Nuclear Spin Singlet Lifetimes – A New Contrast Mechanism for Magnetic Resonance

氧气是生命的燃料，如果没有氧气，大多数细胞和有机体会在几分钟内死亡。血管性认知障碍（VCI）是痴呆的常见原因之一，即血管性痴呆。最终，这种疾病起源于血流受损（低灌注）和氧气输送（缺氧）到大脑。因此，准确的血氧检测有望对更好地理解、识别和分级这种病理有很大的帮助。更好地了解血管性痴呆的出现以及早期发现和准确诊断尤为重要，因为血管性痴呆至少部分是可以预防的。对于早期诊断，新的科学方法是有价值的。因此，我们建议研究核自旋单重态作为磁共振诊断的一种全新的对比机制。正如我们在初步工作中所证明的那样，单线态可以在脑代谢物中填充，其弛豫时间-单线态寿命TS -可以用MR测量。单线态的特殊之处在于，与目前使用的MR对比机制（即T1和t2加权MR）相比，TS对不同的弛豫现象更敏感。事实上，TS是由顺磁弛豫控制的。因此，我们假设TS将以目前不存在的方式证明自己作为一种新的参数来探测组织环境，特别是组织中顺磁分子的存在。核磁共振已经成为VCI的一个重要诊断支柱，因为它是通用的，无创的，不需要电离辐射，在诊所广泛使用。此外，顺磁变化与VCI最相关，因为在低灌注和缺血时，血液中顺磁脱氧血红蛋白的比例增加，O2减少。因此，作为我们新方法的第一个应用，我们设想单线态可以用于在VCI小鼠模型中灵敏地检测大脑中的缺氧，其演示受此提议的影响。为此，我们在此调整方法并确定适当的内源性靶点（代谢物），使我们能够在体内敏感地访问TS。我们在测试溶液中研究了单线态的寿命，并在健康和VCI小鼠体内研究了单线态的寿命。我们期望从单个TS测量中直接量化血氧的可能性。

Oxygen is the fuel of life and in its absence, most cells and organisms die within minutes. Vascular cognitive impairment (VCI) is one common cause of dementia, i.e. vascular dementia. Ultimately, this disease originates from a compromised blood flow (hypoperfusion) and oxygen delivery (hypoxia) to the brain. Thus, accurate detection of blood oxygenation promises to be immensely helpful to better understand, identify and grade this pathology. A better insight into the emergence as well as early detection and accurate diagnosis of VCI are particularly important, also because vascular dementia is – at least partially – preventable. For an early diagnostics new scientific approaches can proof valuable.Therefore, we propose to research nuclear spin singlet states as an entirely new contrast mechanims for diagnostics in magnetic resonance (MR). As we have demonstrated in our preliminary work, singlet states can be populated in brain metabolites and its relaxation time – the singlet lifetime TS – can be measured with MR. The special feature about the singlet state is that TS is more sensitive to different relaxation phenomena than currently used MR contrast mechanisms (i.e. T1- and T2-weighted MR). Indeed, TS is dominated by paramagnetic relaxation. Consequently, we hypothesize that TS will proof itself as a novel parameter to probe the tissue environment and especially the presence of paramagnetic molecules in tissue in a currently non-existent way.MR is already one important diagnostic pillar for VCI as it is versatile, non-invasive, does not require ionizing radiation and is widely available in the clinics. Also paramagnetic changes are most relevant to VCI, because the fraction of paramagnetic deoxygenated hemoglobin in the blood increases and O2 decreases upon hypoperfusion and ischemia.Thus, as a first application of our novel approach, we envision that singlet states can be used to sensitively detect hypoxia in the brain in a VCI mouse model, the demonstration of which is subject to this proposal. To this end, we here tune the methodology and identify appropriate endogenous targets (metabolites) in a way that enables us to access TS in vivo sensitively. We research the lifetime of singlet states in vitro in test solutions, as well as in vivo in healthy and VCI mice. We anticipate the possibility of direct quantification of blood oxygenation from a single TS measurement.