CAREER: Evaluating the distribution of bubble nuclei for acoustic cavitation in tissues

职业：评估组织中声空化气泡核的分布

• 批准号: 1943937
• 负责人: Julianna Simon
• 金额: $ 54.61万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1943937&HistoricalAwards=false
• 关键词: CAREER; Evaluating; distribution; bubble; nuclei

A major concern in every ultrasound application, such as fetal imaging, is acoustic cavitation (the creation, oscillation, and collapse of bubbles in an ultrasound field) because bubbles can damage tissues. In clinical ultrasound imagers, the risk is lessoned by requiring machines to display the mechanical index, which is a measure of the likelihood of cavitation. Yet therapeutic applications of ultrasound make use of acoustic cavitation to break kidney stones or destroy cancerous tissues. Acoustic cavitation arises from nucleation of bubbles, but no one understands what constitutes a bubble nucleus in human tissues and how these bubble nuclei might be influenced by certain diseases that deposit minerals in tissues. Thus, the overall goals of the project are to understand what constitutes a bubble nucleus in healthy tissues and to develop ultrasound to sensitively detect changes in bubble nuclei that occur when minerals are deposited in tissues. This research will provide a basis for developing an interactive classroom activity kit specifically designed to enhance the scientific interest and literacy of children, as well as educate graduate students from all disciplines on scientific communication and outreach, thereby increasing the societal impact of this work beyond what one scientist or lab can do on their own.The Investigator’s long-term career goal is to become a leader in bubble nucleation and acoustic cavitation in biological tissues. Toward this goal, the goal of this CAREER project is to improve the safety of diagnostic and therapeutic ultrasound by determining where bubble nuclei exist in tissues for acoustic cavitation. Using a combination of experimentation and modeling, the Research Plan is organized under three objectives. The FIRST Objective is to evaluate the distribution of bubble nuclei that can undergo acoustic cavitation in healthy biological structures (rat skeletal muscle, hepatocyte, and mammary cells) with varying hydrophobicity and mechanical properties. Studies are designed to test the hypothesis that acoustic cavitation will occur predominantly extracellularly, with increased acoustic cavitation occurring in a mechanically malleable extracellular matrix. Expected results include: 1) identification of whether bubble nuclei exist predominantly intracellularly or extracellularly in 2D and 3D cell culture; 2) evaluation of the effects of mechanical properties in collagen gels and decellularized extracellular matrix on the distribution of bubble nuclei; and 3) an improved metric for the likelihood of cavitation based on a bubble dynamics and fracture model. The SECOND Objective is to determine the effect of biomineralization on the distribution of bubble nuclei for diseases including atherosclerosis (cholesterol crystals), gout (uric acid crystals), heterotopic ossification (calcium phosphate) and breast microcalcifications (calcium oxalate). Studies are designed to test the hypothesis that all forms of pathological biomineralization will have stabilized crevice microbubbles isolated to the surface of the minerals. Expected results include: 1) an understanding of the distribution of bubble nuclei on lab-grown crystals; 2) an evaluation of the effects of surface tension on the distribution of bubble nuclei in lab-grown crystals; and 3) a determination of how the mineral deposition by cells in pathological biomineralization influence the distribution of bubble nuclei. The THIRD Objective is to develop the color Doppler ultrasound twinkling artifact for sensitive detection of mineral deposition through acoustic cavitation. The distribution of bubble nuclei in healthy and mineralized tissues from the first two objectives will be leveraged to improve the color Doppler ultrasound twinkling artifact for detection of all forms of mineralization including gout, atherosclerosis, heterotopic ossifications, breast microcalcifications and kidney stones. Studies are designed to test the hypothesis that crystal composition and the surrounding environment will influence the Doppler imaging protocols for optimal detection of each form of pathological biomineralization. Expected results include: 1) Doppler imaging protocols to enhance twinkling specific to each identified form of pathological biomineralization and 2) prediction of the crystal composition from the raw Doppler ultrasound signals. The results from this fundamental research will provide the first connection between all forms of pathological biomineralization – namely that stabilized crevice microbubbles are present after mineralization occurs and may even cause cells to revert to the diseased or mineral-depositing state.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在每一种超声应用中，例如胎儿成像，一个主要的问题是声空化(超声场中气泡的产生、振荡和崩溃)，因为气泡会损害组织。在临床超声成像仪中，通过要求机器显示机械指数来降低风险，机械指数是衡量空化可能性的指标。然而，超声波的治疗应用是利用声空化来粉碎肾结石或破坏癌症组织。声空化产生于气泡的成核，但没有人知道人类组织中气泡核的组成，以及这些气泡核可能如何受到某些疾病的影响，这些疾病会在组织中沉积矿物质。因此，该项目的总体目标是了解健康组织中气泡核的构成，并开发超声波来灵敏地检测当矿物沉积在组织中时气泡核发生的变化。这项研究将为开发专门用于提高儿童科学兴趣和素养的互动课堂活动套件提供基础，并对所有学科的研究生进行科学交流和拓展方面的教育，从而增加这项工作的社会影响，使其超出一名科学家或实验室自己所能做的范围。研究人员的长期职业目标是成为生物组织中气泡成核和声空化的领导者。为了实现这一目标，这个职业项目的目标是通过确定组织中存在声空化的气泡核的位置来提高诊断和治疗超声的安全性。采用实验和建模相结合的方法，将研究计划组织为三个目标。第一个目标是评估具有不同疏水性和机械性能的健康生物结构(大鼠骨骼肌、肝细胞和乳腺细胞)中可以经历声空化的气泡核的分布。研究旨在验证这一假设，即声空化将主要发生在细胞外，随着声空化增加发生在可机械延展的细胞外基质中。预期结果包括：1)在2D和3D细胞培养中确定气泡核主要存在于细胞内还是细胞外；2)评估胶原凝胶和脱细胞细胞外基质中的机械性能对气泡核分布的影响；以及3)基于气泡动力学和破裂模型改进了空化可能性的度量。第二个目标是确定生物矿化对动脉粥样硬化(胆固醇晶体)、痛风(尿酸晶体)、异位骨化(磷酸钙)和乳房微钙化(草酸钙)等疾病泡状核分布的影响。研究旨在验证这样一种假设，即所有形式的病理性生物矿化都会稳定隔离在矿物表面的裂隙微泡。预期的结果包括：1)了解实验室生长晶体上气泡核的分布；2)评估表面张力对实验室生长晶体中气泡核分布的影响；以及3)确定细胞在病理生物矿化中的矿物沉积如何影响气泡核的分布。第三个目标是开发彩色多普勒超声闪烁伪影，用于通过声空化灵敏地检测矿物沉积。前两个目标中的健康和矿化组织中气泡核的分布将被用来改进彩色多普勒超声闪烁伪影，以检测所有形式的矿化，包括痛风、动脉粥样硬化、异位骨化、乳房微钙化和肾结石。研究旨在检验这一假设，即晶体成分和周围环境将影响多普勒成像方案，以最佳地检测每种形式的病理生物矿化。预期的结果包括：1)多普勒成像方案，以增强每种已识别的病理生物矿化形式的闪烁；2)从原始的多普勒超声信号预测晶体成分。这项基础研究的结果将首次提供所有形式的病理性生物矿化之间的联系-即矿化发生后存在稳定的缝隙微气泡，甚至可能导致细胞恢复到患病或矿物质沉积状态。这一奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Effect of ambient gas and crystal features on Doppler ultrasound twinkling of pathological mineralizations

