Analyse du corps calleux de survivants de la leucémie aiguë lymphoblastique pédiatrique à partir d'imagerie par résonance magnétique du cerveau

Abstract

Although acute lymphoblastic leukemia (ALL) is the most common pediatric cancer in North America, research efforts have resulted in a five-year survival rate of more than 85% today. However, ALL treatments can leave long-term sequelae at many levels in children, including neurocognitive deficits. These decifits are also influenced by three risk factors: sex, age at diagnosis and type of treatment. Since the corpus callosum is the largest bundle of white matter and its main function is to ensure communication between the two hemispheres of the brain, permanent damages in its microstructure may reduce its performance and contribute to the observed deficits. The purpose of this thesis is to determine whether there are long-term sequelae in the corpus callosum in ALL survivors, to validate whether these sequelae are related to the observed neurocognitive deficits, and to evaluate if there is a link between the sequelae observed and the risk factors in ALL survivors. The methodology used in this paper is based on the analysis of the corpus callosum from magnetization transfer (MTR) image sequences in ALL survivors and people without a history of cancer. A semi-automated method is developed to extract the MTR data from the corpus callosum of the study participants. An approach based on the use of the standard deviation is then proposed in order to refine MTR averages calculated from corpus callosum containing slight segmentation errors. Statistical analyses are carried out using the mean and histograms of MTR by combining different clinical variables with statistical tests. Finally, a classification method is proposed to automatically classify some clinical variables from the MTR data of the corpus callosum. The classification is performed using random forests trained from histograms and texture characteristics generated using corpus callosum data. Statistical analyses revealed lower MTR intensities in ALL survivors, mainly in women and in survivors diagnosed at 5 years old or younger. These also revealed negative correlations between MTR and cumulated doses of agents used in chemotherapy, as well as positive correlations between MTR and some cognitive performance indices, including working memory in women. Finally, promising results are obtained in the automatic classification of MTR data of the corpus callosum according to the participant group, methotrexate doses received and the global IQ. In conclusion, the results obtained suggest myelin sequelae in the corpus callosum in ALL survivors, particularly in women and all those diagnosed at 5 years old or younger. They also suggest that intrathecal chemotherapy treatments are neurotoxic and might cause sequelae in the corpus callosum. Finally, these results also suggest that the quality of the brain's white matter, including the corpus callosum, has a direct impact on the performance of some cognitive functions in survivors and in the general population.

Date	30 Oct 2017
Original language	French
Awarding Institution	École de technologie supérieure
Supervisor	Luc Duong (Supervisor) & Sarah Lippé (Co-supervisor)