The thalamus is composed by more than thirty functional nuclei, each connected to specific subcortical and cortical areas (1). This complex hub structure is involved in a wide range of various brain functions such as motor, memory, attention and emotion (2), and has been shown to be affected in most of neurological diseases such as Alzheimer, Schizophrenia, or Multiple Sclerosis (3).

¹H-MRSI is a non-invasive method to explore brain metabolism but it suffers for a poor SNR inducing low spatial resolution which prevents to sample accurately the thalamic nuclei. Nevertheless, 7T MR scanners offer drastic increase in SNR, allowing to reach in time compatible with a clinical exams, 2D-MRSI with voxel size less than 0.1cm³, a spatial resolution sufficient to characterize the neurochemistry of the largest thalamic nuclei.

To determine if thalamic nuclei have specific metabolic fingerprints, we compare in 10 healthy volunteers, the metabolic patterns (relative NAA, Cr and Cho levels) of pulvinar, ventral-lateral, dorsal-medial and anterior nuclei using a high-resolution 2D-semilaser ¹H-MRSI sequence (4, 5) acquired at 7T. We hypothesize that the metabolic profiles of the various thalamic nuclei should be different relative to their functional specificity.

10 healthy volunteers (mean age = 24.5 years± 3, range = 22-32, 4 women, 6 men) gave their written consent to participate to the study, which was approved by the local ethics committee.

MRI: 7T MR explorations were performed on a 7T Magnetom step 2 system (Siemens, Erlangen, Germany), using a volumic transceiver/32-channel receiver head coil (NOVA). After localizer, third order B₀ shimming and B₁ calibration, sagittal T₁-weighted 3D-MP2RAGE was acquired as anatomical reference (TE/TR=3.13/5000ms, TI1/2=900ms/2750ms, FOV=240mm, voxel size=0.6*0.6*0.6mm³, flip angle_1/2 = 6°/5°, partitions = 256, Tacq=10.12min).

MRSI: After manual shimming optimization (water linewidth < 40Hz in VOI ), one axial 2D semi-laser ¹H-MRSI was acquired in the AC-PC plane, centered on thalami (TE/TR=59/2820ms, flip angle=90°, voxel size=3.1*3.1*10 mm³, FOV = 50*50*10 mm³, number of excitation = 8, bandwidth = 4000 Hz, matrix = 16*16, Tacq = 21.42 min) (Figure 1).

Post-processing: To locate more accurately the subparts of thalami, the Oxford thalamic connectivity atlas (6) was projected onto the T₁ weighted images of each subject (Figure 2). MRSI data were post-processed using the CSIAPO software (7). Eight voxels, each totally included in one region composed by a single type of cortical projection according to the atlas were selected and labeled as left or right i) pulvinar (areas projecting toward Parietal-temporal-occipital cortex) ii) ventral-lateral (areas projecting toward pre-central cortex), iii) dorsal-medial (area projecting toward frontal cortex) and iv) anterior (area projecting toward cingulate cortex). Peak fitting was performed using the AMARES (8) (CSIAPO). NAA, Cr and Cho peak areas were normalized by the sum of the three areas (NAA+Cr+Cho) and corrected for chemical shift artifact determined on water phantom measurements with shifted slice selection frequency corresponding to differences in frequency resonances of NAA, Cr and Cho.

ANOVA looking at differences in neurochemical profiles according to nuclei and hemispheres showed a significant global effect (F=5.49, p<0.0001) with significant (metabolism x hemisphere) interaction (p<0.0001), and (metabolism x nuclei) interaction (p=0.031).

Post-hoc Wilcoxon test (p<0.05 corrected for multiple comparisons) showed i) significant higher NAA, Cho and lower Cr levels within the right anterior nuclei relative to the left, ii) higher NAA, Cr and lower Cho levels in the left Pulvinar relative to the right and iii) higher NAA and lower Cho levels within the left ventral-lateral nucleus relative to the right (Figure 3abc). The neurochemical profiles were different Figure 4 (a-f) between the four nuclei, especially in the left hemisphere where NAA pulvinar > NAA ventrolateral > NAA dorsal-medial & NAA anterior (Kruskall Wallis p<0.05 corrected by Steel Dwass).

¹H-semi-laser 2D-MRSI at 7T (4) enabled to acquire high quality spectra with voxel size below 0.1 ml. For the first time, we demonstrate that the neurochemical profiles are different between the pulvinar, the anterior nucleus, the dorsal-medial nucleus and the ventral-lateral nucleus. Interestingly, the presence of left/right differences in neurochemical profiles, especially for NAA levels, showed a left NAA lateralization for the ventral-lateral nucleus and the pulvinar mostly connected to left lateralized prefrontal and temporal-parietal-occipital cortices respectively, and in contrast higher right NAA levels in the anterior nucleus mostly connected to the cingulate cortex. These results suggest that neurochemical profiles of nuclei may be related to their functional specificity.

Further works will aim at confirming these results on a larger cohort of healthy subjects accounting for age, sex and hand lateralization before exploring the specific metabolic disorders of each nucleus in patients suffering for various neurological diseases.