环境气体和晶体特征对病理矿化多普勒超声闪烁的影响

• DOI: 10.1121/10.0022511
• 发表时间: 2023
• 期刊: The Journal of the Acoustical Society of America
• 作者: Rokni, Eric;Simon, Julianna C.
• 通讯作者: Simon, Julianna C.

EVALUATION OF STONE FEATURES THAT CAUSE THE COLOR DOPPLER ULTRASOUND TWINKLING ARTIFACT

• DOI: 10.1016/j.ultrasmedbio.2021.01.016
• 发表时间: 2021-03-23
• 期刊: ULTRASOUND IN MEDICINE AND BIOLOGY
• 影响因子: 2.9
• 作者: Rokni, Eric;Zinck, Scott;Simon, Julianna C.
• 通讯作者: Simon, Julianna C.

The effect of crystal composition and environment on the color Doppler ultrasound twinkling artifact

• DOI: 10.1088/1361-6560/acb2ad
• 发表时间: 2023-01
• 期刊: Physics in Medicine & Biology
• 影响因子: 3.5
• 作者: Eric Rokni;J. Simon

The effects of elastic modulus and impurities on bubble nuclei available for acoustic cavitation in polyacrylamide hydrogels

• DOI: 10.1121/10.0016445
• 发表时间: 2022-12-01
• 期刊: JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
• 影响因子: 2.4
• 作者: Rawnaque，Ferdousi Sabera;Simon，Julianna C.
• 通讯作者: Simon，Julianna C.