Moving the goal posts: PARASHIFT proton magnetic resonance imaging

移动球门柱：PARASHIFT 质子磁共振成像

• 批准号: EP/L01212X/1
• 负责人: David Parker
• 金额: $ 42.99万
• 依托单位: Durham University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL01212X%2F1
• 关键词: Moving; goal; posts; PARASHIFT; proton

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.

磁共振成像 (MRI) 为了解人体提供了一个窗口，并报告水在体内组织中的相对分布。全世界每年都会使用 MRI 扫描进行大约 1 亿次检查，其中 40% 的情况下会向患者注射造影剂以提高图像清晰度，从而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，可以在远离水信号（通常至少 10 kHz）的地方观察到，从而可以选择性地观察到它。通过仔细设计这些系统，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，因为不同区域具有不同的局部 pH 梯度，并且细胞外钙浓度的变化对于评估骨疾病很重要。镁的生理和病理作用被认为在中风和缺血中非常重要，但以前从未对其水平进行过此类实时测量。这种“双重成像”方法的一个关键方面是，可以在低得多的浓度和安全使用的水平下检测到新的造影剂。这些水平处于自 1988 年以来已在临床上使用的批准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基团与嵌入造影剂内的磁性金属中心的接近。这种接近性可以提高灵敏度，因为信号采集序列可以加快，信号强度的采集速度比其他方式快约 20 倍。

项目成果

Comparative Analysis of a Series of pH-Responsive Sulphonated Europium Complexes for Bioassays Monitoring Acidification

一系列 pH 响应型磺化铕配合物用于生物测定监测酸化的比较分析

• DOI: 10.1002/ejic.202200426
• 发表时间: 2022
• 期刊: European Journal of Inorganic Chemistry
• 影响因子: 2.3
• 作者: Fradgley J

PARASHIFT Probes: Solution NMR and X-ray Structural Studies of Macrocyclic Ytterbium and Yttrium Complexes

• DOI: 10.1021/acs.inorgchem.6b02291
• 发表时间: 2017-04-03
• 期刊: INORGANIC CHEMISTRY
• 影响因子: 4.6
• 作者: Mason, Kevin;Rogers, Nicola J.;Parker, David
• 通讯作者: Parker, David

Critical analysis of the limitations of Bleaney's theory of magnetic anisotropy in paramagnetic lanthanide coordination complexes.

• DOI: 10.1039/c4sc03429e
• 发表时间: 2015-03-01
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Funk AM;Finney KNA;Harvey P;Kenwright AM;Neil ER;Rogers NJ;Kanthi Senanayake P;Parker D
• 通讯作者: Parker D

Aggregation of Rare Earth Coordination Complexes in Solution Studied by Paramagnetic and DOSY NMR.

通过顺磁和 DOSY NMR 研究溶液中稀土配位配合物的聚集。

• DOI: 10.1002/chem.201803766
• 发表时间: 2018
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Poh AWJ

Targeted pH switched europium complexes monitoring receptor internalisation in living cells.

• DOI: 10.1039/d1cc01029h
• 发表时间: 2021-05
• 期刊: Chemical communications
• 影响因子: 4.9
• 作者: Jack D. Fradgley;Matthieu Starck;M. Laget;Emmanuel Bourrier;Elodie Dupuis;L. Lamarque;E. Trinquet;J. Zwier;D. Parker