Abstract
Previous diffusion tensor imaging (DTI) studies have detected white matter (WM) integrity abnormalities in some specific fibre bundles in acute lymphoblastic leukaemia (ALL) patients with chemotherapy. However, little is known about the changes in the topological organization of the WM structural network in ALL patients with chemotherapy. In the present study, we acquired DTI datasets from 28 ALL patients (mean age: 40.71 ± 8.58 years, years since diagnosis: 7–38) with chemotherapy and 20 matched healthy controls (mean age: 42.95 ± 6.39 years) and performed WM network analysis using a deterministic fibre-tracking approach. Graph theoretical analysis was used to compare the topological parameters of the WM networks between the two groups. Both ALL patients with chemotherapy and healthy controls had small-worldness in their WM networks. ALL patients showed significantly reduced global network efficiency, as indicated by the abnormally decreased clustering coefficient Cp and the normalized clustering coefficient γ and increased shortest path length Lp compared with healthy controls. Moreover, hubs were located more in parietal regions of healthy controls and in temporal regions in the ALL patients. We revealed the abnormal topological organization of the WM networks of ALL patients with chemotherapy, which may improve our understanding of the neural mechanism of chemotherapy in ALL from a WM topological organization level.
Highlights
Acute lymphoblastic leukaemia (ALL) is the most common cancer among children, accounting for 74% of all leukaemias and 18% of all cancers [1, 2]
We explored whether there were aberrant topological properties in white matter (WM) networks in acute lymphoblastic leukaemia (ALL) patients with chemotherapy treatment and healthy controls
Our main findings were as follows: a) smallworld organizations were present in both ALL patients with chemotherapy and controls, which is agreement with a previous study [42]; b) increased shortest path length Lp (P < 0.01), decreased in clustering coefficient Cp (P < 0.01), and decreased normalized clustering coefficients γ (P < 0.01) were present in ALL patients; c) lower global efficiency Eg (P < 0.01) was present in ALL patients; d) hubs were located more in the parietal regions of healthy controls and in the temporal regions in ALL
Summary
Acute lymphoblastic leukaemia (ALL) is the most common cancer among children, accounting for 74% of all leukaemias and 18% of all cancers [1, 2]. The historical treatment of central nervous system (CNS)-directed therapy has resulted in a 5-year event-free survival rate of approximately 80% [4]. CNSdirected therapies mainly consist of cranial irradiation, chemotherapy, and combinations of these two methods. Among these CNS-directed therapies, cranial irradiation has been implicated as the cause of neurocognitive impairments [5, 6]. Neurocognitive outcomes after chemotherapy treatment without cranial irradiation are inconsistent. Candidate mechanisms for cognitive impairment include direct neurotoxic effects causing atrophy of grey matter (GM) and/or demyelination of the white matter (WM), secondary immunologic responses leading to inflammatory reactions, microvascular damage, and genetic vulnerabilities [7,8,9]
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