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The aural cavity magnetic susceptibility artifact leads to significant echo planar imaging (EPI) signal dropout in rat deep brain that limits acquisition of functional connectivity fcMRI data. In this study, we provide a method that recovers much of the EPI signal in deep brain. Needle puncture introduction of a liquid-phase fluorocarbon into the middle ear allows acquisition of rat fcMRI data without signal dropout. We demonstrate that with seeds chosen from previously unavailable areas, including the amygdala and the insular cortex, we are able to acquire large scale networks, including the limbic system. This tool allows EPI-based neuroscience and pharmaceutical research in rat brain using fcMRI that was previously not feasible.

Whole brain functional connectivity magnetic resonance imaging requires acquisition of a time course of gradient-recalled (GR) volumetric images. A method is developed to accelerate this acquisition using GR echo-planar imaging and radio frequency (RF) slice phase tagging. For N-fold acceleration, a tailored RF pulse excites N slices using a uniform-field transmit coil. This pulse is the Fourier transform of the profile for the N slices with a predetermined RF phase tag on each slice. A multichannel RF receive coil is used for detection. For n slices, there are n/N groups of slices. Signal-averaged reference images are created for each slice within each slice group for each member of the coil array and used to separate overlapping images that are simultaneously received. The time-overhead for collection of reference images is small relative to the acquisition time of a complete volumetric time course. A least-squares singular value decomposition method allows image separation on a pixel-by-pixel basis. Twofold slice acceleration is demonstrated using an eight-channel RF receive coil, with application to resting-state functional magnetic resonance imaging in the human brain. Data from six subjects at 3 T are reported. The method has been extended to half k-space acquisition, which not only provides additional acceleration, but also facilitates slice separation because of increased signal intensity of the central lines of k-space coupled with reduced susceptibility effects.

The signal intensity during the dynamic approach to the equilibrium state of longitudinal magnetization is a function of sequence parameters, such as repetition time and flip angle, and depends on tissue characteristics, including longitudinal relaxation time of stationary tissue and the rate of blood inflow. A method is presented to extract information from data acquired during the transient state prior to T1 equilibrium using echo-planar acquisitions in T2*-weighted functional magnetic resonance imaging (fMRI) experiments. A voxel in a single slice acquisition is assumed to contain either stationary tissue or large vessels with flowing blood. Models are presented to characterize longitudinal magnetization relaxation of heterogeneous stationary tissue and blood inflow. The data were fitted to theoretical models for longitudinal relaxation of stationary tissue and inflowing blood assuming no residual signal prior to each RF excitation. Parameters were estimated at 3 T for each model using least squares estimation. A goodness-of-fit criterion was applied to exclude voxels that have transient data that does not fit the selected (best fit) model. Voxels that best fit the inflow model, measured at various TR and flip angles, were assumed to contain large draining veins and were excluded from functional maps. Histogram analysis of T1 distributions for activated voxels in a visual paradigm demonstrated the distributions are centered at T1 values of gray matter with tails at both sides of the center due to partial voluming of gray matter with white matter and CSF respectively. The mean gray matter volume fraction in activated voxels was about 0.9. The results indicate that transient data sets can provide additional information that is useful for both localization and characterization of the functionally relevant BOLD response.

The spatial relationship between a measured fMRI signal and its underlying neuronal activity remains unclear. One obstacle is the localization of neuronal activity; another is the spatial resolution of fMRI. In the present study, high-resolution BOLD and CBV fMRI experiments (voxel size: 156 x 156 x 2000 microm3) were conducted in the rat whisker barrel cortex at 3 T; neuronal activity across cortical layers was mapped using the Fos expression technique. Results show that BOLD response is weighted by blood volume and that pixels with high BOLD response can be located at the cortical surface or in deep layers, depending on local vasculature. In contrast to BOLD response, the pixels with high CBV response were consistently clustered in the deep cortical layers. Percentage-CBV change in cortical layers IV-V was 7.3 +/- 1.5%, which was significantly higher than in layers I-III (4.1 +/- 0.9%) and VI (4.3 +/- 0.7%) (mean +/- SEM). The laminar distribution of CBV response correlates well with neuronal activity localized by Fos expression. We conclude that neuronal activity can be inferred from CBV fMRI data with high spatial accuracy. The data indicate that both intracolumn functional connectivity and neurovascular coupling can be studied using CBV fMRI., ((c) 2004 Wiley-Liss, Inc.)

