Altered Functional Connectivity Density In Young Survivors Of Acute Lymphoblastic Leukemia At Resting-State Functional MRI

Objective:Using functional connectivity density(FCD) mapping measured by resting-state fMRI,an ultrafast data-driven graph theory approach,we attempted to study the abnormality in neural activity of young survivors of acute lymphoblastic leukemia and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients.Methods:Thirty young survivors of acute lymphoblastic leukemia(ALL) and twenty-two well-matched healthy controls(HCs) were recruited in this study to undergo resting-state fMRI scan,and completed neurocognitive testing including Chinese Wechsler Intelligence Scale Children Fourth Edition(C-WISC-IV),Trail Making Test A(TMTA),Digit Span Test(DST).All young survivors of ALL who met the criteria of acute lymphocytic leukemia at the time of diagnosis,received homogeneous chemotherapy regimen and stopped chemotherapy for at least a year.After data preprocessing,the patients with excessive head movement and incomplete clinical data were excluded.Finally,20 patients in ALL group(18 males and 2females,with an average age of 10.15±3.1 years,and the treatment suspension period of 12-18 months) and 18 patients in HCs group(16 males and 2 females,with an average age of 9.94±3.8 years) were included.In this study,we used functional connectivity mapping(FCDM) and rsFC to explore the altered brain functional connectivity in young survivors of ALL after therapy.First,DPARSF software was used for image preprocessing,with degree centrality(DC) option to calculate the long-range and short-range FCD of ALL group and HC group respectively,and double-sample t-test was conducted between groups to obtain brain regions with significant difference.Then,the brain regions showed differences in long-range FCD were used as the regions of interest for the analysis of whole brain functional connectivity,and the differences in rsFC between the two groups of subjects were compared.Finally,the correlations between the FCD value or rsFC value and each of the neurocognitive outcomes were analyzed in the ALL patients..Results:(1)Between the ALLs and HCs,the group averaged FCD maps showed similar spatial patterns.(2)Compared with the HC,ALL patients showed decreased long-range FCD in regions of bilateral cuneus/ precuneus/lingual lobe/ hippocampus gyrus.Simultaneously,decreased regions in short-range FCD map were bilateral lingual gyrus/ cingulate cortex/ parahippocampa gyrus and right calcarine.And there existed no increased FCD brain areas.(3)Choosing the regions with decreased FCD as ROI,the right middle occipital gyrus/ cuneus/ lingual gyrus showed decreased rsFC and right posterior posterior cerbellar lobe showed increased rsFC.(4)The intelligence quotient(full scale of WAIS-IV) was positively correlated with the decreased long-range FCD value of ALL patients.(5)The score of Trail Making Test A was positively correlated with the decreased FCD value.And DST were negatively correlated with the increased rsFC value of of ALL patients.Conclusion:Using the method of FCD based on voxel in this study,we found the altered importance of brain network node and regions and the change of the whole brain functional connectivity in young survivors of ALL.Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing,which may predict the rs-fMRI could be the neuroimaging marker for neurologic impairment of ALL patients.