Glymphatic system dysfunction in pediatric growth hormone deficiency evidenced by multiple MRI metrics
Shuzhen Huang1, Liping Lin1, Xiang Gao1
1Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Insights
Pediatric growth hormone deficiency (GHD) shows impaired glymphatic function, affecting brain waste clearance. This dysfunction may be a key mechanism in GHD, with imaging metrics potentially serving as biomarkers.
Area of Science:
- Neuroscience
- Pediatric Endocrinology
- Medical Imaging
Background:
- The glymphatic system is crucial for clearing metabolic waste from the brain.
- Pediatric growth hormone deficiency (GHD) may involve alterations in glymphatic function.
Purpose of the Study:
- To investigate glymphatic system function in children with GHD using non-invasive imaging.
- To identify potential imaging biomarkers for assessing glymphatic function in pediatric GHD.
Main Methods:
- Prospective study comparing 40 children with GHD and 40 typically developing (TD) children.
- Assessed cerebrospinal fluid (CSF) production (choroid plexus volume - CPV), influx (perivascular space - PVS burden), and waste clearance (DTI-ALPS) using MRI.
- Correlated MRI metrics with clinical variables in GHD patients.
Main Results:
- Children with GHD had decreased CPV, lower PVS burden, and reduced DTI-ALPS compared to TD children.
- PVS volume correlated positively with Social Competence scores in GHD.
- CPV negatively correlated with Activity Level in GHD.
Conclusions:
- Glymphatic dysfunction appears to be a pathological feature in pediatric GHD.
- CPV, PVS volume, and DTI-ALPS show promise as auxiliary biomarkers for evaluating glymphatic function in pediatric GHD.
Background:
The clearance of brain metabolic waste occurs mainly through the glymphatic system. This study aimed to explore the change of glymphatic function in children with growth hormone deficiency (GHD) using non-invasive imaging methods.
Methods:
This prospective research recruited 40 cases of pediatric GHD and 40 age- and gender-matched typically developing (TD) children. Glymphatic circulation, which includes the production of cerebrospinal fluid (CSF), represented by choroid plexus volume (CPV), influx, evaluated by perivascular space (PVS) burden, and waste clearance, as indirectly assessed by diffusion tensor imaging-based analysis along the perivascular space (DTI-ALPS), was explored for all participants. Partial correlations were conducted between significant magnetic resonance imaging (MRI) metrics and clinical variables in GHD children.
Results:
Considering the production of CSF, decreased CPV was presented in pediatric GHD [0.77±0.15 vs. 0.83±0.19 mL; Pfalse discovery rate (FDR)=0.002]. Considering influx, pediatric GHD exhibited lower PVS burden than did TD children (4.51±1.74 vs. 6.30±3.34 mL; PFDR=0.01). Considering waste clearance, DTI-ALPS decreased significantly in GHD groups (1.35±0.14 vs. 1.49±0.1; PFDR<0.001). Moreover, in children with GHD, Social Competence scores were positively correlated with PVS volume (r=0.358, P=0.032), PVS/white matter volume (WMV; r=0.420, P=0.010), and PVS/intracranial volume (ICV; r=0.410, P=0.010), whereas Activity Level was negatively correlated with CPV (r=-0.377, P=0.023).
Conclusions:
Our findings suggest that glymphatic dysfunction may be a pathological mechanism in pediatric GHD. Furthermore, our study demonstrates that CPV, PVS volume, and DTI-ALPS index could serve as multiple auxiliary biomarkers for assessing the glymphatic function in pediatric GHD.
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