Actively controlled release of Dexamethasone from neural microelectrodes in a chronic in vivo study.

Stable interconnection to neurons in vivo over long time-periods is critical for the success of future advanced neuroelectronic applications. The inevitable foreign body reaction towards implanted materials challenges the stability and an active intervention strategy would be desirable to treat inflammation locally. Here, we investigate whether controlled release of the anti-inflammatory drug Dexamethasone from flexible neural microelectrodes in the rat hippocampus has an impact on probe-tissue integration over 12 weeks of implantation. The drug was stored in a conducting polymer coating (PEDOT/Dex), selectively deposited on the electrode sites of neural probes, and released on weekly basis by applying a cyclic voltammetry signal in three electrode configuration in fully awake animals. Dex-functionalized probes provided stable recordings and impedance characteristics over the entire chronic study. Histological evaluation after 12 weeks of implantation revealed an overall low degree of inflammation around all flexible probes whereas electrodes exposed to active drug release protocols did have neurons closer to the electrode sites compared to controls. The combination of flexible probe technology with anti-inflammatory coatings accordingly offers a promising approach for enabling long-term stable neural interfaces.

Versatile 3D-printed headstage implant for group housing of rodents.

BACKGROUND: An unfavourable yet necessary side-effect of stereotaxic surgery involves the social isolation of post-surgery rats, in order to protect their wound site or skull-mounted implant from damage. Social isolation can cause a myriad of behavioural and physiological changes that are detrimental to the well-being of rats, with potential negative implications for a range of experimental paradigms. New method. Female Sprague Dawley rats (n=40) were implanted onto the skull with a novel 3D-printed headstage socket that surrounded an electrode connector. The socket accommodated a removable stainless-steel headcap for the purposes of protecting the implant. Rats were pair-housed following surgery, and their behaviour was monitored for up to several weeks under two experimental conditions that involved EEG recording and deep-brain stimulation, as well as behavioural test sessions inside an open-field maze. Rat weights were compared between individually- and pair-housed rats at up to 3 weeks post-surgery. RESULTS: These experiments were successfully carried out using pair-housed rats, with no damage or complications observed regarding the implant and its headcap. Rats were able to carry out a range of normal behaviours including running, grooming, foraging and sleeping. Compared to individually-housed rats, pair-housed rats gained less weight over the 3 weeks post-implantation period. Comparison with existing method(s). This method offers additional protection compared to group-housed post-surgical rats that lack the protective headcap. It is also potentially more practical and versatile than a fully-implantable device for the safe post-surgery group housing of rodents. CONCLUSIONS: This implant design can reduce the cost of rodent upkeep, whilst potentially avoiding a myriad of behavioural and physiological changes that are known to result from social isolation.

[Automatic detection of perfusion deficits with Bolus Harmonic Imaging]. / Bolus Harmonic Imaging zur automatischenErkennung ischämiebedingter Perfusionsdefiziteim Gehirn.

PURPOSE: The diagnosis of ischemic stroke relies increasingly on the usage of ultrasound-based methods. One of the recent methods is the transcranial, contrast agent-based Bolus Harmonic Imaging (BHI) method. The captured image sequence is manually examined by clinical experts thus resulting in a time-consuming procedure. The purpose of this study is to evaluate three different methods to analyze BHI image sequences automatically for the detection of ischemic brain tissue. MATERIALS AND METHOD: BHI captures an image sequence that provides information on the dynamic behavior of the ultrasound contrast agents. This image sequence is analyzed using three different procedures. First a system relying on expert knowledge is used to determine perfusion defects. This procedure requires parametric images, which are previously extracted from the image sequence. The parameter images are then categorized by an unsupervised classification method in well-perfused and ischemic tissue by regarding the parametric images as features describing the perfusion. Thirdly, the whole image sequence can be interpreted as a pixel-by-pixel behavior out of contrast agents. The dynamic curve of each pixel can be automatically classified as perfused and ischemic tissue by the K-Means method without extracting parametric images. In all three cases a closing step is necessary for the accurate interpretation of the results. Transcranial ultrasound imaging produces typical stripe artifacts that have to be detected and eliminated. A result image is then created and provides a conclusion about perfusion reduction in brain tissue. RESULTS: All three methods have been validated on the basis of 26 patients by clinical experts. The segmentation on the contrast agent kinetics has proven to be most effective. According to our patient database, it provides the highest detection accuracy, resulting in a sensitivity of 100% and a specificity of 100%. CONCLUSION: The presented methods seem to be adequate for detecting ischemic brain tissue. The classification of contrast agent kinetics provides the best results and has further advantages. It is robust with respect to noise and the calculation is fast because the extraction of parametric images is omitted. The very high sensitivity and specificity must be validated in a larger patient population. Reliable and automated detection of perfusion defects at the bedside seems to be possible.

A robotic assistant for stereotactic neurosurgery on small animals.

BACKGROUND: This work presents the development and performance analysis of a robotic system for stereotactic neurosurgery on small animals. The system is dedicated to the precise placement of probes in the small animal brain, thus providing an improved framework for brain research. METHODS: Based on an analysis of small animal stereotaxy, the mechanical design of the robotic system is presented. Details of the structure and mechanical components and a kinematic description are outlined. The calibration process of the system for arbitrary probes is described. To analyse the mechanical positioning accuracy of the system, a testbed is presented. RESULTS: Positioning performance results show that the system features a mean mechanical positioning accuracy of 32 microm and a mean positioning repeatability of 11 microm. CONCLUSION: The system meets the requirements of targeting small functional areas within the brain of small animals and thus offers a new tool for small animal brain research.

A 64(128)-channel multisite neuronal recording system.

We used a recently described all-dry silicon etch process for SOI wafers to fabricate 64-site electrode arrays in stereotrode arrangement for acute cortical recordings. The fork-like probes are connected to preamplification units by flexible, Y-shaped interconnects. This facilitates maximal experimental flexibility for simultaneously recording from all available channels from the cortex of anaesthetised rats. Preconditioned signals are amplified by a novel modular main amp, which may be software or dial controlled. Signals are 16bit digitized, recorded, analyzed, stored and processed on a DSP-based modular data acquisition system. Digital data is processed, filtered and denoised on all up to (4*32) 128 channels based on an extremely fast wavelet transformation framework.

Investigating the cytoskeleton of chicken cardiocytes with the atomic force microscope.

We have investigated living chicken cardiocytes with an atomic force microscope (AFM). Cytoskeletal structures like stress fibers can easily be imaged with the AFM. Here we have also measured the cell's elastic properties. By taking force curves as a function of lateral position (force mapping) we could compare the elastic properties at different locations of the same cell. In the lamellipodal region investigated here in detail, the elastic moduli range from around 10 up to 200 kPa on top of stress fibers. By degradation with cytochalasin B we can estimate to what extent the elastic properties of this type of cell are determined by the actin network.