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. 2021 Oct 16;11(10):1360.
doi: 10.3390/brainsci11101360.

Diffusion Tensor Imaging Changes Do Not Affect Long-Term Neurodevelopment following Early Erythropoietin among Extremely Preterm Infants in the Preterm Erythropoietin Neuroprotection Trial

Janessa B Law  1 , Bryan A Comstock  2 , Todd L Richards  3 , Christopher M Traudt  1 , Thomas R Wood  1 , Dennis E Mayock  1 , Patrick J Heagerty  2 , Sandra E Juul  1
Affiliations

Diffusion Tensor Imaging Changes Do Not Affect Long-Term Neurodevelopment following Early Erythropoietin among Extremely Preterm Infants in the Preterm Erythropoietin Neuroprotection Trial

Janessa B Law et al. Brain Sci. .

Abstract

We aimed to evaluate diffusion tensor imaging (DTI) in infants born extremely preterm, to determine the effect of erythropoietin (Epo) on DTI, and to correlate DTI with neurodevelopmental outcomes at 2 years of age for infants in the Preterm Erythropoietin Neuroprotection (PENUT) Trial. Infants who underwent MRI with DTI at 36 weeks postmenstrual age were included. Neurodevelopmental outcomes were evaluated by Bayley Scales of Infant and Toddler Development (BSID-III). Generalized linear models were used to assess the association between DTI parameters and treatment group, and then with neurodevelopmental outcomes. A total of 101 placebo- and 93 Epo-treated infants underwent MRI. DTI white matter mean diffusivity (MD) was lower in placebo- compared to Epo-treated infants in the cingulate and occipital regions, and occipital white matter fractional isotropy (FA) was lower in infants born at 24-25 weeks vs. 26-27 weeks. These values were not associated with lower BSID-III scores. Certain decreases in clustering coefficients tended to have lower BSID-III scores. Consistent with the PENUT Trial findings, there was no effect on long-term neurodevelopment in Epo-treated infants even in the presence of microstructural changes identified by DTI.

Keywords: clustering coefficient; diffusion tensor imaging; erythropoietin; preterm.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CONSORT diagram of PENUT MRI cohort.
Figure 2
Figure 2
DTI comparison of Epo-treated and placebo-treated groups using ANTs analysis. MD differences seen in the sagittal (a), coronal (b), and axial (c) views. Highlighted areas signal regions in which the Epo treated group had significantly higher MD values compared to the placebo group prior to evaluation with multiple corrections. p-value color bar shown in (d).
Figure 3
Figure 3
DTI measures by treatment group. Manhattan plot of [GEE-based Wald test] -log (p-values) for differences in (a) regional DTI diffusion values and (b) clustering coefficients by treatment group. Panels (c,d) display boxplots of ROIs with MD values found to be significantly different in the cingulate and occipital white matter ROIs, respectively, by treatment group.
Figure 4
Figure 4
DTI measures by gestational age. Manhattan plots of [GEE-based Wald test] -log (p-values) for differences in (a) regional DTI diffusion values and (b) clustering coefficients by GA. Panel (c) displays boxplots of differences in the FA measurements in the occipital white matter region by GA, and panel (d) presents boxplots of clustering coefficients in the left thalamus found to be different by GA.
Figure 5
Figure 5
DTI measures by gestational age and treatment group. Manhattan plots of [GEE-based Wald test] -log (p-values) for differences in (a) regional DTI diffusion values and (b) clustering coefficients for the interaction between GA and treatment group. Panel (c) displays boxplots of clustering coefficients in the right precentral region that were significantly different [GEE-based Wald test] by GA and treatment group.
Figure 6
Figure 6
Association between DTI measures and BSID-III motor scores. Manhattan plots of [GEE-based Wald test] -log (p-values) for differences in (a) regional DTI diffusion values and (b) clustering coefficients by BSID-III motor scores. Panels (c,d) display scatterplots of BSID-III motor scores and statistically significant GEE-based associations with clustering coefficients. Red dots represent infants treated with Epo; black squares represent infants treated with placebo.
Figure 7
Figure 7
Association between DTI measures and BSID-III cognitive scores. Manhattan plots of [GEE-based Wald test] -log (p-values) for differences in (a) regional DTI diffusion values and (b) clustering coefficients by BSID-III cognitive scores. Panels (c,d) display scatterplots of BSID-III cognitive scores and statistically significant [GEE-based] associations in clustering coefficients. Red dots represent infants treated with Epo; black squares represent infants treated with placebo.
Figure 8
Figure 8
Association between DTI measures and BSID-III language scores. Manhattan plots of [GEE-based Wald test] -log (p-values) for differences in (a) regional DTI diffusion values and (b) clustering coefficients by BSID-III language scores. Panels (c,d) display scatterplots of BSID-III language scores and statistically significant [GEE-based] associations in clustering coefficients. Red dots represent infants treated with Epo; black squares represent infants treated with placebo.
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