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In JoVE (1)
Other Publications (9)
- Journal of Magnetic Resonance Imaging : JMRI
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Journal of Magnetic Resonance Imaging : JMRI
- Korean Journal of Radiology : Official Journal of the Korean Radiological Society
- Magnetic Resonance Imaging
- Journal of Magnetic Resonance Imaging : JMRI
- Brain Structure & Function
- NeuroImage
Articles by Shella Keilholz in JoVE
JoVE Neuroscience
Simultaneous fMRI and Electrophysiology in the Rodent Brain
1Biomedical Engineering, Emory University, 2Biomedical Engineering, Georgia Institute of Technology, 3Biology, Emory University
We have developed a method for simultaneous functional magnetic resonance imaging and electrophysiological recording in the rodent brain, providing a platform for the investigation of the relationship between neural activity and the blood oxygenation level dependent (BOLD) MRI signal.
Other articles by Shella Keilholz on PubMed
Comparison of First-pass Gd-DOTA and FAIRER MR Perfusion Imaging in a Rabbit Model of Pulmonary Embolism
To compare the sensitivity of contrast-enhanced magnetic resonance imaging (MRI) and arterial spin labeling to perfusion deficits in the lung.
Functional MRI of the Rodent Somatosensory Pathway Using Multislice Echo Planar Imaging
A multislice EPI sequence was used to obtain functional MR images of the entire rat brain with BOLD contrast at 11.7 T. Ten to 11 slices covering the rat brain, with an in-plane resolution of 300 microm, provided enough sensitivity to detect activation in brain regions known to be involved in the somatosensory pathway during stimulation of the forelimbs. These regions were identified by warping a digitized rat brain atlas to each set of images. Data analysis was constrained to four major areas of the somatosensory pathway: primary and secondary somatosensory cortices, thalamus, and cerebellum. Incidence maps were generated. Electrical stimulation at 3 Hz led to significant activation in the primary sensory cortex in all rats. Activation in the secondary sensory cortex and cerebellum was observed in 70% of the studies, while thalamic activation was observed in 40%. The amplitude of activation was measured for each area, and average response time courses were calculated. Finally, the frequency dependence of the response to forepaw stimulation was measured in each of the activated areas. Optimal activation occurred in all areas at 3 Hz. These results demonstrate that whole-brain fMRI can be performed on rodents at 11.7 T to probe a well-defined neural network.
BOLD and CBV-weighted Functional Magnetic Resonance Imaging of the Rat Somatosensory System
A multislice spin echo EPI sequence was used to obtain functional MR images of the entire rat brain with blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) contrast at 11.7 T. Maps of activation incidence were created by warping each image to the Paxinos rat brain atlas and marking the extent of the activated area. Incidence maps for BOLD and CBV were similar, but activation in draining veins was more prominent in the BOLD images than in the CBV images. Cerebellar activation was observed along the surface in BOLD images, but in deeper regions in the CBV images. Both effects may be explained by increased signal dropout and distortion in the EPI images after administration of the ferumoxtran-10 contrast agent for CBV fMRI. CBV-weighted incidence maps were also created for 10, 20, and 30 mg Fe/kg doses of ferumoxtran-10. The magnitude of the average percentage change during stimulation increased from 4.9% with the 10 mg Fe/kg dose to 8.7% with the 30-mg Fe/kg dose. Incidence of activation followed a similar trend.
Spatiotemporal Dynamics of Low Frequency Fluctuations in BOLD FMRI of the Rat
To examine spatiotemporal dynamics of low frequency fluctuations in rat cortex.
MR Diagnosis of a Pulmonary Embolism: Comparison of P792 and Gd-DOTA for First-pass Perfusion MRI and Contrast-enhanced 3D MRA in a Rabbit Model
To compare P792 (gadomelitol, a rapid clearance blood pool MR contrast agent) with gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA), a standard extracellular agent, for their suitability to diagnose a pulmonary embolism (PE) during a first-pass perfusion MRI and 3D contrast-enhanced (CE) MR angiography (MRA).
