White matter NAA/Cho and Cho/Cr ratios at MR spectroscopy are predictive of motor outcome in preterm infants.
OBJECTIVE
To determine (a) whether diffuse white matter injury of prematurity is associated with an increased choline (Cho)-to-creatine (Cr) ratio and a reduced N-acetylaspartate (NAA)-to-Cho ratio and whether these measures can be used as biomarkers of outcome and (b) if changes in peak area metabolite ratios at magnetic resonance (MR) spectroscopy are associated with changes in T2 and fractional anisotropy (FA) at MR imaging.


METHODS
The local ethics committee approved this study, and informed parental consent was obtained for each infant. At term-equivalent age, 43 infants born at less than 32 weeks gestation underwent conventional and quantitative diffusion-tensor and T2-weighted MR imaging. Single-voxel point-resolved proton (hydrogen 1) MR spectroscopy was performed from a 2-cm(3) voxel centered in the posterior periventricular white matter. Outcome was evaluated by using Bayley scales at a corrected age of 1 year. Associations were investigated with Pearson product moment or Spearman rank order correlation. Differences in ratios in infants with and infants without impairment were tested by using t tests.


RESULTS
NAA/Cho and Cho/Cr ratios correlated with the scaled gross motor score and the composite motor score, independent of gestational age (P < .05). FA at diffusion-tensor MR imaging and T2 at MR imaging correlated with the NAA/Cho ratio (P < .05 for both) but not with the Cho/Cr ratio. Infants with motor scores of less than 85 (impaired) had an increased Cho/Cr ratio (P < .03) and a reduced NAA/Cho ratio (P < .01) compared to those without impairment. A combination of increased Cho/Cr ratio and decreased NAA/Cho ratio predicted impaired motor outcome at a corrected age of 1 year with a sensitivity of 0.80 (95% confidence interval [CI]: 0.57, 0.94) and a specificity of 0.80 (95% CI: 0.66, 0.88).


CONCLUSIONS
The combination of Cho/Cr and NAA/Cho ratios measured in the posterior periventricular white matter at term-equivalent age is predictive of motor outcome at 1 year in infants born at less than 32 weeks gestation.
From the Department of Academic Neonatology, EGA Institute for Women's Health (G.S.K., A.H.C., N.M., N.J.R.), and Centre for Medical Image Computing (A.M., S.O.), University College London, Medical School Building, 74 Huntley St, London WC1E 6AU, England; Department of Health Sciences, University of Leicester, Leicester, England (S.J.); Department of Medical Physics & Bioengineering, University College Hospital NHS Foundation Trust, London, England (D.P., A.B., E.B.C.); and Department of Neuroradiology, Great Ormond Street Hospital for Children NHS Trust, London, England (R.G.).
Giles S
GS
Kendall
Andrew
A
Melbourne
Samantha
S
Johnson
David
D
Price
Alan
A
Bainbridge
Roxanna
R
Gunny
Angela
A
Huertas-Ceballos
Ernest B
EB
Cady
Sebastian
S
Ourselin
Neil
N
Marlow
Nicola J
NJ
Robertson
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002657:Child Development; D002794:Choline / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009048:Motor Skills; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*
D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline