Animal fMRI Hall B Wednesday 13:30-15:30

BOLD-fMRI in mice using electrical forepaw stimulation was performed with a cryogenic transceive RF probe and a room-temperature receive-only surface coil. The effect of the increased sensitivity of the cryogenic probe on detecting BOLD responses was analyzed. In fMRI experiments, a gain in image SNR and in temporal SNR of a factor of 3.10 and 1.77 was found, respectively. As further optimization parameter adjusting the thermal shield temperature of the cryogenic probe allows for altering baseline perfusion and accordingly BOLD responses. Cryogenic cooling reduces BOLD signal variations by a factor of 1.59 and therefore increases the statistical power of fMRI.

In a comparative study, the visual pathways of two different animal models (rodent vs primate) were probed using high field strength (9.4T) fMRI. The primary goal of this research was to assay the color vision systems of these two species in hope of demonstrating the evolutionary homology thereof. Here we present several techniques that combine to form a unique overall method for probing this pathway; pharmacological intervention (AP4), precession fMRI compatible LED based stimuli, and intra-brain controls.

The BOLD signal is a weak signal, and hence if no BOLD signal is found in an area this does not necessarily mean there is no neural activity in that area. Signal dropout, artifacts, instability, physiological noise, RF-coil inhomogeneity etc. can all reduce the SNR locally leading to decreased detectability of the BOLD signal Here we illustrate that calculation of the spatial distribution of the detection for a given set of experimental conditions allows us to estimate the confidence by which absence of an fMRI signal can be interpreted as an absence of neural activity.

This study reports a robust anesthetized baboon model for BOLD fMRI studies on a clinical 3T human MRI scanner. BOLD fMRI of visual and somatosensory/motor stimulations in anesthetized baboons were investigated. Comparisons of BOLD fMRI sensitivity were made between isoflurane and ketamine anesthetics with and without paralytics. To our knowledge, this is the first report on baboon BOLD fMRI of visual and somatosensory/motor.

By combining BOLD fMRI with T1 mapping, here we study the ipsilateral responses in somatosensory cortex of awake marmosets. Our results show a surprising spatial mismatch between contralateral and ipsilateral representations of the same body part.

Correlations between resting state BOLD signals in widely distributed brain regions is a key signature of consciously driven mental activity in humans. In this work we attempted to explore if a fine scale functional connectivity can be detected within the anatomically well defined primary somatosensory cortex (SI) at high field and whether the functional connectivity reflects anatomical hierarchical relationships in anesthetized monkeys. We found that functional connectivity exists among anatomically interconnected cortical subregions (areas 3a, 3b, 1 and 2) within SI without the involvement of consciousness (or alertness), and the strengths of the correlation among these subregions reflect the strength of their underlying anatomical connections.

The odor-information processing involved in olfactory imprinting and homing of the home-stream odor in the central nervous system of salmon has not been completely elucidated. In this study, to investigate this information-processing mechanism, we used BOLD fMRI to measure the response to home-stream water in the olfactory bulb and telencephalon of sockeye salmon. The presence of BOLD signals in the dorsal area of the telencephalon indicated that the odor information for home-stream water was processed in a specific area in the telencephalon of sockeye salmon.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In this study, 10 rats with TBI and 6 sham operated controls were imaged during electrical stimulation of the forepaws before TBI and 1, 2 and 8 weeks after TBI. fMRI with forepaw stimulation was able to reveal functional deficit after TBI in the somatosensory cortex outside of the main lesion and also detect partial sensory recovery 8 weeks after TBI. The results suggest that fMRI could serve as a non-invasive user independent tool to evaluate functional recovery after TBI.

The aim of this work was to investigate the spatiotemporal changes in hemodynamics that underlie fMRI signal changes in response to stimulus evoked changes in neuronal activity. We used optical imaging spectroscopy in an un-anesthetized rat model, to provide measures of changes in blood volume and oxygenation at higher spatial and temporal resolution than possible with fMRI, without the potentially confounding effects of anesthesia. We found a complex spatiotemporal hemodynamic response function, consisting of both increases and decreases in blood volume and oxygenation as well as oscillatory response components. We discuss the implications of these findings for fMRI.

