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PC.45 Quantification of N-Acetylaspartate Concentration in the Neonatal Brain: Initial Results from the Multi-Centre Marble Study
  1. PJ Lally1,
  2. SS Pauliah1,
  3. DL Price2,
  4. A Bainbridge2,
  5. S Addison1,
  6. A Soe3,
  7. S Pattnayak3,
  8. P Satodia4,
  9. SC Wayte4,
  10. E Ng’andwe4,
  11. P Clarke5,
  12. G Johnson5,
  13. S Harigopal6,
  14. PT English6,
  15. LJ Abernethy7,
  16. MA Turner7,
  17. J Cheong8,
  18. S Shankaran9,
  19. EB Cady2,
  20. S Thayyil1
  1. 1Imperial College, London, UK
  2. 2University College London Hospitals, London, UK
  3. 3Medway Maritime Hospital, Medway, UK
  4. 4Coventry and Warwickshire University Hospitals, Coventry, UK
  5. 5Norfolk and Norwich University Hospital, Norwich, UK
  6. 6Royal Victoria Infirmary, Newcastle
  7. 7Alder Hey Children’s Hospital, Liverpool, UK
  8. 8The Royal Women’s Hospital, Melbourne, Victoria, Australia
  9. 9Wayne State University, Detroit, Michigan, United States of America

Abstract

Background Early cerebral proton magnetic resonance spectroscopy (MRS) predicts medium-term outcomes in neonatal encephalopathy (NE). Metabolite peak-area ratios are most commonly used for prognosis, but conflate pathological information from different metabolites. N-acetylaspartate (NAA) is predominantly neuronal and neuronal loss should result in reduced NAA absolute-concentration ([NAA]). Thus, thalamic [NAA] should offer significant prognostic value but is difficult to measure in a clinical setting. We have established a protocol for multi-centre [NAA] measurement with the aim to use it as a surrogate biomarker in phase II clinical trials.

Objective To investigate the feasibility and utility of [NAA] quantitation across multiple centres.

Design/Methods We recruited cooled, term neonates with NE (by Sarnat grade) with parental consent across participating sites. Using various 3T scanners, thalamic MRS was performed aged 7 ± 4d (PRESS; water-suppressed TR = 2s/TE = 288/60 ms;TR/TE = 5s/60 ms; non-water-suppressed TR = 10s, TE = 60/124/205/316/495/1000 ms, ~30min acquisition). Spectra were post-processed in jMRUI and metabolite contributions determined with LCModel. [NAA] was calculated, correcting for T2 effects and cerebrospinal fluid partial volume.

Results Ten cases had sufficient data for [NAA] quantification. Sarnat grading <6h identified infants with highest [NAA] (median (IQR) 10.0(9.7–10.3) mmol/kg wet weight) as mild NE, with a lower [NAA] range for moderate NE (7.0(5.0–7.8) mmol/kg wet weight).

Conclusions [NAA] quantification is achievable in a multi-centre setting, and agrees with clinical NE grading during the therapeutic window. Follow-up examinations will allow comparison of neonatal [NAA] with later neurodevelopmental outcomes.

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