Integrated functional characterisation in acute vascular syndromes: multimodal MRI / PET-CT imaging combined with leukocyte expression profiling
急性血管综合征的综合功能表征:多模态 MRI / PET-CT 成像结合白细胞表达谱
基本信息
- 批准号:MR/K00266X/1
- 负责人:
- 金额:$ 27.07万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Fellowship
- 财政年份:2012
- 资助国家:英国
- 起止时间:2012 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Circulatory disease, such as heart attacks and strokes, remain the most common cause of death in the UK, contributing to almost one-third of all deaths registered in 2010. Each year, over 180,000 people die from circulatory disease in the UK alone, with 82,000 deaths from coronary heart disease and a further 49,000 from stroke. This costs the UK in excess of £30 billion each year due to healthcare associated costs and loss of workforce productivity. Despite this very substantial burden of disease, tools for identifying patients at high risk of acute vascular events remain extremely limited. As a consequence, a large proportion of events are unheralded. Even in patients with established disease, inability to distinguish patients at high and low risk means that optimal treatments cannot be targeted rationally and cost-effectively.It is well recognised that the final common events of arterial blockage in heart attack and strokes are often the results of arterial thrombosis (blood clots forming within arteries). Arterial thrombosis is commonly triggered by ruptured fatty deposits within the arterial wall known as atherosclerotic plaques. Despite considerable efforts in the past decade, no single imaging modality has succeeded in accurately identifying these high-risk, "vulnerable" plaques. The need for better plaque and patient characterisation has now become even more urgent and pressing, with a new generation of cardiovascular drugs near the clinical horizon, which directly target plaque behaviour and biology with no anticipated effect on plaque size and are therefore not detectable by conventional imaging techniques. The purpose of our proposed research is to use sophisticated, high-end laboratory techniques to first define the characteristics of plaque constituent cells from explanted human tissue following acute stroke. We can then relate this molecular "signature" to plaque imaging characteristic using state-of-the-art techniques with MRI, as well as PET nuclear imaging, which can detect plaques' biological activity. By combining imaging data and cellular analysis, we aim to evaluate the cellular events that drive plaque activity, and to generate a unique characterisation of patients at risk.We will develop a multimodal vascular imaging protocol with MRI/PET-CT in Oxford that can be validated at a cellular or molecular level within the plaque constituent cells. With our new research-dedicated Oxford Acute Vascular Imaging Centre (AVIC), and the strong tie between the University and the NHS, Oxford is strategically poised to lead research into the early phase of acute vascular syndromes. Through this innovative project, we hope to generate tools that will aid (1) diagnosis and risk stratification, (2) monitoring response to treatment (3) evaluation of new drugs and interventions - all of which reflect pressing current clinical unmet need.
循环系统疾病,如心脏病发作和中风,仍然是英国最常见的死亡原因,占2010年登记死亡人数的近三分之一。每年,仅在英国就有超过180,000人死于循环系统疾病,其中82,000人死于冠心病,另有49,000人死于中风。由于医疗保健相关成本和劳动力生产力的损失,英国每年的成本超过300亿英镑。尽管存在这种非常严重的疾病负担,但用于识别急性血管事件高风险患者的工具仍然非常有限。因此,有很大一部分事件是没有预告的。即使在已确诊的患者中,也无法区分高风险和低风险患者,这意味着无法合理且经济有效地针对最佳治疗。众所周知,心脏病发作和中风中动脉阻塞的最终常见事件通常是动脉血栓形成(动脉内形成血块)的结果。动脉血栓形成通常是由动脉壁内破裂的脂肪沉积物(称为动脉粥样硬化斑块)引发的。尽管在过去的十年中做出了相当大的努力,但没有一种单一的成像方式能够成功地准确识别这些高风险的“脆弱”斑块。随着新一代心血管药物接近临床水平,对更好的斑块和患者表征的需求变得更加迫切和紧迫,这些药物直接靶向斑块行为和生物学,对斑块大小没有预期影响,因此无法通过常规成像技术检测。我们提出的研究的目的是使用复杂的,高端的实验室技术,首先定义急性中风后从受损的人体组织中提取的斑块组成细胞的特征。然后,我们可以使用最先进的MRI技术以及PET核成像将这种分子“签名”与斑块成像特征联系起来,PET核成像可以检测斑块的生物活性。通过结合成像数据和细胞分析,我们的目标是评估驱动斑块活动的细胞事件,并产生一个独特的特征的患者在risk.We将开发一个多模式的血管成像协议与MRI/PET-CT在牛津大学,可以验证在细胞或分子水平内的斑块组成细胞。凭借我们新的研究专用牛津急性血管成像中心(AVIC),以及大学与NHS之间的紧密联系,牛津大学在战略上准备领导对急性血管综合征早期阶段的研究。通过这一创新项目,我们希望产生有助于(1)诊断和风险分层,(2)监测对治疗的反应,(3)评估新药和干预措施的工具-所有这些都反映了当前迫切的临床未满足的需求。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Multimeric micro particles of iron oxide (mMPIO) for dual modality molecular imaging with CT and MRI
用于 CT 和 MRI 双模态分子成像的氧化铁多聚微粒 (mMPIO)
- DOI:
- 发表时间:2014
- 期刊:
- 影响因子:39.3
- 作者:Alaa A A Aljabali
- 通讯作者:Alaa A A Aljabali
Nicotinic acid receptor GPR109A is down-regulated in human macrophage-derived foam cells.
- DOI:10.1371/journal.pone.0062934
- 发表时间:2013
- 期刊:
- 影响因子:3.7
- 作者:Chai JT;Digby JE;Ruparelia N;Jefferson A;Handa A;Choudhury RP
- 通讯作者:Choudhury RP
In-vivo quantitative T2 mapping of carotid arteries in atherosclerotic patients: segmentation and T2 measurement of plaque components.
- DOI:10.1186/1532-429x-15-69
- 发表时间:2013-08-16
- 期刊:
- 影响因子:0
- 作者:Biasiolli L;Lindsay AC;Chai JT;Choudhury RP;Robson MD
- 通讯作者:Robson MD
GPR109A and vascular inflammation.
- DOI:10.1007/s11883-013-0325-9
- 发表时间:2013-05
- 期刊:
- 影响因子:5.8
- 作者:Chai, Joshua T.;Digby, Janet E.;Choudhury, Robin P.
- 通讯作者:Choudhury, Robin P.
Differential Gene Expression in Macrophages From Human Atherosclerotic Plaques Shows Convergence on Pathways Implicated by Genome-Wide Association Study Risk Variants.
- DOI:10.1161/atvbaha.118.311209
- 发表时间:2018-11
- 期刊:
- 影响因子:0
- 作者:Chai JT;Ruparelia N;Goel A;Kyriakou T;Biasiolli L;Edgar L;Handa A;Farrall M;Watkins H;Choudhury RP
- 通讯作者:Choudhury RP
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