Comparison of Predictive Values of Magnetic Resonance Biomarkers Based on Scan Timing in Neonatal Encephalopathy Following Therapeutic Hypothermia

J Pediatr. 2021 Dec:239:101-109.e4. doi: 10.1016/j.jpeds.2021.08.011. Epub 2021 Aug 13.

Abstract

Objective: To determine the optimal quantitative magnetic resonance (MR) biomarker in neonatal encephalopathy following therapeutic hypothermia based on scan timing.

Study design: This retrospective study included 98 neonates (35-41 weeks of gestation) with neonatal encephalopathy, who underwent therapeutic hypothermia; diffusion-weighted imaging and proton MR spectroscopy were performed at 24-96 hours (n = 56) and 7-14 days (n = 92) after birth, respectively, to estimate apparent diffusion coefficient (ADC) values, N-acetylaspartate and N-acetylaspartylglutamate (tNAA), lactate, and choline concentrations, and lactate/tNAA, tNAA/choline ratios in the deep gray matter. Adverse outcomes included death or neurodevelopmental impairment at 18-22 months of age. We used receiver operating characteristic curves to examine the prognostic accuracy of each MR biomarker.

Results: Deep gray matter tNAA concentrations showed the best prognostic value, with an area under the curve (AUC) of 0.97 and 1.00 at 24-96 hours and 7-14 days after birth, respectively. At 24-96 hours of age, ADC values, lactate concentrations, and lactate/tNAA ratios showed prognostic value with AUCs of 0.90, 0.95, and 0.97, respectively. At 7-14 days of age, the AUCs of ADC values, lactate, and lactate/tNAA ratios were 0.61, 0.67, and 0.80, respectively; these were lower than those at 24-96 hours of age.

Conclusions: During the first 2 weeks of life, the deep gray matter tNAA concentration was the most accurate quantitative MR biomarker. Although ADC values, lactate levels, and lactate/tNAA ratios also showed high prognostic value during 24-96 hours of life, only tNAA retained high prognostic value in the second week of life.

Keywords: diffusion-weighted imaging; hypoxic ischemic encephalopathy; magnetic resonance spectroscopy; neurodevelopmental outcome; receiver operating characteristic curves analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Biomarkers / metabolism
  • Brain Diseases / diagnostic imaging*
  • Dipeptides / metabolism
  • Gray Matter / diagnostic imaging
  • Gray Matter / metabolism*
  • Humans
  • Hypothermia, Induced
  • Infant, Newborn
  • Lactic Acid / metabolism
  • Magnetic Resonance Imaging / methods*
  • Magnetic Resonance Spectroscopy
  • Predictive Value of Tests
  • Retrospective Studies
  • Severity of Illness Index

Substances

  • Biomarkers
  • Dipeptides
  • isospaglumic acid
  • Aspartic Acid
  • Lactic Acid
  • N-acetylaspartate