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Highlights • We evaluated a large animal model for intrathecal delivery and CSF flow. • 11C- labelled PET-tracer was injected via a surgically placed catheter in cisterna magna. • Continuous infusion with artificial cerebrospinal fluid pushed the tracer, while intracranial pressure was monitored. • Reconstruction of the PET/CT scans visualize the distribution of the 11C tracer in the subarachnoid space. Abstract Background Intrathecal (IT) delivery is useful in both basic research and clinical treatments. Here we aim to test a new minimally invasive distribution route to the subarachnoid space (SAS) and the flow of IT administrations. We placed a radioligand into SAS during positron emission tomography (PET) scanning as a proof of concept. New method We injected a 11C-labeled PET-tracer using a surgically placed catheter in the cisterna magna of anesthetized female pigs. The pigs were scanned for 1.5–2 hours in a PET/CT-scanner. The pressure from continuous infusion of artificial CSF (aCSF) promoted distribution of the tracer. The procedure was done under continuous intracranial pressure (ICP) monitoring. The catheter was made accessible both by externalization through the skin and through a subcutaneously placed sterile titanium port connected to the catheter. After image reconstruction, we used PMOD software to assess the tracer distribution throughout SAS. Internalisation of the catheter to a port enables survival studies. Previous studies performing ventriculography have placed a catheter trough brain cortex and parenchyma; such procedures may affect any behavioural or neurological evaluation, and have an increased risk of bleeding per- and post-operatively (Kaiser & Frühauf, 2007). Results The PET-CT visualized tracer was evenly distributed in the SAS. Furthermore, the ICP measurement made it possible to adjust infusion speed within acceptable pressure levels. Conclusion This new method can be useful for testing distribution of PET-tracers, antibiotics, chemotherapeutics and a wide range of other pharmaceuticals targeting the CNS and spinal cord in large animal models, and potentially later in human. [ABSTRACT FROM AUTHOR]

Background Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large animal models with cortical and subcortical anatomical differences. New method We present a convenient method to make an MRI-visible skull fiducial for 3D MRI-based stereotaxic procedures in larger experimental animals. Plastic screws were filled with either copper-sulfate solution or MRI-visible paste from a commercially available cranial head marker. The screw fiducials were inserted in the animal skulls and T1 weighted MRI was performed allowing identification of the inserted skull marker. Results Both types of fiducial markers were clearly visible on the MRÍs. This allows high precision in the stereotaxic space. Comparison with existing method The use of skull bone based fiducial markers gives high precision for both targeting and evaluation of stereotaxic systems. There are no metal artifacts and the fiducial is easily removed after surgery. Conclusion The fiducial marker can be used as a very precise reference point, either for direct targeting or in evaluation of other stereotaxic systems. [ABSTRACT FROM AUTHOR]

• A pressure sensitive gait mat is a useful tool for quantitative motor assessment. • Pressure sensitive gait mats are simple alternatives to camera-sensor based systems. • The gait of minipigs displays symmetry and a slightly frontal center of gravity. • Subtle motor deterioration is detectable after lesions affecting the motor system. • Lesion-compensatory dynamics involve decreased velocity and increased stance time. [ABSTRACT FROM AUTHOR]

Neuromodulation is a rapidly expanding therapeutic option considered within neuropsychiatry, pain and rehabilitation therapy. Combining electrostimulation with feedback from fMRI can provide information about the mechanisms underlying the therapeutic effects, but so far, such studies have been hampered by the lack of technology to conduct safe and accurate experiments. Here we present a system for fMRI compatible electrical stimulation, and the first proof-of-concept neuroimaging data with deep brain stimulation (DBS) in pigs obtained with the device. The system consists of two modules, placed in the control and scanner room, connected by optical fiber. The system also connects to the MRI scanner to timely initiate the stimulation sequence at start of scan. We evaluated the system in four pigs with DBS in the subthalamic nucleus (STN) while we acquired BOLD responses in the STN and neocortex. We found that the system delivered robust electrical stimuli to the implanted electrode in sync with the preprogrammed fMRI sequence. All pigs displayed a DBS-STN induced neocortical BOLD response, but none in the STN. The system solves three major problems related to electric stimuli and fMRI examinations, namely preventing distortion of the fMRI signal, enabling communication that synchronize the experimental conditions, and surmounting the safety hazards caused by interference with the MRI scanner. The fMRI compatible electrical stimulator circumvents previous problems related to electroceuticals and fMRI. The system allows flexible modifications for fMRI designs and stimulation parameters, and can be customized to electroceutical applications beyond DBS. • The system circumvents previous problems related to electroceuticals and fMRI. • Safe and high performance. • Flexible modifications for fMRI designs and stimulation parameters. • Electroceutical applications even beyond deep brain stimulation. [ABSTRACT FROM AUTHOR]