In vivo detection of (15)N-coupled protons in rat brain by ISIS localization and multiple-quantum editing

Three-dimensional image-selected in vivo spectroscopy (ISIS) was combined with phase-cycled (1)H-(15)N heteronuclear multiple-quantum coherence (HMQC) transfer NMR for localized selective observation of protons J-coupled to (15)N in phantoms and in vivo. The ISIS-HMQC sequence, supplemented by jump-return water suppression, permitted localized selective observation of 2-5 micromol of [(15)N(indole)]tryptophan, a precursor of the neurotransmitter serotonin, through the (15)N-coupled proton in 20-40 min of acquisition in vitro at 4.7 T. In vivo, the amide proton of [5-(15)N]glutamine was selectively observed in the brain of spontaneously breathing (15)NH(4)(+)-infused rats, using a volume probe with homogeneous (1)H and (15)N fields. Signal recovery after three-dimensional localization was 72-82% in phantoms and 59 +/- 4% in vivo. The result demonstrates that localized selective observation of (15)N-coupled protons, with complete cancellation of all other protons except water, can be achieved in spontaneously breathing animals by the ISIS-HMQC sequence. This sequence performs both volume selection and heteronuclear editing through an addition/subtraction scheme and predicts the highest intrinsic sensitivity for detection of (15)N-coupled protons in the selected volume. The advantages and limitations of this method for in vivo application are compared to those of other localized editing techniques currently in use for non-exchanging protons.