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The aim of these studies was to provide reference data on intersubject variability and reproducibility of metabolite ratios for Choline/Creatine (Cho/Cr), N-acetyl aspartate/Choline (NAA/Cho) and N-acetyl aspartate/Creatine (NAA/Cr), and individual signal-intensity normalised metabolite concentrations of NAA, Cho and Cr. Healthy volunteers underwent imaging on two occasions using the same 3T Siemens Verio magnetic resonance scanner. At each session two identical Metabolic Imaging and Data Acquisition Software (MIDAS) sequences were obtained along with standard structural imaging. Metabolite maps were created and regions of interest applied in normalised space. The baseline data from all 32 volunteers were used to calculate the intersubject variability, while within session and between session reproducibility were calculated from all the available data. The reproducibility of measurements were used to calculate the overall and within session 95% prediction interval for zero change. The within and between session reproducibility data were lower than the values for intersubject variability, and were variable across the different brain regions. The within and between session reproducibility measurements were similar for Cho/Cr, NAA/Choline, Cho and Cr (11.8%, 11.4%, 14.3 and 10.6% vs. 11.9%, 11.4%, 13.5% and 10.5% respectively), but for NAA/Creatine and NAA between session reproducibility was lower (9.3% and 9.1% vs. 10.1% and 9.9%; p <0.05). This study provides additional reference data that can be utilised in interventional studies to quantify change within a single imaging session, or to assess the significance of change in longitudinal studies of brain injury and disease.

Ischemia and metabolic dysfunction remain important causes of neuronal loss after head injury, and we have shown that normobaric hyperoxia may rescue such metabolic compromise. This study examines the impact of hyperoxia within injured brain using diffusion tensor imaging (DTI). Fourteen patients underwent DTI at baseline and after 1 hour of 80% oxygen. Using the apparent diffusion coefficient (ADC) we assessed the impact of hyperoxia within contusions and a 1 cm border zone of normal appearing pericontusion, and within a rim of perilesional reduced ADC consistent with cytotoxic edema and metabolic compromise. Seven healthy volunteers underwent imaging at 21%, 60%, and 100% oxygen. In volunteers there was no ADC change with hyperoxia, and contusion and pericontusion ADC values were higher than volunteers (P<0.01). There was no ADC change after hyperoxia within contusion, but an increase within pericontusion (P<0.05). We identified a rim of perilesional cytotoxic edema in 13 patients, and hyperoxia resulted in an ADC increase towards normal (P=0.02). We demonstrate that hyperoxia may result in benefit within the perilesional rim of cytotoxic edema. Future studies should address whether a longer period of hyperoxia has a favorable impact on the evolution of tissue injury.