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).

Surgical assistance for instruments' power control based on navigation and neuromonitoring.

In order to prevent nerve injuries during ear-nose-throat (ENT) and skull base surgery, the method Navigated Control Functional is presented. Thereby, the power of active instruments is controlled based on position information, provided by a surgical navigation system, and nerve activity information, provided by a neurophysiologic monitoring system. Electrical stimulation is usually required for the extraction of distance information from neurophysiologic signals (e.g., Electromyography (EMG)). However, this article presents an experiment to investigate a possible relationship between EMG signals and the nerve-instrument distance without additional electrical stimulation. The EMG signals and position information were recorded intra-operatively during ear surgery. An off-line statistical analysis with Spearman's rank correlation coefficient was accomplished. The results show that there is occasionally some correlation at a statistically significant level of 5%. They highly depend on time range, the selected threshold value and time window. Moreover, all the observed correlations are positive against an expected negative correlation.

Method, accuracy and limitation of computer interaction in the operating room by a navigated surgical instrument.

This article describes a new interaction device for surgical navigation systems--the so-called navigation mouse system. The idea is to use a tracked instrument of a surgical navigation system like a pointer to control the software. The new interaction system extends existing navigation systems with a microcontroller-unit. The microcontroller-unit uses the existing communication line to extract the needed 3D-information of an instrument to calculate positions analogous to the PC mouse cursor and click events. These positions and events are used to manipulate the navigation system. In an experimental setup the reachable accuracy with the new mouse system is shown.