Jessica Lee Wisnowski PhD, Presenter: Nothing to Disclose

Tai-Wei Wu, Abstract Co-Author: Nothing to Disclose

Aaron Jordan Reitman DO, Abstract Co-Author: Nothing to Disclose

Robert Giesler RN, Abstract Co-Author: Nothing to Disclose

Eugenia Ho MD, Abstract Co-Author: Nothing to Disclose

Claire McLean, Abstract Co-Author: Nothing to Disclose

Phillip Friedlich, Abstract Co-Author: Nothing to Disclose

Istvan Seri MD, PhD, Abstract Co-Author: Grant, Covidien AG

Ashok Panigrahy MD, Abstract Co-Author: Nothing to Disclose

Marvin Dale Nelson MD, Abstract Co-Author: Nothing to Disclose

Stefan Bluml PhD, Abstract Co-Author: Nothing to Disclose

Phosphocreatine (PCr) provides a critical source of ATP when oxidative metabolism is impaired and is an in vivo biomarker for refractory energy failure. We investigated energy metabolism and key energy reserves, including PCr, during and after therapeutic hypothermia (TH) in neonates with suspected hypoxic-ischemic encephalopathy (HIE). 

We present results from 15 neonates (mean gestational age = 38.9 ± 1.9 weeks) with moderate-HIE (12) and severe-HIE (3), based on Sarnat staging, who underwent MRS during and after TH. MRS was acquired on a Philips 3.0T Achieva using a SV-PRESS sequence (TE = 35ms, TR = 2000ms) with regions of interest (ROIs) localized to the basal ganglia, thalamus and parietal grey matter. During TH, hypothermia was maintained using a Blanketrol system (CSZ Medical; modified with extension tubing) and continuously monitored with a rectal temperature probe. Absolute concentrations were quantitated using LCModel (V6.3-1C, Stephen Provencher). Paired t-tests were used to compare concentrations during and after TH while non-parametric tests (Mann-Whitney U) were used to compare neonates with moderate- and severe-HIE (SPSS v.21, IBM Corporation). 

Total Cr (=PCr + free creatine (fCr)) was 5% lower during TH relative to after rewarming (p < 0.05). However, PCr was 22% higher during TH while fCr was reduced by 23% (both p < 0.01). There were no differences observed for other metabolites associated with energy metabolism, i.e., levels of glucose, lactate, alanine, acetoacetate and acetone were indistinguishable during and after TH. Relative to those with moderate-HIE, neonates with severe-HIE had lower PCr, lower acetoacetate and concomitant elevations in lactate and alanine during and after TH (all p < 0.05). 

TH for neonatal HIE is associated with increased PCr; however, decreased PCr amongst neonates with severe-HIE, coupled with increased anaerobic metabolism, suggests ongoing energy failure in this subpopulation.

The findings from this study not only suggest that current TH protocols may be insufficient to mitigate energy failure in severe-HIE, but also suggest a new role for MRI in the acute management of HIE. 

Wisnowski, J, Wu, T, Reitman, A, Giesler, R, Ho, E, McLean, C, Friedlich, P, Seri, I, Panigrahy, A, Nelson, M, Bluml, S, Therapeutic Hypothermia Increases Phosphocreatine, A Critical ATP Reserve, in Neonatal Hypoxic-ischemic Encephalopathy: An In Vivo 1H MRS Investigation.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14015017.html