Improved localization, spectral quality, and repeatability with advanced MRS methodology in the clinical setting

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Proton magnetic resonance spectroscopy (1H MRS) provides a wealth of biochemical and metabolic information complementary to conventional structural MRI, as it enables noninvasive and regional quantification of endogenous neurochemicals. The international MRS Consensus Group has recently documented the clinical utility of MRS for diagnostic and prognostic purposes in common disorders of the central nervous system 1. The group also emphasized that a lack of quality assurance is a current impediment to widespread diagnostic and prognostic use in the clinical setting. Thus, the compromised data quality obtained with standard clinical MRS packages may result in poor reproducibility of neurochemical concentrations, thereby limiting clinical utility. Meanwhile, an increasing volume of high‐quality MRS data is being generated in the research setting from centers that specialize in MR methods development, as well as at sites that obtain advanced MRS protocols via customer‐to‐customer sequence transfer agreements. However, the feasibility of using such advanced MRS protocols, including nonstandard adjustments such as voxel‐based B0 and B1 calibrations 2, has not been evaluated in the clinical setting. Furthermore, the potential benefits of using an advanced MRS protocol over a conventional protocol for data quality have not been evaluated systematically by parallel acquisitions in the same MR session.
For clinical 1H MRS, stimulated echo acquisition mode (STEAM) 4 and point resolved spectroscopy (PRESS) 5 are the standard pulse sequences provided in commercial MRS packages. Although STEAM provides good localization due to high bandwidth of the 90° pulses, requires low radiofrequency (RF) power, and allows ultrashort echo time (TE), it produces only half the signal compared with a spin‐echo sequence. In comparison, PRESS retains full signal intensity and achieves relatively short TE (∼30 ms). However, because of increased spectral dispersion at 3 T and above, chemical shift displacement error (CSDE) becomes unacceptable with PRESS 6.
In contrast, several highly optimized pulse sequences, such as STEAM, SPECIAL and semi‐LASER (sLASER), have been used to generate high‐quality MRS data from healthy and diseased brain in the research setting 3. Of these, the sLASER sequence 13 provides single‐shot full‐intensity signal with clean localization and minimal CSDE as a result of high bandwidth adiabatic full‐passage (AFP) pulses. Pairs of AFP pulses in sLASER further suppress J‐evolution and prolong apparent transverse relaxation times (T2) 18. When combined with voxel‐based B0 and B1 calibration routines, sLASER was shown to provide neurochemical profiles with high within‐ 2 and between‐site reproducibility at 3 and 7 T 3. Of note, five major metabolites (N‐acetylaspartate (NAA), total creatine (tCr), total choline (tCho), glutamate (Glu), and myo‐inositol (Ins)) were quantified with a test‐retest coefficient of variance (CV) ≤ 5% from spectra averaged over 5 min 2.
Therefore, we chose to compare the vendor‐provided full‐intensity MRS protocol using the PRESS sequence with an advanced protocol that uses the sLASER sequence 14 that has been validated for within‐ and between‐site reproducibility 3. The aim of the study was to (i) evaluate the feasibility of executing an advanced MRS protocol in the clinical setting with rotating MR technologists, and (ii) compare the spectral quality and quantification precision between the standard vendor‐provided and the advanced protocols on a 3T scanner. We studied the posterior cingulate cortex (PCC) in a healthy elderly cohort, because of its role in age‐related neurodegenerative diseases such as Alzheimer's disease. Moreover, the technologists who participated in the study were well‐trained to position this voxel based on anatomical landmarks. Finally, the healthy elderly population presented a clinically relevant cohort with smaller brain volumes than a young cohort, and associated challenges for MRS such as compromised signal‐to‐noise ratio (SNR).

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