USE OF MULTIMODAL MRI TO ASSESS STATIN EFFECTS ON SINGLE GENE (NF1) AUTISM

UoM administered thesis: Phd

  • Authors:
  • Maria Tziraki

Abstract

Background: Monogenic causes of autism such as Neurofibromatosis Type 1 (NF1), with known neurobiology from animal models, provide a key method in autism biological research. Multimodal magnetic resonance imaging (MRI) can be profoundly effective in examining this phenotypic heterogeneity, but its utility in child subjects has been limited by implementation challenges such as the need for sedation, which is incompatible with the use of advanced imaging methods such as Resting State functional MRI (RS fMRI). Aim: To develop and implement an awake multimodal imaging protocol for use in an intervention trial with young children with NF1-Autism Methods: Feasibility was tested on children (n=30; mean age 8.5 years) enrolled in a world first placebo-controlled simvastatin trial in NF1 autism. Derived from literature review scanning protocol in awake children included 1) High resolution T1 volume; 2) RS fMRI; 3) Diffusion imaging; 4) Arterial Spin Labelling 5) GABA Proton magnetic resonance spectroscopy; 6) T2 imaging. Results: Scanning preparation procedure and processing of imaging data was carefully adapted, which allowed analysis and hypothesis testing on high quality usable data. The results identified statin effects on GABA, Glx, Perfusion and Diffusion metrics, as well as determination of higher level functional connectivity. These results gave evidence of some microstructural and functional normalisation in the treatment cohort after statin exposure. Conclusion: Non-sedated multimodal MRI can be used in monitoring therapeutic agent impact in developmental disorders with a complex phenotype. Statins may produce microstructural and vascular changes resulting in better neurotransmitter regulation.

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Original languageEnglish
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Award date1 Aug 2018