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Dynamics of Vascular Microbubbles and Microdroplets in Gas Embolotherapy

气体栓塞治疗中血管微泡和微滴的动力学

基本信息

批准号：
9475379
负责人：
JOSEPH L BULL
金额：
$ 40.72万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-12 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9475379
关键词：
Dynamics Vascular Microbubbles Microdroplets Gas

项目摘要

DESCRIPTION (provided by applicant): Embolotherapy involves the occlusion of blood flow for therapy, such as treatment of tumors or fibroids, and has traditionally used solid emboli.1 In our novel approach, gas bubbles, rather than solid particles are used for occlusion. The bubbles originate as < 6 �m-diameter albumin- or lipid- encapsulated liquid droplets of perfluorocarbon (PFC), mixed in saline,2, 3 and are injected into the vascular system. The droplets are small enough to pass through capillary beds, so they can circulate until the next stage of the therapy. By strategic placement of an ultrasound source, vaporization of the droplets, which we have termed Acoustic Droplet Vaporization (ADV), can be induced in or near the tumor. The resulting bubble volume is ~125-150 times the droplet volume, and the bubbles resulting from an approximately 5 �m droplet are large enough to lodge in the microcirculation and occlude blood flow to the tumor. This gas embolotherapy approach is minimally invasive, would allow selective delivery of gas emboli to the tumor or fibroid, and is well suited to repeated doses and long-term use. The first funding period of this grant was focused on understanding the underlying biofluid mechanics involved in ADV, transport, and lodging of these novel emboli. Now that we understand the bubble and droplet dynamics well enough to allow us to effectively target regions of healthy tissue for occlusion, we are ready to apply this knowledge to study the potential for lodged microbubbles to induce bioeffects that may lead to localized hypoxia and tissue necrosis. Successful treatment of cancer by the proposed methodology is one of our long-term goals, and understanding how lodged microbubbles affect tumors is essential to reaching that goal. Therefore, the specific aims of this renewal application are: 1. Characterize ADV of adherent droplets, and transport and lodging of resulting bubbles, including ability of functionalized droplets to increase residence time of resulting bubbles. 2. Characterize the ability of lodged bubbles to induce hypoxia. 3. Characterize the ability of lodged bubbles to induce hypoxia related changes in tumors. 4. Assess the ability of lodged bubbles to induce tumor cell apoptosis and to slow tumor growth.

描述（由申请人提供）：栓塞治疗涉及闭塞血流进行治疗，例如治疗肿瘤或肌瘤，传统上使用固体栓塞。1在我们的新方法中，使用气泡而不是固体颗粒进行闭塞。气泡起源于直径小于6 μ m的白蛋白或脂质包裹的全氟化碳（PFC）液滴，混合在盐水中，2，3并注入血管系统。液滴小到足以通过毛细血管床，因此它们可以循环直到治疗的下一阶段。通过超声源的战略性放置，可以在肿瘤中或肿瘤附近诱导液滴的汽化，我们称之为声学液滴汽化（ADV）。产生的气泡体积是液滴体积的125-150倍，大约5 μ m的液滴产生的气泡足够大，可以停留在微循环中，阻塞流向肿瘤的血流。这种气体栓塞治疗方法是微创的，可以选择性地将气体栓塞物输送到肿瘤或肌瘤，并且非常适合重复剂量和长期使用。这项资助的第一个资助期的重点是了解基本的生物流体力学参与ADV，运输和住宿的这些新的栓子。现在，我们已经足够好地理解了气泡和液滴动力学，使我们能够有效地靶向健康组织的区域进行闭塞，我们准备应用这些知识来研究滞留微泡诱导可能导致局部缺氧和组织坏死的生物效应的潜力。通过所提出的方法成功治疗癌症是我们的长期目标之一，了解微泡如何影响肿瘤对于实现这一目标至关重要。因此，本次续展申请的具体目的是：1.表征粘附液滴的ADV以及所得气泡的运输和停留，包括官能化液滴增加所得气泡停留时间的能力。2.表征滞留气泡诱导缺氧的能力。3.表征滞留气泡诱导肿瘤缺氧相关变化的能力。4.评估滞留气泡诱导肿瘤细胞凋亡和减缓肿瘤生长的能力。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of Bioeffects on Endothelial Cells under Acoustic Droplet Vaporization.

DOI：
10.1016/j.ultrasmedbio.2015.07.019
发表时间：
2015-12
期刊：
Ultrasound in medicine & biology
影响因子：
2.9
作者：
Seda R;Li DS;Fowlkes JB;Bull JL
通讯作者：
Bull JL

Microbubble transport through a bifurcating vessel network with pulsatile flow.

微泡通过脉动流的分叉血管网络传输。

DOI：
10.1007/s10544-011-9591-x
发表时间：
2012
期刊：
Biomedical microdevices
影响因子：
2.8
作者：
Valassis,DougT;Dodde,RobertE;Esphuniyani,Brijesh;Fowlkes,JBrian;Bull,JosephL
通讯作者：
Bull,JosephL

Dynamics of micro-bubble sonication inside a phantom vessel.

模型容器内微泡超声处理的动力学。

DOI：
10.1063/1.4773909
发表时间：
2013
期刊：
Applied physics letters
影响因子：
4
作者：
Qamar,Adnan;Samtaney,Ravi;Bull,JosephL
通讯作者：
Bull,JosephL

Lipid Shell Retention and Selective Binding Capability Following Repeated Transient Acoustic Microdroplet Vaporization.

DOI：
10.1021/acs.langmuir.0c00320
发表时间：
2020-06-23
期刊：
LANGMUIR
影响因子：
3.9
作者：
Harmon, Jonah S.;Celingant-Copie, Chloe A.;Kabinejadian, Foad;Bull, Joseph L.
通讯作者：
Bull, Joseph L.

Evolution of acoustically vaporized microdroplets in gas embolotherapy.