Department of Radiology & Tianjin Key Lab of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
Department of Medical Imaging, Henan Provincial People's Hospital, Zhengzhou 450003, China.
Neuroimage Clin. 2021;30:102619. doi: 10.1016/j.nicl.2021.102619. Epub 2021 Mar 8.
The purpose of this study was to investigate whether the large-scale structural rich club organization was abnormal in patients with Leber's hereditary optic neuropathy (LHON) using diffusion tensor imaging (DTI), and the associations among disrupted brain structural connectivity, disease duration, and neuro-ophthalmological impairment.
Nineteen acute, 34 chronic LHON patients, and 36 healthy controls (HC) underwent DTI and neuro-ophthalmological measurements. The brain structural network and rich club organization were constructed based on deterministic fiber tracking at the individual level. Then intergroup differences among the acute, chronic LHON patients and healthy controls (HC) in three types of structural connections, including rich club, feeder, and local ones, were compared. Network-based Statistics (NBS) was also used to test the intergroup connectivity differences for each fiber. Several linear and nonlinear curve fit models were applied to explore the associations among large-scale brain structural connectivity, disease duration, and neuro-ophthalmological metrics.
Compared to the HC, both the acute and chronic LHON patients had consistently significantly lower fractional anisotropy (FA) and higher radial diffusion (RD) for feeder connections (p < 0.05, FDR correction). Acute LHON patients had significantly lower FA and higher RD for local connections (p < 0.05, FDR correction). There was no significant difference in large-scale brain structural connectivity between acute and chronic LHON (p > 0.05, FDR correction). NBS also identified reduced FA of three feeder connections and five local ones linking visual, auditory, and basal ganglia areas in LHON patients (p < 0.05, FDR correction). No structural connections showed linear or nonlinear association with either disease duration or neuro-ophthalmological indicators (p > 0.05, FDR correction). A significant negative correlation was shown between the retinal nerve fiber layer (RNFL) thickness and disease duration (p < 0.05, FDR correction).
Abnormal rich club organization of the structural network was identified in both the acute and chronic LHON. Furthermore, our findings suggest the coexistence of both primary and secondary connectivity damage in the LHON.
本研究旨在通过弥散张量成像（DTI）探讨 Leber 遗传性视神经病变（LHON）患者是否存在大规模结构丰富俱乐部组织异常，并探讨脑结构连接中断与疾病持续时间和神经眼科损害之间的相关性。
19 例急性 LHON 患者、34 例慢性 LHON 患者和 36 例健康对照者（HC）接受了 DTI 和神经眼科测量。在个体水平上，基于确定性纤维追踪构建脑结构网络和丰富俱乐部组织。然后比较急性、慢性 LHON 患者与健康对照组（HC）在三种结构连接（包括丰富俱乐部、馈送和局部连接）之间的组间差异。还使用基于网络的统计学（NBS）来测试每种纤维的组间连接差异。应用几种线性和非线性曲线拟合模型来探讨大脑大尺度结构连接、疾病持续时间和神经眼科指标之间的相关性。
与 HC 相比，急性和慢性 LHON 患者的馈送连接的各向异性分数（FA）均显著降低，各向异性分数（RD）均显著升高（p<0.05，FDR 校正）。急性 LHON 患者的局部连接的 FA 显著降低，RD 显著升高（p<0.05，FDR 校正）。急性和慢性 LHON 患者的大脑大尺度结构连接无显著差异（p>0.05，FDR 校正）。NBS 还确定了 LHON 患者中三个馈送连接和五个连接视觉、听觉和基底神经节区域的局部连接的 FA 降低（p<0.05，FDR 校正）。没有结构连接与疾病持续时间或神经眼科指标呈线性或非线性相关（p>0.05，FDR 校正）。视网膜神经纤维层（RNFL）厚度与疾病持续时间呈显著负相关（p<0.05，FDR 校正）。
在急性和慢性 LHON 中均发现结构网络的丰富俱乐部组织异常。此外，我们的研究结果表明，LHON 中存在原发性和继发性连接损伤。
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