Malnutrition is a main public health problem in developing countries. Incidence is increasing and the mortality rate is still high. Functional Magnetic Resonance Imaging (BOLD) was used for mapping brain activity of malnourished rats. The food competition method was applied to a rat model to provoke malnutrition during lactation. The vibrissae-barrel axis was also used due to its advantages for studying structure, function, development and plasticity within the somatosensory cortex. BOLD response changes caused by the trigeminal nerve stimulation on brain activity of malnourished and control rats were obtained at 7T. Results showed a major neuronal activity in malnourished rats.

The neurovascular response to electric forepaw stimulation (EFS) was observed with BOLD signal in the contralateral somatosensory cortex in 11 rats with normal blood gas physiology under alpha-chloralose anesthesia. Serial CBF maps were also acquired during EFS in a subset of these rats. BOLD activation and CBF maps showed elevated blood flow in the contralateral somatosensory cortex at the time of stimulation, after which the regional activation and increases in CBF spread to cortex in the ipsilateral hemisphere.

Electrical stimulation of the forepaws is a widely used stimulation paradigm in functional magnetic resonance imaging (fMRI). We used transgenic mice lacking the voltage-gated sodium channel Nav 1.7 specifically at the nociceptors (Nav1.7R-/-) to study altered pain sensitivity. Nav1.7R-/-, WT littermates and WT animals of our lab were examined using BOLD fMRI. The detected BOLD signal changes of the Nav1.7R-/- animals were significantly reduced as compared to the two WT groups. This is in line with behavioral data reported for these mice. This proves our method to be a valuable tool to non-invasively study pain processing in mice.

The present study examined the BOLD fMRI response of the rat barrel cortex upon sustained trigeminal nerve stimulation. Moreover, the alterations in the barrel cortex metabolite concentration due to prolonged functional activation were measured using 1H-MRS at 9.4T. The results demonstrate that sustained BOLD responses can be obtained reproducibly in the rat barrel cortex following prolonged trigeminal nerve stimulation. Furthermore, preliminary functional MRS (fMRS) results show changes in several metabolites in the barrel cortex and in particular an increase in lactate levels during barrel cortex activation.

In this study brain reorganization following nerve injury and repair was followed for a twelve week period with BOLD fMRI in a rat model. Primary sensory functional return progressed over the entire study period whereas thalamic areas did not functionally return until the twelve week time point. This study demonstrates the utility of using BOLD fMRI as a substitute for conventional electrophysiology in studies of brain plasticity and has many applications outside of peripheral nerve injury and repair.

Human and animal studies suggest the involvement of the transcallosal projection in shaping neuroplasticity following injury may be crucial in dictating the rehabilitation probability. This study was designed to investigate the role of the transcallosal pathways in mediating neuroplasticity following injury in a rat model of sensory deprivation. Using fMRI, we have studied the time course and the age-dependency of which the transcallosal projections effect cortical reorganization. The results demonstrate that the transcallosal projections involvement in neuroplasticity varies dependent on the age and the time following the injury and may introduce a critical consideration when choosing the right rehabilitation strategy.

Some aspects of taste information processing have not been conclusively clarified, such as the process by which the gustatory cortex uses spatial codes to characterize taste information.We used BOLD fMRI measurements obtained at 7 T in an animal system to investigate the process by which taste information is encoded. Sucrose yielded a reproducible BOLD signal increase in the gustatory cortex. During taste stimulation, BOLD signals were also detected in the lip region of the primary somatosensory cortex, secondary somatosensory cortex, and amygdalae. This is the first study that used BOLD fMRI to observe gustatory activation in the rat brain.

This paper proposes a novel flexible MRI-compatible microelectrode array that leverages the stimulation and recording properties for neuroscience application. We perform functional MRI to investigate the cortico-striato-thalamal circuit with thalamic stimulation. Significant positive BOLD responses were observed in receptive field in upper lip region (S1ULp), barrel field (S1BF) and secondary somatosensory cortex (S2). Negative BOLD responses were revealed in caudate putamen (CPu). We inferred a limbic cortico-striatal loop might exist.

