Imaging Methods of Tissue Physiology

在过去的十年里，磁共振已经成为最通用的成像技术之一，这主要是因为它不仅能够可视化形态特征，而且由于它可以描绘生物物质和其他材料的功能状态。我们感兴趣的是通过利用这些代谢物的氢与水氢交换的倾向来描述代谢物的分布，这被称为化学交换饱和转移(CEST)效应。*研究计划*本建议制定了一项研究计划，以研究化学交换饱和转移效应，表征其使用的物理化学条件，并开发生物物质成像的方法学。这项建议侧重于通过创造新的非侵入性成像技术来确定生物组织状态的更大研究努力的三个方面。*研究挑战*？各种生物相关化学物质(如酰胺、胺和糖)中化学交换氢的交换速率对重要的组织环境因素非常敏感，如温度、pH和细胞微结构。我们将量化和验证CEST光谱的pH敏感性，以研究肿瘤组织微环境的变化。*我们将开发动态成像序列，随着组织对药物的给药反应，在体内跟踪CEST对比度。实施这种动态实验所需的工具是加快数据采集的方案。此外，充分利用这种多维数据集中包含的信息的分析技术。在过去，我们的实验室已经成功地使用贝叶斯数据分析技术来阐明组织增强曲线中包含的信息的限制，因为小分子药物分布在其血管系统中。我们将更进一步，调整我们的分析工具，以设计出合成动态对比增强的化学交换转移饱和实验的实验结果的方法。*另一个有希望的研究途径是使用具有理想性能的试剂，这些试剂非常适合在拟议的化学交换饱和转移实验中使用。这些试剂具有交换的质子，其化学位移与大多数质子的化学位移相去甚远，因此即使是非常宽的带宽饱和方案也可以清楚地识别。*一个相关但不同的项目是肿瘤模型中治疗干预响应的表观扩散系数的时间演变。早期迹象表明，表观扩散系数可能会有一过性的下降，其生物物理基础可能会导致对肿瘤组织走向坏死命运的深入了解。**

Introduction***MR has emerged as one of the most versatile imaging techniques over the past decade largely due to its ability to visualize not just morphological features but due to its promise for depicting the functional state of biological matter and other materials. We are interested in depicting metabolite distributions by exploiting the propensity of these metabolites' hydrogens to exchange with the water hydrogens referred to as the Chemical Exchange Saturation Transfer (CEST) effect.******Program of Research ***This proposal lays out a program of research to investigate the chemical exchange saturation transfer effect, to characterize the physico-chemical conditions for its use and to develop the methodology for imaging biological matter. This proposal is focussed on three aspects of a larger research effort to determine the status of biological tissues through the creation of new non-invasive imaging technologies. ******Research Challenges***?Exchange rates of chemically exchanging hydrogens in a variety of biologically relevant chemicals such as amides, amines, and sugars are sensitive to important tissue-environmental factors such as temperature, pH, and cellular microstructure. We will quantify and validate the pH sensitivity of CEST spectra so as to study changes in tumour tissue microenvironment. ******We will develop dynamic imaging sequences to follow CEST contrast through time in vivo as tissue responds to drug administration. Tools required for implementation of such dynamic experiments are schemes to speed up the data acquisition. Further, analysis techniques that fully exploit the information contained in such multi-dimensional data sets. In the past, our lab has had success using Bayesian data analysis techniques to elucidate the limits of information contained in tissue enhancement curves as small-molecular agents distribute in its vasculature. We will take this further and adapt our analytical tools to devise means of synthesizing experimental results from chemical exchange transfer saturation experiments with dynamic contrast-enhanced.******One further promising avenue of research is the use of agents with properties that are ideally suited to the use in the proposed chemical exchange saturation transfer experiments. These agents possess exchanging protons whose chemical shift is far from that of most protons and hence allows a clear identification with even very wide-bandwidth saturation schemes.******One related but distinct project is the temporal evolution of apparent diffusion coefficients in response to treatment intervention in tumour models. Early indications are that there can be a transient decrease of apparent diffusion coefficients the biophysical basis of which might lead to insights into the progression to a necrotic fate in tumour tissue.**