Hyperpolarised Liquids for Magnetic Resonance

用于磁共振的超极化液体

• 批准号: EP/N032446/1
• 负责人: John Owers-Bradley
• 金额: $ 56.25万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN032446%2F1
• 关键词: Hyperpolarised; Liquids; Magnetic; Resonance

Magnetic resonance imaging (MRI) and spectroscopy are two highly influential branches of the technique known as nuclear magnetic resonance (NMR). MRI has had a major impact in disease diagnosis; NMR spectroscopy provides a powerful method of investigating molecular structure, has proved invaluable in many areas of science and medicine, and is exploited widely in industry. NMR detects the magnetic properties characteristic of certain atomic nuclei, most notably the hydrogen (1H) nucleus; other magnetic nuclei of interest include carbon (in the form of 13C), nitrogen (15N), and phosphorus (31P). Despite the great success of NMR, its lack of sensitivity imposes a number of constraints on the quantities of material that can be detected and/or on the spatial and temporal resolution that can be achieved. This has proved to be a major limitation, for example, in the use of NMR spectroscopy as a means of studying tissue chemistry in vivo. The sensitivity of NMR is poor because, unlike compass needles, nuclear magnets (or spins) do not all point in the same direction when subjected to a strong magnetic field. This is because of the randomising effects of thermal agitation. As a result, the nuclei are very weakly polarised, and the detectable NMR signal arises from only a small proportion (typically about 1 in 100,000) of nuclear spins. It would clearly be an attractive proposition to increase the polarisation and hence tap into a larger proportion of the nuclei. Over the years, several strategies have been developed for generating high levels of nuclear spin polarisation. Here, we propose to develop and establish methods, based on the so-called brute-force approach, for achieving dramatic (up to 100,000-fold) gains in nuclear polarisation. The method is conceptually straightforward as it simply involves exposure of the material to very low temperature (as low as 0.01 K) and very high magnetic field (up to 14 T) leading to polarisation levels of more than 10%. However, this is not as straightforward as it sounds because of the time taken for the polarisation process to build up, characterised by the relaxation time, T1. Reducing the thermal agitation by lowering the temperature allows a high degree of alignment of the nuclear spins with the magnetic field, but as the lattice vibrations and hence the magnetic fluctuations that cause the relaxation are frozen out, the relaxation time T1 can become excessively long. Our recent research demonstrates that we are now well placed to overcome this problem as we have discovered a new class of materials that greatly reduce the relaxation time at very low temperatures.In the proposed research, we shall polarise selected agents at very low temperatures and high fields using this relaxation-assisted brute-force method. The frozen, polarised material will then be removed and rewarmed rapidly and dissolved using hot solvent for use in the liquid state. One of our aims is to find ways of storing the frozen, polarised material ready for rewarming and dissolution at a later time. Our proposal details methods for overcoming the technical issues and for making the brute-force method competitive with alternative approaches to achieving high levels of polarisation. The proposed methods build on our own research over the last few years in which we have used nanoparticles to reduce the time required to polarise the nuclei, linked in to the research of our partners Bruker, who have successfully integrated 'brute-force' and rapid warming/dissolution technology. Our main aim is to achieve polarisation levels of at least 10% in a range of 13C-containing compounds. We envisage a wide range of biomedical applications, both in vitro and in vivo; prominent amongst these applications would be the use of hyperpolarised 13C-labelled metabolites for the investigation of tumour biochemistry and response to treatment.

磁共振成像（MRI）和光谱学是核磁共振（NMR）技术的两个非常有影响力的分支。核磁共振成像在疾病诊断中有着重要的影响;核磁共振波谱提供了一种研究分子结构的强大方法，在许多科学和医学领域都被证明是非常宝贵的，并在工业中得到了广泛的应用。核磁共振检测某些原子核的磁性特征，最值得注意的是氢（1H）核;其他感兴趣的磁性核包括碳（以13 C的形式），氮（15 N）和磷（31 P）。尽管NMR取得了巨大的成功，但其灵敏度的缺乏对可以检测的材料的量和/或可以实现的空间和时间分辨率施加了许多限制。这已被证明是一个主要的限制，例如，在使用NMR光谱作为一种手段，研究组织化学在体内。核磁共振的灵敏度很差，因为与指南针不同，当受到强磁场时，核磁体（或自旋）并不都指向同一方向。这是因为热搅动的随机效应。因此，原子核的极化非常弱，可检测的NMR信号仅来自一小部分（通常约为100，000分之一）的核自旋。显然，增加极化并因此利用更大比例的原子核是一个有吸引力的提议。多年来，已经开发了几种策略来产生高水平的核自旋极化。在这里，我们建议开发和建立基于所谓的蛮力方法的方法，以实现核极化的戏剧性（高达100，000倍）增益。该方法在概念上是简单的，因为它简单地涉及将材料暴露于非常低的温度（低至0.01 K）和非常高的磁场（高达14 T），导致超过10%的极化水平。然而，这并不像听起来那么简单，因为极化过程建立所花费的时间，其特征在于弛豫时间T1。通过降低温度来减少热扰动允许核自旋与磁场的高度对准，但是随着晶格振动以及因此导致弛豫的磁波动被冻结，弛豫时间T1可能变得过长。我们最近的研究表明，我们现在已经很好地克服了这个问题，因为我们已经发现了一类新的材料，大大减少了弛豫时间在非常低的温度。在拟议的研究中，我们将极化选定的代理在非常低的温度和高领域使用这种弛豫辅助蛮力方法。然后将冷冻的极化材料取出并快速重新加热，并使用热溶剂溶解以用于液态。我们的目标之一是找到储存冷冻的极化材料的方法，以便在以后的时间里复温和溶解。我们的提案详细介绍了克服技术问题的方法，并使蛮力方法与其他方法竞争，以实现高水平的极化。我们提出的方法建立在我们自己过去几年的研究基础上，我们使用纳米颗粒来减少极化原子核所需的时间，这与我们的合作伙伴布鲁克公司的研究有关，布鲁克公司成功地将“蛮力”和快速升温/溶解技术相结合。我们的主要目标是在一系列含13 C的化合物中实现至少10%的极化水平。我们设想了广泛的生物医学应用，在体外和体内;突出的这些应用将是使用超极化13 C-标记的代谢物的肿瘤生物化学和治疗反应的调查。