Plasma microRNAs as prognostic biomarkers for development of severe epilepsy after experimental traumatic brain injury-EpiBioS4Rx Project 1 study.

Objective: To test a hypothesis that acutely regulated plasma microRNAs (miRNAs) can serve as prognostic biomarkers for the development of post-traumatic epilepsy (PTE).

Methods: Adult male Sprague-Dawley rats (n = 245) were randomized to lateral fluid-percussion-induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, United States). Video-electroencephalography (vEEG) was performed on the seventh post-injury month to detect spontaneous seizures.

Whisker stimulation with different frequencies reveals non-uniform modulation of functional magnetic resonance imaging signal across sensory systems in awake rats.

Primary sensory systems are classically considered to be separate units, however there is current evidence that there are notable interactions between them. We examined the cross-sensory interplay by applying a quiet and motion-tolerant zero echo time functional magnetic resonance imaging (fMRI) technique to elucidate the evoked brain-wide responses to whisker pad stimulation in awake and anesthetized rats. Specifically, characterized the brain-wide responses in core and non-core regions to whisker pad stimulation by the varying stimulation-frequency, and determined whether isoflurane-medetomidine anesthesia, traditionally used in preclinical imaging, confounded investigations related to sensory integration.

Resting-state functional MRI of the nose as a novel investigational window into the nervous system.

Besides being responsible for olfaction and air intake, the nose contains abundant vasculature and autonomic nervous system innervations, and it is a cerebrospinal fluid clearance site. Therefore, the nose is an attractive target for functional MRI (fMRI). Yet, nose fMRI has not been possible so far due to signal losses originating from nasal air-tissue interfaces.

Modeling the stress and forces on multi-channel TMS coil arrays in high-field MRI scanners.

Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the cortex. Concurrent functional magnetic resonance imaging can show changes in TMS-induced activity in the whole brain, with the potential to inform brain function research and to guide the development of TMS therapy. However, the interaction of the strong current pulses in the TMS coil in the static main magnetic field of the MRI produces high Lorentz forces, which may damage the coil enclosure and compromise the patient's safety.

ComBating inter-site differences in field strength: harmonizing preclinical traumatic brain injury MRI data.

Integrating datasets from multiple sites and scanners can increase statistical power for neuroimaging studies but can also introduce significant inter-site confounds. We evaluated the effectiveness of ComBat, an empirical Bayes approach, to combine longitudinal preclinical MRI data acquired at 4.7 or 9.

Image data harmonization tools for the analysis of post-traumatic epilepsy development in preclinical multisite MRI studies.

Preclinical MRI studies have been utilized for the discovery of biomarkers that predict post-traumatic epilepsy (PTE). However, these single site studies often lack statistical power due to limited and homogeneous datasets. Therefore, multisite studies, such as the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx), are developed to create large, heterogeneous datasets that can lead to more statistically significant results.

Orientation selective stimulation with tetrahedral electrodes of the rat infralimbic cortex to indirectly target the amygdala.

Introduction: Deep brain stimulation (DBS) is a rapidly developing therapeutic intervention with constantly expanding neurological and psychiatric indications. A major challenge for the approach is the precise targeting and limitation of the effect on the desired neural pathways. We have introduced a new approach, orientation selective stimulation (OSS) that allows free rotation of the induced electric field on a plane when using a probe with three parallel electrodes forming an equilateral triangle at the tip.

Axon fiber orientation as the source of T relaxation anisotropy in white matter: A study on corpus callosum in vivo and ex vivo.

Purpose: Recent studies indicate that T in white matter (WM) is influenced by fiber orientation in B . The purpose of the study was to investigate the interrelationships between axon fiber orientation in corpus callosum (CC) and T relaxation time in humans in vivo as well as in rat brain ex vivo.

Methods: Volunteers were scanned for relaxometric and diffusion MRI at 3 T and 7 T.

Diffusion MRI approaches for investigating microstructural complexity in a rat model of traumatic brain injury.

Our study explores the potential of conventional and advanced diffusion MRI techniques including diffusion tensor imaging (DTI), and single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD) to investigate complex microstructural changes following severe traumatic brain injury in rats at a chronic phase. Rat brains after sham-operation or lateral fluid percussion (LFP) injury were scanned ex vivo in a 9.4 T scanner.

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI.

Plasma neurofilament light chain (NF-L) levels were assessed as a diagnostic biomarker for traumatic brain injury (TBI) and as a prognostic biomarker for somatomotor recovery, cognitive decline, and epileptogenesis. Rats with severe TBI induced by lateral fluid-percussion injury (n = 26, 13 with and 13 without epilepsy) or sham-operation (n = 8) were studied. During a 6-month follow-up, rats underwent magnetic resonance imaging (MRI) (day (D) 2, D7, and D21), composite neuroscore (D2, D6, and D14), Morris-water maze (D35−D39), and a 1-month-long video-electroencephalogram to detect unprovoked seizures during the 6th month.

Acute Hippocampal Damage as a Prognostic Biomarker for Cognitive Decline but Not for Epileptogenesis after Experimental Traumatic Brain Injury.

It is necessary to develop reliable biomarkers for epileptogenesis and cognitive impairment after traumatic brain injury when searching for novel antiepileptogenic and cognition-enhancing treatments. We hypothesized that a multiparametric magnetic resonance imaging (MRI) analysis along the septotemporal hippocampal axis could predict the development of post-traumatic epilepsy and cognitive impairment. We performed quantitative T and T* MRIs at 2, 7 and 21 days, and diffusion tensor imaging at 7 and 21 days after lateral fluid-percussion injury in male rats.

