Magnetic Particle Imaging for High-Resolution Functional Brain Imaging

用于高分辨率功能性脑成像的磁粒子成像

• 批准号: 10007168
• 负责人: STEVEN M CONOLLY
• 金额: $ 81.51万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10007168
• 关键词: Animals; BRAIN initiative; Back; Blood Vessels; Blood capillaries; Brain; Brain imaging; Breathing; Cardiac; Chronic Kidney Failure; Collaborations; Core-Binding Factor; Development; Development Plans; Discipline of Nuclear Medicine; Dose; Electroencephalography; Electromagnetics; Electronics; Functional Imaging; Functional Magnetic Resonance Imaging; Gadolinium; Goals; Half-Life; Heating; Hour; Human; Hypercapnia; Image; Imaging Device; Imaging Techniques; Imaging technology; Inflammatory; Iodine; Label; Magnetic Resonance Imaging; Magnetism; Maps; Measurement; Medical Imaging; Methods; Motion; Neurosciences; Noise; North America; Patients; Penetration; Peripheral Nerve Stimulation; Physics; Physiological; Positron-Emission Tomography; Process; Publishing; Radiation; Radionuclide Imaging; Regulation; Reporter; Research; Resolution; Rodent; Rodent Model; Roentgen Rays; Safety; Scanning; Signal Transduction; Study of magnetics; Tissues; Tracer; Translations; Traumatic Brain Injury; United States National Institutes of Health; X-Ray Computed Tomography; absorption; biomaterial compatibility; cerebral blood volume; cost; data acquisition; design; fluorescence imaging; high resolution imaging; human tissue; imaging modality; imaging study; imaging system; improved; in vivo evaluation; innovation; insight; iron oxide; neuroimaging; next generation; novel; novel strategies; optogenetics; particle; perfusion imaging; response; safety study; single photon emission computed tomography; spatiotemporal; superparamagnetism; tomography

Project Summary / Abstract Magnetic Particle Imaging (MPI) is a novel tomographic imaging modality, with unprecedented contrast, depth of penetration and sensitivity (1 micromolar sensitivity today; 100 nM soon). MPI is only being actively researched in a few labs in North America, and in a dozen labs in the EU. Still, MPI already competes with nuclear medicine in terms of dose-limited sensitivity, and already surpasses scintigraphy in terms of safety (zero radiation), convenience (no “hot” labeling) and reporter persistence (infinite duration magnetization instead of half life limited to hours or days). Prof. Conolly's lab at UC Berkeley and his lab's startup company (Magnetic Insight, Alameda CA) have designed and built nearly all the high-resolution MPI scanners now in North America. MPI tracers (superparamagnetic iron oxides, SPIOs) are safe for human use, and some are already approved for human use by the FDA. It is believed that SPIO tracers are safer for chronic kidney disease (CKD) patients than the standard angiographic tracers, Iodine (X-ray and X-ray CT) and Gadolinium (MRI). This proposal is in response to the BRAIN initiative goal to develop new imaging systems that use disruptive, new approaches to dramatically improve spatiotemporal resolution of current human neuroimaging. The physics of MPI offers unprecedented vascular contrast at the capillary level with no background tissue clutter, because human tissues produce zero MPI signal and are completely transpar- ent. The absence of a background signal could reduce physiologic noise significantly. We have already studied the brain vascular response to hypercapnia, neuro-inflammatory processes in traumatic brain injury (TBI), and performed the world's first (unpublished) CBF/CBV measurements in a rodent model. The only significant physical weakness holding MPI back from human translation is its poor spatial reso- lution, now about 1.4 mm in a small animal. The resolution in MPI is determined entirely by two parameters: the tracer magnetic resolution (typically 10 mT), and the selection field gradient (roughly 7 T/m), leading to roughly 10 mT/(7 T/m) ⇡ 1.4 mm resolution. FDA electromagnetic safety constraints (dB/dt and SAR) preclude us from increasing the gradient strength further. Hence, to make MPI safe and high resolution, we must develop far higher resolution MPI tracers. Here we introduce a dramatic advance in MPI technology, which we call strong interacting MPI (siMPI), which has experimentally demonstrated 10-fold resolution im- provement, with 1 mT magnetic resolution. The impact of the tracer resolution improvement will be nothing short of revolutionary: siMPI could reduce the cost of human MPI scanners by 100-fold and improve sensitivity per gram of tracer by 10-fold! Moreover, siMPI will permit MPI scanning with dramatically mit- igated FDA electromagnetic safety concerns (dB/dt and SAR). In short, siMPI is precisely disruptive new approach to dramatically improve spatiotemporal resolution of a current neuroimaging method. 2

项目总结/摘要 磁粒子成像（MPI）是一种新型的断层成像模式，具有前所未有的对比度， 渗透深度和灵敏度（目前灵敏度为1微摩尔;即将达到100 nM）。MPI只是 在北美的几个实验室和欧盟的十几个实验室中进行了积极的研究。尽管如此，MPI已经 在剂量限制敏感性方面与核医学竞争，并且在 安全性（零辐射）、便利性（无“热”标签）和报告者持久性（有限持续时间 磁化而不是半衰期限于数小时或数天）。康诺利教授在加州大学伯克利分校的实验室和他的实验室 一家初创公司（Magnetic Insight，阿拉米达CA）已经设计并制造了几乎所有的高分辨率 MPI扫描仪现在在北美。MPI示踪剂（超顺磁性氧化铁，SPIO）对 人类使用，有些已经被FDA批准用于人类使用。据信SPIO示踪剂 对于慢性肾脏病（CKD）患者，比标准血管造影示踪剂碘（X射线）更安全 和X射线CT）和钆（MRI）。 该提案是为了响应BRAIN倡议的目标，即开发新的成像系统， 颠覆性的新方法，以显着提高当前人类的时空分辨率 神经成像MPI的物理特性在毛细血管水平提供了前所未有的血管对比度， 背景组织杂波，因为人体组织产生零MPI信号并且完全透明， 树人没有背景信号可以显著减少生理噪声。我们已经 研究了创伤性脑损伤后高碳酸血症时的脑血管反应、神经炎症过程 (TBI)，并在啮齿动物模型中进行了世界上第一次（未发表）CBF/CBV测量。 阻碍MPI进行人类翻译的唯一明显的物理弱点是其糟糕的空间分辨率。 lution，现在约1.4毫米的小动物。MPI中的分辨率完全由两个参数决定： 示踪剂磁分辨率（通常为10 mT）和选择场梯度（约为7 T/m）， 到大约10 mT/（7 T/m）× 1.4 mm分辨率。FDA电磁安全限制（dB/dt和SAR） 阻止我们进一步增加梯度强度。因此，为了使MPI安全和高分辨率，我们 必须开发更高分辨率的MPI示踪剂。在这里，我们介绍了MPI技术的一个巨大进步， 我们称之为强相互作用MPI（siMPI），它已经在实验上证明了10倍的分辨率， 磁分辨率为1 mT。示踪剂分辨率提高的影响将是微不足道的 缺乏革命性：siMPI可以将人类MPI扫描仪的成本降低100倍， 每克示踪剂的灵敏度提高了10倍此外，siMPI将允许MPI扫描与显着mit- FDA电磁安全问题（dB/dt和SAR）。简而言之，siMPI是一种颠覆性的新技术， 这是一种显著提高当前神经成像方法的时空分辨率的方法。 2