A multishot partial-k-space EPI technique is presented and validated by fMRI at high spatial resolution. High-resolution phase maps corrected by phase-encoded reference scans have less off-resonance effects. Phantom studies demonstrate that this method can substantially improve partial-k-space EPI image formation. BOLD fMRI at submillimeter spatial resolution (156 x 156 x 2000 microm(3), 0.049 microl) was achieved in a rat whisker barrel stimulation model using this technique. The study included eight rats, five of which were administered an intravascular contrast agent (monocrystalline iron oxide nanocolloid (MION)) after the BOLD experiments. In two rats the highest BOLD responses were in the deep layers (IV-VI), and in six rats the highest responses were on the surface and in the deep cortical layers. Most of the pixels that exhibited high BOLD responses had high blood volume weightings. The benefits of this technique are expected to increase for high-resolution fMRI at higher magnetic fields, where T(2) (*) is shorter., (Copyright 2003 Wiley-Liss, Inc.)

A technique for acquiring magnetic field maps simultaneously with gradient-recalled echo-planar time-course data is described. This technique uses a trajectory in which the central part of k-space is collected twice. For a 64 x 64 image acquired with a 125-kHz bandwidth, a field map suitable for geometric correction can be collected simultaneously with the echo-planar time-course data in <70 ms. The field maps generated by this technique are registered with the magnitude images because they are calculated using the same data. They do not suffer from errors due to subject motion, or from different geometric distortions that can result from using different pulse sequences. In addition to correcting geometric distortions that resulted from dynamic magnetic field perturbations, this method was used to measure field shifts arising from respiration and jaw motion across five subjects. Values ranged from 0.035 to 0.165 parts per million (ppm)., (Copyright 2003 Wiley-Liss, Inc.)

The premises of this work are: 1) the limit of spatial resolution in fMRI is determined by anatomy of the microcirculation; 2) because of cortical gray matter tortuosity, fMRI experiments should (in principle) be carried out using cubic voxels; and 3) the noise in fMRI experiments is dominated by low-frequency BOLD fluctuations that are a consequence of spontaneous neuronal events and are pixel-wise dependent. A new model is proposed for fMRI contrast which predicts that the contrast-to-noise ratio (CNR) tends to be independent of voxel dimensions (in the absence of partial voluming of activated tissue), TE, and scanner bandwidth. These predictions have been tested at 3 T, and results support the model. Scatter plots of fMRI signal intensities and low-frequency fluctuations for activated pixels in a finger-tapping paradigm demonstrated a linear relationship between signal and noise that was independent of TE. The R(2) value was about 0.9 across eight subjects studied. The CNR tended to be constant across pixels within a subject but varied across subjects: CNR = 3.2 +/- 1.0. fMRI statistics at 20- and 40-ms TE values were indistinguishable, and TE values as short as 10 ms were used successfully. Robust fMRI data were obtained across all subjects using 1 x 1 x 1 mm(3) cubic voxels with 10 contiguous slices, although 1.5 x 1.5 x 1.5 mm(3) was found to be optimum. Magn Reson Med 46:114-125, 2001., (Copyright 2001 Wiley-Liss, Inc.)

