Background Although diffusion tensor imaging (DTI) fractional anisotropy (FA) is commonly used to quantify neural injury, it is non-specific and affected by a number of microstructural changes. Objective To examine alterations in white matter (WM) associated with neonatal encephalopathy (NE), and relate these to tangible biophysical changes using the neurite orientation dispersion and density imaging (NODDI) model. Design/Methods We recruited with parental consent consecutive encephalopathic neonates (Thompson score ≥6) admitted to Calicut Medical College, India over a 6 month period. At age <3 wk diffusion tensor magnetic resonance imaging (DTI, TR/TE = 2800 ms/94 ms, 20 directions, b = 0&1000 s/mm2, 1.8 × 1.8 × 5 mm3) was performed at 1.5T (Siemens Avanto). Sarnat encephalopathy stage (none, mild, moderate or severe) was allocated at day 3. DTI data were fitted to the NODDI model, generating maps of orientation dispersion index (ODI) and neurite density index (NDI). These were compared between infants grouped by encephalopathy severity using tract-based spatial statistics (TBSS). Results Fifty-four infants were recruited; 31 had usable data. The mean FA skeleton is shown in green (Figure 1a). Compared to normal/mild (n = 22) the moderate/severe encephalopathy group (n = 9) had significantly reduced WM FA (Figure 1b: red p < 0.05; yellow p < 0.01) and increased radial diffusivity (RD, Figure 1c). This corresponded to a decrease in NDI (Figure 1d), but not ODI (Figure 1e). Conclusions In this cohort, NODDI fitting indicates that microstructural changes in NE may be due to a reduced neurite density. Further work will establish whether these findings are consistent with those obtained from gold-standard multi-shell diffusion data. Abstract 8.9 Figure 1

Background: Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring hormone, anti-oxidant and cellular pro-survival factor, used safely in children with sleep disorders. Melatonin is beneficial following brain injury in adult animals. It is unknown if melatonin augments hypothermic neuroprotection in the developing brain.

A 27-year-old woman with a post-partum psychosis developed NMS which proved difficult to diagnose because of the organic features of the presenting illness. Possible contributory factors to the development of NMS included exhaustion, a non-specific viral illness, and rapid loading with haloperidol.

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. Abstract PC.45 Figure