Glymphatic system dysfunction in pediatric acute lymphoblastic leukemia without clinically diagnosed central nervous system infiltration: a novel DTI-ALPS method
Glymphatic system dysfunction in pediatric acute lymphoblastic leukemia without clinically diagnosed central nervous system infiltration: a novel DTI-ALPS method
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DOI：
10.1007/s00330-023-09473-8
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发表时间：
2023-03
影响因子：
5.9
通讯作者：
Liping Lin;Shu Su;Weifeng Hou;Libin Huang;Qina Zhou;Mengsha Zou;Long Qian;Wei Cui;Zhiyun Yang;Yanlai Tang;Yingqian Chen
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作者：
Liping Lin;Shu Su;Weifeng Hou;Libin Huang;Qina Zhou;Mengsha Zou;Long Qian;Wei Cui;Zhiyun Yang;Yanlai Tang;Yingqian Chen
背景与目的急性淋巴细胞白血病（ALL）患儿常发生中枢神经系统（CNS）浸润.然而，CNS浸润很少在初步诊断时检测到。调节脑脊液（CSF）和间质液转运的胶质淋巴系统被认为是白血病细胞浸润CNS的可能途径之一。在这项研究中，我们使用扩散张量图像分析沿着血管周围空间（DTI-ALPS）的方法来研究胶质淋巴系统的功能，并获得CSF体积使用合成磁共振成像（SyMRI）在儿科ALL临床诊断CNS infiltration.Materials和methodsTwenty-nine ALL和29个典型的发展（TD）的儿童前瞻性招募（年龄4 - 16岁）在本研究中。在控制年龄、性别和利手因素后，对脑体积参数、脑水扩散率和ALPS指数的组间差异进行评价。此外，显着的组不同的参数与临床信息，使用偏相关性analysis.ResultsLowDxassoc和ALPS指数，并增加CSF体积被发现在小儿ALL（所有pFDR校正<0.05）。此外，ALPS指数与儿童ALL的风险分类呈负相关（r =-0.59，pFDR校正= 0.04）。结论儿童ALL无临床诊断的CNS浸润，表现为胶质淋巴系统功能障碍和CSF蓄积。这些新的发现表明胶质淋巴系统可能在ALL CNS浸润的早期过程中起重要作用，这为探索儿童ALL CNS浸润的潜在机制和早期检测提供了新的方向。关键点·在儿童ALL中发现较低的Dxasin和ALPS指数，以及增加的CSF体积（所有pFDR校正<0. 05）。ALPS指数与儿童ALL的风险分类呈负相关（r =-0.59，pFDR校正= 0.04）。在临床上未诊断为CNS浸润的儿童ALL中，存在胶质淋巴系统功能障碍和CSF蓄积，这表明ALPS指数和CSF体积可能是早期检测儿童ALL CNS浸润的有希望的影像学标志物。
Background and objectiveCentral nervous system (CNS) infiltration commonly occurs in children with acute lymphoblastic leukemia (ALL). Nevertheless, CNS infiltration is rarely detected at the initial diagnosis. The glymphatic system, which regulates cerebrospinal fluid (CSF) and interstitial fluid transport, is considered one of the possible routes of CNS infiltration by leukemia cells. In this study, we used diffusion tensor image analysis along the perivascular space (DTI-ALPS) method to investigate glymphatic system function and obtained CSF volume using synthetic magnetic resonance imaging (SyMRI) in pediatric ALL without clinically diagnosed CNS infiltration.Materials and methodsTwenty-nine ALL and 29 typically developing (TD) children were prospectively recruited (age 4–16 years) in the present study. Group differences in brain volumetric parameters, brain water diffusivities, and the ALPS index were evaluated after controlling for age, gender, and handedness. Furthermore, significant group-different parameters were correlated with clinical information using partial correlations analysis.ResultsLower Dxassocand ALPS index, and increased CSF volume were found in pediatric ALL (allpFDR-corrected< 0.05). Moreover, the ALPS index was negatively associated with the risk classification (r= − 0.59,pFDR-corrected= 0.04) in pediatric ALL.ConclusionsDysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration. These novel findings suggested that the glymphatic system might be essential in the early-stage process of ALL CNS infiltration, which provides a new direction for exploring underlying mechanisms and early detection of pediatric ALL CNS infiltration.Key Points• Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all pFDR-corrected< 0.05).• The ALPS index was negatively associated with the risk classification (r = −0.59, pFDR-corrected= 0.04) in pediatric ALL.• Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration, which suggested that the ALPS index and CSF volume might be promising imaging markers for early detection of pediatric ALL CNS infiltration.