Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analyses

Objective: We explored macrostructural and microstructural changes in the hippocampal subregions of patients with type 2 diabetes mellitus (T2DM) and compared the effectiveness of neurite orientation dispersion and density imaging (NODDI) with that of traditional diffusion tensor imaging (DTI) and v...

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Main Authors: Xuan Huang, Ziyu Diao, Die Shen, Jianyu Li, Jiahe Wang, Kun Wang, Shijun Qiu
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025002291
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author Xuan Huang
Ziyu Diao
Die Shen
Jianyu Li
Jiahe Wang
Kun Wang
Shijun Qiu
author_facet Xuan Huang
Ziyu Diao
Die Shen
Jianyu Li
Jiahe Wang
Kun Wang
Shijun Qiu
author_sort Xuan Huang
collection DOAJ
description Objective: We explored macrostructural and microstructural changes in the hippocampal subregions of patients with type 2 diabetes mellitus (T2DM) and compared the effectiveness of neurite orientation dispersion and density imaging (NODDI) with that of traditional diffusion tensor imaging (DTI) and volumetric analysis in detecting structural alterations. Methods: A total of 302 participants (128 T2DM patients and 174 healthy controls) underwent 3.0-T magnetic resonance imaging and neuropsychological assessments. Hippocampal subregions were segmented and registered using FreeSurfer and SPM, with DTI and NODDI analyses being performed to assess microstructural changes. Neuropsychological and clinical data were further analyzed to explore correlations with cognitive function. Results: Significant microstructural alterations were observed in the hippocampal subregions of T2DM patients, with NODDI detecting abnormalities in approximately 70 % of the subregions, which were characterized by increased neurite density index (NDI), orientation dispersion index (ODI), and free water fraction (FWF) values, thus suggesting increased neurite density, disrupted orientation, and elevated free water content across most hippocampal subfields. DTI and NODDI analyses consistently identified the hippocampus-amygdala transition area (HATA) as a subregion that is particularly sensitive to microstructural changes in T2DM patients. Moreover, the NDI and FWF values were significantly correlated with cognitive performance, with the molecular layer and hippocampal tail exhibiting the strongest associations between microstructural indices and cognitive function. Conclusion: This study reveals microstructural alterations in the hippocampal subregions of T2DM patients, with particular changes being observed in the HATA region, moreover, this study highlights the advantages of the NODDI model in detecting these subtle changes, thereby providing important theoretical insights for future research.
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spelling doaj-art-561010aa1ffc4f44bcdbbeba498b21e32025-08-20T02:05:12ZengElsevierBrain Research Bulletin1873-27472025-08-0122811141710.1016/j.brainresbull.2025.111417Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analysesXuan Huang0Ziyu Diao1Die Shen2Jianyu Li3Jiahe Wang4Kun Wang5Shijun Qiu6The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou, China; Corresponding author at: Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.Objective: We explored macrostructural and microstructural changes in the hippocampal subregions of patients with type 2 diabetes mellitus (T2DM) and compared the effectiveness of neurite orientation dispersion and density imaging (NODDI) with that of traditional diffusion tensor imaging (DTI) and volumetric analysis in detecting structural alterations. Methods: A total of 302 participants (128 T2DM patients and 174 healthy controls) underwent 3.0-T magnetic resonance imaging and neuropsychological assessments. Hippocampal subregions were segmented and registered using FreeSurfer and SPM, with DTI and NODDI analyses being performed to assess microstructural changes. Neuropsychological and clinical data were further analyzed to explore correlations with cognitive function. Results: Significant microstructural alterations were observed in the hippocampal subregions of T2DM patients, with NODDI detecting abnormalities in approximately 70 % of the subregions, which were characterized by increased neurite density index (NDI), orientation dispersion index (ODI), and free water fraction (FWF) values, thus suggesting increased neurite density, disrupted orientation, and elevated free water content across most hippocampal subfields. DTI and NODDI analyses consistently identified the hippocampus-amygdala transition area (HATA) as a subregion that is particularly sensitive to microstructural changes in T2DM patients. Moreover, the NDI and FWF values were significantly correlated with cognitive performance, with the molecular layer and hippocampal tail exhibiting the strongest associations between microstructural indices and cognitive function. Conclusion: This study reveals microstructural alterations in the hippocampal subregions of T2DM patients, with particular changes being observed in the HATA region, moreover, this study highlights the advantages of the NODDI model in detecting these subtle changes, thereby providing important theoretical insights for future research.http://www.sciencedirect.com/science/article/pii/S0361923025002291T2DMNODDIDTIMicrostructureHippocampal subregions
spellingShingle Xuan Huang
Ziyu Diao
Die Shen
Jianyu Li
Jiahe Wang
Kun Wang
Shijun Qiu
Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analyses
Brain Research Bulletin
T2DM
NODDI
DTI
Microstructure
Hippocampal subregions
title Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analyses
title_full Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analyses
title_fullStr Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analyses
title_full_unstemmed Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analyses
title_short Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analyses
title_sort macrostructural and microstructural alterations of hippocampal subregions in t2dm noddi provides added value to dti and volumetric analyses
topic T2DM
NODDI
DTI
Microstructure
Hippocampal subregions
url http://www.sciencedirect.com/science/article/pii/S0361923025002291
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