Data_Sheet_1_Diffusion and functional MRI reveal microstructural and network connectivity impairment in adult-onset neuronal intranuclear inclusion disease.docx

ObjectivesNeuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable neuroimaging biomarkers. This study aimed to evaluate microstructural and functional connectivity alterations using diffusion kurtosis imaging (DKI) and resting-state fMRI (rs-fMRI), and to investigate their diagnostic potential as biomarkers.
MethodsTwenty-three patients with NIID and 40 matched healthy controls (HCs) were recruited. Firstly, gray matter (GM) and white matter (WM) changes were assessed by voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Then we explored modifications in brain functional networks connectivity by independent component analysis. And the relationship between the altered DKI parameters and neuropsychological evaluation was analyzed. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different gray matter and white matter parameters.
ResultsCompared with the HCs, NIID patients showed reduced mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), and kurtosis fractional anisotropy (KFA) values in deep gray matter regions. Significantly decreased MK, RK, AK, KFA and fractional anisotropy (FA), and increased mean diffusivity (MD) values were observed in extensive white matter fiber tracts. Notable alterations in functional connectivity were also detected. Among all DKI parameters, the diagnostic efficiency of AK in GM and FA in WM regions was the highest.
ConclusionAdult-onset NIID patients exhibited altered microstructure and functional network connectivity. Our findings suggest that DKI parameters may serve as potential imaging biomarkers for diagnosing adult-onset NIID.

目的：神经元核内包涵体病（Neuronal intranuclear inclusion disease, NIID）是一种罕见的神经退行性疾病，目前缺乏可靠的神经影像学生物标志物。本研究旨在利用扩散峰度成像（diffusion kurtosis imaging, DKI）与静息态功能磁共振成像（resting-state fMRI, rs-fMRI）评估脑微观结构与功能连接的异常，并探究其作为生物标志物的诊断潜力。

方法：本研究共招募23例NIID患者与40例匹配的健康对照（healthy controls, HCs）。首先，采用基于体素的形态学分析（voxel-based analysis, VBA）与基于纤维束追踪的空间统计分析（tract-based spatial statistics, TBSS）评估灰质（gray matter, GM）与白质（white matter, WM）的变化；随后通过独立成分分析探究脑功能网络连接的改变；并分析异常的DKI参数与神经心理学评估结果之间的关联；最后采用受试者工作特征（receiver operating characteristic, ROC）曲线评估不同灰质与白质参数的诊断效能。

结果：与健康对照相比，NIID患者在深部灰质区域的平均峰度（mean kurtosis, MK）、径向峰度（radial kurtosis, RK）、轴向峰度（axial kurtosis, AK）及峰度各向异性（kurtosis fractional anisotropy, KFA）值均显著降低；在广泛的白质纤维束中，其MK、RK、AK、KFA各参数与各向异性分数（fractional anisotropy, FA）均显著下降，而平均扩散系数（mean diffusivity, MD）值则显著升高。此外，研究还检测到脑功能连接存在显著异常。在所有DKI参数中，灰质区域的AK与白质区域的FA具有最高的诊断效能。

结论：成人起病的NIID患者存在脑微观结构与功能网络连接的异常。本研究结果提示，DKI参数有望成为诊断成人起病NIID的潜在影像学生物标志物。