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Tract Based Spatial Statistics Analysis of White Matter Fractional Anisotropy in Neonatal Encephalopathy: Correlation with Thalamic Proton Magnetic Resonance Spectroscopy Metabolite Peak-Area Ratios

Presented at the Neonatal Society 2013 Spring Meeting.

Lally PJ1, Price DL2, Pauliah SS1, Shankaran S3, Guhan B4, Bainbridge A2, Cady EB2, Thayyil S1 on behalf of Peacock Trial Collaborators

1 Academic Neonatology, University College London, London, UK
2 Medical Physics & Bioengineering, University College London Hospitals, London, UK
3 Neonatal-Perinatal Division, Wayne State University, Detroit, USA
4 Neonatal Medicine, Calicut Medical College, Calicut, India

Background: Both white matter (WM) fractional anisotropy (FA) in magnetic resonance imaging (MRI) analysed by tract-based spatial statistics (TBSS) and thalamic proton magnetic resonance spectroscopy (MRS) metabolite peak-area ratios correlate with adverse neurological outcome following neonatal encephalopathy (1,2). TBSS WM changes correlate with short term morbidities and with conventional MRI grading (3,4), and MRS enables visualisation of WM injury associated with abnormal thalamic metabolism (the latter is poorly understood). 

Methods: Consecutive infants with neonatal encephalopathy (5 min Apgar score <5 and Thompson score >5 at <6 h age) admitted to Calicut Medical College over a 6-month period were recruited after parental consent. Conventional MRI, diffusion tensor imaging (DTI, 21 directions, b = 0 &1000 s/mm2) and MRS (echo time 288 ms, 37×8 echoes summed) were performed aged <3 wk at 1.5 Tesla (Siemens Avanto, Erlangen, Germany). MRS data were post-processed using jMRUI software (5,6). Image analysis used the FMRIB Software Library (7,8), incorporating a gestational age correction. The study was approved by the Calicut Medical College and University College London ethics committees.

Results: Fifty-four infants with neonatal encephalopathy were recruited; 12 were therapeutically cooled. Thirty-one had usable TBSS data of which 20 also had usable MRS results. Mean FA axial, coronal and sagittal image skeletons are shown in green (figure). Significantly reduced WM FA (yellow p<0.01; red p<0.05; see figure) was observed globally when thalamic N-acetylaspartate (NAA)/total choline (Cho) was ≤ 0.72 (2/20 infants). A small region of significant WM FA reduction was observed when lactate (Lac)/NAA was ≥ 0.29 (2/20 infants). WM FA was not associated with Lac/total creatine (Cr) (3/20 infants with Lac/Cr ≥ 0.39).

Tract Based Spatial Statistics Analysis of White Matter Fractional Anisotropy in Neonatal Encephalopathy: Correlation with Thalamic Proton Magnetic Resonance Spectroscopy Metabolite Peak-Area Ratios

Figure: Summary of TBSS results. Projections in 1b) are shown through more inferior and lateral slices which
better display the region of significant WM FA change.

Conclusion: TBSS WM FA correlated well with NAA/Cho and to a lesser extent with Lac/NAA, but not with Lac/Cr. Combining DTI and MRS biomarkers shows promise in highlighting characteristic thalamic metabolism and WM integrity abnormalities in neonatal encephalopathy. A large prospective international study qualifying such biomarkers is currently in progress (MARBLE: Magnetic Resonance Biomarkers in Neonatal Encephalopathy).

Corresponding author: peter.lally@ucl.ac.uk

1. Tusor N et al. 2012 Pediatr Res 72(1):63-9
2. Thayyil S et al. 2010 Pediatr Res 125(2):382-95
3. Thayyil S et al. 2011 Neonatal Society Autumn Meeting, London
4. Price DL et al. 2012 Proceedings of Eur Soc Magn Reson Med Biol 29th Annual Meeting, Lisbon, p114
5. van den Boogaart A 1996 Proceedings of Eur Soc Magn Reson Med Biol 13th Annual Meeting, Prague, p318
6. Vanhamme L et al. 1997 J Magn Reson 129(1):35-43
7. Smith S et al. 2004 NeuroImage 23(S1):208-19
8. Smith S et al. 2006 Neuroimage 31(4):1487-505

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