Localization of Metal Electrodes in the Intact Rat Brain Using Registration of 3D Microcomputed Tomography Images to a Magnetic Resonance Histology Atlas

Abstract

Simultaneous neural recordings taken from multiple areas of the rodent brain are garnering growing interest because of the insight they can provide about spatially distributed neural circuitry. The promise of such recordings has inspired great progress in methods for surgically implanting large numbers of metal electrodes into intact rodent brains. However, methods for localizing the precise location of these electrodes have remained severely lacking. Traditional histological techniques that require slicing and staining of physical brain tissue are cumbersome and become increasingly impractical as the number of implanted electrodes increases. Here we solve these problems by describing a method that registers 3D computed tomography (CT) images of intact rat brains implanted with metal electrode bundles to a magnetic resonance imaging histology (MRH) atlas. Our method allows accurate visualization of each electrode bundle’s trajectory and location without removing the electrodes from the brain or surgically implanting external markers. In addition, unlike physical brain slices, once the 3D images of the electrode bundles and the MRH atlas are registered, it is possible to verify electrode placements from many angles by “reslicing” the images along different planes of view. Furthermore, our method can be fully automated and easily scaled to applications with large numbers of specimens. Our digital imaging approach to efficiently localizing metal electrodes offers a substantial addition to currently available methods, which, in turn, may help accelerate the rate at which insights are gleaned from rodent network neuroscience.

Coupling multielectrode array recordings with silver labeling of recording sites to study cervical spinal network connectivity

“…Published methods for marking the location of MEAs include iontophoresis of neural tracers (Fekete et al 2015;Haidarliu et al 1999;Kovács et al 2005), topical application of fluorescent dyes (DiCarlo et al 1996;Naselaris et al 2005), lesioning (Brozoski et al 2006;Townsend et al 2002), electrical imaging (Li et al 2015), and imaging-based approaches (Borg et al 2015;Fung et al 1998;Koyano et al 2011;Matsui et al 2007). The silver-labeling method offers several advantages over these previous techniques.…”

“…One of the foremost challenges is simultaneously recording numerous cells, and this can be addressed through the use of multielectrode arrays (MEAs). The MEA approach enables simultaneous recordings of multiple sites, but histologically identifying each recording location (vs. the electrode track) while also preserving tissue integrity poses a further challenge (Borg et al 2015;Li et al 2015;Nuding et al 2015). Thus the initial thrust of the current work was modification and validation of a silver-labeling technique (Spinelli 1975) to enable postrecording deposition of a small amount of silver (i.e., for histological marking) from the tip of each electrode in an MEA.…”

In vivo localization of chronically implanted electrodes and optic fibers in mice

“…Structural imaging has been used to localize implants in humans, monkeys, and rats. For instance, Borg et al 26 used micro-CT imaging in rats for localizing 50-μm-diameter microwire electrode arrays postmortem with an accuracy sufficient for the larger structures of the rat brain (with at least 1000-µm width and height). Also in rats, Rangarajan et al 27 localized 200-μmdiameter electrodes and lesions in vivo with CT and MRI, respectively.…”

“…In order to improve the efficiency of these experiments, we developed a new procedure in mice inspired by techniques used in human deep-brain surgery and brain radiation therapy [22][23][24][25] . CT imaging has been used to localize 50-µm-diameter electrodes postmortem with an accuracy sufficient for larger (>1000 µm) structures of the rat brain 26 and large (200-µm-diameter) electrodes and lesion sites were localized with CT and MRI in rats in vivo 27 . However, the twofold size difference between mouse and rat brains and the need for targeting small nuclei makes sufficiently detailed imaging and localization challenging, and do not allow direct implementation of these methods for precisely localizing small-diameter implants in the mouse brain.…”

Small Animal X-ray Computed Tomography

“…However, since the brain resides in a cavity that is circumscribed by the cranial bones of the skull, micro-CT can become useful. For example, micro-CT has been used to locate metallic electrodes in the brain for neural recording studies (Borg et al 2015). Simultaneous neural recordings taken from multiple areas of the rodent brain can provide insight about spatially distributed neural circuitry.…”