Introduction
Functional neuroimaging studies using positron emission tomography (PET) have demonstrated prolonged disturbance of oxidative metabolism following traumatic brain injury (TBI). Metabolic disturbance has been found in pericontusional brain areas, but may also extend well beyond the abnormal-appearing areas. Profoundly elevated interstitial lactate pyruvate ratio (LPR) measured in microdialysis studies on TBI patients also indicate the presence of oxidative metabolic disturbance within pericontusional and distant normal-appearing regions. We used 1 H Magnetic Resonance Spectroscopic Imaging (1H-MRSI) and microdialysis in acute TBI cases to determine whether 1H-MRSI is sensitive to the disturbance of oxidative metabolism that occurs in TBI.
Methods
We studied pericontusional versus normal N-acetylaspartate signal (NAA) and microdialysis versus NAA correlations in 15 and 6 (respectively) acute TBI subjects within 36 hours of injury by microdialysis and 1H-MRSI. 1H-MRSI was performed as part of a multiparametric 1.5 T MRI procedure with a Siemens Sonata MRI unit. 1H-MRSI acquisitions used the single slice (2-dimensional) chemical shift imaging pulse sequence as provided by the manufacturer with TR/TE = 1500/136 (msec). The spatial resolution was of 10 × 10 × 15 mm. Slice locations and volume excitation were adjusted to obtain spectra from regions within 10 mm of the microdialysis probe tip and pericontusional regions. 1H-MRSI acquisitions were performed at different brain locations, namely a supratentorial dorsal frontal-parietal region, and a middle fossa region incorporating the mesial temporal lobes and midbrain. Voxel spectra generated by the target regions (pericontusional, normal appearing white matter, and within 10 mm of the microdialysis probe) from the spectroscopic imaging arrays were selected for analysis. NAA levels were assessed using the manufacturer's software which performs non-linear curve fitting of the spectra. Absolute signal levels were determined by calibration against a phantom having known NAA concentrations.
Results
Identification and quantification of lactate MRS signal was frequently complicated by the presence of large lipid signals that most often originated in the corners of the large selected volumes used in this study. Importantly, however, NAA signal was not affected by this localization artifact. NAA signal was reduced in pericontusional regions by 51% compared with normal appearing white matter (p = 0.0030). An inverse logarithmic relationship was found between LPR and NAA level (p = 0.0027, r2 = 0.92) and between LPR and NAA/CR (p = 0.0052, r2 = 0.88) measured in the vicinity of the microdialysis probe. No statistically significant correlations between the other MRS metabolites (lactate, creatine, choline) and LPR were found, suggesting that the NAA findings are the result of a disturbance in NAA metabolism rather than overall cell loss. Further study is underway to establish whether the NAA signal losses are the result of metabolic dysfunction or tissue loss.
Conclusion
The results suggest that NAA measures made by 1H-MRSI are sensitive to oxidative metabolic disturbance following TBI. 1H-MRSI may therefore provide a safer alternative to PET functional neuroimaging and microdialysis for the identification of oxidative stress in acute TBI.