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.

Event-recurring multiband SWIFT functional MRI with 200-ms temporal resolution during deep brain stimulation and isoflurane-induced burst suppression in rat.

Purpose: To develop a high temporal resolution functional MRI method for tracking repeating events in the brain.

Methods: We developed a novel functional MRI method using multiband sweep imaging with Fourier transformation (SWIFT), termed event-recurring SWIFT (EVER-SWIFT). The method is able to image similar repeating events with subsecond temporal resolution.

Spinal cord fMRI with MB-SWIFT for assessing epidural spinal cord stimulation in rats.

Purpose: Electrical epidural spinal cord stimulation (SCS) is used as a treatment for chronic pain as well as to partially restore motor function after a spinal cord injury. Monitoring the spinal cord activity during SCS with fMRI could provide important and objective measures of integrative responses to treatment. Unfortunately, spinal cord fMRI is severely challenged by motion and susceptibility artifacts induced by the implanted electrode and bones.

Brain fMRI during orientation selective epidural spinal cord stimulation.

Epidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI).

Long-lasting blood-brain barrier dysfunction and neuroinflammation after traumatic brain injury.

Background: Traumatic brain injury (TBI) causes 10-20% of acquired epilepsy, which typically develops within 2 years post-injury with poorly understood mechanisms. We investigated the location, severity, evolution and persistence of blood-brain barrier (BBB) dysfunction and associated neuroinflammation after TBI, and their contribution to post-traumatic seizure susceptibility.

Methods: TBI was induced with lateral fluid-percussion in adult male Sprague-Dawley rats (6 sham, 12 TBI).

Orientation-selective and directional deep brain stimulation in swine assessed by functional MRI at 3T.

Functional MRI (fMRI) has become an important tool for probing network-level effects of deep brain stimulation (DBS). Previous DBS-fMRI studies have shown that electrical stimulation of the ventrolateral (VL) thalamus can modulate sensorimotor cortices in a frequency and amplitude dependent manner. Here, we investigated, using a swine animal model, how the direction and orientation of the electric field, induced by VL-thalamus DBS, affects activity in the sensorimotor cortex.

Orientation selective deep brain stimulation of the subthalamic nucleus in rats.

Deep brain stimulation (DBS) has become an important tool in the management of a wide spectrum of diseases in neurology and psychiatry. Target selection is a vital aspect of DBS so that only the desired areas are stimulated. Segmented leads and current steering have been shown to be promising additions to DBS technology enabling better control of the stimulating electric field.

Multi-band SWIFT enables quiet and artefact-free EEG-fMRI and awake fMRI studies in rat.

Functional magnetic resonance imaging (fMRI) studies in animal models provide invaluable information regarding normal and abnormal brain function, especially when combined with complementary stimulation and recording techniques. The echo planar imaging (EPI) pulse sequence is the most common choice for fMRI investigations, but it has several shortcomings. EPI is one of the loudest sequences and very prone to movement and susceptibility-induced artefacts, making it suboptimal for awake imaging.

Tuning Neuromodulation Effects by Orientation Selective Deep Brain Stimulation in the Rat Medial Frontal Cortex.

Previous studies that focused on treating major depressive disorder with conventional deep brain stimulation (DBS) paradigms produced inconsistent results. In this proof-of-concept preclinical study in rats ( = 8), we used novel paradigms of orientation selective DBS for stimulating the complex circuitry crossing the infralimbic cortex, an area considered analogous to human subgenual cingulate cortex. Using functional MRI at 9.

Clinical deep brain stimulation strategies for orientation-selective pathway activation.

Objective: This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants.

Approach: Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain.

Lysophosphatidyl Choline Induced Demyelination in Rat Probed by Relaxation along a Fictitious Field in High Rank Rotating Frame.

In this work a new MRI modality entitled Relaxation Along a Fictitious Field in the rotating frame of rank 4 (RAFF4) was evaluated in its ability to detect lower myelin content in lysophosphatidyl choline (LPC)-induced demyelinating lesions. The lesions were induced in two areas of the rat brain with either uniform or complex fiber orientations, i.e.

