Monodisperse Microbubbles for Noninvasive Pressure Estimation

用于无创压力估计的单分散微泡

• 批准号: 10676271
• 负责人: John Eisenbrey
• 金额: $ 58.1万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676271
• 关键词: Acoustics; Blood Vessels; Cardiac; Catheters; Clinical; Clinical Trials; Computer software; Contrast Media; Cost Measures; Custom; Data; Data Collection; Devices; Diagnosis; Disease; Equation; Estimation Techniques; Exhibits; Frequencies; Gases; Goals; Heart; Hydrostatic Pressure; In Vitro; Intracranial Pressure; Lipids; Liquid substance; Measurement; Measures; Microbubbles; Microfluidics; Modeling; Monitor; Nature; Needles; Parameter Estimation; Patients; Pharmacological Treatment; Population; Portal Hypertension; Portal Pressure; Portal vein structure; Pre-Clinical Model; Property; Reference Standards; Research; Rheology; Risk; Signal Transduction; Surface; Techniques; Testing; Theoretical model; Translating; Variant; Water; Work; clinical care; clinical translation; cost; fabrication; improved; in vitro testing; in vivo Model; individual response; interfacial; interstitial; intravenous injection; meter; pressure; response; success; transmission process; treatment response; tumor; ultrasound

Project Summary The current clinical standard for quantifying fluid pressures relies on the invasive placement of pressure catheters or needles. These measures are costly and not without risk, thereby reducing how often data is collected. Ultrasound contrast agents (UCA) are gas-filled microbubbles that, when insontated at a fundamental frequency (f0), act as nonlinear oscillators, generating signal components ranging from the subharmonic (f0/2) through higher harmonics. The subharmonic amplitude of UCA exhibits a linear relationship with hydrostatic pressure, leading to the technique of subharmonic-aided pressure estimation (SHAPE). SHAPE optimizations to date have relied primarily on empirical evidence to identify optimal acoustic parameters and select a commercially available UCA. Currently, SHAPE provides up to 14 dB reduction in the subharmonic amplitude over a pressure increase of 180 mmHg (0.6 dB/kPa). Clinical trials using SHAPE for the diagnosis of portal pressures, cardiac pressures, and interstitial tumoral pressures during therapy have all shown success. However, large variations in SHAPE have been observed at lower fluid pressures, indicating a need to improve the technique's overall sensitivity. Using a variation of the Rayleigh–Plesset equation, our group and others have modeled the SHAPE response of individual commercial bubbles and identified potential sensitivities > 2 dB/kPa using optimized acoustic parameters. Thus, the potential exists to more than triple the current sensitivity of SHAPE, thereby greatly reducing the overall errors associated with lower pressure measurements. Monodisperse microbubbles can be created using either buoyancy separation of existing UCAs or microfluidic techniques. We hypothesize these agents will allow us to better refine previous modeling efforts, while also greatly improving the overall sensitivity of SHAPE by tailoring the UCA to its application. To support this hypothesis, we recently showed that monodisperse UCA nearly doubled the sensitivity of SHAPE (even without full acoustic optimization). This proposal will be a first step towards the long-term goal of translating SHAPE-specific UCA into clinical trials for improving the overall sensitivity of SHAPE as a noninvasive pressure estimation technique. As part of this application, we propose to test the in vitro sensitivity of SHAPE using monodisperse UCA using two fabrication approaches, to refine and validate our prior models of SHAPE with empirical evidence from monodisperse UCA, and finally, to determine the ability of a customized, monodisperse UCA to improve the sensitivity of SHAPE in in vivo models of cardiac pressures and portal hypertension. At the conclusion of this project, we will have developed and validated a SHAPE-specific UCA, capable of improving the sensitivity of SHAPE. These findings are expected to reduce the variability of SHAPE as a noninvasive clinical measure of fluid pressures, enabling safer and more available clinical care.

项目摘要 目前量化液体压力的临床标准依赖于压力的侵入性放置。 导管或针头。这些措施成本高昂，并不是没有风险，从而降低了数据传输的频率 收好了。超声造影剂(UCA)是一种充气的微泡，当在 基频(F0)，充当非线性振荡器，产生从 次谐波(f0/2)通过更高的谐波。UCA的次谐振幅值呈线性关系 在静水压力作用下，次谐辅助压力估计技术应运而生。 到目前为止，形状优化主要依靠经验证据来确定最佳声学 参数，并选择商业上可用的UCA。目前，SHAPE提供了高达14分贝的 压力增加180毫米汞柱(0.6分贝/千帕)时的亚谐振幅。使用SHAPE治疗的临床试验 治疗期间门脉压力、心脏压力和间质肿瘤压力的诊断都有 取得了成功。然而，在较低的流体压力下观察到形状的巨大变化，表明 需要提高这项技术的整体灵敏度。使用Rayleigh-Plesset方程的一个变体，我们的 该小组和其他人模拟了单个商业泡沫的形状反应，并确定了潜在的 灵敏度&gt；2分贝/千帕，使用优化的声学参数。因此，存在着超过三倍的潜力 SHAPE的电流灵敏度，从而大大减少了与较低压力相关的总体误差 测量。 可使用现有UCA的浮力分离或微流体产生单分散微泡 技巧。我们假设这些代理将允许我们更好地改进之前的建模工作，同时还 通过根据其应用定制UCA，极大地提高了SHAPE的整体灵敏度。为了支持这一点 假设，我们最近发现单分散UCA几乎使SHAPE的敏感度增加了一倍(甚至 没有完全的声学优化)。这项提议将是朝着翻译的长期目标迈出的第一步 将特定形状的UCA纳入临床试验，以提高SHAPE作为非侵入性治疗的整体敏感性 压力估算技术。作为这一应用的一部分，我们建议测试SHAPE的体外敏感性 使用使用两种制造方法的单分散UCA来改进和验证我们先前的形状模型 来自单分散UCA的经验证据，最后，确定定制的能力， 单分散UCA改善在体心压和门静脉模型中SHAPE的敏感性 高血压。在本项目结束时，我们将开发并验证特定于形状的UCA， 能够提高形状的灵敏度。这些发现有望降低SHAPE的可变性 作为液体压力的非侵入性临床测量，实现更安全和更可用的临床护理。