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An optimized single-shot proton double-quantum (DQ) filter for the quantification of ␥-aminobutyric acid (GABA) levels in human brain is reported. It is demonstrated that creation of DQ coherences following dual-resonance-selective refocusing gives a theoretical editing efficiency of 50% for the detection of the GABA resonance at 3.01 ppm. The sequence times are optimized with both numerical and experimental analyses of the editing performance, giving an experimental editing efficiency of 42%. It is acknowledged that homocarnosine is partially coedited, leading to a 20% contribution to the edited signal; however, macromolecule contamination is negligible in vivo under these experimental conditions. The GABA concentration in human prefrontal cortex is estimated to be 0.8 ؎ 0.1 mol/g (mean ؎ SD, n ‫؍‬ 6), with reference to the internal standard creatine at 9 mol/g. The in vivo measurement of ␥-aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, has considerable potential for the investigation of a wide variety of neurologic and psychiatric disorders. GABA is, however, difficult to measure using conventional 1 H MRS because of its low concentration and the spectral overlap of neighboring resonances. The overlap is usually overcome by means of some form of spectral editing that utilizes the scalar coupling evolution of the GABA spins. One example is double-quantum filtering (DQF), which provides an effective way for the selective detection of metabolites with coupled spins, because signals from uncoupled spins are completely eliminated, even in the presence of subject motion and inhomogeneity of static and RF fields. The 3.01-ppm GABA resonance, which is the primary target of many reported editing strategies (1-18), is potentially a benefactor of DQF detection because its principal background contamination is the uncoupled singlet from creatine (Cr). However, a significant shortcoming of the DQF methodology is its reduced signal yield, although design steps can often be taken to mitigate this loss of yield. One such design step for the GABA DQF enhanced the theoretical yield from 25 to 37.5% by utilizing the thermal equilibrium magnetization of both 3.01-and 1. 89-ppm resonances (19). Another is that recently reported by Shen et al. (15), who introduced a 180°pulse into the first echo period of a GABA DQF that was selective to 3.01 and 1.89 ppm. This pulse was designed and implemented for the suppression of unwanted signals, especially the macromolecule (MM) signal. Their implementation of the dual-banded 180°pulse reduced the contaminating background, thereby improving the resolution of the small GABA peak.In the present report, the DQF with dual-resonance refocusing is further extended for the detection of the 3.01-ppm resonance of GABA in human brain. Initially under Methods we exploit previous product-operator calculations to provide an intuitive, but preliminary estimate of the theoretical editing efficiency of the proposed sequence, which suggests a 50% yield. To our knowledge a...

In birds, the nucleus of the basal optic root (nBOR) of the accessory optic system (AOS) and the pretectal nucleus lentiformis mesencephali (LM) are involved in the analysis of optic flow and the generation of the optokinetic response. In several species, it has been shown that the AOS and pretectum receive input from visual areas of the telencephalon. Previous studies in pigeons using anterograde tracers have shown that both nBOR and LM receive input from the visual Wulst, the putative homolog of mammalian primary visual cortex. In the present study, we used retrograde and anterograde tracing techniques to further characterize these projections in pigeons. After injections of the retrograde tracer cholera toxin subunit B (CTB) into either LM or nBOR, retrograde labeling in the telencephalon was restricted to the hyperpallium apicale (HA) of the Wulst. From the LM injections, retrograde labeling appeared as a discrete band of cells restricted to the lateral edge of HA. From the nBOR injections, the retrograde labeling was more distributed in HA, generally dorsal and dorso-medial to the LM-projecting neurons. In the anterograde experiments, biotinylated dextran amine (BDA) was injected into HA and individual axons were reconstructed to terminal fields in the LM and nBOR. Those fibers projecting to the nBOR also innervated the adjacent ventral tegmental area. However, tracing of BDA-labeled axons revealed no evidence that individual neurons project to both LM and nBOR. In summary, our results suggest that the nBOR and LM receive input from different areas of the Wulst. We discuss how these projections may transmit visual and/or somatosensory information to the nBOR and LM.

A new proton NMR single-voxel spectral editing strategy for the rapid measurement of myo-inositol in human brain is proposed. The spectral editing detects the 4.06-ppm, weakly coupled resonance by means of selective J rewinding. An 84.6-ms-long quadruple-resonance selective 180°radiofrequency pulse, implemented within an adiabatic-refocused localization sequence, induces an in-phase triplet at 4.06 ppm, while eliminating the contribution from creatine, phosphorylethanolamine, lactate, and serine in this spectral region. The myo-inositol concentration in human prefrontal cortex is estimated to be 5.7 ؎ 0.9 mol/g (mean ؎ SD, n ‫؍‬ 7), with reference to NAA at 10 mol/g. Prior measurements of myo-inositol (mI) have focused on the multiplet at ϳ3.56 ppm; however, the spins associated with this multiplet are strongly coupled (1,2), and as a result, the signal degrades severely as the echo time increases (3). Measurements with short TE (4 -7) can be employed to minimize signal loss due to J evolution and spin-spin relaxation, but the relative contribution of macromolecule (MM) signals with much shorter T 2 consequently increases (8), mitigating some of the benefits from using a short TE. With the neighboring interferences of taurine, glutamate, glutamine, glutathione, etc., spectral fitting therefore must be employed to estimate the contribution of mI on a complex background. The glycine (Gly) resonance at 3.55 ppm also affects the measurement of the mI 3.56-ppm multiplet. Because the Gly spins are uncoupled, the resulting singlet cannot be neglected simply because of its low concentration. Separation between mI and Gly is not feasible with conventional spectroscopy methods. Although such separation can be achieved with multiple-quantum coherence filtering (9), the low intrinsic yield of this approach reduces its feasibility for clinical applications. It has been reported recently that coupledspin systems such as mI can be separated by means of a chemical-shift-selective two-dimensional filter (10). However, the encoding of NMR signals along two directions requires considerable measurement time to achieve an acceptable S/N ratio. The potential utility of mI measures and the limitations of current approaches indicate that a robust method for the measurement of mI is highly desirable.The current paper therefore proposes a new spectral editing strategy for the rapid, contamination-free measurement of mI in vivo, targeting its weakly coupled single-spin resonance at 4.06 ppm. An 84.6-ms-long quadruple-resonance selective 180°radiofrequency (RF) pulse, implemented within an adiabatic-refocused PRESS (point-resolved spectroscopy) sequence, is used to generate a triplet at 4.06 ppm. With this narrow-band editing pulse, the neighboring creatine (Cr) 3.92-ppm singlet, which is the major confound, is readily suppressed to noise level. Signals from additional contaminants, such as phosphorylethanolamine (PE), lactate (Lac), and serine (Ser), are also eliminated. Advantages of the new method are demonstrated using simulation and p...