Influence of Glycemic Control on Endogenous Circulating Ketone Concentrations in Adults Following Traumatic Brain Injury.

BACKGROUND: The objective was to investigate the impact of targeting tight glycemic control (4.4-6.1 mM) on endogenous ketogenesis in severely head-injured adults. METHODS: The data were prospectively collected during a randomized, within-patient crossover study comparing tight to loose glycemic control, defined as 6.7-8.3 mM. Blood was collected periodically during both tight and loose glycemic control epochs. Post hoc analysis of insulin dose and total nutritional provision was performed. RESULTS: Fifteen patients completed the crossover study. Total ketones were increased 81 µM ([38 135], p < 0.001) when blood glucose was targeted to tight (4.4-6.1 mM) compared with loose glycemic control (6.7-8.3 mM), corresponding to a 60 % increase. There was a significant decrease in total nutritional provisions (p = 0.006) and a significant increase in insulin dose (p = 0.008). CONCLUSIONS: Permissive underfeeding was tolerated when targeting tight glycemic control, but total nutritional support is an important factor when treating hyperglycemia.

Longitudinal quantification and visualization of intracerebral haemorrhage using multimodal magnetic resonance and diffusion tensor imaging.

OBJECTIVE: To demonstrate a set of approaches using diffusion tensor imaging (DTI) tractography whereby pathology-affected white matter (WM) fibres in patients with intracerebral haemorrhage (ICH) can be selectively visualized. METHODS: Using structural neuroimaging and DTI volumes acquired longitudinally from three representative patients with ICH, the spatial configuration of ICH-related trauma is delineated and the WM fibre bundles intersecting each ICH lesion are identified and visualized. Both the extent of ICH lesions as well as the proportion of WM fibres intersecting the ICH pathology are quantified and compared across subjects. RESULTS: This method successfully demonstrates longitudinal volumetric differences in ICH lesion load and differences across time in the percentage of fibres which intersect the primary injury. CONCLUSIONS: Because neurological conditions such as intracerebral haemorrhage (ICH) frequently exhibit pathology-related effects which lead to the exertion of mechanical pressure upon surrounding tissues and, thereby, to the deformation and/or displacement of WM fibres, DTI fibre tractography is highly suitable for assessing longitudinal changes in WM fibre integrity and mechanical displacement.

pH-weighted molecular MRI in human traumatic brain injury (TBI) using amine proton chemical exchange saturation transfer echoplanar imaging (CEST EPI).

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTRasym at 3 ppm) in areas of T2 hyperintensity or edema (P < 0.0001), and a strong negative correlation with Glasgow Coma Scale (GCS) at the time of the MRI exam (R2 = 0.4777, P = 0.0021), Glasgow Outcome Scale - Extended (GOSE) at 6 months from injury (R2 = 0.5334, P = 0.0107), and a non-linear correlation with the time from injury to MRI exam (R2 = 0.6317, P = 0.0004). This evidence suggests clinical feasibility and potential value of pH-weighted amine CEST EPI as a high-resolution imaging tool for identifying tissue most at risk for long-term damage due to cerebral acidosis.