Dopamine release and blood flow changes during induced epileptic seizures assessed with simultaneous PET-MR-EEG

使用同时 PET-MR-EEG 评估诱发癫痫发作期间的多巴胺释放和血流变化

• 批准号: MR/N013042/1
• 负责人: Alexander Hammers
• 金额: $ 84.09万
• 依托单位: King's College London
• 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=MR%2FN013042%2F1
• 关键词: Dopamine; release; blood; flow; changes

Epilepsy is a brain disorder. People with epilepsy have epileptic seizures, which are brief periods of "short-circuiting" in the brain. During seizures, people may simply stare ahead and not be responsive ("absence" seizures). During other seizures, they might have abnormal movements, or fall to the ground, and injure themselves. Epilepsy is a frequent disease, affecting about 1 in 100 people in the UK.People with epilepsy are normally treated with medication (drugs). However, these drugs only completely stop seizures in about 2 out of 3 people. It would be useful to have more drugs to treat epilepsy, particularly drugs that work in different ways to the ones that already exist.We do not understand completely how seizures start - or stop. One possible mechanism is by neurotransmitters. Neurotransmitters are "messengers" that nerve cells in the brain use to talk to each other. Dopamine is such a neurotransmitter. Scientists have shown changes in dopamine messaging in all types of epilepsy they have studied so far.In this project, we want to demonstrate whether seizures release dopamine in the brain. For this, patients who can trigger a harmless "absence" seizure by breathing hard (hyperventilation) will be asked to do so inside a special brain scanner.Dopamine release can be seen with a powerful brain scanning technology, Positron Emission Tomography (PET). PET has recently become even more powerful by combining it with another technique for taking images of the brain, Magnetic Resonance Imaging (MRI). There are only two such simultaneous PET-MR machines in the UK. The second one has recently been installed in our centre at St Thomas' Hospital.We will use MRI to get as much information as we can about patients' brains - what they look like, how they are wired, and how blood flows in them. We are especially interested in how blood flow changes when the volunteer patients have their "absence" seizures. We also want to check whether dopamine release is independent of blood flow changes.In order to know exactly when patients have an "absence" seizure, we need yet another technique, EEG. The EEG (electro-encephalogram) allows us to see the electrical activity in the brain, which changes very clearly during an "absence" seizure from one second to the next. Over the past months, we have managed to record EEG inside the PET-MR scanner, which is quite difficult due to the strong magnetic fields inside. We therefore now have a PET-MR-EEG scanner.PET-MR-EEG will be the ideal technique to work out whether dopamine is released at the time of seizures. We have also worked on making all three techniques as fast as possible. We therefore think that we can even work out whether dopamine is released before the seizures, or after seizures have started.We think it will be released after seizures have started. This would mean that dopamine makes seizures stop. That would be good news for epilepsy patients, because drug companies can then develop new drugs that work through the dopamine system. Such drugs do not currently exist.Another benefit would be to show exactly where dopamine is released thanks to the very clear MRI pictures. If we find such small areas of the brain, then surgeons may be able to target them with deep brain stimulators to try and stop seizures. Some scientists are also developing systems that can release a tiny amount of drug directly into a small brain area to stop seizures.There are many different types of seizures, but we believe that dopamine may be a general way for the brain to stop seizures. Therefore, epilepsy patients with all kinds of seizures may benefit from this research.We also think that many other scientists will benefit from the PET-MR-EEG technique we are developing in this proposal. Getting simultaneous information will be particularly important for diseases which come in attacks, for example migraine or stroke, but also for normal brain workings.

