目的:儿童脑肾上腺脑白质营养不良(C-ALD)是一种严重的炎症性脱髓鞘疾病,必须在早期阶段进行治疗,以防止永久性脑损伤和神经认知功能下降。在标准临床实践中,通过检查解剖MRI扫描的神经放射学家来检测和表征C-ALD病变。我们旨在评估扩散张量成像(DTI)是否对C-ALD病变的存在和严重程度敏感,并研究造血细胞治疗(HCT)后与神经认知结果的关系。
方法:在这项回顾性队列研究中,我们分析了高分辨率解剖MRI,DTI,2011年至2021年在明尼苏达大学接受HCT的C-ALD男孩的神经认知评估。将纵向DTI数据与年龄匹配的ALD且无病变(NL-ALD)男孩组进行比较。在call体(CC)的3个细分范围内,获得了基于地图集的感兴趣区域(ROI)的DTI指标,皮质脊髓束(CST),和总白质(WM)。组间基线和各向异性分数(FA)和轴向(AD)的斜率差异,径向(RD),和平均(MD)扩散率进行了比较,采用年龄的协方差分析,MRI严重程度(Loes评分),和病变位置。
结果:在NL-ALD患者中(n=14),稳定或增加FA,稳定的AD,在所有ROI的1年研究期间,通常观察到稳定或降低的RD和MD。相比之下,轻度后部病变的患者(Loes1-2;n=13)在CCsplenium中显示较低的基线FA(C-ALD0.50±0.08对NL-ALD0.58±0.04;pBH=0.022调整的Benjamini-Hochbergp值),跨ROI的较低基线AD(例如,C-ALD1.34±0.03×10-9m2/s总WM与NL-ALD1.38±0.04×10-9m2/s;pBH=0.005),CC主体和CST的较低基线RD,除CCsplenium外,ROI的基线MD较低。CCsplenium的纵向斜率在区分早期C-ALD和NL-ALD方面显示出很高的敏感性和特异性。在所有C-ALD患者中(n=38),基线Loes评分和DTI指标与HCT后神经认知功能相关,包括处理速度(例如,FAWMSpearman相关系数R=0.64)和视觉-运动整合(例如,FAWMR=0.71)。
结论:DTI对C-ALD的病变存在和严重程度以及临床神经认知效应敏感。DTI度量甚至在早期阶段量化C-ALD。
OBJECTIVE: Childhood cerebral
adrenoleukodystrophy (C-ALD) is a severe inflammatory demyelinating disease that must be treated at an early stage to prevent permanent brain injury and neurocognitive decline. In standard clinical practice, C-ALD lesions are detected and characterized by a neuroradiologist reviewing anatomical MRI scans. We aimed to assess whether diffusion tensor imaging (DTI) is sensitive to the presence and severity of C-ALD lesions and to investigate associations with neurocognitive outcomes after hematopoietic cell therapy (HCT).
METHODS: In this retrospective cohort study, we analyzed high-resolution anatomical MRI, DTI, and neurocognitive assessments from boys with C-ALD undergoing HCT at the University of Minnesota between 2011 and 2021. Longitudinal DTI data were compared with an age-matched group of boys with ALD and no lesion (NL-ALD). DTI metrics were obtained for atlas-based regions of interest (ROIs) within 3 subdivisions of the corpus callosum (CC), corticospinal tract (CST), and total white matter (WM). Between-group baseline and slope differences in fractional anisotropy (FA) and axial (AD), radial (RD), and mean (MD) diffusivities were compared using analysis of covariance accounting for age, MRI severity (Loes score), and lesion location.
RESULTS: Among patients with NL-ALD (n = 14), stable or increasing FA, stable AD, and stable or decreasing RD and MD were generally observed during the 1-year study period across all ROIs. In comparison, patients with mild posterior lesions (Loes 1-2; n = 13) demonstrated lower baseline FA in the CC splenium (C-ALD 0.50 ± 0.08 vs NL-ALD 0.58 ± 0.04; pBH = 0.022 adjusted Benjamini-Hochberg p-value), lower baseline AD across ROIs (e.g., C-ALD 1.34 ± 0.03 ×10-9 m2/s in total WM vs NL-ALD 1.38 ± 0.04 ×10-9 m2/s; pBH = 0.005), lower baseline RD in CC body and CST, and lower baseline MD across ROIs except CC splenium. Longitudinal slopes in CC splenium showed high sensitivity and specificity in differentiating early C-ALD from NL-ALD. Among all patients with C-ALD (n = 38), baseline Loes scores and DTI metrics were associated with post-HCT neurocognitive functions, including processing speed (e.g., FA WM Spearman correlation coefficient R = 0.64) and visual-motor integration (e.g., FA WM R = 0.71).
CONCLUSIONS: DTI was sensitive to lesion presence and severity as well as clinical neurocognitive effects of C-ALD. DTI metrics quantify C-ALD even at an early stage.