结构性MRI测量对脊髓小脑共济失调3型的诊断价值

Diagnostic Value of Structural MRI in Spinocerebellar Ataxia Type 3

【目的】本研究拟探讨结构性MRI测量对脊髓小脑共济失调3型(SCA3)的诊断价值,并进一步评估其与疾病的严重程度及病程的相关性。【方法】前瞻性收集2018年5月至2021年11月于中山大学附属第一医院经基因诊断确诊的SCA3患者81例(症状组sym-SCA3):59,症状前组(pre-SCA3):22,同时收集年龄、性别匹配的正常对照(HCs)35例。受试者均采集MRI结构像(3D T1WI MPRAGE)并收集其相应的临床资料。三位具不同临床经验的观察者分别通过第三方软件测量双侧小脑上、中、下脚宽度、脑桥及不同平面脊髓前后径(平枕骨大孔、颈3-5椎体上缘),其中一位观察者2个月后对上述指标进行重复测量。分别计算观察者内及观察者间可重复性,采用单因素方差分析、秩和检验、ROC曲线及随机森林方法评估上述指标对SCA3的诊断价值,并与临床资料进行相关性分析。【结果】基于形态学MRI脑结构测量指标,无论是观察者内或观察者间,均具有较高的可重复性且不依赖于观察者的临床经验,其中双侧小脑上、中脚具有最高的一致性。HCs、pre-SCA3和sym-SCA3三组的双侧小脑上、中、下脚、脑桥及脊髓前后径(除颈5椎体上缘水平)分别依次减小并具有统计学差异(P<0.017)。ROC示左侧小脑中脚对pre-SCA3的诊断价值最高(AUC=0.911),其敏感度、特异度和cut-off值分别为85.7%,95.5%和10.15 mm,而右侧小脑上脚对sym-SCA3的诊断价值最高(AUC=0.999),其临界值为2.62 mm,敏感度和特异度分别是100%和98.3%。进一步,基于上述指标的随机森林模型区分三组同样有着很高的诊断效能(AUC=0.970,特异度=93.1%),其中左侧小脑中脚对模型的贡献度最大。此外,相关分析表明上述指标同SARA和病程存在中等程度或显著负相关(P<0.05)。【结论】基于形态学MRI的脑结构测量可重复性好、不依赖于临床经验,可以帮助诊断SCA3并预测疾病的严重程度和病程,左侧小脑中脚及右侧小脑上脚分别用于预测pre-SCA3和sym-SCA3价值最优。由此,本研究推荐临床纳入MRI脑结构测量协助评估SCA3。

【Objective】 To explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3(SCA3) and further evaluate its correlation with disease severity and disease duration.【Methods】 We prospectively enrolled 81 genetically diagnosed SCA3 patients [59 symptomatic(sym-SCA3) and 22 pre-symptomatic(pre-SCA3)] and 35 age-and sex-matched healthy controls(HCs). MRI structural images(3D T1 MPRAGE) and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior, middle and inferior cerebellar peduncle(SCP, MCP and ICP), the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra-and inter-observer reliability, respectively. One-way ANOVA, rank-sum test, ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3, and the correlation between the metrics and clinical variables was analyzed.【Results】 Not depending on the radiological experience, the metrics based on morphological MRI showed high intra-and inter-observer reliability, among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP, MCP, ICP, pons and spinal cord(except spinal cord at the level of the upper edge of the 5th cervical vertebra) decreased successively in HCs, pre-SCA3 and sym-SCA3 with a statistical difference(P<0.017). ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3(AUC=0.911), with sensitivity, specificity and a cut-off value of 85.7%, 95.5% and 10.15 mm, respectively. In contrast, the right SCP had the highest diagnostic value for sym-SCA3(AUC=0.999), with sensitivity, specificity and a cut-off value of 100%, 98.3% and 2.62 mm, respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency(AUC= 0.970, specificity=93.1%), and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia(SARA) and disease duration(P<0.05).【Conclusion】 Not depending on radiological experience, measurements of brain structure based on morphological MRI are reliable, which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3, respectively. Therefore, the structural MRI is recommended for assisting the clinical diagnosis of SCA3.