Quantitative synchrotron X-ray tomography of the material-tissue interface in rat cortex implanted with neural probes

Thomas Böhm,Ulrich G Hofmann,Carola A Haas,Matthias Kirsch,Riko Moroni,Markus Osenberg,Ingo Manke,Simon Thiele,Kevin Joseph,Midori Johnston,Thomas Stieglitz,André Hilger

doi:10.1038/s41598-019-42544-9

Abstract

Neural probes provide many options for neuroscientific research and medical purposes. However, these implantable micro devices are not functionally stable over time due to host-probe interactions. Thus, reliable high-resolution characterization methods are required to understand local tissue changes upon implantation. In this work, synchrotron X-ray tomography is employed for the first time to image the interface between brain tissue and an implanted neural probe, showing that this 3D imaging method is capable of resolving probe and surrounding tissue at a resolution of about 1 micrometer. Unstained tissue provides sufficient contrast to identify electrode sites on the probe, cells, and blood vessels within tomograms. Exemplarily, we show that it is possible to quantify characteristics of the interaction region between probe and tissue, like the blood supply system. Our first-time study demonstrates a way for simultaneous 3D investigation of brain tissue with implanted probe, providing information beyond what was hitherto possible.

Highlights

Www.nature.com/scientificreports designs towards reducing the foreign body response in order to maintain high quality signals over long periods of time[5,6]
The spatial resolution is expected to increase within the years, the high magnetic field strengths required for high resolution magnetic resonance imaging (MRI) increase the effect of metallic artifacts on data quality[29,30]
Blood vessels could still be identified in the semi-thin section, they largely lost their lumen, which explains why they could not be identified in the X-ray tomography

Summary

Introduction

Www.nature.com/scientificreports designs towards reducing the foreign body response in order to maintain high quality signals over long periods of time[5,6]. Confocal laser scanning microscopy is one of the methods capable of 3D imaging at a spatial resolution of less than one micrometer[7] Recent advances in this field even allow optical microscopes to circumvent the classical resolution limit and reach the two-digit nanometer range[8]. While not being able to deliver the outstanding sub-nanometer spatial resolution of transmission electron microscopy[15], SEM provides the possibility to image the surface of embedded tissue blocks. Array tomography uses serial sections of resin embedded tissue which are stained sequentially for confocal microscopy and subsequently contrasted for SEM20. In concert with multi-beam SEM devices, the imaging process is accelerated and automated[23] Despite these advances imaging is still time consuming and the sampling volume is very limited especially when imaging at a high spatial resolution is required. ΜCT is a valuable tool for neuroscientists and has been adopted quickly by the community within the last few years[32,35,37,38,39]

Methods

Results

Conclusion