期刊
JAMA NEUROLOGY
卷 73, 期 5, 页码 542-550出版社
AMER MEDICAL ASSOC
DOI: 10.1001/jamaneurol.2016.0091
关键词
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资金
- National Institute of Academic Anaesthesia
- Raymond Beverly Sackler studentship
- Societe Francaise d'Anesthesie et de Reanimation
- Health Foundation/Academy of Medical Sciences
- National Institute for Health Research
- Wellcome Trust [WT093267]
- Medical Research Council [G9439390 ID 65883]
- UK National Institute of Health Research Biomedical Research Centre at Cambridge
- UK Department of Health
- MRC [G9439390] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-CSF4-Newcombe] Funding Source: researchfish
- Medical Research Council [G1000183B] Funding Source: researchfish
- National Institute for Health Research [ACF-2009-14-007] Funding Source: researchfish
IMPORTANCE Combined oxygen 15-labeled positron emission tomography (O-15 PET) and brain tissue oximetry have demonstrated increased oxygen diffusion gradients in hypoxic regions after traumatic brain injury (TBI). These data are consistent with microvascular ischemia and are supported by pathologic studies showing widespread microvascular collapse, perivascular edema, and microthrombosis associated with selective neuronal loss. Fluorine 18-labeled fluoromisonidazole ([F-18]FMISO), a PET tracer that undergoes irreversible selective bioreduction within hypoxic cells, could confirm these findings. OBJECTIVE To combine [F-18]FMISO and O-15 PET to demonstrate the relative burden, distribution, and physiologic signatures of conventional macrovascular and microvascular ischemia in early TBI. DESIGN, SETTING, AND PARTICIPANTS This case-control study included 10 patients who underwent [F-18]FMISO and O-15 PET within 1 to 8 days of severe or moderate TBI. Two cohorts of 10 healthy volunteers underwent [F-18]FMISO or O-15 PET. The study was performed at the Wolfson Brain Imaging Centre of Addenbrooke's Hospital. Cerebral blood flow, cerebral blood volume, cerebral oxygen metabolism (CMRO2), oxygen extraction fraction, and brain tissue oximetry were measured in patients during [F-18]FMISO and O-15 PET imaging. Similar data were obtained from control cohorts. Data were collected from November 23, 2007, to May 22, 2012, and analyzed from December 3, 2012, to January 6, 2016. MAIN OUTCOMES AND MEASURES Estimated ischemic brain volume (IBV) and hypoxic brain volume (HBV) and a comparison of their spatial distribution and physiologic signatures. RESULTS The 10 patients with TBI (9 men and 1 woman) had a median age of 59 (range, 30-68) years; the 2 control cohorts (8 men and 2 women each) had median ages of 53 (range, 41-76) and 45 (range, 29-59) years. Compared with controls, patients with TBI had a higher median IBV (56 [range, 9-281] vs 1 [range, 0-11] mL; P < .001) and a higher median HBV (29 [range, 0-106] vs 9 [range, 1-24] mL; P = .02). Although both pathophysiologic tissue classes were present within injured and normal appearing brains, their spatial distributions were poorly matched. When compared with tissue within the IBV compartment, the HBV compartment showed similar median cerebral blood flow (17 [range, 11-40] vs 14 [range, 6-22] mL/100 mL/min), cerebral blood volume (2.4 [range, 1.6-4.2] vs 3.9 [range, 3.4-4.8] mL/100 mL), and CMRO2 (44 [range, 27-67] vs 71 [range, 34-88] mu mol/100 mL/min) but a lower oxygen extraction fraction (38%[range, 29%-50%] vs 89%[range, 75%-100%]; P < .001), and more frequently showed CMRO2 values consistent with irreversible injury. Comparison with brain tissue oximetry monitoring suggested that the threshold for increased [F-18]FMISO trapping is probably 15 mm Hg or lower. CONCLUSIONS AND RELEVANCE Tissue hypoxia after TBI is not confined to regions with structural abnormality and can occur in the absence of conventional macrovascular ischemia. This physiologic signature is consistent with microvascular ischemia and is a target for novel neuroprotective strategies.
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