Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustment

IntroductionWhile 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 a...

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Main Authors: Benedictor Alexander Nguchu, Jing Zhao, Jiajun Fan, Yifei Han, Yu Lu, Han Jin, Yanming Wang, Hongjun Li, Peter Shaw
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1516168/full
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author Benedictor Alexander Nguchu
Benedictor Alexander Nguchu
Jing Zhao
Jiajun Fan
Yifei Han
Yu Lu
Han Jin
Yanming Wang
Hongjun Li
Peter Shaw
author_facet Benedictor Alexander Nguchu
Benedictor Alexander Nguchu
Jing Zhao
Jiajun Fan
Yifei Han
Yu Lu
Han Jin
Yanming Wang
Hongjun Li
Peter Shaw
author_sort Benedictor Alexander Nguchu
collection DOAJ
description IntroductionWhile 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.MethodsTo 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.ResultsOur 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).ConclusionWe 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.
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spelling doaj-art-b3daa76606c045f7bf67b2a10c44e8782025-08-20T03:53:46ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-05-011610.3389/fneur.2025.15161681516168Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustmentBenedictor Alexander Nguchu0Benedictor Alexander Nguchu1Jing Zhao2Jiajun Fan3Yifei Han4Yu Lu5Han Jin6Yanming Wang7Hongjun Li8Peter Shaw9Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaSchool of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaSchool of Electronic Engineering, Tianjin University of Technology and Education, Tianjin, China Tianjin, ChinaCenter for Biomedical Imaging, University of Science and Technology of China, Hefei, Anhui, ChinaDepartment of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaIntroductionWhile 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.MethodsTo 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.ResultsOur 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).ConclusionWe 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.https://www.frontiersin.org/articles/10.3389/fneur.2025.1516168/fullintracranial volumelateral ventricle volumebasal gangliaHippocampusthalamusregion volume proportion
spellingShingle Benedictor Alexander Nguchu
Benedictor Alexander Nguchu
Jing Zhao
Jiajun Fan
Yifei Han
Yu Lu
Han Jin
Yanming Wang
Hongjun Li
Peter Shaw
Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustment
Frontiers in Neurology
intracranial volume
lateral ventricle volume
basal ganglia
Hippocampus
thalamus
region volume proportion
title Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustment
title_full Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustment
title_fullStr Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustment
title_full_unstemmed Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustment
title_short Ventricular volume adjustment of brain regions depicts brain changes associated with HIV infection and aging better than intracranial volume adjustment
title_sort ventricular volume adjustment of brain regions depicts brain changes associated with hiv infection and aging better than intracranial volume adjustment
topic intracranial volume
lateral ventricle volume
basal ganglia
Hippocampus
thalamus
region volume proportion
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1516168/full
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