CAREER: Interactions of Radiofrequency Electromagnetic Fields with Biological Tissue: New Tools to Address Challenges and Exploit Opportunities

非技术：尽管随着时间的推移，已经进行了大量的离体或原位动物测量，但对人体组织体内电特性分布的实验途径仍然非常有限，实际上，关于这些特性的起源和分布的基本问题已经困扰了科学家几十年。本CAREER提案的研究目标是基于磁共振成像系统获得的测量数据，开发、验证和推广一种可靠的、无创的组织电学特性横断面测绘的新方法。这将提供对组织中电磁（EM）场分布的洞察，在这个项目中，它将用于提高MR成像的诊断能力，但也可以显著提高速度和准确性，超过目前用于满足无线设备安全法规要求的基于探针的EM场映射方法。此外，体内电特性图可以作为癌症（和其他病理）的生物标志物，以及提高现有治疗方式的有效性，如射频（RF）消融、射频热疗和电化学疗法。首席研究员（PI）还期望电学性质的知识将为研究组织结构和功能提供一个重要的新窗口，并将为基础和应用研究提供一个丰富的新领域。这项建议的一个高度优先事项是教育和研究活动的整合。PI将开发提供实践培训活动的新课程，并将指导和激励学生进行研究。不同层次和年级的学生将学习如何在各个学科之间建立广泛的联系，包括电动力学、物理学、生物医学工程和医学等概念。PI将公开发布各种软件和教程，预计将产生新的研究项目，并对其他机构的教育和培训产生影响。技术：该项目旨在扩展对电磁场与生物组织相互作用的一般理解，以显着提高高场磁共振成像性能。麦克斯韦方程组规定了物体的电导率和介电常数与施加在该物体上的电磁场曲率之间的关系。“局部麦克斯韦层析成像”（LMT）是最近推出的一项技术，它利用基于磁共振的局部场曲率测量来推导未知的电性分布，有效地反演麦克斯韦方程。该项目将建立一种新的通用的LMT技术，该技术允许高空间分辨率的地图，并考虑实际体内利用的电特性边界。这将用于广泛的应用，如：i)开发技术，首次允许在磁共振成像中进行局部射频功率沉积监测和预测；ii)设计定制的射频脉冲，实现对MR信号轮廓和本地射频功率分布的实际控制；iii)创建新颖的射频线圈类型和设计概念，使用理论上最优性能的电动力学模拟作为指导。体内实验将集中于收集脑组织类型电特性的高分辨率体内信息。这一信息目前还无法获得，但预计会对各个领域（如经颅磁刺激）的研究人员产生兴趣。作为未来研究的先导，PI将开始研究观察到的电磁对比的生物学基础。因为，根据测量频率，介电常数和电导率被认为代表了组织细胞度、细胞膜完整性和含水量的某种组合，电导率图像与自旋密度MR图像之间的相关性程度将被评估，以开始梳理出这种混合物的一些成分。

Abstract Nontechnical:Although numerous ex vivo or in situ animal measurements have been made over time, experimental access to in vivo electrical property distributions of human tissue have remained extremely limited, and indeed fundamental questions regarding the origin and distribution of these properties have tantalized scientists for decades. The research objective of this CAREER proposal is to develop, validate and disseminate a new method for reliable, non-invasive cross-sectional mapping of tissue electrical properties, based on measurements obtained with magnetic resonance (MR) imaging systems. This will provide insight on the distribution of electromagnetic (EM) fields in tissue, which in this project will be used to improve the diagnostic power of MR imaging, but could also enable marked improvement in speed and accuracy over current probe-based EM field mapping approaches used to satisfy safety regulatory requirements for wireless devices. Furthermore, in vivo electrical properties maps could be employed as biomarkers for cancer (and other pathologies), as well as to improve the effectiveness of existing therapeutic modalities, such as radiofrequency (RF) ablation, RF hyperthermia and electrochemotherapy. The Principal Investigator (PI) also expects that knowledge of electrical properties will provide an important new window into tissue structure and function, and will represent a rich new area for basic and applied research. A high priority of this proposal is the integration of educational and research activities. The PI will develop new courses that offer hands-on training activities, and will mentor and motivate students in research. Students at various levels and grades will learn how to make broad connections across disciplines, embracing concepts from electrodynamics, physics, biomedical engineering and medicine. The PI will publicly release a variety of software and tutorials, which is expected to generate new research projects and have an impact in education and training at other institutions. Technical:This project aims at extending general understanding of the interactions of EM fields with biological tissue, in order to dramatically improve high-field MR imaging performance. Maxwell's equations dictate the relationship between the electrical conductivity and permittivity of a body and the curvature of electromagnetic fields applied to that body. "Local Maxwell Tomography" (LMT) is a recently introduced technique that uses MR-based measurements of local field curvature to derive unknown electrical property distributions, effectively inverting Maxwell's equations. This project will establish a new generalized LMT technique that allows for high spatial resolution maps and accounts for boundaries of electrical properties for practical in vivo utilization. This will be employed for a wide range of applications, as: i) develop techniques to allow for the first time local RF power deposition monitoring and prediction in MR imaging; ii) engineer tailored RF pulses that enable practical control of MR signal profile and local RF power distribution; iii) create novel RF coil types and design concepts, using electrodynamic simulations of the theoretically optimal performance as a guideline. In vivo experiments will focus on collecting high-resolution in vivo information on electrical properties of brain tissue types. This information, currently not available, is expected to be of interest to researchers in a variety of fields (e.g, transcranial magnetic stimulation). As a lead-in to future studies, the PI will begin to investigate the biological basis of observed electromagnetic contrast. Since, depending upon the measurement frequency, permittivity and conductivity are believed to represent some combination of tissue cellularity, cell membrane integrity, and water content, the degree of correlation between conductivity images with spin-density MR images will be assessed to begin to tease out some of the components of this mixture.