In vivo monitoring of rat brain metabolites during vigabatrin treatment using localized 2D‐COSY

Abstract

A two-dimensional COSY-based localization sequence was designed to allow the in vivo monitoring of proton metabolites in rat brain [particularly gamma-aminobutyric acid (GABA), glutamine, taurine and myo-inositol]. The sequence incorporated OSIRIS signal localization, B1-insensitive water suppression and phase-sensitive COSY acquisition. The method was used to study the effects of the GABA-transaminase inhibitor vigabatrin on rat brain metabolite concentrations. Wistar rats were treated daily for 3 days with an oral dose of vigabatrin (200 mg/kg, n = 4). Localized COSY spectra were obtained during a 120 min acquisition from a 270 microl central brain voxel and compared with nine untreated control animals. Significant elevations were observed in GABA (267% of control, p < 0.005, Mann-Witney test), glutamine (130% of control, p < 0.005) and taurine (113% of control, p < 0.05). Changes in GABA and taurine were consistent with previous data on the action of Vigabatrin, and support a previously hypothesized link between these compounds. The increase in glutamine was more surprising and may reflect the balance between the level and/or site of GABA-transaminase inhibition and downregulation of GABA synthesis.

In vivo 2D magnetic resonance spectroscopy of small animals

“…13) [66,110]. These studies were found to be even more effective when they were associated with intracerebral microdialysis to determine the extracellular amino acid contents [109].…”

“…These studies were found to be even more effective when they were associated with intracerebral microdialysis to determine the extracellular amino acid contents [109]. 2D COSY was first applied to the investigation of the GABA metabolism, with regard to its role in epilepsy [66,110], but its applications were later extended to the investigation of drugs involved in other fields, such as stroke and brain activation. With regard to stroke, Loubinoux et al [113] have investigated the direct effects on brain metabolism of a putative neuro-protector, MK801 a noncompetitive blocker of the NMDA sub-type of the cerebral glutamate receptor.…”

“…Some of them use conventional, 2D-correlation shift spectroscopy sequence placed before or after a localization sequence [63]. In this case, the localization can be performed using an outer volume suppression technique such as LOCUS (Localization of Unaffected Spins) [64], or by a volume-selective excitation method, such as SPACE (Spatial and Chemical-shift-encoded Excitation) [65], or ISIS [66]. All these sequences require several acquisitions to achieve complete localization, and methods that could achieve this in a single experiment would seem to be more appropriate.…”

Two-dimensional MR spectroscopy of healthy and cancerous prostates in vivo

“…This sequence has been successfully implemented and tested using both GE and Siemens 1.5 and 3 T whole-body MRI scanners. Other researchers have also reported the implementation of different versions of 2D COSY [100][101][102][103][104]. Figure 9 shows a 2D L-COSY spectrum of the same prostate phantom containing eight metabolites (Cit, Cr, Ch, PCh, PE, Spm, Tau and mI) which was used for recording JPRESS as in Fig.…”

A new strategy for in vivo spectral editing. Application to GABA editing using selective homonuclear polarization transfer spectroscopy

“…Essentially, most existing GABA editing methods fall into the following categories: (1) subtraction methods for canceling the full or partial intensity of overlapping creatine signal at 3.03 ppm based on the J interaction between GABA-3 and GABA-4 including the two-step spin-echo J editing methods [2][3][4][5][6][7][8] and the longitudinal two-spin order method [9]; (2) multiple quantum filtering methods for selection of GABA-3,4 double quantum (DQ) coherence while suppressing overlapping signals remaining in the single quantum state [10][11][12][13][14][15][16]; and (3) two-dimensional (2D) methods for separation of GABA-4 or GABA-3,4 cross-peaks from overlapping signals in the second spectral dimension [16][17][18]. The subtraction methods are very susceptible to movement, instrument instability, and magnetic field drifts.…”