title: Late-stage α-synuclein accumulation in TNWT-61 mouse model of Parkinson's disease detected by diffusion kurtosis imaging.
abstract: Diffusion kurtosis imaging (DKI) by measuring non-Gaussian diffusion allows an accurate estimation of the distribution of water molecule displacement and may correctly characterize microstructural brain changes caused by neurodegeneration. The aim of this study was to evaluate the ability of DKI to detect changes induced by α-synuclein (α-syn) accumulation in α-syn over-expressing transgenic mice (TNWT-61) in both gray matter (GM) and white matter (WM) using region of interest (ROI) and tract-based spatial statistics analyses, respectively, and to explore the relationship between α-syn accumulation and DKI metrics in our regions of interest. Fourteen-month-old TNWT-61 mice and wild-type (WT) littermates underwent in vivo DKI scanning using the Bruker Avance 9.4 Tesla magnetic resonance imaging system. ROI analysis in the GM regions substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus and tract-based spatial statistics analysis in WM were performed. Immunohistochemistry for α-syn was performed in TNWT-61 mice and correlated with DKI findings. We found increased kurtosis and decreased diffusivity values in GM regions such as the thalamus and sensorimotor cortex, and in WM regions such as the external and internal capsule, mamillothalamic tract, anterior commissure, cingulum, and corpus callosum in TNWT-61 mice as compared to WT mice. Furthermore, we report for the first time that α-syn accumulation is positively correlated with kurtosis and negatively correlated with diffusivity in the thalamus. The study provides evidence of an association between the amount of α-syn and the magnitude of DKI metric changes in the ROIs, with the potential of improving the clinical diagnosis of Parkinson's disease. We propose diffusion kurtosis imaging as a sensitive method for detecting human α-synuclein accumulation-induced changes in brain tissue, which may be reflective of Parkinson disease stage. Boxplots show the averaged mean kurtosis (orange) and mean diffusivity (blue) under the results of the analysis (*p < 0.05) in brains of wild-type (WT) and α-synuclein over-expressing (TNWT-61) mice. This approach might represent a novel biomarker for the early diagnosis of Parkinson's disease. Read the Editorial Highlight for this article on page 1117.
authors.affiliation: Applied Neuroscience Research Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Amit
authors.initials: A
authors.lastname: Khairnar
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.|Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Ruda-Kucerova
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Institute of Scientific Instruments, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Drazanova
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Szabó
authors.affiliation: Multimodal and Functional Imaging Laboratory, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Latta
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Anas
authors.initials: A
authors.lastname: Arab
authors.affiliation: QPS Austria GmbH, Grambach, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hutter-Paier
authors.affiliation: QPS Austria GmbH, Grambach, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Havas
authors.affiliation: NeuroScios GmbH, Graz, Austria.
authors.forename: Manfred
authors.initials: M
authors.lastname: Windisch
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sulcova
authors.affiliation: Institute of Scientific Instruments, Academy of Sciences of the Czech Republic, Brno, Czech Republic.|Multimodal and Functional Imaging Laboratory, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Zenon
authors.initials: Z
authors.lastname: Starcuk
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.|Multimodal and Functional Imaging Laboratory, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: András
authors.initials: A
authors.lastname: Király
authors.affiliation: Applied Neuroscience Research Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Irena
authors.initials: I
authors.lastname: Rektorova
keywords: Parkinson's disease; TBSS; TNWT-61; diffusion kurtosis imaging; mean kurtosis; transgenic mice; α-syn