Magnetic Resonance Chemical Exchange Saturation Transfer Imaging of Physiological Parameters

本研究计划的总体目标是开发新的磁共振成像（MRI）方法来绘制生物体的组织pH值。组织pH值调节许多细胞过程，在正常情况下受到严格控制。因此，pH值是细胞功能障碍和窘迫的敏感指标，特别是当正常功能所需的氧气不足时。目前，还没有高分辨率和高灵敏度的方法来绘制生物体内的pH值。最近，人们发现MRI造影剂可以被设计成产生依赖于组织pH的图像对比度。这些造影剂在溶液中可以很好地测量pH值，但在生物体中不能有效地工作，因为检测灵敏度降低了。我们最近开发了两种不同的测量组织ph的方法。一种利用造影剂信号的新方面，另一种使用在组织中自然发现的信号。然而，这两种方法都需要进一步的改进和优化才能充分发挥其潜力。我们将重点从三个方面提高图像质量。首先，我们将表征pH响应、温度响应和检测灵敏度，以及设计和合成的新试剂的物理性质，以改善pH映射。利用这些特性，我们将对药剂的反应进行数学建模，以确定我们是否可以预测它在组织中的工作效果。其次，我们将继续开发更有效的MRI采集方法和优化采集参数，以最大限度地提高组织对比度。我们将利用囊泡开发一个组织模型系统。囊泡系统将使我们能够控制囊泡内部和外部的空间，模拟组织中的细胞内和细胞外空间。最后，我们将使用西方核磁共振扫描仪检查我们的方法在不同磁场强度（9.4特斯拉，7特斯拉和3特斯拉）下的工作效果。体内高分辨率组织pH图谱将为生物体中进化的生物过程提供新的信息，为医学和制药工业的应用铺平道路。

The overall goal of this research program is to develop novel magnetic resonance imaging (MRI) methods to map tissue pH in living organisms. Tissue pH regulates many cellular processes and is tightly controlled under normal conditions. Therefore, pH is a sensitive indicator of cellular dysfunction and distress, particularly when there is insufficient oxygen for normal function. Currently, there are no methods to map pH in living organisms with high resolution and sensitivity. Recently, it was discovered that MRI contrast agents could be designed to generate image contrast that is dependent on tissue pH. These agents perform pH measurement well in solution, but don't work as effectively in living organisms because detection sensitivity is reduced. We have recently developed two different methods of measuring tissue pH. One utilizes a new aspect of the contrast agent signal, the other uses signals found naturally in tissue. However, both methods require further refinement and optimization to realize their full potential. We will focus efforts in three areas designed to improve image quality. First, we will characterize pH response, temperature response, and detection sensitivity, as well as the physical properties of new agents designed and synthesized to improve pH mapping. Using these properties, we will mathematically model the response of the agent to determine whether we can predict how well it will work in tissue. Second, we will continue to develop more efficient MRI acquisition methods and optimize acquisition parameters to maximize contrast in tissue. We will develop a model system of tissue using vesicles. The vesicle system will allow us to control the space inside the vesicle separately from the outside, mimicking the intracellular and extracellular space in tissue. Finally, we will examine how well our methods work at different magnetic field strengths (9.4 Tesla, 7 Tesla, and 3 Tesla) using MRI scanners that are available at Western. In-vivo high-resolution tissue pH mapping will provide new information about evolving biological processes in living organisms, paving the way for applications in medicine and the pharmaceutical industry.