Quantitative MRI Characterization of the Extremely Preterm Brain at Adolescence: Atypical versus Neurotypical Developmental Pathways

Abstract

Background Extremely preterm (EP) birth is associated with higher risks of perinatal white matter (WM) injury, potentially causing abnormal neurologic and neurocognitive outcomes. MRI biomarkers distinguishing individuals with and without neurologic disorder guide research on EP birth antecedents, clinical correlates, and prognoses. Purpose To compare multiparametric quantitative MRI (qMRI) parameters of EP-born adolescents with autism spectrum disorder, cerebral palsy, epilepsy, or cognitive impairment (ie, atypically developing) with those without (ie, neurotypically developing), characterizing sex-stratified brain development. Materials and Methods This prospective multicenter study included individuals aged 14-16 years born EP (Extremely Low Gestational Age Newborns-Environmental Influences on Child Health Outcomes Study, or ELGAN-ECHO). Participants underwent 3.0-T MRI evaluation from 2017 to 2019. qMRI outcomes were compared for atypically versus neurotypically developing adolescents and for girls versus boys. Sex-stratified multiple regression models were used to examine associations between spatial entropy density (SE_d) and T1, T2, and cerebrospinal fluid (CSF)-normalized proton density (nPD), and between CSF volume and T2. Interaction terms modeled differences in slopes between atypically versus neurotypically developing adolescents. Results A total of 368 adolescents were classified as 116 atypically (66 boys) and 252 neurotypically developing (125 boys) participants. Atypically versus neurotypically developing girls had lower nPD (mean, 557 10 × percent unit [pu] ± 46 [SD] vs 573 10 × pu ± 43; P = .04), while atypically versus neurotypically developing boys had longer T1 (814 msec ± 57 vs 789 msec ± 82; P = .01). Atypically developing girls versus boys had lower nPD and shorter T2 (eg, in WM, 557 10 × pu ± 46 vs 580 10 × pu ± 39 for nPD [P = .006] and 86 msec ± 3 vs 88 msec ± 4 for T2 [P = .003]). Atypically versus neurotypically developing boys had a more moderate negative association between T1 and SE_d (slope, -32.0 msec per kB/cm³ [95% CI: -49.8, -14.2] vs -62.3 msec per kB/cm³ [95% CI: -79.7, -45.0]; P = .03). Conclusion Atypically developing participants showed sexual dimorphisms in the cerebrospinal fluid-normalized proton density (nPD) and T2 of both white matter (WM) and gray matter. Atypically versus neurotypically developing girls had lower WM nPD, while atypically versus neurotypically developing boys had longer WM T1 and more moderate T1 associations with microstructural organization in WM. © RSNA, 2022 Online supplemental material is available for this article.

Graphical abstract

Figure 1:

Flowchart of participant selection from each of the 12 participating institutions. ELGAN-ECHO = Extremely Low Gestational Age Newborns–Environmental Influences on Child Health Outcomes, qMRI = quantitative MRI, TSE = turbo spin echo.

Figure 2:

Example triple turbo spin-echo brain MRI scans in (A) neurotypically developing and (B) atypically developing extremely preterm–born adolescents. Proton density (PD)–weighted, T2-weighted, and T1-weighted images are provided. MRI scans in the atypically developing participant (full-scale intelligence quotient <85) demonstrated qualitatively smaller white and gray matter volumes and nearly indistinguishable tissue contrast compared with the neurotypically developing participant.

Figure 3:

Multiparametric quantitative MRI parameters versus spatial entropy density (SE_d). Scatterplots and linear fitting of the mean (A) T1, (B) normalized proton density, and (C) T2 values versus SE_d of the white matter (WM) and gray matter (GM) for neurotypically and atypically developing extremely preterm (EP)–born adolescents. Differences in the associations of T1 and SE_d were observed in the WM between atypically and neurotypically developing boys. pu = percent unit.

Figure 4:

T2 versus cerebrospinal fluid (CSF) volume. Scatterplots and linear fitting of ventricular CSF relaxation times and volume for (A) boys and (B) girls. The presence of functional abnormality had limited impact on the association between the T2 relaxation and volume of CSF.