Generation of synthetic training data for SEEG electrodes segmentation.

PURPOSE: Stereoelectroencephalography (SEEG) is a minimally invasive surgical procedure, used to locate epileptogenic zones. An accurate identification of the metallic contacts recording the SEEG signal is crucial to ensure effectiveness of the upcoming treatment. However, due to the presence of metal, post-operative CT scans contain strong streak artefacts that interfere with deep learning segmentation algorithms and require a lot of training data to distinguish from actual contacts. We propose a method to generate synthetic data and use them to train a neural network to precisely locate SEEG electrode contacts. METHODS: Random electrodes were generated following manufacturer's specifications and dimensions and placed in acceptable regions inside metal-free CT images. Metal artefacts were simulated in the generated data set using radon transform, beam hardening, and filtered back projection. A UNet neural network was trained for the contacts segmentation task using various training set-ups combining real data, basic augmented data, and synthetic data. The results were compared. RESULTS: We reported a higher accuracy when including synthetic data during the network training, while training only on real and basic augmented data more often led to misclassified artefacts or missed contacts. The network segments post-operative CT slices in less than 2 s using 4 GeForce RTX2080 Ti GPUs and in under a minute using a standard PC with GeForce GTX1060. CONCLUSION: Using synthetic data to train the network significantly improves contact detection and segmentation accuracy.

Specific Knockdown of α-Synuclein by Peptide-Directed Proteasome Degradation Rescued Its Associated Neurotoxicity.

α-Synuclein (α-syn) overload is strongly associated with Parkinson disease (PD), and reduction of the α-syn level by targeting the peptide-based system through the autophagy-lysosomal pathway (ALP) is a promising strategy to delay PD progression. However, if the ALP is comprised, targeting the peptide-based proteasomal degradation system would be a good alternative. In this study, we designed a fusion peptide containing an α-syn-binding domain and a short strong proteasome-targeting motif. Our results reveal that this peptide could specifically bind to α-syn, and direct it to the proteasomes for degradation in a recombinant expression system. Furthermore, by adding a membrane-penetrating motif to this fusion peptide, we demonstrated that it could penetrate into cells and consequently suppress the cellular α-syn level through proteasome degradation in a dose- and time-dependent manner. Functionally, these effects rescued the mitochondrial dysfunction and cellular defects caused by α-syn overexpression in the cultured cells and primary neurons.

Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson's Disease Model.

The α-synuclein aggregates are the main component of Lewy bodies in Parkinson's disease (PD) brain, and they showed immunotherapy could be employed to alleviate α-synuclein aggregate pathology in PD. Recently we have generated DNA aptamers that specifically recognize α-synuclein. In this study, we further investigated the in vivo effect of these aptamers on the neuropathological deficits associated with PD. For efficient delivery of the aptamers into the mouse brain, we employed modified exosomes with the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface. We demonstrated that the aptamers were efficiently packaged into the RVG-exosomes and delivered into neurons in vitro and in vivo. Functionally, the aptamer-loaded RVG-exosomes significantly reduced the α-synuclein preformed fibril (PFF)-induced pathological aggregates, and rescued synaptic protein loss and neuronal death. Moreover, intraperitoneal administration of these exosomes into the mice with intra-striatally injected α-synuclein PFF reduced the pathological α-synuclein aggregates and improved motor impairments. In conclusion, we demonstrated that the aptamers targeting α-synuclein aggregates could be effectively delivered into the mouse brain by the RVG-exosomes and reduce the neuropathological and behavioral deficits in the mouse PD model. This study highlights the therapeutic potential of the RVG-exosome delivery of aptamer to alleviate the brain α-synuclein pathology.