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

“痴呆症”一词用来描述一种综合征，这种综合征最初会导致认知功能受损，在许多情况下会导致心理功能障碍，最终导致死亡。这是一项重大的社会经济挑战，医疗费用接近全球GDP的1%。导致认知能力严重丧失的几种情况可归为该综合征，包括阿尔茨海默病（AD）、血管性痴呆（VaD）、额颞叶痴呆等。2012年，英国首相发表了一份高调的声明，强调应高度重视与痴呆症相关的研究，并将在不久的将来增加一倍以上的资金，以部分弥补该综合征的压倒性影响被忽视的事实（卫报，2012年3月26日）。2013年12月，在伦敦举行的八国集团首脑会议汇集了八国集团部长、研究人员、制药公司和慈善机构，制定了针对痴呆症的协调全球行动。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，并对医疗保健系统施加了巨大的压力，特别是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的选择。全球约有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，加剧了医疗保健服务的影响。临床相关性：血管性认知障碍（VCI）。VCI定义了可归因于脑血管原因的认知改变，范围从细微或固定的缺陷到全面痴呆。VCI是一个被广泛接受的术语，指的是“具有临床中风或亚临床血管性脑损伤证据和至少影响一个认知领域的认知障碍的综合征”，其中导致的VaD是其最严重的形式。VaD至少占痴呆症的20%，仅次于AD，患病率每5年翻一番。3年。几项试验检验了胆碱酯酶抑制剂治疗血管性痴呆的效果，但除了对阿尔茨海默病和血管性痴呆合并的个体外，效果非常有限。血管变化导致白质（WM）损伤（白质变病），从而深刻影响信息传递的保真度，从而影响大脑功能和认知健康8。脑磁共振成像（MRI）的扩散和灌注。MRI是一种医学成像技术，可对解剖和组织功能进行无创调查，因其灵敏度和可靠性特别适合于研究认知障碍。我们的主要兴趣是利用定量扩散和灌注MR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信号模型和基于新的人类大脑健康和疾病组织形态学数据的最佳MR序列设计，表征和量化脑血液运输的早期差异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.