A resource for magnetic resonance and opitcal imaging

描述（由申请人提供）：我校生物医学技术研究中心（BTRC）的使命是为生物医学研究开发创新的磁共振和光学成像技术。在本研究的竞争性补充中，我们请求支持开发用于测量心肌中肌酸激酶（CK）代谢的新型成像技术。心脏病是美国人死亡的主要原因，2010年的医疗费用高达3160亿美元。与CK反应相关的分子变化在心肌能量学中起着至关重要的作用。CK代谢的无创成像有可能在疾病过程的各个阶段识别冠状动脉疾病患者。具体来说，组织CK代谢物可以作为临床上有用的生物标志物，用于衰竭心脏的能量剥夺和局部缺血损伤的生存能力。目前，有31种P和1h磁共振波谱（MRS）方法用于测量CK代谢；然而，这些方法固有的局限性是低分辨率和较长的采集时间。因此，本提案的总体目标是解决这些代谢物体内高分辨率成像的未满足需求。具体来说，我们利用CK代谢物上胺质子交换率的差异来开发一类新的MR成像技术来空间绘制心肌肌酸（Cr）。探讨了化学交换饱和转移（CrEST）和交换增强弛豫时间（施加）对散装水的影响。两种方法的理论设计和实验验证都将在生理幻影和心肌组织上进行。整合心脏和呼吸门控方案的时间高效MRI脉冲序列将开发并实施体内应用。这些发展将由我们的合作者的两个驱动生物医学项目（DBP）推动，作为拟议开发和验证的试验台。一旦得到验证，该技术将为正在进行的dbp研究中的高能磷酸盐代谢测绘提供无创成像分析。这些方法不涉及任何辐射，也不需要任何外源性造影剂。与传统的MRS相比，它们提供了2个量级的灵敏度优势，并且可以很容易地在临床环境中实施。本建议的目标的成功实现将导致评估心肌代谢的分子成像技术，这将有很大的潜力来提高病人的护理。

DESCRIPTION (provided by applicant): The mission of our Biomedical Technological Research Center (BTRC) is to develop innovative magnetic resonance and optical imaging technologies for biomedical research. In this competitive supplement to our grant, we are requesting support for developing novel imaging technologies for measuring creatine kinase (CK) metabolism in the myocardium. Heart disease is the leading cause of death in the US with $316 billion in healthcare costs in 2010. The molecular changes associated with the CK reaction play vital role in the myocardial energetics. Noninvasive imaging of CK metabolism has the potential to identify patients with coronary artery disease at various stages in the disease process. Specifically, the tissue CK metabolites may serve as clinically useful biomarkers for the energy deprivation in the failing heart and local viability in ischemic injury. Currently, 31 P and1 H magnetic resonance spectroscopy (MRS) methods are used to measure CK metabolism; however, the inherent limitations of these methods are low resolution and long acquisition times. Accordingly, the overarching goals of this proposal are to address this unfulfilled need for high resolution imaging of these metabolites in vivo. Specifically, we exploit the differences in exchange rates of amine protons on CK metabolites to develop a novel class of MR imaging techniques to spatially map myocardial creatine (Cr) in this proposal. The effects of chemical exchange saturation transfer (CrEST) and exchange enhanced relaxation times (EXERT) on bulk water will be explored. Both theoretical design and experimental validation of both methods will be carried out on physiological phantoms and myocardial tissue. Time efficient MRI pulse sequences that integrate cardiac and respiratory gating schemes will be developed and implemented for in vivo applications. These developments will be driven by two driving biomedical projects (DBP) from our collaborators that serve as test beds for the proposed development and validation. Once validated, the techniques will provide noninvasive imaging assays for mapping high-energy phosphate metabolism in the ongoing studies of the DBPs. These methods neither involve any radiation nor require any exogenous contrast agents. They provide ~2 orders of sensitivity advantage over conventional MRS and can be readily implemented in a clinical setting. Successful accomplishment of the aims of this proposal will lead to molecular imaging techniques for assessing myocardial metabolism, which would have great potential to enhanced patient care.