Iron Based Coupling Media (IBCM) for MRI-guided Transcranial Ultrasound Surgeries

项目摘要/摘要 致命性或损害性神经系统疾病，包括运动障碍、脑癌、心理疾病 精神障碍、癫痫、畸形和记忆障碍，给个人和 整个社会。经颅磁共振引导的聚焦超声手术是一种 非常有希望的，微创的神经系统疾病的治疗方式，声波 集中在大脑的特定区域。因为它是无创的，所以tMRgFUS手术的疗效 在很大程度上依赖于制导技术的准确性和信息量。 这项研究建议通过消除一种治疗方法来提高几乎所有tMRgFUS手术的疗效。 准确和信息丰富的引导磁共振成像普遍存在的障碍：声学耦合媒介。 耦合介质和引导成像之间的相互作用阻碍了tMRgFUS的效果和翻译。为 例如，虽然FDA批准的tMRgFUS治疗特发性震颤和帕金森病可以依赖于 实时患者反馈以补偿引导MR成像中的错误，其他tMRgFUS适应症无法 访问患者反馈，因为患者处于昏迷状态，或者是治疗错误的后果 几天后才出现。在这些情况下，由耦合槽施加的制导成像误差不能 代偿降级治疗效果 为了满足这一需求，我们的研究提出了一种稀释的铁基耦合介质(IBCM)，它将消除耦合- 在保持耦合和冷却功能至关重要的同时，MRI引导成像中的介质引起的误差 到声学传输。本研究的具体目的如下。 目的1：研制用于IBCM的新型表面修饰纳米氧化铁。稀释，含水，表面- 经过修饰的氧化铁纳米颗粒可以加速MRI信号的衰减，从而在图像采集期间， 耦合介质对制导成像的影响可以忽略不计。然而，含水纳米颗粒也 凝聚和种子处理--阻止震源前声场中的空化成核。这一目标将 开发新型表面修饰颗粒，悬浮时加速MRI信号衰减，而不需要 促进焦前成核。 目的：研究IBCM悬浮液性质对空化成核的影响。流体 特性在颗粒悬浮、声学耦合、对象冷却和空化中起着关键作用 成核作用。这一目标将研究IBCM内的空化成核以及悬浮液的性质， 如pH、温度、气体含量和流动状态，可以改变或抑制成核过程，而 保持悬浮、耦合和冷却能力。 目的3：通过使用IBCM增强MRI对tMRgFUS的指导作用。这一目标将把价值量化 在AIMS 1和AIMS 2中为tMRgFUS设计的IBCM通过测量来自制导的图像质量度量 人类受试者的核磁共振扫描。这一目标还将开发新的MRI引导技术，这些技术以前是 由于声学耦合介质造成的严重图像损坏而不可能实现。 由此产生的IBCM将改善在过程中或正在进行的几乎所有制导技术的图像质量 TMRgFUS的开发，通过使声学耦合介质对MRI扫描仪不可见而不 牺牲了必要的声学耦合和冷却功能。

Project Summary/Abstract Fatal or impairing neurological diseases, including movement disorders, brain cancers, psychological disorders, epilepsies, malformations, and memory disorders, impose heavy burdens on both individuals and society at large. Transcranial magnetic resonance guided focused ultrasound surgery (tMRgFUS) is an extremely promising, minimally invasive treatment modality for neurological diseases whereby sound waves are focused to a specific region of the brain. Because it is noninvasive, the efficacy of tMRgFUS procedure heavily relies on the accuracy and information content of the guidance technology. This study proposes to improve the treatment efficacy of nearly all tMRgFUS surgeries by eliminating a ubiquitous impediment to accurate and information-rich guidance MRI: the acoustic coupling medium. Interactions between the coupling media and guidance imaging impede tMRgFUS efficacy and translation. For example, while FDA-approved tMRgFUS treatments for essential tremor and Parkinson’s disease can rely on real-time patient feedback to compensate for errors in guidance MR imaging, other tMRgFUS indications cannot access patient feedback because either the patient is unconscious, or the consequences of treatment errors appear only days later. In these cases, guidance imaging errors imposed by the coupling bath cannot be compensated and degrade treatment efficacy To meet this need, our study proposes a dilute, iron-based coupling media (IBCM) that will eliminate coupling- media-induced errors in MRI guidance imaging while maintaining the coupling and cooling functionality critical to acoustic transmission. The specific aims of the study are as follows. Aim 1: Develop novel surface–modified iron oxide nanoparticles for an IBCM. Dilute, aqueous, surface- modified iron oxide nanoparticles can accelerate MRI signal decay such that, during image acquisition, a coupling medium will contribute negligible effects to guidance imaging. However, aqueous nanoparticles also agglomerate and seed treatment-impeding cavitation nucleation in the prefocal acoustic field. This aim will develop novel surface-modified particles that, upon suspension, accelerate MRI signal decay without promoting prefocal nucleation. Aim 2: Investigate the effects of IBCM suspension fluid properties on cavitation nucleation. Fluid properties play a critical role in particle suspension, acoustic coupling, subject cooling, and cavitation nucleation. This aim will investigate cavitation nucleation within the IBCM and how suspension fluid properties, such as pH, temperature, gas content, and flow state, can modify or suppress the nucleation process while maintaining suspension, coupling, and cooling capabilities. Aim 3: Enhance MRI guidance for tMRgFUS through the use of an IBCM. This aim will quantify the value of the IBCM designed in Aims 1 and 2 for tMRgFUS by measuring image quality metrics derived from guidance MRI scans of human subjects. This aim will also develop novel MRI guidance techniques that were previously rendered impossible due to severe image corruptions imposed by the acoustic coupling medium. The resulting IBCM will improve image quality for nearly all guidance techniques employed during, or undergoing development for, tMRgFUS, by rendering the acoustic coupling medium invisible to the MRI scanner without sacrificing necessary acoustic coupling and cooling functionality.