Combination of blood– oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) and electrical hindpaw stimulation has been used as a standard model to study the somatosensory pathway and brain rehabilitation in rats. In the present study, we examined the feasibility of performing BOLD fMRI experiments on rat to investigate the activity of the basal ganglia (BG)-cortex circuit associated to hindpaw sensitive stimulation. These findings will have relevance in the fMRI studies dealing with physiopathology of neurodegenerative diseases such as Parkinson

The purpose of this study is to further define the ratunculus by observing cortical activity using BOLD fMRI during direct stimulation of the C7 nerve root. In this study, 7 Sprague-Dawley rats underwent implantable electrode placement on the C7 nerve root. BOLD response to nerve stimulation was then studied using a Bruker 9.4T MRI scanner. C7 nerve stimulation resulted in a small amount of activation in the S1FL region along with a large amount of activation within the M1/M2 regions. These findings are similar to the sensory and motor distributions described in human C7 nerve root literature.

We used functional magnetic resonance imaging (fMRI) in rats to investigate whether following 20 repeatedly elicited seizures there are seizure-induced alterations in the somatosensory maps to forepaw stimulation. We observed increased areas of activation both acutely (1-3 days) and chronically (3-5 weeks) after experimental kindling induced epilepsy. The data indicate that there is considerable neuroplasticity and development of new pathways during the progression of epilepsy. Whether comparable plasticity of cortical maps is present in humans should be tested using fMRI in future studies, considering that such seizure-induced changes may be involved in producing interictal behavioural disturbances.

The retina is about 276 micron thick including the choroid and has highly organized laminar structures. This study reports, for the first time, the feasibility of high-resolution blood-volume fMRI to image layer specific (retinal and choroidal) visual responses in the rat retina at 11.7T up to 40x40x600 micron nominal resolution. Given that the choroid is behind the retina and the retinal pigment epithelium, it is generally inaccessible by optical techniques. Blood-volume fMRI thus could provide a unique means to evaluate lamina-specific functional changes in the rat retina where many retinal disease models are readily available.

BOLD fMRI of the thin retina with the widely used EPI acquisition is challenging because the eye is a region of large magnetic inhomogeneity and high-resolution EPI is pushing the limits of gradient performance, resulting in susceptibility-induced signal drop out and image distortion. To overcome these limitations, we implemented a pass-band balanced steady state free precession (bSSFP) sequence for fMRI of the mouse retina at 45x45x500 µm. bSSFP has comparable temporal resolution and SNR per unit time as EPI, without the artifacts common in EPI. bSSFP fMRI could reliably detect layer-specific responses to hypoxic challenge in the mouse retina.

Long-term in-vivo electrochemistry (LIVE) enables real-time measurement of brain metabolites. Here we have simultaneously obtained BOLD fMRI and amperometric LIVE tissue oxygen data from rat cerebral cortex, during both increases and decreases in inspired oxygen. BOLD and tissue oxygen measurements demonstrated close correlation during both complete oxygen removal (negative responses) and increases in inspired oxygen (positive responses). Our findings demonstrate the feasibility of obtaining real-time metabolite information during fMRI acquisition. The results show that the BOLD signal provides a close correlate of the tissue oxygen dynamics or, alternatively, that tissue oxygen concentration can predict the magnitude of the BOLD response.

The cerebral metabolic rate of oxygen (CMRO₂) is a physiological parameter closely linked to neural activation as well as to various disease states. Hypercapnic calibration is used to calibrate the BOLD-CBF-CBV relationship under the assumption of iso-metabolic blood flow increase during CO₂ inhalation. Simultaneous near infrared optical measurements of cerebral blood volume, blood flow and oxygen extraction can also be used to monitor CMRO₂ changes, albeit at low spatial resolution. We use these optical measurements during graded hypercapnia to test the iso-metabolic assumption, and demonstrate an apparent increase in brain metabolism at higher inhaled CO₂ levels.

To examine what extent consistence of the measurements between BOLD fMRI and local field potential (LFP), we evaluated BOLD and LFP simultaneously in rat somatosensory cortex with a combined measurement technique. The preliminary results indicated a dissociation between BOLD and LFP during low-level neural activity, which might mirror the limitation of neurovascular coupling, the bridge between BOLD and neural activity.

Low freqnecy fluctuations in resting state BOLD data have often been used to map functional connectivity in the rat brain. These low frequency BOLD fluctuations contain contributions from CBF, CBV, and CMRO2. Each of these components have unique physiological time signatures and effective echo times; therefore, modification of the TR and TE used in resting state scans should result in altered contributions from each BOLD component. In this study we examine the dependence of the selection of the TR and TE variables on low frequency resting state data.

