Early Metabolic Characteristics of Lesion and Nonlesion Tissue after Head Injury

Abstract

We defined lesion and structurally normal regions using magnetic resonance imaging at follow-up in patients recovering from head injury. Early metabolic characteristics in these regions of interest (ROIs) were compared with physiology in healthy volunteers. Fourteen patients with severe head injury had positron emission tomography within 72 h, and magnetic resonance imaging at 3 to 18 months after injury. Cerebral blood flow (CBF), oxygen utilization (CMRO(2)), and oxygen extraction fraction (OEF) were all lower in lesion ROIs, compared with nonlesion and control ROIs (P<0.001); however, there was substantial overlap in physiology. Control ROIs showed close coupling among CBF, blood volume (CBV), and CMRO(2), whereas relationships within lesion and nonlesion ROIs were abnormal. The relationship between CBF and CMRO(2) generally remained coupled but the slope was reduced; that for CBF and OEF was variable; whereas that between CBF and CBV was highly variable. There was considerable heterogeneity between and within patients. Although irreversibly damaged tissue is characterized by marked derangements in physiology, a more detailed analysis shows acute changes in physiology and physiologic relationships within regions of the brain that appear structurally normal at follow-up. Such pathophysiological derangements may result in selective neuronal loss and impact on functional outcome.

In vivo monitoring of neuronal loss in traumatic brain injury: a microdialysis study

“…New data suggest that short periods (1–2 h) of normobaric hyperoxia may improve the aerobic metabolism and cerebral blood flow (Shin et al ., 2007; Nortje et al ., 2008; Tisdall et al ., 2008). Additionally, there is considerable heterogeneity for cerebral blood flow and oxygen utilization between patients (Coles et al ., 2009). At present the routine clinical use of prolonged hyperoxia is not recommended (Diringer, 2008), but extracellular fluid NfH levels offer a potential safety biomarker for future trials investigating whether targeted short normobaric hyperoxia may emerge as a neuroprotective treatment strategy (Fig.…”

Pathophysiologic Mechanisms of Cerebral Ischemia and Diffusion Hypoxia in Traumatic Brain Injury

“…5 After TBI, increased FLAIR signal can disappear on sequential imaging 41 and is not predictive of pan necrosis for all lesion voxels. 5 Because derangements are often found in normal-appearing regions, 6 we examined the whole brain, but highlighted when these regions were found within the vicinity of lesions using standard magnetic resonance imaging sequences. The mean HBV found outside contusion and pericontusion areas was 30 (0-75) mL, and 4 participants had greater than 50 mL of such tissue.…”

“…Although other 15 O PET studies 3,4 have found less convincing evidence of ischemia, they typically demonstrate evidence of metabolic dysfunction that correlates with focal microdialysis. The relevance of such early physiologic derangements are evidenced by their association with local tissue fate, 5,6 chronic brain atrophy, 4 and clinical outcome. 1 Although nonischemic derangements after TBI 7 have been attributed to mitochondrial dysfunction, 3,8,9 studies have shown reductions in brain tissue PO 2 (PbtO 2 ).…”

Validation of reference tissue modelling for [11C]flumazenil positron emission tomography following head injury

“…Although it has been reported that there is some specific binding in pons [31], the use of the pons as a reference tissue for [ 11 C]FMZ has been validated in controls [6,[18][19][20][21][22] and other neuronal conditions [20,21]. Head injury is known to result in damage across the brain, even in regions which appear structurally normal [7,32]. Previous studies have failed to assess the impact this damage may have on PET Fig.…”