Advanced MR diffusion imaging and chemotherapy‐related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

Abstract

With the increase of survival rates of pediatric cancer patients, the number of children facing potential cognitive sequelae has grown. Previous adult studies suggest that white matter (WM) microstructural changes may contribute to cognitive impairment. This study aims to investigate WM microstructure in childhood bone and soft tissue sarcoma. Differences in (micro-)structure can be investigated using diffusion MRI (dMRI). The typically used diffusion tensor model (DTI) assumes Gaussian diffusion, and lacks information about fiber populations. In this study, we compare WM structure of childhood bone and soft tissue sarcoma survivors (n = 34) and matched controls (n = 34), combining typical and advanced voxel-based models (DTI and NODDI model, respectively), as well as recently developed fixel-based models (for estimations of intra-voxel differences, apparent fiber density [AFD] and fiber cross-section [FC]). Parameters with significant findings were compared between treatments, and correlated with subscales of the WAIS-IV intelligence test, age at diagnosis, age at assessment and time since diagnosis. We encountered extensive regions showing lower fractional anisotropy, overlapping with both significant NODDI parameters and fixel-based parameters. In contrast to these diffuse differences, the fixel-based measure of AFD was reduced in the cingulum and corpus callosum only. Furthermore, AFD of the corpus callosum was significantly predicted by chemotherapy treatment and correlated positively with time since diagnosis, visual puzzles and similarities task scores. This study suggests altered WM structure of childhood bone and soft tissue sarcoma survivors. We conclude global chemotherapy-related changes, with particular vulnerability of centrally located WM bundles. Finally, such differences could potentially recover after treatment.

<p>Neurite orientation and dispersion density imaging: clinical utility, efficacy, and role in therapy</p>

“…Other studies focused on perinatal encephalopathy, 83 SYN1Q555X mutation, 84 C9orf72 disease, 85 and sarcoma survivors. 86 Spine NODDI is also feasible for evaluating the human spinal cord. 87 In addition to its use for the spinal lesions of MS, 26,88 some studies have focused on cervical spondylotic myelopathy.…”

Long-term impact of prenatal exposure to chemotherapy on executive functioning: An ERP study

“…Chemotherapy-induced neurotoxicity has been documented in pediatric (Sleurs et al 2016(Sleurs et al , 2018) and adult (McDonald et al 2013;Janelsins et al 2014; Ahles and Root 2018) cancer populations. Though most chemotherapeutic agents only partially cross the placental barrier (Berveiller et al 2016), cancer and chemotherapy in utero could also affect neurodevelopment through indirect pathways, such as maternal nutrition (Veena et al 2016), inflammation (Richetto and Riva 2014), stress (Richetto and Riva 2014;Bock et al 2015) and anxiety (Mennes et al 2006(Mennes et al , 2009 , as well as other factors (Vercruysse et al 2016).This further emphasizes the need for a long-term cognitive follow-up of children who are prenatally exposed to cancer therapy.…”

The impact of cancer and chemotherapy during pregnancy on child neurodevelopment: A multimodal neuroimaging analysis

“…The differences observed in this study cannot be solely ascribed to the effect of chemotherapy, but rather to a combination of secondary mechanisms. Indeed, although differences in WM microstructure resemble results in literature of cancer survivors receiving intravenous chemotherapy [ 42 , 43 ], chemotherapy during pregnancy was not identified as a significant risk factor in any of the post-hoc analyses. The psychosocial impact of a cancer diagnosis during pregnancy might partially explain these findings.…”