癫痫是一种脑部疾病。癫痫患者有癫痫发作，这是大脑中短暂的“短路”。在癫痫发作期间，人们可能只是盯着前方而没有反应（“失神”癫痫发作）。在其他癫痫发作期间，他们可能会出现异常动作，或摔倒在地，并伤害自己。癫痫是一种常见的疾病，在英国每100人中就有1人患病。癫痫患者通常用药物治疗。然而，这些药物只能完全阻止大约三分之二的癫痫发作。有更多的药物来治疗癫痫会很有用，特别是那些与现有药物作用方式不同的药物。我们还不完全了解癫痫发作是如何开始或停止的。一种可能的机制是通过神经递质。神经递质是大脑中神经细胞用来相互交流的“信使”。多巴胺就是这样一种神经递质。到目前为止，科学家们已经在他们研究的所有类型的癫痫中显示了多巴胺信息的变化。在这个项目中，我们想证明癫痫发作是否会在大脑中释放多巴胺。为此，那些可以通过呼吸困难（过度换气）引发无害的“失神”癫痫发作的患者将被要求在一个特殊的大脑扫描仪内进行呼吸，多巴胺的释放可以通过强大的大脑扫描技术--正电子发射断层扫描（PET）来观察。PET最近通过与另一种用于拍摄大脑图像的技术磁共振成像（MRI）相结合而变得更加强大。在英国只有两台这样的同步PET-MR机器。第二台最近已经安装在我们位于圣托马斯医院的中心。我们将使用核磁共振成像来获得尽可能多的关于病人大脑的信息--它们看起来像什么，它们是如何连接的，以及血液如何在其中流动。我们特别感兴趣的是，当志愿者患者发生“缺席”癫痫发作时，血流如何变化。我们还想验证多巴胺的释放是否与血流变化无关，为了准确地知道患者何时出现“失神”发作，我们还需要另一种技术，即脑电图。EEG（脑电图）使我们能够看到大脑中的电活动，在“失神”癫痫发作期间，从一秒到下一秒的变化非常明显。在过去的几个月里，我们设法在PET-MR扫描仪内记录EEG，由于内部的强磁场，这是相当困难的。因此，我们现在有了PET-MR-EEG扫描仪，PET-MR-EEG将是确定癫痫发作时多巴胺是否释放的理想技术。我们也在努力使这三种技术尽可能快。因此，我们认为我们甚至可以计算出多巴胺是在癫痫发作之前还是发作之后释放的，我们认为多巴胺是在癫痫发作之后释放的。这意味着多巴胺可以阻止癫痫发作。这对癫痫患者来说是个好消息，因为制药公司可以开发出通过多巴胺系统发挥作用的新药。这样的药物目前还不存在。另一个好处是，由于非常清晰的MRI图像，可以准确地显示多巴胺的释放部位。如果我们找到了大脑中如此小的区域，那么外科医生就可以用深部脑刺激器来靶向它们，试图阻止癫痫发作。一些科学家也正在开发一种系统，可以直接向大脑的一个小区域释放微量的药物来阻止癫痫发作。癫痫发作有很多不同的类型，但我们相信多巴胺可能是大脑阻止癫痫发作的一种通用方法。因此，各种癫痫发作的癫痫患者可能会从这项研究中受益，我们也认为许多其他科学家将受益于我们正在开发的PET-MR-EEG技术。同时获得信息对于发作的疾病特别重要，例如偏头痛或中风，但对于正常的大脑工作也很重要。

项目成果

Guided Image Reconstruction for Multi-Tracer PET

多示踪剂 PET 引导图像重建

• DOI: 10.1109/nssmic.2017.8533140
• 发表时间: 2017
• 作者: Ellis S

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

• DOI: 10.1007/s00415-020-09806-3
• 发表时间: 2020-03-26
• 期刊: JOURNAL OF NEUROLOGY
• 影响因子: 6
• 作者: Carotenuto, Antonio;Wilson, Heather;Politis, Marios
• 通讯作者: Politis, Marios

MR-Guided Kernel EM Reconstruction for Reduced Dose PET Imaging.

• DOI: 10.1109/trpms.2017.2771490
• 发表时间: 2018-05
• 期刊: IEEE transactions on radiation and plasma medical sciences
• 影响因子: 4.4
• 作者: Bland J;Mehranian A;Belzunce MA;Ellis S;McGinnity CJ;Hammers A;Reader AJ
• 通讯作者: Reader AJ

Single-Modality Supervised Joint PET-MR Image Reconstruction

• DOI: 10.1109/trpms.2023.3283786
• 发表时间: 2023-09-01
• 期刊: IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES
• 影响因子: 4.4
• 作者: Corda-D'Incan, Guillaume;Schnabel, Julia A.;Reader, Andrew J.
• 通讯作者: Reader, Andrew J.

Intercomparison of MR-Informed Methods for PET Image Reconstruction

PET 图像重建 MR-Informed 方法的相互比较

• DOI: 10.1109/nssmic.2018.8824610
• 发表时间: 2018
• 作者: Bland J