Objective: To evaluate structural magnetic resonance imaging (MRI) pattern modifications in an α-synuclein model of Parkinson’s disease (PD).

Background: As an early driver of α-synucleinopathies’ pathogenesis, aggregated α-synuclein could be a suitable imaging biomarker. However, to date, there is no method for its direct measurement. Nuclear medicine modalities allow only the detection of dopaminergic deficits but not the quantification of the protein as is the case in Alzheimer’s disease with radiotracers having the required sensitivity for amyloid-beta or Tau.

Method: Experiments were carried out using male adult Sprague Dawley rats. Two groups were formed, an ASYN group (n=10) that received bilateral intranigral injection of adeno-associated virus (AAV) carrying the human mutant p53T alpha-synuclein gene and a CTRL group (n= 9) that received AAV green fluorescent protein (GFP). Three MRI acquisitions were held at 2,10 and 18-weeks post-injection (PI), including a structural T2w image. Images were analyzed using two complementary approaches, the first based on a whole brain analysis using voxel-based morphometry (VBM) and the second a region-based method using texture analysis. This method allows measuring statistical features that quantify signal distribution in a defined region.

Four months PI, the animals were sacrificed for histological analyses of the brains evaluating accumulation and human α-synuclein propagation in the brain.

Associations between texture features and α-synuclein load were examined.

Results: Histological analyses showed diffuse alpha-synucleinopathy in different regions including the substantia nigra, the striatum, the hippocampus, prefrontal, cingulate and perirhinal cortices. VBM analysis showed progressive morphological differences between MRI sessions, culminating in alterations in the nigrostriatal pathway, the hippocampus, the fimbria, as well as the parietal, insular, and prefrontal cortex of the ASYN group, at 4-months PI while the association analyses revealed significant correlations between the texture features in substantia nigra, striatum, thalamus, hippocampus and associative and cingulate cortices, with α-synuclein quantified in these regions.

Conclusion: These preliminary results suggest that MR imaging patterns reflect the underlying tissue changes occurring in the brain and can be an indirect method to quantify alpha-synuclein.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/structural-magnetic-resonance-imaging-patterns-reflect-%ce%b1-synuclein-propagation-in-a-model-of-parkinsons-disease/