MB-SWIFT functional MRI during deep brain stimulation in rats.

Recently introduced 3D radial MRI pulse sequence entitled Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) having virtually zero acquisition delay was used to obtain functional MRI (fMRI) contrast in rat's brain at 9.4 T during deep brain stimulation (DBS). The results demonstrate that MB-SWIFT allows functional images free of susceptibility artifacts, and provides an excellent fMRI activation contrast in the brain.

Orientation selective deep brain stimulation.

Objective: Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS.

Magnetization transfer SWIFT MRI consistently detects histologically verified myelin loss in the thalamocortical pathway after a traumatic brain injury in rat.

Traumatic brain injury (TBI) is associated with various neurocognitive deficits, and rapid assessment of the damage is potentially important for the prevention and treatment of these deficits. Imaging assessment of mild or moderate damage outside the primary lesion area after TBI, however, remains challenging. Magnetization transfer (MT) has clearly been underutilized in imaging the damage caused by TBI.

Phase imaging in brain using SWIFT.

The majority of MRI phase imaging is based on gradient recalled echo (GRE) sequences. This work studies phase contrast behavior due to small off-resonance frequency offsets in brain using SWIFT, a FID-based sequence with nearly zero acquisition delay. 1D simulations and a phantom study were conducted to describe the behavior of phase accumulation in SWIFT.

Measurement of T relaxation time of osteochondral specimens using VFA-SWIFT.

Purpose: To evaluate the feasibility of SWIFT with variable flip angle (VFA) for measurement of T relaxation time in Gd-agarose-phantoms and osteochondral specimens, including regions of very short T *, and compare with T measured using standard methods METHODS: T s of agarose phantoms with variable concentration of Gd-DTPA and nine pairs of native and trypsin-treated bovine cartilage-bone specimens were measured. For specimens, VFA-SWIFT, inversion recovery (IR) fast spin echo (FSE) and saturation recovery FSE were used. For phantoms, additionally spectroscopic IR was used.

Osteochondral repair: evaluation with sweep imaging with fourier transform in an equine model.

Purpose: To evaluate the status of articular cartilage and bone in an equine model of spontaneous repair by using the sweep imaging with Fourier transform (SWIFT) magnetic resonance (MR) imaging technique.

Materials And Methods: Experiments were approved by the Utrecht University Animal Ethics Committee. Six-millimeter-diameter chondral (n = 5) and osteochondral (n = 5, 3-4 mm deep into subchondral bone) defects were created in the intercarpal joints of seven 2-year-old horses and examined with SWIFT at 9.

Detection of calcifications in vivo and ex vivo after brain injury in rat using SWIFT.

Calcifications represent one component of pathology in many brain diseases. With MRI, they are most often detected by exploiting negative contrast in magnitude images. Calcifications are more diamagnetic than tissue, leading to a magnetic field disturbance that can be seen in phase MR images.

Minor influence of lifelong voluntary exercise on composition, structure, and incidence of osteoarthritis in tibial articular cartilage of mice compared with major effects caused by growth, maturation, and aging.

We investigated the effects of lifelong voluntary exercise on articular cartilage of mice. At the age of 4 weeks C57BL mice (n = 152) were divided into two groups, with one group serving as a sedentary control whereas the other was allowed free access to a running wheel from the age of 1 month onward. Mice were euthanized at four different time points (1, 2, 6, and 18 months of age).

Evoked local field potentials can explain temporal variation in blood oxygenation level-dependent responses in rat somatosensory cortex.

The aim of this study was to explain the temporal variations between subjects in the blood oxygenation level-dependent (BOLD) response. Somatosensory responses were elicited with the electrical forepaw stimulus at a frequency of 10 Hz in urethane-anesthetized rats, and functional magnetic resonance imaging (fMRI) with BOLD contrast and local field potential (LFP) measurements were performed simultaneously. BOLD fMRI activation was evaluated by two different models, one based on the stimulus paradigm (the block model) and the other on the simultaneously measured evoked LFP responses.