Wei Ke, Liang Yiwen, Yang Binrang, Liu Longping, Cao Weiguo, Li Tian, Wang Rong
Department of Radiology, Shenzhen Children's Hospital, Shenzhen, China.
China Medical University, Shenyang, China.
Quant Imaging Med Surg. 2022 Apr;12(4):2474-2486. doi: 10.21037/qims-21-748.
For children diagnosed with acute lymphoblastic leukemia (ALL), methotrexate (MTX) treatment carries the risk of leukoencephalopathy and other treatment-related brain damage. However, earlier and more sensitive evaluation is needed to elucidate the specific effects of MTX treatment in this group. This study aimed to evaluate changes in brain metabolites, diffusion and anisotropy features, and cognitive performance in children with ALL after MTX treatment.
In this observational study conducted from December 2013 to December 2015, 30 children with ALL and 30 healthy children were recruited and evaluated using baseline magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and neurocognitive tests. After MTX treatment and ALL remission, the children with ALL underwent MR examination and neurocognitive tests again. Quantitative alterations of MR and cognitive test results from the baseline data were calculated.
At baseline, the ALL group (age 6.9±3.3 years; 14 boys) and the healthy controls (age 6.0±3.1 years, 14 boys) had comparable neurocognitive performance and MR results. After MTX treatment, 6.7% (2/30) of children with ALL showed abnormalities on diffusion- and T1- and T2-weighted images. The N-acetylaspartate/creatine and N-acetylaspartate/choline values of children with ALL decreased, whereas their choline/creatine values increased significantly. The fractional anisotropy (FA) values decreased in the frontal lobe (P=0.03) and the genu of the corpus callosum (P=0.01). The FA values in the genu of the internal capsule (P=0.08), the occipital lobe (P=0.20) and the splenium of the corpus callosum (P=0.30) did not change from baseline. The apparent diffusion coefficient (ADC) values decreased in the frontal lobe (P=0.03). The ADC values in the genu of the corpus callosum (P=0.11), the genu of the internal capsule (P=0.93), and the occipital lobe (P=0.65) did not change from baseline. Due to the presence of outliers and the small sample, the ADC values in the splenium of the corpus callosum were discarded. Neurocognitive performance decreased slightly after MTX treatment, with noticeable declines in working memory and processing speed. Changes in FA values were positively correlated with the reduction in the N-acetylaspartate/creatine ratio at the genu of the corpus callosum of children with ALL aged above 6 years.
MTX treatment causes subtle cognitive decline in children with ALL in remission and dramatically affects their brain metabolites, but changes in white matter diffusion features are limited to the frontal lobe and corpus callosum.
对于诊断为急性淋巴细胞白血病（ALL）的儿童，甲氨蝶呤（MTX）治疗存在发生白质脑病和其他治疗相关脑损伤的风险。然而，需要更早且更敏感的评估来阐明MTX治疗对该群体的具体影响。本研究旨在评估ALL患儿在MTX治疗后脑代谢物、扩散及各向异性特征以及认知功能的变化。
在2013年12月至2015年12月进行的这项观察性研究中，招募了30例ALL患儿和30例健康儿童，并使用基线磁共振成像（MRI）、磁共振波谱（MRS）、扩散张量成像（DTI）和神经认知测试进行评估。在MTX治疗及ALL缓解后，ALL患儿再次接受磁共振检查和神经认知测试。计算了与基线数据相比磁共振和认知测试结果的定量变化。
在基线时，ALL组（年龄6.9±3.3岁；14名男孩）和健康对照组（年龄6.0±3.1岁，14名男孩）具有相当的神经认知表现和磁共振结果。MTX治疗后，6.7%（2/30）的ALL患儿在扩散加权、T1加权和T2加权图像上显示异常。ALL患儿的N-乙酰天门冬氨酸/肌酸和N-乙酰天门冬氨酸/胆碱值降低，而其胆碱/肌酸值显著升高。额叶（P=0.03）和胼胝体膝部（P=0.01）的分数各向异性（FA）值降低。内囊膝部（P=0.08）、枕叶（P=0.20）和胼胝体压部（P=0.30）的FA值与基线相比未发生变化。额叶的表观扩散系数（ADC）值降低（P=0.03）。胼胝体膝部（P=0.11）、内囊膝部（P=0.93）和枕叶（P=0.65）的ADC值与基线相比未发生变化。由于存在离群值且样本量小，胼胝体压部的ADC值被舍弃。MTX治疗后神经认知功能略有下降，工作记忆和处理速度有明显下降。FA值的变化与6岁以上ALL患儿胼胝体膝部N-乙酰天门冬氨酸/肌酸比值的降低呈正相关。
MTX治疗导致缓解期ALL患儿出现轻微认知下降，并显著影响其脑代谢物，但白质扩散特征的变化仅限于额叶和胼胝体。
