壳微泡的非球形振荡和稳定性。

• DOI: 10.1121/1.4707479
• 发表时间: 2012
• 期刊: The Journal of the Acoustical Society of America
• 作者: Loughran J

Evaluation of methods for sizing and counting of ultrasound contrast agents.

• DOI: 10.1016/j.ultrasmedbio.2012.01.012
• 发表时间: 2012-05
• 期刊: ULTRASOUND IN MEDICINE AND BIOLOGY
• 影响因子: 2.9
• 作者: Sennoga, Charles A.;Yeh, James S. M.;Alter, Julia;Stride, Eleanor;Nihoyannopoulos, Petros;Seddon, John M.;Haskard, Dorian O.;Hajnal, Joseph V.;Tang, Meng-Xing;Eckersley, Robert J.
• 通讯作者: Eckersley, Robert J.