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.

项目概要 当前量化流体压力的临床标准依赖于压力的侵入性放置 这些措施成本高昂且存在风险，从而降低了数据获取的频率。 超声造影剂 (UCA) 是充满气体的微泡，当以声波照射时，会产生微泡。 基频（f0），充当非线性振荡器，生成范围从 次谐波 (f0/2) 到高次谐波 UCA 的次谐波幅度呈现线性关系。 与静水压力，导致了次谐波辅助压力估计（SHAPE）技术。 迄今为止，SHAPE 优化主要依赖于经验证据来确定最佳声学效果 参数并选择市售 UCA 目前，SHAPE 可将噪声降低高达 14 dB。 使用 SHAPE 进行的临床试验显示压力增加 180 mmHg (0.6 dB/kPa) 时的次谐波振幅。 治疗期间门脉压、心脏压和间质肿瘤压的诊断均具有 然而，在较低的流体压力下观察到形状的巨大变化，这表明 需要使用瑞利-普莱塞方程的变体来提高技术的整体灵敏度。 小组和其他人对单个商业泡沫的 SHAPE 响应进行了建模，并确定了潜在的 使用优化的声学参数，灵敏度 > 2 dB/kPa 因此，有可能提高三倍以上。 SHAPE 的电流灵敏度，从而大大减少与较低压力相关的总体误差 测量。 单分散微泡可以使用现有 UCA 的浮力分离或微流体来产生 我们追求的这些代理将使我们能够更好地完善以前的建模工作，同时也 通过根据其应用定制 UCA，大大提高了 SHAPE 的整体灵敏度。 假设，我们最近表明单分散 UCA 几乎使 SHAPE 的灵敏度提高了一倍（甚至 没有全面的声学优化）。该提案将是实现翻译长期目标的第一步。 SHAPE 特异性 UCA 进入临床试验，以提高 SHAPE 作为无创治疗的整体敏感性 作为该应用的一部分，我们建议测试 SHAPE 的体外灵敏度。 使用单分散 UCA 和两种制造方法来完善和验证我们之前的 SHAPE 模型 根据单分散 UCA 的经验证据，最后确定定制的能力， 单分散 UCA 可提高心脏压力和门脉体内模型中 SHAPE 的敏感性 在该项目结束时，我们将开发并验证 SHAPE 特异性 UCA， 能够提高 SHAPE 的敏感性，这些发现有望减少 SHAPE 的变异性。 作为流体压力的无创临床测量，可实现更安全、更可用的临床护理。