Publications Date
Authors
Sultan LR, Ramirez-Suarez KI, Schenkel SR, Schaeubinger MM, Cerron-Vela C, Kgole SW, Masasa G, Phale B, Makhema J, Mokane T, Lowenthal ED, Powis KM, Otero HJ.
Journal
Early Hum Dev.
PMID
40780081
DOI
10.1016/j.earlhumdev.2025.106368.
Abstract

Background: Over 1 million infants born annually with fetal exposure to HIV and maternal antiretroviral treatment (ART) who remain HIV-uninfected (HEU) are at higher risk of neurodevelopmental delays compared to infants HIV-unexposed (HU).

Objective: We explored the use of brain ultrasound radiomics, specifically texture analysis, as an early imaging neurodevelopmental biomarker, comparing findings by newborn in utero HIV exposure status.

Methods: Brain ultrasound was performed on full-term newborns (≥ 37 weeks gestation) enrolled in a prospective observational study in Botswana. Radiomic ultrasound features, including first-order statistics, run-length, and co-occurrence matrix parameters, were extracted from the basal ganglia and periventricular white matter. Statistical comparisons were conducted based on fetal exposure to maternal HIV. The diagnostic performance of individual features was assessed, and logistic regression was used to combine the features for overall performance evaluation.

Results: Thirty-three infants (HEU: 20, HU: 13) were included in the analysis. The basal ganglia of HEU infants exhibited significantly lower heterogeneity (176.6 ± 10.76 vs. 205.97 ± 13.26, p = 0.04) and entropy (0.37 ± 0.01 vs. 0.41 ± 0.01, p = 0.03), and marginally lower gray level non-uniformity (310.04 ± 15.32 vs. 352.37 ± 24.20, p = 0.06) compared to HU infants, suggesting reduced parenchymal complexity. These combined radiomic features yielded an AUC of 0.72 with a specificity of 0.86. Similar trends were observed in the white matter, where HEU infants demonstrated marginally lower heterogeneity (191.66 ± 14.32 vs. 231.76 ± 17.34, p = 0.06). Gray level non-uniformity and run length non-uniformity were significantly lower in the HEU group (1996.87 ± 157.06 vs. 2487.43 ± 223.67, p = 0.04 and 284.66 ± 20.37 vs. 406.61 ± 47.77, p = 0.01, respectively). The combined white matter model demonstrated an AUC of 0.76 and a sensitivity of 0.86, indicating greater discriminatory power compared to the basal ganglia.

Conclusion: Ultrasound radiomics reveals distinct differences in brain texture between HEU and HU newborns, with significant findings in both basal ganglia and white matter features. These results highlight the potential of radiomics in identifying subtle neuroanatomical variations. Further research is needed to explore the neurodevelopmental implications of these findings.

Keywords: Antiretroviral exposure; Basal ganglia; Brain ultrasound; Early brain development; HIV-exposed uninfected newborns; Neonatal neuroimaging; Neurodevelopmental risk assessment; Periventricular white matter; Quantitative imaging biomarkers; Radiomics.