Methodological aspects of in vivo imaging of mutant huntingtin in a mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant disorder characterized by a progressive neurodegeneration of the striatum in the early stage and several other brain regions in a later stage. The mutation responsible for this disease is an abnormal expansion of trinucleotide CAG repeats leading to the production of a huntingtin protein with an expanded polyglutamine stretch (mHTT). Longitudinal monitoring of mHTT in a HD mouse model is thus of interest to characterize disease progression and to evaluate response to mHTT lowering therapy. Therefore the development of an objective measure of disease progression in preclinical and early HD is necessary. Current state of the art molecular imaging techniques such as positron emission tomography (PET) allow longitudinal and non-invasive visualisation and quantification of biological processes. To visualize the mHTT protein the radiotracer [11C] CHDI-180 has been established as a potential candidate for mHTT PET imaging and therefore an objective quantification of this radiotracer is necessary.In this project we will optimize and validate quantification methods for PET imaging of [11C] CHDI-180 binding to the mHTT that accumulates in the brain of patients suffering from HD. Several methodological aspects will be considered, optimized and validated through additional magnetic resonance (MR) imaging, autoradiography and immunohistochemistry.

Keywords:HUNTINGTON DISEASE, SMALL ANIMAL IMAGING, IMAGE PROCESSING

Disciplines:Biological system engineering, Biomaterials engineering, Biomechanical engineering, Medical biotechnology, Other (bio)medical engineering, Medical imaging and therapy, Neurosciences, Other paramedical sciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing