Prognostic value of early, conventional proton magnetic resonance spectroscopy in cooled asphyxiated infants

Abstract

BackgroundNeonatal hypoxic-ischemic encephalopathy (HIE) commonly leads to neurodevelopmental impairment, raising the need for prognostic tools which may guide future therapies in time. Prognostic value of proton MR spectroscopy (H-MRS) between 1 and 46 days of age has been extensively studied; however, the reproducibility and generalizability of these methods are controversial in a general clinical setting. Therefore, we investigated the prognostic performance of conventional H-MRS during first 96 postnatal hours in hypothermia-treated asphyxiated neonates.MethodsFifty-one consecutive hypothermia-treated HIE neonates were examined by H-MRS at three echo-times (TE = 35, 144, 288 ms) between 6 and 96 h of age, depending on clinical stability. Patients were divided into favorable (n = 35) and unfavorable (n = 16) outcome groups based on psychomotor and mental developmental index (PDI and MDI, Bayley Scales of Infant Development II) scores (≥ 70 versus < 70 or death, respectively), assessed at 18–26 months of age. Associations between 36 routinely measured metabolite ratios and outcome were studied. Age-dependency of metabolite ratios in whole patient population was assessed. Prognostic performance of metabolite ratios was evaluated by Receiver Operating Characteristics (ROC) analysis.ResultsThree metabolite ratios showed significant difference between outcome groups after correction for multiple testing (p < 0.0014): myo-inositol (mIns)/N-acetyl-aspartate (NAA) height, mIns/creatine (Cr) height, both at TE = 35 ms, and NAA/Cr height at TE = 144 ms. Assessment of age-dependency showed that all 3 metabolite ratios (mIns/NAA, NAA/Cr and mIns/Cr) stayed constant during first 96 postnatal hours, rendering them optimal for prediction. ROC analysis revealed that mIns/NAA gives better prediction for outcome than NAA/Cr and mIns/Cr with cut-off values 0.6798 0.6274 and 0.7798, respectively, (AUC 0.9084, 0.8396 and 0.8462, respectively, p < 0.00001); mIns/NAA had the highest specificity (95.24%) and sensitivity (84.62%) for predicting outcome of neonates with HIE any time during the first 96 postnatal hours.ConclusionsOur findings suggest that during first 96 h of age even conventional H-MRS could be a useful prognostic tool in predicting the outcome of asphyxiated neonates; mIns/NAA was found to be the best and age-independent predictor.Electronic supplementary materialThe online version of this article (10.1186/s12887-018-1269-6) contains supplementary material, which is available to authorized users.

Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis

“…Twenty-two studies reported scoring methods to assess cerebral injury using T1-and T2-weighted imaging [4,18,20,23,27,34,35,38,39,[51][52][53][54][55][56][57][58][59][60][61][62][63]. Thirteen of those studies also used diffusion-weighted imaging (DWI) or [67] in 1 study, and a new score in the study of Weeke et al [63].…”

Predictors of Long-Term Neurodevelopmental Outcome of Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia

“…Diffusionweighted imaging (DWI) and MR spectroscopy are more sensitive to acute brain injury than conventional MRI in the first days of life. [100][101][102][103][104] For DWI, restricted diffusion can be seen in the first 24 hours after hypoxic-ischemic brain injury, will usually progress up to days 2 to 6, and then appear to normalize ("pseudonormalization"). 100,101,105 In HIE infants treated with therapeutic hypothermia, pseudonormalization occurs at approximately 11 to 12 days, versus 6 to 8 days in normothermic infants.…”

Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study

“…There are some aspects of the study that can be considered as limitations, the first is the retrospective nature of the data presented. A prospective trial could allow for better controlled patient selection, and could also lead to more consistent data acquisition, nevertheless clinical data obtained in a general setting is equally important [35]. While our data derived from 210 consecutive patients gives a cross sectional overview of the patient population we observed in a 9-year period, it has its own inconsistencies regarding imaging and follow-up, eventually leading to a relatively high rate of exclusion.…”

“…Trained pediatric radiologist blinded to the clinical history and neurodevelopmental results retrospectively evaluated the imaging signs of HIE and the presence and type of hemorrhage. HIE related abnormality was reported, when a lactate peak and relatively low values of normal metabolites (represented by Lac/NAA height ratios measured on MRS with TE = 144 ms) were present on MR-spectroscopy [34, 35] AND/OR HIE related diffusion restriction or signal abnormalities on T1- and T2 weighted images were present [36–38]. Predominantly basal-ganglia-thalamus pattern was reported when central grey matter nuclei and perirolandic cortex involvement was seen bilaterally with or without associated hippocampal and brain stem involvement and the absence of a normal high-signal intensity of the posterior limb of the internal capsule [37].…”