MRI Brain Atrophy Measures in α-Synuclein PFF Seeding Model

Table of Contents

Abstract

Presentation

01. Introduction 02. Regional Volumes Analysis Methods 03. Cortical Thickness Analysis Methods 04. TDP-43 Model 05. TDP-43 Model MR Images 06. TDP-43 Model MRI Analysis 07. Alpha-Synuclein Model 08. Synuclein Model MR Images 09. Synuclein Model MRI Analysis 10. Summary

Regional Volumes

https://opt003stagmediafiles.blob.core.windows.net/image/8de656fd095c4308a9b5f3e10d74cd5b

https://opt003stagmediafiles.blob.core.windows.net/image/727e97b665aa42429b48185f033d17da

https://opt003stagmediafiles.blob.core.windows.net/image/93cc215918794b5c8668614d6c364439

https://opt003stagmediafiles.blob.core.windows.net/image/4f9fbb8068024f709dabafdc9f32b95c

Brain volumes in various cortical and subcortical regions at Baseline and Weeks 8, 12, and 16 (t0, t8, t12, and 16, respectively) post-inoculation. Note the progressive brain atrophy in regions of accumulating synuclein burden (piriform cortex, entorhinal cortex, hippocampus), which have direct or higher order connections to the AON. There is no volumetric change in regions without synuclein pathology (e.g. thalamus). * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001

Cortical Thickness

https://opt003stagmediafiles.blob.core.windows.net/image/2b66f6fbaaff4637a93c2914424c1582

Cortical thinning with disease progression.

https://opt003stagmediafiles.blob.core.windows.net/image/198f750405f64c02837dd1909784d942

Spatiotemporal pattern of cortical thinning. The colder colors (blue and purple) represent greater cortical thinning. * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001

--:--

We have been able to show highly significant brain atrophy in this model. Regional brain atrophy is a well-established imaging biomarker in human Parkinson's disease. The Anterior Olfactory Nucleus (AON), piriform cortex, and entorhinal cortex show early and progressive atrophy in the ipsilateral hemisphere. We see late changes in the hippocampus and contralateral piriform and entorhinal regions, which reflect the spread of synuclein to these higher-order structures. Note that we do not see atrophy in regions without synuclein pathology, such as the thalamus.

In this AON model, the cortical thickness measures are extremely sensitive, with highly significant thinning seen in the piriform and entorhinal cortices. The cortical surface maps nicely demonstrate the spatiotemporal pattern of cortical thinning, which follows the spread of synuclein pathology. In these maps, the blue and purple colors represent thinner cortex which starts in the ipsilateral piriform cortex and then becomes more extensive and severe. This thinning then progresses to the contralateral piriform cortex between 12-16 weeks post-inoculation.