Moving the goal posts: PARASHIFT proton magnetic resonance imaging

磁共振成像（MRI）提供了一个人体窗口，并报告了体内组织中水的相对分布。MRI扫描在世界各地使用，每年约有1亿次检查，其中40%的情况下会向患者提供造影剂以帮助图像清晰度，帮助放射科医生解释观察到的扫描结果。扫描仪被调谐到水氢原子核共振的频率，该频率位于射频范围内。我们建议开发一系列安全、耐受性良好的造影剂，可以在观察水信号的同时进行观察。这些基于稀土金属络合物的造影剂将具有报告质子信号，其可以在远离水信号的地方（通常至少10 kHz）观察到，从而允许选择性地观察到水信号。通过精心设计这些系统，我们将使探针共振频率对局部生理参数敏感，例如pH值或某些必需金属离子（如镁和钙）的局部细胞外浓度。这将允许在观察到的感兴趣区域中评估这些参数。这项工作很重要，因为不同的区域具有不同的局部pH梯度，并且细胞外钙浓度的变化在评估骨疾病中很重要。镁的生理和病理作用被认为在中风和缺血中非常重要，但以前没有对其水平进行实时测量。这种“双重成像”方法的一个关键方面是，新的造影剂可以在低得多的浓度下被检测到，并且在安全使用的水平下。这些水平处于自1988年以来已批准用于临床的钆造影剂的当前范围内。这种增强的灵敏度源于报告质子信号传导基团与嵌在造影剂内的磁性金属中心的接近。这种接近导致增强的灵敏度，因为信号采集序列可以加速，允许信号强度以比其他方式快约20倍的速度采集。

Magnetic resonance imaging (MRI) offers a window on the human body and reports the relative distribution of water in tissues within the body. MRI scans are used around the world with about 100 million examinations per year, and in 40% of these cases a contrast agent is given to the patient to assist in image clarity, aiding the radiologist in interpreting the scans observed. The scanner is tuned to the frequency at which the water hydrogen nuclei resonate, which lies in the radiofrequency range. We propose to develop a series of safe, well tolerated contrast agents that can be observed in parallel to observation of the water signal. These contrast agents, based on rare earth metal complexes, will possess a reporting proton signal that can be observed far away from the water signal, typically at least 10 kHz away, allowing it to be selectively observed. By careful design of these systems, we will make the probe resonant frequency sensitive to local physiological parameters, such as pH or the local extracellular concentration of certain essential metal ions like magnesium and calcium. This will allow these parameters to be assessed in the region of interest that is observed. Such work is important as different regions have differing local pH gradients, and changes in extracellular calcium concentration is important in assessing bone disorders. The physiological and pathological role of magnesium is believed to be very important in stroke and ischemia, but no such real-time measurements of its levels have been made before. A key aspect of this 'dual imaging' approach is that the new contrast agents can be detected at much lower concentration, and at levels that are safe to use. These levels lie within the current range of the approved gadolinium contrast agents 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. This proximity leads to enhanced sensitivity because the signal acquisition sequence can be speeded up, allowing signal intensity to be acquired about 20 times faster than would otherwise be possible.