In vivo ¹⁷O NMR approaches for brain study at high field

¹⁷O is the only stable oxygen isotope that can be detected by NMR. The quadrupolar moment of ¹⁷O spin (I = 5/2) can interact with local electric field gradients, resulting in extremely short T₁ and T₂ relaxation times which are in the range of several milliseconds. One unique NMR property of ¹⁷O spin is the independence of ¹⁷O relaxation times on the magnetic field strength, and this makes it possible to achieve a large sensitivity gain for in vivo ¹⁷O NMR applications at high fields. In vivo ¹⁷O NMR has two major applications for studying brain function and cerebral bioenergetics. The first application is to measure the cerebral blood flow (CBF) through monitoring the washout of inert H₂ ¹⁷O tracer in the brain tissue following an intravascular bolus injection of the ¹⁷O-labeled water. The second application, perhaps the most important one, is to determine the cerebral metabolic rate of oxygen utilization (CMRO₂) through monitoring the dynamic changes of metabolically generated H₂ ¹⁷O from inhaled ¹⁷O-labeled oxygen gas in the brain tissue. One great merit of in vivo ¹⁷O NMR for the determination of CMRO₂ is that only the metabolic H₂ ¹⁷O is detectable. This merit dramatically simplifies both CMRO₂ measurement and quantification compared to other established methods. There are two major NMR approaches for monitoring H₂ ¹⁷O in vivo, namely direct approach by using ¹⁷O NMR detection (referred as direct in vivo ¹⁷O NMR approach) and indirect approach by using ¹H NMR detection for measuring the changes in T₂- or T_1ρ-weighted proton NMR signals caused by the ¹⁷O-¹H scalar coupling and proton chemical exchange (referred as indirect in vivo ¹⁷O NMR approach). Both approaches are suitable for CBF measurements. However, recent studies indicated that the direct in vivo ¹⁷O NMR approach at high/ultrahigh fields appears to offer significant advantages for quantifying and imaging CMRO₂. New developments have further demonstrated the feasibility for establishing a completely noninvasive in vivo ¹⁷O NMR approach for imaging CMRO₂ in a rat brain during a brief ¹⁷O₂ inhalation. This approach should be promising for studying the central role of oxidative metabolism in brain function and neurological diseases. Finally, the similar approach could potentially be applied to image CMRO₂ noninvasively in human brain.