Triple Imaging with PARASHIFT Probes

磁共振成像(MRI)为人体提供了一个窗口，报告体内组织中水的相对分布。核磁共振扫描用于临床诊断，每年有1亿次检查，其中40%使用造影剂，给患者增强图像清晰度，帮助放射科医生解释观察到的扫描。扫描仪被调到水氢原子核共振的频率。这位于射频范围内。我们将开发一系列可以与水信号同时观察的造影剂。这些基于稀土金属络合物的造影剂具有强烈的报告质子信号，可以在远离水信号的地方观察到，通常是10到20 kHz，允许他们进行选择性观察。通过仔细设计它们的分子结构，探针的共振频率不仅可以对局部温度敏感，还可以对其他生理参数敏感，如pH或局部细胞外钠浓度。通过同时给药，两种不同金属的稀土络合物(如Tu/Dy或Er/Tb)，每个探头定位在身体的同一区域，它们的移位信号可以与水信号同时观察到。这被称为三重成像实验，通过测量例如肝脏或肾脏的两个探针频率，可以评估所研究的感兴趣区域的温度和pH。一般来说，肝脏或肾脏的局部体温升高是疾病的指标，特别是炎症，如肝炎或肝纤维化。类似地，细胞外pH的改变表明组织缺血，这在许多血流受限的疾病中都会发生，例如冠心病和终末期肾脏疾病。这种“三重成像”方法的一个关键方面是，新的造影剂可以在相对较低的浓度下被检测到，而且使用起来是安全的。这些水平处于目前批准的基于环状结构的Gd造影剂的范围内，自1988年以来一直在临床使用。这种增强的灵敏度源于报告质子信令组与嵌在造影剂内的磁性金属中心的接近：信号采集序列可以加快，从而允许信号强度的采集速度比其他方式快约20倍。

Magnetic resonance imaging (MRI) affords a window to the human body reporting the relative distribution of water in tissues within the body. MRI scans are used for clinical diagnosis with 100 million examinations per year, wherein 40% use a contrast agent that is given to the patient to enhance image clarity, aiding the radiologist in interpreting the scans observed. The scanner is tuned to the frequency where the water hydrogen nuclei resonate. This lies in the radiofrequency range. We will develop a series of contrast agents that can be simultaneously observed with the water signal. These contrast agents, based on rare earth metal complexes, possess an intense reporting proton signal that can be observed far away from the water signal, typically 10 to 20 kHz away, allowing their selective observation. By carefully designing their molecular structure , the probe resonant frequency can be made to be sensitive not only to local temperature but also to other physiological parameters, such as pH or the local extracellular concentration of sodium. By administering at the same time, two rare earth complexes with different metals (such as thulium/dysprosium or erbium/terbium), each probe localises to the same region of the body and their shifted signals can be observed simultaneously with the water signal. This is termed a triple imaging experiment, and by measuring the two probe frequencies in, for example, the liver or the kidney, both the temperature and the pH can be assessed in the region of interest that is studied. In general, local temperature increases in the liver or kidney are indicators of disease, especially inflammation, as occurs in hepatitis or fibrosis of the liver. Similarly, altered extracellular pH is indicative of tissue ischaemia as occurs in many diseases where blood flow has been restricted , e.g. coronary heart disease and end stage renal disease. A key aspect of this 'triple imaging' approach is that the new contrast agents can be detected at relatively low concentration, and at levels that are safe to use. These levels lie within the current range of the approved gadolinium contrast agents based on a cyclic ring structure that have been used clinically since 1988. This enhanced sensitivity arises from the closeness of the reporting proton signalling group to a magnetic metal centre that is incarcerated within the contrast agent: the signal acquisition sequence can be speeded up, allowing signal intensity to be acquired about 20 times faster than otherwise possible.