OCEAN: One-stop-shop microstructure-sensitive perfusion/diffusion MRI: Application to vascular cognitive impairment

“痴呆症”一词被用来描述一种综合征，最初导致认知功能障碍，在许多情况下，导致心理障碍的下降阶梯，最终导致死亡。护理费用接近全球GDP的1%，这是一个重大的社会经济挑战。导致认知能力严重丧失的几种疾病被归类为这种综合征，包括阿尔茨海默病(AD)、血管性痴呆(VAD)、额颞痴呆等。2012年，首相发表了一项高度宣传的声明，强调应高度重视与痴呆症相关的研究，并表示资金将在不久的将来增加一倍以上，以部分纠正该综合征的压倒性影响被忽视的事实(卫报，26/3/12)。2013年12月，在伦敦举行的八国集团峰会将八国集团的部长、研究人员、制药公司和慈善机构聚集在一起，制定针对痴呆症的全球协调行动。痴呆症对数千万人(包括患者和护理人员)的生活质量产生了显著的不利影响，并对医疗系统构成巨大压力，特别是在考虑到人口老龄化的明显趋势、不断变化的环境影响和当代生活方式选择的情况下。加州全球有3500万人患有痴呆症，到2050年，这一数字将翻两番。欧洲和北美分担着不成比例的沉重负担：老龄化对这些地区的影响尤为明显，加剧了医疗保健提供的影响。临床相关性：血管认知障碍(VCI)。VCI定义了可归因于脑血管原因的认知变化，范围从轻微或固定的缺陷到全面的痴呆症。VCI是一个被广泛接受的术语，指的是“有证据表明临床中风或亚临床血管脑损伤和认知损害至少影响一个认知领域的综合征”，导致的VAD是其最严重的形式。至少20%的痴呆症是由VaD引起的，仅次于AD，患病率每5.3年翻一番。有几项试验检测了胆碱酯酶抑制剂治疗血管性痴呆的效果，但效果非常有限，除非是在AD和VAD合并的患者中。血管变化导致脑白质(WM)损伤(脑白质疏松)，这将深刻影响大脑功能和认知健康基础上的信息传递的保真度8。弥散和灌注的磁共振成像(MRI)磁共振成像是一种医学成像技术，提供了对解剖和组织功能的非侵入性研究，由于其敏感性和可靠性，特别适合于研究认知障碍。我们的主要兴趣是使用定量扩散和灌注MR来表征血管和非血管组织。我们的总体目标是利用一站式灌注/扩散MR GSI结合新的MR信号模型和基于健康和疾病中新的人脑组织形态测量数据的最佳MR序列设计来表征和量化脑血液运输中的早期差异性改变和随后的微结构组织损伤。

The term "dementia" is used to describe a syndrome that results, initially, in cognitive function impairment and in many cases, a descending staircase of psychological dysfunction, leading eventually to death. It is a major socio-economic challenge with care costs approaching 1% of global GDP. Several conditions that lead to serious loss of cognitive ability are grouped under this syndrome, including Alzheimer's disease (AD), Vascular Dementia (VaD), Frontotemporal Dementia, etc. A high publicity announcement was made in 2012, by the Prime Minister, emphasising the high priority that should be given to dementia-related research and that funding will more than double in the immediate future, to partially remedy the fact that the overwhelming impact of the syndrome has been over-looked (Guardian, 26/3/12). On Dec 2013, the G8 Summit hosted in London brought together G8 ministers, researchers, pharmaceutical companies, and charities to develop co-ordinated global action on dementia. Dementia has marked adverse effects on the quality of life of tens of millions of people (both patients and carers) and exerts tremendous pressure on healthcare systems, especially when clear trends towards an ageing population, changing environmental influences and contemporary lifestyle choices are considered. Ca. 35M people suffer from dementia worldwide, a figure to quadruple by 2050. Europe and North America share a disproportionally high burden: the effects of ageing are particularly stark for these regions, exacerbating the healthcare provision implications. The Clinical Relevance: Vascular Cognitive Impairment (VCI). VCI defines alterations in cognition attributable to cerebrovascular causes, ranging from subtle or fixed deficits to full-blown dementia. VCI is a wide and accepted term referring to the "syndrome with evidence of clinical stroke or subclinical vascular brain injury and cognitive impairment affecting at least one cognitive domain", with resulting VaD being its most severe form. VaD is responsible for at least 20% of dementias, second only to AD, with a prevalence doubling every 5. 3 years. Several trials examined cholinesterase inhibitors for the treatment of vascular dementia, but the benefits are very modest, except in the individuals with a combination of AD and VaD. Vascular changes result in white matter (WM) damage (leukoaraiosis), which profoundly affect the fidelity of the information transfer underlying brain function and cognitive health8. Cerebral Magnetic Resonance Imaging (MRI) of Diffusion and Perfusion. MRI is a medical imaging technique affording non-invasive investigation of anatomy and tissue function, which is particularly suited to studying cognitive disorders due to its sensitivity and reliability. Our main interest is to characterise vascular and non-vascular tissues using quantitative diffusion and perfusion MR. Our overall aim is to characterise and quantify early differential alterations in brain blood transport and subsequent microstructural tissue damage using one-stop-shop perfusion/diffusion MR GSI incorporating novel MR signal models and optimal MR sequence design based on new human brain histomorphometric data in health and disease.