Half k-space gradient-recalled echo-planar imaging (GR-EPI) is discussed in detail. T2* decay during full k-space GR-EPI gives rise to unequal weighting of the lines of k-space, loss of signal intensity at the center of k-space, and a point-spread function that limits resolution. In addition, the long readout time for high-resolution full k-space acquisition gives rise to severe susceptibility effects. These problems are substantially reduced by acquiring only half of k-space and filling the empty side by Hermitian conjugate formation. Details of the pulse sequence and image reconstruction are presented. The point-spread function is 3(1/2) times narrower for half than full k-space acquisition. Experiments as well as theoretical considerations were carried out in a context of fMRI using a whole-brain local gradient and an RF coil at 3 Tesla. Using a bandwidth of +/-83 kHz, well-resolved single-shot images of the human brain, as well as good quality fMRI data sets were obtained with a matrix of 192 x 192 over 16 x 16 cm2 FOV using half k-space techniques. The combination of high spatial resolution using the methods presented in this article and the high temporal resolution of EPI opens opportunities for research into fMRI contrast mechanisms. Increase of percent signal change as the resolution increases is attributed to reduction of partial volume effects of activated voxels. Histograms of fMRI pixel responses are progressively weighted to higher percent signal changes as the resolution increases. The conclusion has been reached that half k-space GR-EPI is generally superior to full k-space GR-EPI and should be used even for low-resolution (64 x 64) EPI.

The goal of this study was to evaluate the usefulness of blood oxygenation level-dependent (BOLD) methodologies to provide temporal and spatial information about skeletal muscle perfusion. A simultaneous gradient echo (GE) and spin-echo (SE) imaging sequence (GE/SE) with alternating TE was used to acquire images of leg skeletal muscle throughout a stepped reactive hyperemia paradigm. The change in both the GE and SE relaxation rates (deltaR2*, deltaR2) measured during ischemia and reactive hyperemia scaled with the duration of cuff inflation (the ischemic period) plateaued for cuff inflations lasting longer than 120 seconds and were greater in soleus muscle than in gastrocnemius. The ratio deltaR2*/deltaR2 was found to be less during the reactive hyperemia period relative to ischemia. Considering that a greater proportion of capillary vessels are perfused during reactive hyperemia than during ischemia, this finding suggests that magnetic susceptibility methodologies, with their dependence on compartment size, may provide a measure of the relative distribution of small and large vessels in skeletal muscle.

A method is introduced by which brain activation caused by the acoustic noise associated with echo planar imaging (EPI) is mapped. Two types of time series were compared. The first time series, considered the "task," involved applying only EPI gradients for 20 s without the application of RF pulses, then, without pause, starting image collection. The second, considered the "control," involved typical sequential image acquisition without the prior gradient pulses. Subtraction of the first 5 s of the two time series revealed signal enhancement mainly in the primary auditory cortex. The technique was validated using a motor cortex task that mimicked the hypothesized scanner noise induced activation.

An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (< 0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10(-3)) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.

Unexpectedly large fluctuations in signal intensity were identified in the functional MRI (FMRI) of normal subjects breathing pure oxygen intermittently. To test the hypothesis that the signal changes were due to fluctuating concentrations of gaseous (paramagnetic) oxygen in the magnetic field, echo planar gradient echo images were acquired of a phantom contiguous to an oxygen mask through which pure oxygen was administered intermittently via plastic tubing. As a control, room air was administered intermittently or oxygen continuously in the same experimental protocol. Signal intensity changes of up to 60% temporally correlated with the administration of oxygen were produced in the phantom. In functional images prepared from the echo planar images, the signal intensity changes resulted in artifacts especially at interfaces in the phantom. The intermittent administration of pure oxygen during acquisition of data for FMRI may produce signal intensity changes that stimulate or obscure function.

Two single-shot volume imaging techniques are described. The first, single-echo echo-volume imaging, is essentially the echo-volume imaging (EVI) sequence suggested by Mansfield (J. Phys. C. 10, L55 (1977)). The second is a multi-spin-echo approach in which one plane of k-space is collected during each spin echo. In both techniques, phase encoding gradients are applied in the z direction, and three-dimensional k-space is filled by a raster pattern in Cartesian coordinates. Spatial saturation is used to avoid aliasing in the y direction, and a selctive pulse is applied to excite the desired slab of tissue and eliminate aliasing in z. The average echo-times, measured from the center of the 90 degrees pulse to the center of the acquisition k-space (kx = ky = kz = 0), were 45 and 104 ms for single echo and multi-echo methods, respectively. Images of the human brain using both sequences are shown.