To the Editor The Original Investigation by Veenith et al1 represents a fascinating and critical effort to elucidate the mechanisms of brain tissue hypoxia in patients with severe traumatic brain injury. The authors used 2 different positron emission tomographic protocols and tracers (oxygen 15–labeled positron emission tomography and fluorine 18–labeled fluoromisonidazole) in 10 patients with traumatic brain injury and 2 different control groups to describe pathophysiologic differences among ischemic and hypoxic brain areas. To be more precise, the authors attempted to differentiate ischemic from potentially nonischemic impairments in cerebral oxidative metabolism (as represented by cerebral oxygen metabolic rate [CMRO2] measurements). Ischemia was defined as a state of reduced cerebral blood flow, decreased CMRO2, and increased oxygen extraction fraction (OEF). Nonischemic (yet hypoxic) areas had similarly reductions in CMRO2 and cerebral blood flow, although they distinctly had not achieved an increase in OEF, a feature of shunt physiology. The authors explain this inability to extract more oxygen as a consequence of diffusion limitation based on their prior work.2 It should also be noted that all measurements of partial brain tissue oxygen tension were 16 mm Hg or greater and no brain around the partial brain tissue oxygen tension probes met criteria for either type of oxidative metabolism impairment.
Lazaridis C. Diffusion Hypoxia and/or Primary Mitochondrial Failure?. JAMA Neurol. 2016;73(11):1372-1373. doi:10.1001/jamaneurol.2016.3260