Longitudinal Relaxation Enhancement in ¹H NMR Spectroscopy of Tissue Metabolites via Spectrally Selective Excitation

Abstract

Nuclear magnetic resonance spectroscopy is governed by longitudinal (T1) relaxation. For protein and nucleic acid experiments in solutions, it is well established that apparent T1 values can be enhanced by selective excitation of targeted resonances. The present study explores such longitudinal relaxation enhancement (LRE) effects for molecules residing in biological tissues. The longitudinal relaxation recovery of tissue resonances positioned both down- and upfield of the water peak were measured by spectrally selective excitation/refocusing pulses, and compared with conventional water-suppressed, broadband-excited counterparts at 9.4 T. Marked LRE effects with up to threefold reductions in apparent T1 values were observed as expected for resonances in the 6-9 ppm region; remarkably, statistically significant LRE effects were also found for several non-exchanging metabolite resonances in the 1-4 ppm region, encompassing 30-50 % decreases in apparent T1 values. These LRE effects suggest a novel means of increasing the sensitivity of tissue-oriented experiments, and open new vistas to investigate the nature of interactions among metabolites, water and macromolecules at a molecular level.

Metabolic properties in stroked rats revealed by relaxation-enhanced magnetic resonance spectroscopy at ultrahigh fields

“…1). While numerous variants of this scheme can be conceived, a key common element is the avoidance of long-term perturbations of water or macromolecular resonances based on a RE strategy 25 . In RE MRS, the data are collected using a highly spectrally selective spin echo sequence targeting only the resonances of interest; for instance, the methyl peaks of Lac, NAA, Cre and Cho.…”

“…The method yields 1 H MRS with high signalto-noise ratio (SNR) per unit time by harnessing two complementary features: the use of a non-water-suppressed sequence 25 that benefits from an enhanced relaxation arising from selective frequency excitation 26 , and the execution of these experiments at ultrahigh magnetic fields for which 1 H MRS is greatly facilitated by polarization, spectral and-foremostrelaxation characteristics. Sensitized in this fashion, the duration of localized in vivo MRS measurements can be remarkably reduced, enabling the observation of novel, metabolite-specific behaviours based on restricted diffusion, relaxation and exchange.…”

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

“…The bulk water is, by RF pulse design, left nearly unperturbed and, therefore, does not attenuate signal arising from exchanging spins. Furthermore, in some cases, the large reservoir of unperturbed water can induce “relaxation enhancement,” polarization transfer and/or exchange that contributes to an apparent decrease in metabolite T 1 s. Such RE‐MRS experiments have been used for studying the downfield spectrum of fresh ex vivo rat brain and revealed relaxation enhancement effects . RE‐MRS was then extended to in vivo settings, where localization has been achieved using LASER, thereby enabling characterization of the downfield spectrum as well as providing a useful platform for imparting different contrast mechanisms, such as double‐diffusion‐encoding, for metabolic signals .…”

“…Short TE acquisition schemes could thus potentially “rescue” TE‐driven attenuation and increase the signal‐to‐noise ratio (SNR) of the measured signal. However, LASER localization is typically very demanding in terms of TE; RE‐MRS at 21.1T was performed using TEs around 60 ms. de Graaf and Behar managed to reduce the TE at 11.7T to 14 ms by using minimum‐phase excitation pulses and very short adiabatic refocusing pulses made possible using specialized hardware . Given that many of the downfield linewidths can approach (at least) ~50‐100 Hz at high magnetic fields, there would be a clear incentive for achieving even shorter TEs for downfield spectroscopy.…”

Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale

“…We demonstrated these remarkable improvements to 1 H MRS at 21.1 T in live rodent brains (Fig. 6) with spectra acquired in 6 s from a 125-µL volume and with SNR of 50:1 [64]. With this unprecedented SNR we can determine single-metabolite diffusion, providing clues into neuronal microstructure that might be obscured due to the contribution of bulk water.…”