Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia.

OBJECTIVE: To determine cerebral glucose concentration and its relationship with glucose infusion rate (GIR) and blood glucose concentration in neonatal encephalopathy during therapeutic hypothermia (TH). METHODS: This was an observational study in which cerebral glucose during TH was quantified by magnetic resonance (MR) spectroscopy and compared with mean blood glucose at the time of scan. Clinical data (gestational age, birth weight, GIR, sedative use) that could affect glucose use were collected. The severity and pattern of brain injury on MR imaging were scored by a neuroradiologist. Student t test, Pearson correlation, repeated measures ANOVA, and multiple regression analysis were performed. RESULTS: Three-hundred-sixty blood glucose values and 402 MR spectra from 54 infants (30 female infants; mean gestational age 38.6 ± 1.9 weeks) were analyzed. In total, 41 infants had normal-mild and 13 had moderate-severe injury. Median GIR and blood glucose during TH were 6.0 mg/kg/min (IQR 5-7) and 90 mg/dL (IQR 80-102), respectively. GIR did not correlate with blood or cerebral glucose. Cerebral glucose was significantly greater during than after TH (65.9 ± 22.9 vs 60.0 ± 25.2 mg/dL, P < .01), and there was a significant correlation between blood glucose and cerebral glucose during TH (basal ganglia: r = 0.42, thalamus: r = 0.42, cortical gray matter: r = 0.39, white matter: r = 0.39, all P < .01). There was no significant difference in cerebral glucose concentration in relation to injury severity or pattern. CONCLUSIONS: During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.

An In Vivo Assessment of Regional Brain Temperature during Whole-Body Cooling for Neonatal Encephalopathy.

OBJECTIVE: To assess differences in regional brain temperatures during whole-body hypothermia and test the hypothesis that brain temperature profile is nonhomogenous in infants with hypoxic-ischemic encephalopathy. STUDY DESIGN: Infants with hypoxic-ischemic encephalopathy were enrolled prospectively in this observational study. Magnetic resonance (MR) spectra of basal ganglia, thalamus, cortical gray matter, and white matter (WM) were acquired during therapeutic hypothermia. Regional brain tissue temperatures were calculated from the chemical shift difference between water signal and metabolites in the MR spectra after performing calibration measurements. Overall difference in regional temperature was analyzed by mixed-effects model; temperature among different patterns and severity of injury on MR imaging also was analyzed. Correlation between temperature and depth of brain structure was analyzed using repeated-measures correlation. RESULTS: In total, 53 infants were enrolled (31 girls, mean gestational age: 38.6 ± 2 weeks; mean birth weight: 3243 ± 613 g). MR spectroscopy was acquired at mean age of 2.2 ± 0.6 days. A total of 201 MR spectra were included in the analysis. The thalamus, the deepest structure (36.4 ± 2.3 mm from skull surface), was lowest in temperature (33.2 ± 0.8°C, compared with basal ganglia: 33.5 ± 0.9°C; gray matter: 33.6 ± 0.7°C; WM: 33.8 ± 0.9°C, all P < .001). Temperatures in more superficial gray matter and WM regions (depth: 21.9 ± 2.4 and 21.5 ± 2.2 mm) were greater than the rectal temperatures (33.4 ± 0.4°C, P < .03). There was a negative correlation between temperature and depth of brain structure (rrm = -0.36, P < .001). CONCLUSIONS: Whole-body hypothermia was effective in cooling deep brain structures, whereas superficial structures were warmer, with temperatures significantly greater than rectal temperatures.

Clinical Factors Associated with Cerebral Metabolism in Term Neonates with Congenital Heart Disease.

OBJECTIVE: To determine associations between patient and clinical factors with postnatal brain metabolism in term neonates with congenital heart disease (CHD) via the use of quantitative magnetic resonance spectroscopy. STUDY DESIGN: Neonates with CHD were enrolled prospectively to undergo pre- and postoperative 3T brain magnetic resonance imaging. Short-echo single-voxel magnetic resonance spectroscopy of parietal white matter was used to quantify metabolites related to brain maturation (n-acetyl aspartate, choline, myo- inositol), neurotransmitters (glutamate and gamma-aminobutyric acid), energy metabolism (glutamine, citrate, glucose, and phosphocreatine), and injury/apoptosis (lactate and lipids). Multivariable regression was performed to search for associations between (1) patient-specific/prenatal/preoperative factors with concurrent brain metabolism and (2) intraoperative and postoperative factors with postoperative brain metabolism. RESULTS: A total of 83 magnetic resonance images were obtained on 55 subjects. No patient-specific, prenatal, or preoperative factors associated with concurrent metabolic brain dysmaturation or elevated lactate could be identified. Chromosome 22q11 microdeletion and age at surgery were predictive of altered concurrent white matter phosphocreatine (P < .0055). The only significant intraoperative association found was increased deep hypothermic circulatory arrest time with reduced postoperative white matter glutamate and gamma-aminobutyric acid (P < .0072). Multiple postoperative factors, including increased number of extracorporeal membrane oxygenation days (P < .0067), intensive care unit, length of stay (P < .0047), seizures in the intensive care unit (P < .0009), and home antiepileptic use (P < .0002), were associated with reduced postoperative white matter n-acetyl aspartate. CONCLUSION: Multiple postoperative factors were found to be associated with altered brain metabolism in term infants with CHD, but not patient-specific, preoperative, or intraoperative factors.

Brain temperature in neonates with hypoxic-ischemic encephalopathy during therapeutic hypothermia.

OBJECTIVE: To noninvasively determine brain temperature of neonates with hypoxic-ischemic encephalopathy (HIE) during and after therapeutic hypothermia. STUDY DESIGN: Using a phantom, we derived a calibration curve to calculate brain temperature based on chemical shift differences in magnetic resonance spectroscopy. We enrolled infants admitted for therapeutic hypothermia and assigned them to a moderate HIE (M-HIE) or severe HIE (S-HIE) group based on Sarnat staging. Rectal (core) temperature and magnetic resonance spectroscopy data used to derive regional brain temperatures (basal ganglia, thalamus, and cortical gray matter) were acquired concomitantly during and after therapeutic hypothermia. We compared brain and rectal temperature in the M-HIE and S-HIE groups during and after therapeutic hypothermia using 2-tailed t-tests. RESULTS: Eighteen patients (14 with M-HIE and 4 with S-HIE) were enrolled. As expected, both brain and rectal temperatures were lower during therapeutic hypothermia than after therapeutic hypothermia. Brain temperature in patients with S-HIE was higher than in those with M-HIE both during (35.1 ± 1.3°C vs 33.7 ± 1.2°C; P < .01) and after therapeutic hypothermia (38.1 ± 1.5°C vs 36.8 ± 1.3°C; P < .01). The brain-rectal temperature gradient was also greater in the S-HIE group both during and after therapeutic hypothermia. CONCLUSION: For this analysis of a small number of patients, brain temperature and brain-rectal temperature gradient were higher in neonates with S-HIE than in those with M-HIE during and after therapeutic hypothermia. Further studies are needed to determine whether further decreasing brain temperature in neonates with S-HIE is safe and effective in improving outcome.