Validating a minipig model of reversible cerebral demyelination using human diagnostic modalities and electron microscopy.

BACKGROUND: Inflammatory demyelinating diseases of the central nervous system, such as multiple sclerosis, are significant sources of morbidity in young adults despite therapeutic advances. Current murine models of remyelination have limited applicability due to the low white matter content of their brains, which restricts the spatial resolution of diagnostic imaging. Large animal models might be more suitable but pose significant technological, ethical and logistical challenges. METHODS: We induced targeted cerebral demyelinating lesions by serially repeated injections of lysophosphatidylcholine in the minipig brain. Lesions were amenable to follow-up using the same clinical imaging modalities (3T magnetic resonance imaging, 11C-PIB positron emission tomography) and standard histopathology protocols as for human diagnostics (myelin, glia and neuronal cell markers), as well as electron microscopy (EM), to compare against biopsy data from two patients. FINDINGS: We demonstrate controlled, clinically unapparent, reversible and multimodally trackable brain white matter demyelination in a large animal model. De-/remyelination dynamics were slower than reported for rodent models and paralleled by a degree of secondary axonal pathology. Regression modelling of ultrastructural parameters (g-ratio, axon thickness) predicted EM features of cerebral de- and remyelination in human data. INTERPRETATION: We validated our minipig model of demyelinating brain diseases by employing human diagnostic tools and comparing it with biopsy data from patients with cerebral demyelination. FUNDING: This work was supported by the DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and TRR 274/1 2020, 408885537 (projects B03 and Z01).

Concept and first Implementation of an intracochlearly navigated Electrode Array for Cochlear Implantation.

Cochlear implants (CI) are an established treatment for people with deafness or severe hearing loss. To restore patients' hearing an electrode array (EA) of the CI is inserted into the cochlea to stimulate the auditory nerve. Thereby, the exact positioning and gentle insertion of the EA is crucial for optimal hearing perception outcome. Currently, only microscopic vision is available for entering the cochlea, but the critical intracochlear process during EA insertion is like a "black box" and the surgeon has to rely on haptic feedback. Methods for visualizing the insertion process during surgery are inaccurate or not suitable for routine use due to radiation exposure. To address this problem, we developed a computer-assisted and image-guided cochlear implantation system with an exact real-time visualization of the EA position during the insertion process. The system is based on an electromagnetic tracking system that measures the position and orientation of a sensor integrated into the tip of a EA prototype and visualizes it in presurgical image data. A first experiment with our system showed that a EA prototype could be inserted into a cochlea of a human temporal bone and placed with an accuracy of [Formula: see text]. A maximum insertion angle of 120° was achieved.