The feasibility of saturation-recovery T1 MRI for imaging and quantifying absolute CBF change was further tested at 9.4T using a rat hypercapnia model on two aspects: using diffusion gradients to investigate macrovascular inflow contribution; and slab saturation with varied thickness to test the effects of blood transit distance on measuring CBF. The results indicate that the outcomes of CBF changes induced by hypercapnia were coincident with the literature reports, and not significantly affected by large-vessel inflow effect and blood transit time. The overall results demonstrate that the saturation-recovery T1 MRI is sensitive to microvascular perfusion; it provides a noninvasive and reliable imaging approach for studying cerebral perfusion changes induced by physiology or pathology perturbation.

Mouse models are increasingly used to investigate functional and cardiovascular parameters. In this work we present an approach to noninvasively estimate the arterial pulse pressure by measuring the time dependant blood flow pulse and the local pulse wave velocity. By determining the complex impedance with solutions from the Navier-Stokes equations for incompressible fluids, the pressure pulse could be calculated from the accordant flow pulse. The present results are in good agreement with results from the literature obtained by invasive methods.

The undesired motion, which is correlated with the fMRI paradigm (often present in experiments which are using mechanical stimulation or painful stimulus) can create false areas of an activity, which could remain real BOLD activity areas and a signal time course. Here we present series of fMRI experiment with phantoms and dead animals to which the motion was induced by using an air driven device integrated into the animal cradle. Using results from these experiments we suggest strategy, how to deal with this problem even if conventional motion correction algorithm are not able to remove these false areas completely.

Functional MRI (fMRI) in animals at high magnetic fields keeps expanding our knowledge about the basics of neural processing but the specificity of the fMRI-signal is still under ongoing investigation. Yet, as the signal to noise ratio in MRI depends linearly on the magnetic field strength and calls for even stronger magnets for the detection of even smaller anatomical details, the relation between the functional MR-response and field strength can only be approximated with complex models. In this study the blood oxygenation dependent (BOLD) effect was measured and compared at 9.4 T and 16.4 T in the same animal with segmented gradient-echo (GE) and spin-echo (SE) echo planar imaging (EPI) sequence using optimal echo times for the respective field. Furthermore, high resolution fMRI acquisition at 16.4 T was performed up to a 50 µm in-plane accuracy and for an 8 s temporal resolution without the use of cryo-coils or coil-arrays.

In central nervous system, neuronal activity generally leads to increases in local venous blood oxygenation level (BOLD), cerebral blood flow (CBF), and cerebral blood volume (CBV). However, previous studies have reported that the neural activity in rat caudate putamen (CPu) during noxious electrical stimulation (NES) of paws causes BOLD and CBV decreases. To further understand the specific hemodynamic response in this anatomical structure and its temporal characteristics, BOLD, CBV, and CBF fMRI studies were performed in a rat brain slice containing the CPu. Our results suggest that the neural activity in the CPu during NES causes decreases in CBV and CBF, and an increase in CMRO2 which lasts >2 minutes after stopping the NES.

n this study we tested the feasibility of rat fMRI at highest field strength in combination with an implanted optical fiber. We aim for the combination of fiber based optical Ca2+ imaging with functional magnetic resonance imaging (fMRI) at 17.6 T in vivo. We increased the temporal resolution of fMRI to 20 ms by applying k-space segmentation. Additionally, we conducted fiber-based Ca2+ imaging in mice upon electric forepaw stimulation, detecting neuronal population activity. Our study indicates that a multimodal approach combining a global method like fMRI with a spatially confined, highly specific method as optical Ca2+ imaging becomes amenable.

We investigated the laminar dependence of cortico-cortical interactions induced by paired bi-lateral somatosensory stimulation in α-chloralose anesthetized rats. When compared to the response obtained at 0 ms ISI, the BOLD percent signal change in the S1FL responding to the late stimulus was decreased by 47 % at 40 ms ISI. The degree of suppression in layers III to V was stronger than suppression of fMRI changes in layers I-II and in bottom of layer VI. Our data shows that BOLD fMRI has sufficient spatial and temporal resolution to study cortical circuits, within functional columns and layers.