Zika virus and the brain: a functional and structural magnetic resonance imaging study of infants with congenital microcephaly associated to Zika virus exposure

• Ano de defesa: 2020
• Autor(a) principal: Esper, Nathalia Bianchini
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul; Escola de Medicina; Brasil; PUCRS; Programa de Pós-Graduação em Medicina e Ciências da Saúde
• Palavras-chave em Português: Brain Development; Congenital Microcephaly; Magnetic Resonance Imaging; Zika Virus; CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/9507

The outbreak of Zika Virus infections, occurred in all Brazilian territory in 2015, brought a significant increase in the number of cases with congenital microcephaly in newborns, increasing researchers’ interest in how this virus influences the brain development in patients with this neurological condition. Since that, several studies showed the anatomical changes in the microcephalic brain, without a focus on functional neurodevelopment. The present work provides a structural and functional MRI study in infants with congenital microcephaly associated to Zika Virus infection. The work is divided in two studies. The first study is a cross-sectional investigation of 42 infants born with Zika virus congenital microcephaly. Bayley-III developmental evaluations and MRI scans were carried out at ages 13-39 months (mean age = 24.83 months, SD = 5.82 months). Here we propose a microcephaly severity classification, called ZikV-Microcephaly Severity Score. The severity score was generated based on neuroradiologist evaluations of brain malformations. Next, we established a distribution of ZikV-Microcephaly into mild, moderate and severe and investigated the association of severity with developmental scores. Finally, we propose a simplified procedure for estimating the severity score and a prediction of the score, using only volumetric measures. Results from the first study showed ZikV-Microcephaly Severity Score negatively correlated with neurodevelopmental scores and correlated with trimester of infection. The semi-automated method, in turn, correlated with the neuroradiological severity score, and thus may be an alternative for prediction of severity of microcephaly using one MRI sequence. Both methods may be used to evaluate severity of microcephaly and possible associated developmental consequences. The second study is a cross-sectional investigation of the functional connectivity in 28 infants with congenital microcephaly (mean age = 26.75 months, SD = 5.82 months). Here we developed a brain MRI template for infants with moderate microcephaly, called ZikaBraIns template. The functional connectivity was assessed through an independent component analysis followed by a correlation analysis with the Bayley-III scales. Results from the second study showed that the ZikaBraIns template can be used for processing data from infants with moderate microcephaly and presented expected results in the correlation analysis. Results showed a correlation in the supplementary motor area between the supplementary motor network and the Bayley-III score for gross motor. The group analysis results showed a correlation between the temporal network and the Bayley-III scores for expressive communication in the superior temporal area. In conclusion, the severity classification allowed for the development of a brain MRI template for infants with moderate microcephaly for fMRI analyses, which was subsequently used to investigate well-established resting-state fMRI networks, such as the auditory, visual, and temporal networks.