Short-echo, single-shot, full-intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: Validation in the cerebellum and brainstem

Short echo time (TE) 1H MR spectroscopy techniques are critical for extending the neurochemical information beyond NAA, creatine and choline as they facilitate the detection of brain metabolites with J-coupled spin systems, such as glutamate and glutamine. Short TE minimizes signal loss due to J-evolution and T2 relaxation, which is especially detrimental at high fields in the human brain where T2 values are relatively short (1,2). Neurochemical profiles have so far been mostly quantified using localization with the ultra-short TE stimulated-echo acquisition mode (STEAM) sequence (3–5), because T2 relaxation and J-evolution are negligible at ultra-short TE making metabolite quantification straightforward. However, the STEAM sequence utilizes only half of the available Mz magnetization, which limits the achievable spatial resolution of MRS that permits reliable metabolite quantification. Using the STEAM sequence to acquire spectra from small volumes in deep brain regions is even more difficult because the intrinsic sensitivity of volume RF coils is substantially lower than surface coils. While reasonably short TEs can be achieved with point resolved spectroscopy (PRESS) sequences that also utilize the full available Mz magnetization (6,7), the limited bandwidth of 180° refocusing pulses in these sequences may result in substantial chemical shift displacement errors at high fields. Recently, a new localization pulse sequence termed SPECIAL (spin echo full intensity acquired localization) was introduced (8), which enables full signal intensity acquisition at ultra-short TEs. The feasibility of obtaining neurochemical profiles with the SPECIAL sequence was successfully demonstrated in the rat (9) and human (10) brain. However, localization with this hybrid ISIS/spin echo sequence relies on an add-subtract scheme. Single-shot methods simplify frequency and phase correction of individual FIDs (11) and are therefore desirable for localized spectroscopy, especially in clinical populations where motion artifacts are frequently encountered (12). The localization by adiabatic selective refocusing (LASER) sequence (13) is a single-shot technique and also enables localization with full signal intensity, but requires relatively longer TEs because of 3 pairs of adiabatic 180° pulses. The TE of the LASER sequence can be shortened by replacing one of the 180° pairs by a slice selective excitation pulse in the so-called semi-LASER sequence (14), which enables TEs as short as 30 ms with a surface coil and 50 ms with a volume coil at 7T (15). The LASER sequence has the advantage that apparent T2 relaxation times of metabolites are longer than those measured with conventional Hahn spin echo sequences (1), resulting in less signal attenuation at longer TEs. In addition, J-evolution is partially suppressed in LASER due to the series of 180° pulses, also favoring signal retention. Further shortening of the TE of semi-LASER is desirable, especially for volume RF coils as the limited B1(max) of these coils require longer RF pulses. In addition, neurochemical profiles obtained at the longer TEs of semi-LASER relative to STEAM need to be validated in multiple brain regions such that the sequence can be utilized for neurochemical profiling in clinical populations. Specifically, the acceptability of approximations, such as neglecting a correction for T2 relaxation, needs to be investigated for absolute metabolite quantification. The aims of this study were 1) to design and optimize a single-shot, semi-adiabatic localization method with full signal intensity, short TE and minimal chemical shift displacement error and 2) to validate neurochemical profiling using this new sequence in multiple, clinically relevant brain regions in humans. To achieve these goals, we modified the semi-LASER sequence to minimize TE and then tested its performance at 4T with a surface and a volume RF coil. To validate neurochemical profiles obtained with the newly developed semi-LASER sequence, we compared neurochemical profiles quantified from semi-LASER and STEAM spectra acquired from the cerebellum and brainstem, brain regions affected in various movement disorders (16).