School of Biological Science and Medical Engineering, Beihang University, Beijing 100069, China.
Department of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
Chin Med J (Engl). 2023 Sep 20;136(18):2178-2186. doi: 10.1097/CM9.0000000000002829. Epub 2023 Aug 22.
Changes in white matter (WM) underlie the neurocognitive damages induced by a human immunodeficiency virus (HIV) infection. This study aimed to examine using a bundle-associated fixel-based analysis (FBA) pipeline for investigating the microstructural and macrostructural alterations in the WM of the brain of HIV patients.
This study collected 93 HIV infected patients and 45 age/education/handedness matched healthy controls (HCs) at the Beijing Youan Hospital between January 1, 2016 and December 30, 2016.All HIV patients underwent neurocognitive evaluation and laboratory testing followed by magnetic resonance imaging (MRI) scanning. In order to detect the bundle-wise WM abnormalities accurately, a specific WM bundle template with 56 tracts of interest was firstly generated by an automated fiber clustering method using a subset of subjects. Fixel-based analysis was used to investigate bundle-wise differences between HIV patients and HCs in three perspectives: fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). The between-group differences were detected by a two-sample t -test with the false discovery rate (FDR) correction ( P <0.05). Furthermore, the covarying relationship in FD, FC and FDC between any pair of bundles was also accessed by the constructed covariance networks, which was subsequently compared between HIV and HCs via permutation t -tests. The correlations between abnormal WM metrics and the cognitive functions of HIV patients were explored via partial correlation analysis after controlling age and gender.
Among FD, FC and FDC, FD was the only metric that showed significant bundle-wise alterations in HIV patients compared to HCs. Increased FD values were observed in the bilateral fronto pontine tract, corona radiata frontal, left arcuate fasciculus, left corona radiata parietal, left superior longitudinal fasciculus III, and right superficial frontal parietal (SFP) (all FDR P <0.05). In bundle-wise covariance network, HIV patients displayed decreased FD and increased FC covarying patterns in comparison to HC ( P <0.05) , especially between associated pathways. Finally, the FCs of several tracts exhibited a significant correlation with language and attention-related functions.
Our study demonstrated the utility of FBA on detecting the WM alterations related to HIV infection. The bundle-wise FBA method provides a new perspective for investigating HIV-induced microstructural and macrostructural WM-related changes, which may help to understand cognitive dysfunction in HIV patients thoroughly.
人类免疫缺陷病毒（HIV）感染导致的神经认知损伤的基础是白质（WM）的变化。本研究旨在通过束相关固定点分析（FBA）管道，研究 HIV 患者脑 WM 的微观和宏观结构改变。
本研究于 2016 年 1 月 1 日至 2016 年 12 月 30 日期间，在北京佑安医院收集了 93 名 HIV 感染患者和 45 名年龄/教育/惯用手匹配的健康对照（HC）。所有 HIV 患者均进行神经认知评估和实验室检查，随后进行磁共振成像（MRI）扫描。为了准确检测束状 WM 异常，首先使用自动纤维聚类方法，使用部分受试者生成特定的 WM 束模板，其中包含 56 个感兴趣的束。利用基于固定点的分析，从三个方面研究了 HIV 患者和 HC 之间的束状差异：纤维密度（FD）、纤维横截面（FC）和纤维密度与横截面（FDC）。通过双样本 t 检验检测组间差异，采用虚假发现率（FDR）校正（P <0.05）。此外，还通过构建的协方差网络，评估了任意两束之间 FD、FC 和 FDC 的协变关系，然后通过置换 t 检验，在 HIV 和 HC 之间进行比较。在控制年龄和性别后，通过偏相关分析，探讨了 WM 异常指标与 HIV 患者认知功能的相关性。
在 FD、FC 和 FDC 中，FD 是 HIV 患者与 HC 相比唯一显示出明显束状改变的指标。与 HC 相比，HIV 患者双侧脑桥额部束、放射冠额部、左弓状束、左放射冠顶叶、左上纵束 III 和右额顶浅层束（SFP）的 FD 值均升高（均 FDR P <0.05）。在束状协方差网络中，与 HC 相比，HIV 患者表现出 FD 降低和 FC 增加的协变模式（P <0.05），特别是在相关通路之间。最后，几个束的 FC 与语言和注意力相关功能显著相关。
本研究表明 FBA 在检测与 HIV 感染相关的 WM 改变方面具有实用性。束状 FBA 方法为研究 HIV 引起的微观和宏观 WM 相关变化提供了新视角，有助于全面了解 HIV 患者的认知功能障碍。
