New Frontiers

There is increasing worldwide interest in developing new kinds of endogenous tracers based on molecules normally present in the human body that could be „labelled" in order to be detected on MRI. This would enable the same advantages to be obtained as for PET in terms of accurate quantitative evaluation of blood flow at lower cost without using radioactive isotopes.

Studies of these new endogenous tracers can be grouped under two major branches: research into oxy-gen-17 water (H217O) and studies of hyperpolarized molecules [7, 100-103]. In both approaches, studies are currently limited to animals, but promising results have been obtained, encouraging their extension to human research.

Oxygen-17 is a non-radioactive isotope that occurs naturally at low concentrations (0.038%) [7, 100]. When enriched and incorporated into a water molecule (H217O), it can be used as a weak MRI contrast agent, either imaged directly with a dedicated 17O-receiver coil or through the decrease in T2 that it causes in protons [7, 100, 102]. This molecule has ideal physiochemical properties for monitoring blood flow since it is freely diffusible in the extravascular compartment, is stable and is non-radioactive.

It is important to note that the mathematical model used for H215O PET can be directly applied to the 17O-method allowing true quantitative evaluation of CBF via a simple washout measurement, which is independent of delay and dispersion (measured in seconds), because the washout time is measured in minutes [7, 100].

Currently, a considerable limitation of this method is the high cost of enrichment even though it is likely to drop with increased demand. In order to reduce the costs some authors also proposed intra-arterial injection.

Another approach is based on hyperpolarized molecules. Conventional MRI depends on the high concentration of water protons because even at high field strengths the relative polarization (i.e. the number of excess spins directed along the main magnetic field) is very small, in the order of 1 in millions of spins.

Several methods can be adopted to create a non-equilibrium state in which polarization is so increased that imaging nuclei with far lower concentration than protons becomes feasible [7, 102]. Among these, the techniques based on electron-proton spin exchange rely on the concept that manipulation of electron spins using microwave energy can be transferred to the nu clear spins to create large non-equilibrium nuclear magnetization [7, 102].

Recently a system has been shown in which high degrees of polarization (up to 37%) of 13C and 15N nuclei can be created at an extremely low temperature in the solid state and then dissolved to liquid state at body temperature [7, 103]. This method offers a very high SNR (about 10,000) with a sensitivity equal or superior to conventional MRI. It has recently been applied to evaluate brain perfusion by using 13C attached to an in-travascularly confined small molecule [7, 103].

Advantages of these techniques include insensitivity to the static field (since the coils are tuned to the 13C resonance frequency) and to contamination due to recirculation (as the hyperpolarization is completely destroyed at the end of the pulse sequence) [7].

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