MRI-Guided Electrode Implantation for Chronic Intracerebral Recordings in a Rat Model of Post-Traumatic Epilepsy-Challenges and Gains.

Brain atrophy induced by traumatic brain injury (TBI) progresses in parallel with epileptogenesis over time, and thus accurate placement of intracerebral electrodes to monitor seizure initiation and spread at the chronic postinjury phase is challenging. We evaluated in adult male Sprague Dawley rats whether adjusting atlas-based electrode coordinates on the basis of magnetic resonance imaging (MRI) increases electrode placement accuracy and the effect of chronic electrode implantations on TBI-induced brain atrophy. One group of rats (EEG cohort) was implanted with two intracortical (anterior and posterior) and a hippocampal electrode right after TBI to target coordinates calculated using a rat brain atlas.

Histopathological modeling of status epilepticus-induced brain damage based on diffusion tensor imaging in rats.

Non-invasive magnetic resonance imaging (MRI) methods have proved useful in the diagnosis and prognosis of neurodegenerative diseases. However, the interpretation of imaging outcomes in terms of tissue pathology is still challenging. This study goes beyond the current interpretation of diffusion tensor imaging (DTI) by constructing multivariate models of quantitative tissue microstructure in status epilepticus (SE)-induced brain damage.

A companion to the preclinical common data elements and case report forms for in vivo rodent neuroimaging: A report of the TASK3-WG3 Neuroimaging Working Group of the ILAE/AES Joint Translational Task Force.

The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force established the TASK3 working groups to create common data elements (CDEs) for various aspects of preclinical epilepsy research studies, which could help improve the standardization of experimental designs. In this article, we discuss CDEs for neuroimaging data that are collected in rodent models of epilepsy, with a focus on adult rats and mice. We provide detailed CDE tables and case report forms (CRFs), and with this companion manuscript, we discuss the methodologies for several imaging modalities and the parameters that can be collected.

Relaxation anisotropy of quantitative MRI parameters in biological tissues.

Quantitative MR relaxation parameters vary in the sensitivity to the orientation of the tissue in the magnetic field. In this study, the orientation dependence of multiple relaxation parameters was assessed in various tissues. Ex vivo samples of each tissue type were prepared either from bovine knee (tendon, cartilage) or mouse (brain, spinal cord, heart, kidney), and imaged at 9.

Spatial signatures of anesthesia-induced burst-suppression differ between primates and rodents.

During deep anesthesia, the electroencephalographic (EEG) signal of the brain alternates between bursts of activity and periods of relative silence (suppressions). The origin of burst-suppression and its distribution across the brain remain matters of debate. In this work, we used functional magnetic resonance imaging (fMRI) to map the brain areas involved in anesthesia-induced burst-suppression across four mammalian species: humans, long-tailed macaques, common marmosets, and rats.

Orientation selective DBS of entorhinal cortex and medial septal nucleus modulates activity of rat brain areas involved in memory and cognition.

The recently introduced orientation selective deep brain stimulation (OS-DBS) technique freely controls the direction of the electric field's spatial gradient by using multiple contacts with independent current sources within a multielectrode array. The goal of OS-DBS is to align the electrical field along the axonal track of interest passing through the stimulation site. Here we utilized OS-DBS with a planar 3-channel electrode for stimulating the rat entorhinal cortex (EC) and medial septal nucleus (MSN), two promising areas for DBS treatment of Alzheimer's disease.

Chronic hypometabolism in striatum and hippocampal network after traumatic brain injury and their relation with memory impairment - [18F]-FDG-PET and MRI 4 months after fluid percussion injury in rat.

Hippocampal and thalamo-cortico-striatal networks are critical for memory function as well as execution of a variety of learning strategies. In subjects with memory impairment as a sequel of traumatic brain injury (TBI), the contribution of late metabolic depression across these networks to memory deficit is poorly understood. We used [18F]-FDG-PET to measure chronic post-TBI glucose uptake in the striatum and connected brain areas (septal and temporal hippocampus, thalamus, entorhinal cortex, frontoparietal cortex and amygdala) in rats with lateral fluid-percussion injury (LFPI).

Hippocampal position and orientation as prognostic biomarkers for posttraumatic epileptogenesis: An experimental study in a rat lateral fluid percussion model.

Objective: This study was undertaken to identify prognostic biomarkers for posttraumatic epileptogenesis derived from parameters related to the hippocampal position and orientation.

Methods: Data were derived from two preclinical magnetic resonance imaging (MRI) follow-up studies: EPITARGET (156 rats) and Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx; University of Eastern Finland cohort, 43 rats). Epileptogenesis was induced with lateral fluid percussion-induced traumatic brain injury (TBI) in adult male Sprague Dawley rats.

Convolutional Neural Networks Enable Robust Automatic Segmentation of the Rat Hippocampus in MRI After Traumatic Brain Injury.

Registration-based methods are commonly used in the automatic segmentation of magnetic resonance (MR) brain images. However, these methods are not robust to the presence of gross pathologies that can alter the brain anatomy and affect the alignment of the atlas image with the target image. In this work, we develop a robust algorithm, MU-Net-R, for automatic segmentation of the normal and injured rat hippocampus based on an ensemble of U-net-like Convolutional Neural Networks (CNNs).