Noninvasive assessment of brain injury in a canine model of hypothermic circulatory arrest using magnetic resonance spectroscopy

Background. Studies have confirmed the neuroprotective effect of diazoxide in canines undergoing hypothermic circulatory arrest ( HCA). A decreased N- acetyl- asparate: choline ( NAA: Cho) ratio is believed to reflect the severity of neurologic injury. We demonstrated that noninvasive measurement of NAA: Cho with magnetic resonance spectroscopy facilitates assessment of neuronal injury after HCA and allows for evaluation of neuroprotective strategies. Methods. Canines underwent 2 hours of HCA at 18 degrees C and were observed for 24 hours. Animals were divided into three groups ( n = 15 in each group): normal ( unoperated), HCA ( HCA only), and HCA + diazoxide ( pharmacologic treatment before HCA). The NAA: Cho ratios were obtained 24 hours after HCA by spectroscopy. Brains were immediately harvested for fresh tissue NAA quantification by mass spectrometry. Separate cohorts of HCA ( n = 16) and HCA + diazoxide ( n = 23) animals were kept alive for 72 hours for daily neurologic assessment. Results. Cortical NAA: Cho ratios were significantly decreased in HCA versus normal animals ( 1.01 +/- 0.29 versus 1.31 +/- 0.23; p = 0.004), consistent with severe neurologic injury. Diazoxide pretreatment limited neurologic injury versus HCA alone, reflected in a preserved NAA: Cho ratio ( 1.21 +/- 0.27 versus 1.01 +/- 0.29; p = 0.05). Data were substantiated with fresh tissue NAA extraction. A significant decrease in cortical NAA was observed in HCA versus normal ( 7.07 +/- 1.9 versus 8.54 +/- 2.1 mu mol/ g; p = 0.05), with maintenance of normal NAA levels after diazoxide pretreatment ( 9.49 +/- 1.1 versus 7.07 +/- 1.9 mu mol/ g; p = 0.0002). Clinical neurologic scores were significantly improved in the HCA + diazoxide group versus HCA at all time points. Conclusions. Neurologic injury remains a significant complication of cardiac surgery and is most severe after HCA. Magnetic resonance spectroscopy assessment of NAA: Cho ratios offers an early, noninvasive means of potentially evaluating neurologic injury and the effect of neuroprotective agents.