In vivo characterization of neuronal metabolism after stroke in rats as studied by 1H/13C MRS

Background and Aims: Acute loss of sensorimotor function after stroke is often followed by spontaneous functional recovery, which may be correlated with survival or recovery of neuronal tissue. Metabolic changes in neurons play a major role in brain pathophysiology, however, these changes have been incompletely characterized in relation to neuronal death, survival and recovery after stroke. Dynamic in vivo 1H/13C magnetic resonance spectroscopy (MRS) of incorporation of 13C-label into MRS-detectable glutamate (Glu) and glutamine (Gln) during infusion of 13C -labeled glucose can provide unique information on changes in glucose metabolism and glutamergic neurotransmission.1 The aim of the study was to assess differences in brain metabolism in lesion core, lesion borderzone and unaffected brain areas after experimental stroke in rats, using in vivo 1H/13C MRS. Methods: Transient focal cerebral ischemia was induced in male Wistar rats (n = 3) by 90-minutes intraluminal occlusion of the right middle cerebral artery.2 At three weeks after stroke, in vivo MR was performed on an 11.7 T horizontal bore MR sytem (Bruker BioSpin). Ischemic lesions were characterized using T2-weighted MRI. In addition, repetitive two-dimensional 1H-observed/13C-edited MRS imaging (MRSI)1 of a column through dorsal ipsi- and contralateral cerebral cortex was performed during infusion of 13C ?labeled glucose (spatial resolution: 1 ′ 2′ 5 mm3; temporal resolution: 11.1 minutes). From these experiments, dynamic incorporation of the 13C label into metabolic products Glu and Gln was measured. For data analysis, ipsilesional MRSI voxels were divided in three different regions based on T2 data: lesion core (T2 > mean contralateral T2 + 2SD); lesion border (voxel adjacent to T2-lesion area); healthy tissue. Homologous contralateral MRSI voxels served as control areas. Good sensitivity and optimal spectral resolution of the 1H/13C MR spectra allowed separate detection of [4-13C]Glu and [4-13C]Gln signals using the LCModel approach.3 Glu and Gln turnover were determined from [4-13C]Glu and [4-13C]Gln time curves in ipsi- and contralateral MRSI voxels. Results and Conclusions: In contralesional volumes, clear Glu and Gln turnover was observed. At three weeks after stroke, there was significant loss of Glu or Gln turnover in the lesion core (9 ± 14% and 25 ± 25%, resp., as compared to contralateral), reflective of severe neuronal damage. In perilesional regions, i.e. outside the T2 lesion area, Glu and Gln turnover were reduced (76 ± 11% and 74 ± 23%, resp., relative to contralateral). Thus, despite normal appearance on MRI, diminished Glu and Gln turnover point toward disturbed neuronal metabolism in perilesional tissue. Our study shows that dynamic in vivo 1H/13C MRSI can detect metabolically compromised tissue that appears unaffected on conventional MRI. Thereby, it may offer a unique tool to obtain detailed insights into neuronal tissue status in relation to functional loss and recovery after stroke.