O-Labeled water

Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used to create images because of their abundance in water molecules, which comprise >80% of most soft tissues. The contrast of proton MRI images depends mainly on the density of nuclear proton spins, the relaxation times of the nuclear magnetization (T1, longitudinal; T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the T1 and T2 relaxation of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide (CLIO) and other iron oxide formulations affect T2 primarily and lead to a decreased signal. On the other hand, paramagnetic T1 agents, such as gadolinium (Gd) and manganese (Mn), accelerate T1 relaxation and lead to brighter contrast images. The human brain (5% of total body weight) accounts for 20% of total body oxygen consumption (2). Oxygen is consumed to produce water oxidative phosphorylation and reoxidation of reduced molecules in the mitochondria. The cerebral rate of oxygen consumption (CMRO) and the cerebral blood flow (CBF) are sensitive and quantitative indicators of the health of the brain. Reduced cerebral perfusion and oxygen consumption have been observed in neurodegenerative and cerebrovascular diseases. CMRO has been imaged using O positron emission tomography (PET) to monitor the HO concentration in the brain during inhalation of O (3, 4). However, O PET is not popular because of the short half-life (2 min) of O, on-site generation of O, and high background noise (O bound to hemoglobin HO). CMRO has also been measured with O nuclear magnetic resonance (NMR) spectroscopy and MRI after inhalation of O, which is converted to HO (5, 6). O cannot be detected because molecular O is dissolved in the blood or is bound to hemoglobin as O. O is detectable as in HO. O decreases the proton T2 relaxation time of water as the direct method of NMR/MRI measurement. The other method is indirect MRI measurement based on the enhancement of T1p relaxation of protons in water by O. CMRO and CBF can be measured with O NMR spectroscopy and MRI after inhalation of O. CBF can be measured with O NMR spectroscopy and MRI after injection of HO.