Improved reproducibility of MRS regional brain thermometry by 'amplitude-weighted combination'

Brain temperature is important in stroke and trauma. In birth asphyxia, hypothermia improves outcome, but local brain temperature information is needed to optimise therapy. The proton MRS water chemical shift (δ(water) ) is temperature dependent, and the in vivo brain temperature has often been estimated by measuring δ(water) relative to the N-acetylaspartate (NAA) singlet methyl resonance. However, the NAA peak amplitude may be reduced if cerebrospinal fluid occupies part of the MRS voxel and because of the lower concentration in immaturity, pathology and neonatal white matter. These factors can increase random and systematic δ(NAA) errors and also, therefore, MRS brain temperature errors. The aim of this study was to improve MRS brain temperature reproducibility and resilience to pathological, developmental and regional peak amplitude variations by amplitude-weighted combination (AWC) of brain temperatures (T(Cho) , T(Cr) and T(NAA) ) determined using the prominent choline (Cho), total creatine (Cr) and NAA resonances separately as chemical shift references. δ(water) - δ(Cho) , δ(water) - δ(Cr) and δ(water) - δ(NAA) were calibrated against tympanic temperature in piglet brain at 7 T (2.5-cm-diameter surface coil over the parietal lobes; binomial water suppression spin-echo sequence; TE = 540 ms; TR = 5 s). Eight normal human infants underwent thalamic region (Thal) and five occipito-parietal (OP) cerebral MRS at 2.4 T [point-resolved spectroscopy (PRESS) localisation; cubic voxel, 8 mL; water suppression off; TE = 270 ms; TR = 2 s]. AWC with T(Cho) , T(Cr) and T(NAA) weighted by the squared Cho, Cr and NAA peak amplitudes provided the smallest intersubject standard deviations: Thal, 0.45°C; OP, 0.33°C (for T(NAA) values of 0.65°C and 1.12°C, respectively). AWC provided resilience against simulated pathological alterations in Cho, Cr and NAA peak amplitudes, with Thal and OP T(AWC) changing by less than 0.04°C. AWC improves both intersubject reproducibility of MRS temperature estimation and resilience against pathological, anatomical and developmental variation of Cho, Cr and NAA peak amplitudes.