Multimodal magnetic resonance neuroimaging measures characteristic of early cART-treated pediatric HIV: A feature selection approach

Abstract

Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV-related brain alterations can be investigated separately using proton magnetic resonance spectroscopy (¹ H-MRS), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI), a set of multimodal MRI measures characteristic of children on cART has not been previously identified. We used the embedded feature selection of a logistic elastic-net (EN) regularization to select neuroimaging measures that distinguish CPHIV from controls and measured their classification performance via the area under the receiver operating characteristic curve (AUC) using repeated cross validation. We also wished to establish whether combining MRI modalities improved the models. In single modality analysis, sMRI volumes performed best followed by DTI, whereas individual EN models on spectroscopic, gyrification, and cortical thickness measures showed no class discrimination capability. Adding DTI and ¹ H-MRS in basal measures to sMRI volumes produced the highest classification performance $\left(\text{validation accuracy}=85\%,\mathrm{AUC}=0.80\right)$ . The best multimodal MRI set consisted of 22 DTI and sMRI volume features, which included reduced volumes of the bilateral globus pallidus and amygdala, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the right corticospinal tract in cART-treated CPHIV. Consistent with previous studies of CPHIV, select subcortical volumes obtained from sMRI provide reasonable discrimination between CPHIV and controls. This may give insight into neuroimaging measures that are relevant in understanding the effects of HIV on the brain, thereby providing a starting point for evaluating their link with cognitive performance in CPHIV.

Keywords: DTI; HIV; MR spectroscopy; MRI; classification; elastic net; neuroimaging; pediatric; regularization; sMRI.

FIGURE 1

Illustration of classification and feature selection using repeated 10‐fold cross validation employed in this study.

FIGURE 2

Anatomical locations of the relevant features from the sMRI volume feature set. The sMRI volumes were from an automatic segmentation with FreeSurfer (Fischl et al., 2002). CWM, cerebellar white matter; CC, corpus callosum; CSF, cerebrospinal fluid).

FIGURE 3

Selected relevant DTI tracts. The regions of interest for the DTI feature set were from the John Hopkins University (JHU) atlas (Mori et al., 2005).

FIGURE 4|

Four extra features that appear in the multimodal analysis and were not part of the single modality analyses of sMRI volumes and DTI. These are in addition to all except three (right choroid plexus and ventral diencephalon, and posterior corpus callosum) of the sMRI features in Figure 2 and the DTI tracts, except left corticospinal tract, in Figure 3. The DTI regions of interest are from the John Hopkins University (JHU) atlas (Mori et al., 2005) and the sMRI volumes from FreeSurfer (Fischl et al., 2002).