Ware Jeffrey B, Hart Tessa, Whyte John, Rabinowitz Amanda, Detre John A, Kim Junghoon
1 Department of Radiology, Hospital of the University of Pennsylvania , Philadelphia, Pennsylvania.
2 Moss Rehabilitation Research Institute , Philadelphia, Pennsylvania.
J Neurotrauma. 2017 Jul 15;34(14):2243-2253. doi: 10.1089/neu.2016.4817. Epub 2017 May 3.
Traumatic brain injury (TBI) is a leading cause of cognitive morbidity worldwide for which reliable biomarkers are needed. Diffusion tensor imaging (DTI) is a promising biomarker of traumatic axonal injury (TAI); however, existing studies have been limited by a primary reliance on group-level analytic methods not well suited to account for inter-subject variability. In this study, 42 adults with TBI of at least moderate severity were examined 3 months following injury and compared with 35 healthy controls. DTI data were used for both traditional group-level comparison and subject-specific analysis using the distribution-corrected Z-score (DisCo-Z) approach. Inter-subject variation in TAI was assessed in a threshold-invariant manner using a threshold-weighted overlap map derived from subject-specific analysis. Receiver operator curve analysis was used to examine the ability of subject-specific DTI analysis to identify TBI subjects with significantly impaired processing speed in comparison with region of interest-based fractional anisotropy (FA) measurements and clinical characteristics. Traditional group-wise analysis demonstrated widespread reductions of white matter FA within the TBI group (voxel-wise p < 0.05, corrected), despite relatively low consistency of subject-level effects secondary to widespread variation in the spatial distribution of TAI. Subject-specific mapping of TAI with the DisCo-Z approach was the best predictor of impaired processing speed, achieving high classification accuracy (area under the curve [AUC] = 0.94). In moderate-to-severe TBI, there is substantial inter-subject variation in TAI, with extent strongly correlated to post-traumatic deficits in processing speed. Significant group-level effects do not necessarily represent consistent effects at the individual level. Better accounting for inter-subject variability in neurobiological manifestations of TBI may substantially improve the ability to detect and classify patterns of injury.
创伤性脑损伤（TBI）是全球认知功能障碍的主要原因，因此需要可靠的生物标志物。扩散张量成像（DTI）是创伤性轴索损伤（TAI）的一种有前景的生物标志物；然而，现有研究主要依赖于不太适合解释个体间变异性的组水平分析方法。在本研究中，对42名至少为中度严重程度的TBI成年患者在受伤后3个月进行了检查，并与35名健康对照者进行比较。DTI数据用于传统的组水平比较和使用分布校正Z分数（DisCo-Z）方法的个体特异性分析。使用从个体特异性分析得出的阈值加权重叠图，以阈值不变的方式评估TAI中的个体间变异。使用受试者工作特征曲线分析来检验个体特异性DTI分析与基于感兴趣区域的分数各向异性（FA）测量和临床特征相比，识别处理速度显著受损的TBI患者的能力。传统的组间分析表明，TBI组内白质FA广泛降低（体素水平p < 0.05，校正后），尽管由于TAI空间分布的广泛变异，个体水平效应的一致性相对较低。使用DisCo-Z方法对TAI进行个体特异性映射是处理速度受损的最佳预测指标，分类准确率高（曲线下面积[AUC] = 0.94）。在中度至重度TBI中，TAI存在大量个体间变异，其程度与创伤后处理速度缺陷密切相关。显著的组水平效应不一定代表个体水平的一致效应。更好地考虑TBI神经生物学表现中的个体间变异性可能会显著提高检测和分类损伤模式的能力。
