Development of Quantitative In Vivo Cellular and Molecular MR Imaging Techniques

问题所在 关于细胞和分子在体内的行为，有许多重要的但尚未解答的生物学问题。尽管研究人员已经使用尖端工具发现了大量信息，将单个细胞向下映射到基因组，但在许多情况下，我们仍然不了解整个细胞群体实际上是如何在体内相互作用和行为的。已经开发了几种成像技术，可以在体内随着时间的推移监测细胞，但提供最高质量图像的技术只会产生定性信息，限制了我们的观察。 目前还没有现有的成像技术可以在体内提供非侵入性的、可以长时间测量的定量信息。定量信息至关重要，可以让我们评估细胞和分子如何迁移到身体不同区域的微妙变化，以应对各种类型的外部扭曲，如疾病和药物。这些信息将对各种生物学过程产生有价值的见解，特别是在免疫学领域，在该领域，有许多类型的细胞具有非常复杂的相互作用，如癌症。 解决方案 磁共振成像(MRI)是一种众所周知的成像技术，它能够对从人体组织到混凝土的各种材料成像。它还可以用来跟踪单个细胞和分子，这些细胞和分子已经被对比剂标记。该计划将开发和评估基于MRI的超顺磁性氧化铁(SPIO)标记生物制剂的定量测量方法。 对于SPIO标记细胞的量化，我计划的第一部分将涉及开发和评估一种名为TurboSPI的新MRI方法。我将努力提高这项技术的成像速度和定量准确性，使其能够在生物系统中使用，因为它可以为我们提供重要信息，不仅可以确定铁的浓度，而且还可以确定细胞数量和总体积。 对于多肽等SPIO标记分子的定量，我建议开发一种新的定量序列，该序列基于一种令人兴奋的新技术，称为磁共振指纹分析(MRF)，并结合已被证明对SPIO标记细胞具有高度敏感性的方法。这项技术将允许生成几个MRI参数图，从而能够准确量化SPIO标记的分子，以及潜在的细胞。 影响 这项研究计划描述了一系列连贯的项目，这些项目将开发和验证用于使用MRI对SPIO标记的单个细胞和分子进行量化的新工具。这项工作将产生先进的成像技术，可以广泛应用于许多生物学领域，并可以提高我们对基本免疫学行为的理解，特别是在癌症治疗方面。

The Problem There are a number of important yet unanswered biological questions about how cells and molecules behave in the body, i.e. in vivo. Although researchers have discovered a large amount of information using cutting edge tools to map individual cells down to the genome, in many cases we still don’t understand how overall cell populations actually interact and behave in the body. Several imaging techniques have been developed that allow monitoring of cells over time in vivo, but the techniques that offer the best quality images only result in qualitative information, limiting our observations. There are no existing imaging technologies to provide non-invasive, quantitative information in the body that can be measured over long periods of time. Quantitative information is essential to allow us to evaluate subtle changes in how cells and molecules migrate to different areas around the body in response to various types of external distortions like diseases and drugs. This information will yield valuable insight into a variety of biological processes, particularly in the field of immunology, where there are a number of types of cells with very complex interactions, such as cancer. The Solution Magnetic resonance imaging (MRI) is an imaging technique well known for its ability to image a large variety of materials, from human tissue to concrete. It can also be used to track individual cells and molecules that have been labeled with a contrast agent. This program will develop and evaluate MRI-based quantitative measures of biological agents tagged with superparamagnetic iron oxide (SPIO). For quantification of SPIO-labeled cells, the first part of my program will involve developing and evaluating an novel MRI method called TurboSPI. I will be working to increase imaging speed and quantitative accuracy of this technique to enable its use in biological systems, as it could give us important information on determining not only concentrations of iron, but cell number and total volume. For the quantification of SPIO-labeled molecules such as peptides, I am proposing the development of a novel quantitative sequence based on an exciting new technique called magnetic resonance fingerprinting (MRF) combined with a method that has already been shown to have high sensitivity to SPIO-labeled cells. This technique will allow the generation of several MRI parameter maps, allowing accurate quantification of SPIO-labeled molecules, and potentially cells as well. Impact This program of research describes a coherent sequence of projects that will develop and validate novel tools for use in quantification of individual cells and molecules labeled with SPIO using MRI. This work will result in advanced imaging technologies that can be broadly applied in a number of biological fields and can improve our understanding of basic immunological behavior, particularly with respect to cancer therapies.