Development of Magnetic Particle Imaging

我的研究项目专注于开发技术，以推进细胞和分子成像（CMI），重点是成像细胞。CMI能够可视化和定量的细胞和分子事件在活的对象。CMI研究包括多种成像方式、细胞标记剂和标记技术。十多年来，我们的实验室一直在开发细胞磁共振成像（MRI）工具，使用超顺磁性氧化铁（SPIO）和氟-19 （19F）为基础的造影剂，用于许多重要应用。我们已经证明，基于spio的MRI细胞跟踪具有非常高的灵敏度（我们是世界上第一个证明单细胞检测的），但特异性较低。相比之下，我们的工作已经证明19F-MRI细胞跟踪具有高特异性，但灵敏度低。磁粉成像（MPI）是一种直接检测SPIO的新型成像方式。SPIO-MPI细胞跟踪可以克服基于mri的细胞跟踪的挑战，允许高灵敏度和高特异性的细胞检测。与19F细胞跟踪一样，MPI解决了铁基MRI细胞跟踪的特异性和定量问题。使用MPI，我们只能“看到”身体任何部位的示踪剂，与深度无关，没有来自背景组织或空气的信号，并且由于图像强度与示踪剂浓度呈线性关系，因此MPI是定量的。此外，MPI还解决了基于19F的细胞跟踪的灵敏度问题。目前MPI的检测限尚不清楚，但估计在体外约有200个标记细胞，在体内约有500个细胞。2019年7月，加拿大首个MPI系统（Momentum MPI扫描仪）在罗伯茨研究所安装。我的研究项目的首要主题是创新和推进细胞成像技术。我的长期目标是发现、开发和验证细胞跟踪技术，这些技术将改善和扩大监测和量化体内细胞命运的能力。这包括：(i)优化和实施新的MRI细胞跟踪方法，以改进细胞检测，（ii）实施互补的，多模态的细胞跟踪方法，（iii）细胞成像探针的表征，（iv）培养新一代跨学科的HQP，即“细胞和分子成像科学家”，他们在一系列成像模式方面具有专业知识。我的短期目标围绕着MPI作为一种敏感的、定量的细胞跟踪技术的发展，以补充我们的先进细胞成像方法。我们的具体目标是提高MPI的灵敏度和分辨率。为了实现这一目标，我们有以下目标：目的1：研究和优化MPI成像参数和细胞标记方法，以提高MPI对细胞的检测。目的2：为MPI开发、表征和测试不同的spio。

My research program is focused on developing technologies to advance cellular and molecular imaging (CMI) with an emphasis on imaging cells. CMI enables the visualization and quantitation of cellular and molecular events in living subjects. CMI research includes multiple imaging modalities, cell labeling agents and labeling techniques. Our lab has been developing cellular magnetic resonance imaging (MRI) tools for more than a decade using both superparamagnetic iron oxide- (SPIO) and fluorine-19 (19F)-based contrast agents for numerous important applications. We have shown that SPIO-based MRI cell tracking has very high sensitivity (we were first in the world to demonstrate single cell detection), but low specificity. Contrastingly, our work has demonstrated that 19F-MRI cell tracking has high specificity, but low sensitivity. Magnetic Particle Imaging (MPI) is a new imaging modality that directly detects SPIO. SPIO-MPI cell tracking could overcome the challenges of MRI-based cell tracking allowing for both high sensitivity and high specificity cell detection. Like 19F cell tracking, MPI addresses the specificity and quantitation issues of iron-based MRI cell tracking. With MPI we "see" only the tracer, anywhere in the body, independent of depth, and with no signal from background tissue or air, and it is quantitative since image intensity is linear with the tracer concentration. Furthermore, MPI also addresses the sensitivity issue of 19F based cell tracking. The current detection limit for MPI is unknown but it has been estimated at approximately 200 labeled cells in vitro and 500 cells in vivo. In July 2019, Canada's first MPI system, a Momentum MPI scanner, was installed at the Robarts Research Institute. The overarching theme of my research program is to innovate and advance cellular imaging technologies. My long term goal is to discover, develop and validate cell tracking technologies that will improve and expand capabilities for monitoring and quantifying the fate of cells in vivo. This includes: (i) optimization and implementation of novel MRI cell tracking methods for improved cell detection, (ii) implementing complementary, multi-modality approaches for cell tracking, (iii) characterization of cellular imaging probes and (iv) to train a new generation of interdisciplinary HQP known as "Cellular and Molecular Imaging Scientists." who have expertise in a range of imaging modalities. My short-term goals revolve around the development of MPI as a sensitive, quantitative cell tracking technique to complement our suite of advanced cellular imaging approaches. Our specific goal is to improve MPI sensitivity and resolution. To achieve this goal, we have the following aims: Aim 1: To investigate and optimize MPI imaging parameters and cell labeling methods for improving cell detection by MPI. Aim 2: To develop, characterize and test different SPIOs for MPI.