Abstract
INTRODUCTION: While the adjustment of intracranial volume (ICV) is reported to have a significant influence in the outcomes of the analyses of brain structural measures, our study offers a paradigm shift, positing that adjusting for lateral ventricle (LV) inter-individual variability may reveal more atrophic patterns that might be overlooked in analyses without this adjustment,-and such LV-adjusted atrophic patterns may reduce discrepancies observed in earlier studies and better elucidate complex conditions associated with HIV, such as HAND. METHODS: To test this hypothesis, we employed a number of adjustment strategies on MRI T1-image-derived data extracted using deep learning models and compared their ability to identify the presence and extent of HIV-specific atrophic patterns based on statistical measures and strength. RESULTS: Our results show that both ICV adjustments may be effective to identify atrophic patterns associated with either aging or HIV in areas of the thalamus, basal ganglia, ventral DC and lateral ventricle, some of which may be overlooked without these adjustments. We also report that LV adjustmenst detect most atrophic patterns associated with HIV and HAND across multiple subcortical regions with more strong statistical strengths, especially the areas of the basal ganglia (putamen, pallidum, caudate nucleus), hippocampus, thalamus, ventral DC, basal forebrain, third ventricle, fourth ventricle, and inferior lateral ventricle. The analyses of LV-adjusted metrics also show that atrophic patterns observed in the hippocampus, thalamus and pallidum were strongly correlated with HAND(especially dysfunction in executive function) and clinical markers (i.e., CD4/CD8 ratio). CONCLUSION: We conclude that models that control for individual variability in intracranial and ventricular volumes have the potential to minimize discrepancies and variations in structural reports of HIV, improving the diagnostic power of identified patterns and fostering greater consistency across research studies. More importantly, adjusting for LV may not only detect atrophic patterns that could be overlooked in analyses performed without any adjustments, but the outcomes obtained from the adjustments may better explain HIV-associated conditions such as HAND and underlying immunological issues often observed in subjects with HIV treated with combination antiretroviral therapy, considering that the adjustments account for certain aspects of regional interaction.