Elucidation of the downfield spectrum of human brain at 7 T using multiple inversion recovery delays and echo times

Abstract

Methods: This work includes water-suppressed echo time and inversion recovery series in healthy volunteers to investigate, respectively, T 2 and T 1 values of peaks in grey matter at 7T.The spectra were fitted in a 2D fashion to a heuristic model of a series of Voigt lines, and the relaxation times were obtained for twelve peaks of interest. Results

Short echo time relaxation‐enhanced MR spectroscopy reveals broad downfield resonances

“…The spectral peaks appearing between 6.5 and 7.5 ppm (‘b’ , ‘c’ , ‘d’ , and ‘e’ in Figure ) probably originate from metabolites such as ATP, creatine, phosphocreatine or glutamine . The multiple peaks in the range between 8 and 8.5 ppm (labeled ‘a’ , ‘f’ , and ‘g’ in Figure ) likely arise from amide protons in peptides/proteins and/or metabolites such as glutathione and homocarnosine .…”

“…5,6,11 The exchanging nature of downfield signals and the inherent line broadening associated with exchange suggests that downfield MRS can significantly benefit from TE reduction. In previous studies, short-TE MRS 39 has already been used for downfield MRS with minimal TEs of the order of 10-13 ms. 30,31 However, broadband excitation and STEAM were necessary, carrying a 50% signal penalty and a mixing time period that could facilitate proton exchange with saturated water. de Graaf and Behar 33 reached TEs as short as 14 ms using minimum phase pulses and LASER localization but harnessing unconventional high-performance gradient systems and RF power.…”

“…D, Enhanced view of (B) from metabolites such as ATP, creatine, phosphocreatine or glutamine. 31 The multiple peaks in the range between 8 and 8.5 ppm (labeled 'a', 'f', and 'g' in Figure 6) likely arise from amide protons in peptides/proteins and/or metabolites such as glutathione and homocarnosine. 42 The spectral range from ~8.8 to 10 ppm exhibits 3 small peaks (labeled 'h', 'I', and 'j' in Figure 6) that probably correspond to the H2, H6, and H4 proton resonances in NAD + previously reported at a higher field strength.…”

“…ISIS, on the other hand, localizes the volume of interest (VOI) using slice-selective inversion pulses that follow a Hadamard scheme 13 thereby canceling signals outside of the VOI, 14 followed by a spectrally-selective broadband excitation. Typically, the short excitation pulse will be immediately followed by acquisition, furnishing ISIS with very short TE capabilities and making it particularly useful for acquiring signals arising from short T 2 spins, such as e.g., 31 P. [15][16][17][18][19] The vast majority of MRS studies explored the spectral region upfield of water, which contains, among others, nonoxygenated aliphatic protons, aliphatic/aromatic acetoxyl protons, as well as methoxy protons. 20 However, the spectrum downfield of the water signal is very rarely investigated by MRS, even though it contains highly relevant chemical functional groups, such as hydroxyls, amines, amides, aldehydes, aromatic, and carboxylic protons, among others.…”

“…Some of the downfield signals have been tentatively assigned, in particular, the amide peak around 7.8 ppm was assigned to N-acetyl aspartate (NAA) (although other amides cannot be a priori ruled out), homocarnosine at 7.05 and 8.02 ppm, α-glucose at 5.22 ppm and NAD + in the range 8.7-9.5 ppm. 22,31,33 Relaxation-enhanced MRS (RE-MRS) 34,35 has been recently proposed as a powerful method for downfield spectroscopy. RE-MRS avoids water presaturation by foregoing broadband perturbations, rather replacing them with frequency-selective pulses targeting only resonances (or spectral bands) of interest.…”