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

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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.