Comparison of Alpha-chloralose, Medetomidine and Isoflurane Anesthesia for Functional Connectivity Mapping in the Rat
Functional connectivity measures based upon low-frequency blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) signal fluctuations have become a widely used tool for investigating spontaneous brain activity in humans. Still unknown, however, is the precise relationship between neural activity, the hemodynamic response and fluctuations in the MRI signal. Recent work from several groups had shown that correlated low-frequency fluctuations in the BOLD signal can be detected in the anesthetized rat - a first step toward elucidating this relationship. Building on this preliminary work, through this study, we demonstrate that functional connectivity observed in the rat depends strongly on the type of anesthesia used. Power spectra of spontaneous fluctuations and the cross-correlation-based connectivity maps from rats anesthetized with alpha-chloralose, medetomidine or isoflurane are presented using a high-temporal-resolution imaging sequence that ensures minimal contamination from physiological noise. The results show less localized correlation in rats anesthetized with isoflurane as compared with rats anesthetized with alpha-chloralose or medetomidine. These experiments highlight the utility of using different types of anesthesia to explore the fundamental physiological relationships of the BOLD signal and suggest that the mechanisms contributing to functional connectivity involve a complicated relationship between changes in neural activity, neurovascular coupling and vascular reactivity.
Functional Connectivity in Blood Oxygenation Level-dependent and Cerebral Blood Volume-weighted Resting State Functional Magnetic Resonance Imaging in the Rat Brain
To directly compare functional connectivity and spatiotemporal dynamics acquired with blood oxygenation level-dependent (BOLD) and cerebral blood volume (CBV)-weighted functional magnetic resonance imaging (fMRI) in anesthetized rats.
Evaluation of Data-driven Network Analysis Approaches for Functional Connectivity MRI
Correlated low frequency fluctuations in the blood oxygenation level dependent signal have been widely observed in highly connected brain regions and are considered to be indicative of coordinated activity within those regions. A typical functional connectivity MRI study consists of hundreds of time points acquired from thousands of image voxels, and thus exploratory data analysis is a significant challenge. This paper investigates the utilization of analytical methods based upon graph theory that can potentially provide a data-driven approach to examining the relationships between and within groups of voxels. Three algorithms, based on reachable groups, path-length analysis, and hierarchical clustering, are described and evaluated in the relatively simple context of the rodent brain. Analysis indicates that (based on the cross-correlation coefficient) cortical voxels are the most strongly connected network nodes. These voxels exhibit stronger clustering than would be expected in a randomly connected graph, and the amount of clustering is dependent on the cross-correlation threshold chosen. The analysis algorithms identify core groups in somatosensory areas and indicate that left and right somatosensory regions are more strongly connected to each other than to midline cortical areas. The results show that algorithms based on graph theory are well-suited for the data-driven analysis of functional connectivity studies.
Spatiotemporal Dynamics of Low Frequency BOLD Fluctuations in Rats and Humans
Most studies involving spontaneous fluctuations in the BOLD signal extract connectivity patterns that show relationships between brain areas that are maintained over the length of the scanning session. In this study, however, we examine the spatiotemporal dynamics of the BOLD fluctuations to identify common patterns of propagation within a scan. A novel pattern finding algorithm was developed for detecting repeated spatiotemporal patterns in BOLD fMRI data. The algorithm was applied to high temporal resolution T2*-weighted multislice images obtained from rats and humans in the absence of any task or stimulation. In rats, the primary pattern consisted of waves of high signal intensity, propagating in a lateral to medial direction across the cortex, replicating our previous findings (Majeed et al., 2009a). These waves were observed primarily in sensorimotor cortex, but also extended to visual and parietal association areas. A secondary pattern, confined to subcortical regions consisted of an initial increase and subsequent decrease in signal intensity in the caudate-putamen. In humans, the most common spatiotemporal pattern consisted of an alteration between activation of areas comprising the "default-mode" (e.g., posterior cingulate and anterior medial prefrontal cortices) and the "task-positive" (e.g., superior parietal and premotor cortices) networks. Signal propagation from focal starting points was also observed. The pattern finding algorithm was shown to be reasonably insensitive to the variation in user-defined parameters, and the results were consistent within and between subjects. This novel approach for probing the spontaneous network activity of the brain has implications for the interpretation of conventional functional connectivity studies, and may increase the amount of information that can be obtained from neuroimaging data.
