Hyperpolarized Magnetic Resonance Imaging and Spectroscopy of the Brain

The emergence of hyperpolarization, a method that can transiently increase magnetic resonance (MR) sensitivity of the 13 C and 15 N nuclei by up to 50- to 250,000-fold, in biomedical MR research is a little more than 10 years old. Due to the short lifetime of hyperpolarized precursors much of the initial focus has been on single reactions, particularly conversion of pyruvate to lactate in cancer. As a result very few hyperpolarized MR studies have involved the brain (the topic of this chapter). Here we describe the first generation of in vivo brain imaging and spectroscopy studies utilizing such methods with an emphasis on new neuroscience thereby illuminated. After more than a decade of effort it may be that hyperpolarization research is entering a “second generation” and new investigators have an opportunity to refocus on new goals. Knowing a little more about the strengths and weaknesses of hyperpolarization per se, and with the successful resolution of many of the problems inherent in ultrafast signal decay, recasting conventionally proton-only imaging to encompass the heteronuclei, four broad areas of potential application suggest themselves. First, can “hyperpolarization” inject new life into clinical neurospectroscopy, by its speed or its increased chemical specificity, thereby avoiding radioactivity and becoming the “poor man’s PET”? Might hyperpolarization of 13 C designer reagents for molecular and receptor imaging in the brain supplant PET? The answer in part depends upon an unresolved question: Does hyperpolarization of 13 C within a small-molecule imaging reagent survive tight binding with a protein receptor? Third, can we make a “virtue of necessity”’ given the (generally) very brief survival time of all hyperpolarized nuclei? These questions are addressed in this chapter including examples of promising initial work along these directions.