Altered glymphatic-related MRI markers in children with acute lymphoblastic and myeloid leukemia at diagnosis

While the discovery of the glymphatic system has greatly advanced our understanding of waste clearance and fluid dynamics in central nervous system diseases, the neurofluid dynamics in pediatric acute leukemia remain to be elucidated. This study sought to evaluate MRI markers putatively related to neurofluid dynamics in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), including perivascular space (PVS) burden, free water (FW) fraction, and diffusion tensor imaging along the PVS (DTI-ALPS).

Seventy-two children with acute leukemia and 72 age- and sex-matched typically developing (TD) children (50 ALL and TDs1; 22 AML and TDs2) were included in this prospective study. Group differences in brain volumetric measures and glymphatic-related MRI markers were evaluated. In addition, MRI metrics that differed significantly between groups were further examined for associations with clinical variables and total sleep scale scores using partial correlation analyses.

Compared to TDs, ALL and AML showed no significant differences in intracranial volume. Compared with TDs, decreased brain parenchymal volume and gray matter volume were found in both children with ALL and AML (all FDR-corrected P ≤ 0.04). Compared with TDs, the ALL group exhibited reduced white matter volume and increased cerebrospinal fluid volume (all FDR-corrected P ≤ 0.001), while the AML group showed no significant differences in these measures. For glymphatic-related MRI markers, decreased PVS volume and count, FW value, and DTI-ALPS index were observed in both ALL and AML (all FDR-corrected P ≤ 0.02). In addition, the DTI-ALPS index was negatively correlated with risk stratification and total scale scores in children with ALL (all P ≤ 0.03).

This preliminary, cross-sectional study identified a neuroimaging pattern in pediatric acute leukemia, characterized by reduced brain parenchyma volume and alterations in MRI markers putatively linked to neurofluid dynamics. In patients with ALL, a lower ALPS index was correlated with higher clinical risk stratification and greater sleep disturbance. These observations support future studies to clarify the biological relevance of neurofluid-related imaging features in acute leukemia.

ChiCTR2000031353; registered date: 2020-04.