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Purpose: Achieving a reduction in scan time with minimal inter-slice signal leakage is one of the significant obstacles in parallel MR imaging. In fMRI, multiband-imaging techniques accelerate data acquisition by simultaneously magnetizing the spatial frequency spectrum of multiple slices. The SPECS model eliminates the consequential inter-slice signal leakage from the slice unaliasing, while maintaining an optimal reduction in scan time and activation statistics in fMRI studies., Materials and Methods: When the combined k-space array is inverse Fourier reconstructed, the resulting aliased image is separated into the un-aliased slices through a least squares estimator. Without the additional spatial information from a phased array of receiver coils, slice separation in SPECS is accomplished with acquired aliased images in shifted FOV aliasing pattern, and a bootstrapping approach of incorporating reference calibration images in an orthogonal Hadamard pattern., Result: The aliased slices are effectively separated with minimal expense to the spatial and temporal resolution. Functional activation is observed in the motor cortex, as the number of aliased slices is increased, in a bilateral finger tapping fMRI experiment., Conclusion: The SPECS model incorporates calibration reference images together with coefficients of orthogonal polynomials into an un-aliasing estimator to achieve separated images, with virtually no residual artifacts and functional activation detection in separated images., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The somatosensory functional magnetic resonance imaging (fMRI) response to electrical stimulation of the middle phalange of the second digit of four rats at a spatial resolution of 200 μm cubic at 9.4 T is reported. At high threshold (p<0.002), activated voxels encompass a penetrating vein that passes across the gray matter. These voxels lie mostly in three contiguous slices perpendicular to the pial surface. This activation is assigned to the representation in the forepaw barrel subfield (FBS) of a single cortical column of this phalange. In addition, the activation of the indusium griseum (IG) is visualized robustly. Voxels revealed by fMRI were used to observe functional connectivity to other voxels of the sensorimotor cortex using fcMRI. Results of this experiment were analyzed as a function of decreasing threshold, which exhibited spreading connectivity that revealed S2, M1/M2, and contralateral S1. Noting that every cubic millimeter of tissue contains 125 voxels, connectivity patterns are complex. It is hypothesized that they reflect connections within gray matter by association fibers. S2 and IG revealed connectivities with many voxels across the sensorimotor cortex. These regions also showed subregional variation of connectivity. A 1-cm-diameter surface coil with a local low-noise RF amplifier was used in these studies. The usual region of sensitivity (ROS) of such a coil is 1 cm diameter by 0.5 cm depth. Significant connectivity was observed between time courses of voxels that were within the ROS and voxels that were outside, which extends the volume of tissue that can be observed by the methods of this article.

Purpose: A scalable multiband and multichannel digital magnetic resonance imaging system has been developed with the goal of reducing the time needed for acquisition of a single volume of gradient-recalled echo-planar images of the brain., Methods: Transmit pulses are created by an offline computer equipped with a Pentek excitation card (PCIe model 78621) that was built around the Texas Instruments D/A converter (DAC5688)., Results: The spectral purity of pulses made in this way surpasses the quality of pulses made by the standard modulators of the scanner, even when using the same pulse-creation algorithm. There is no need to mix reference waveforms with the magnetic resonance imaging signal to obtain inter-k-space coherency for different repetitions. The key was the use of a system clock to create the Larmor frequency used for pulse formation. The 3- and 4-fold slice accelerations were tested using phantoms as well as functional and resting-state magnetic resonance imaging of the human brain., Conclusion: Synthesizers with limited modulation-time steps should be replaced not only because of the improved spectral quality of radiofrequency pulses but also for the exceptional coherence of pulses at different slice-selection frequencies., (Copyright © 2013 Wiley Periodicals, Inc.)

Introduction: In this study we used a rat model to elucidate the linear make-up of each major nerve of the upper limb by the C7 root through sensory stimulation and functional magnetic resonance imaging (fMRI)., Methods: The C7 nerve root and major nerves of the right forelimb were stimulated electrically. Blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) was performed concurrently. Voxel overlap within the primary sensory cortex was calculated., Results: C7 comprised sensation in <1% in the musculocutaneous nerve, 6% in the ulnar nerve, 16% in the radial nerve, and 19% in the median nerve (P<0.005 for each). The overlap was always <25% for each major nerve., Conclusions: This study helps explain why C7 is a suitable donor for brachial plexus injury treatment and why there is only a transient sensory deficit after transfer.

The discovery of functional MRI (fMRI), with the first papers appearing in 1992, gave rise to new categories of data that drove the development of new signal-processing strategies. Workers in the field were confronted with image time courses, which could be reshuffled to form pixel time courses. The waveform in an active pixel time-course was determined not only by the task sequence but also by the hemodynamic response function. Reference waveforms could be cross-correlated with pixel time courses to form an array of cross-correlation coefficients. From this array of numbers, colorized images could be created and overlaid on anatomical images. An early paper from the authors' laboratory is extensively reviewed here (Bandettini et al., 1993. Magn. Reson. Med. 30:161-173). That work was carried out using the vocabulary of vector algebra. Cross-correlation methodology was central to the discovery of functional connectivity MRI (fcMRI) by Biswal et al. (1995. Magn. Reson. Med. 34:537-541). In this method, a whole volume time course of images is collected while the brain is nominally at rest and connectivity is studied by cross-correlation of pixel time courses., (Copyright © 2011. Published by Elsevier Inc.)

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon&#95;1000/.

Functional connectivity magnetic resonance imaging (fcMRI) studies in rat brain show brain reorganization following peripheral nerve injury. Subacute neuroplasticity was observed 2 weeks following transection of the four major nerves of the brachial plexus. Direct stimulation of the intact radial nerve reveals a functional magnetic resonance imaging (fMRI) activation pattern in the forelimb regions of the sensory and motor cortices that is significantly different from that observed in normal rats. Results of this fMRI experiment were used to determine seed voxel regions for fcMRI analysis. Intrahemispheric connectivities in the sensorimotor forelimb representations in both hemispheres are largely unaffected by deafferentation, whereas substantial disruption of interhemispheric sensorimotor cortical connectivity occurs. In addition, significant intra- and interhemispheric changes in connectivities of thalamic nuclei were found. These are the central findings of the study. They could not have been obtained from fMRI studies alone-both fMRI and fcMRI are needed. The combination provides a general marker for brain plasticity. The rat visual system was studied in the same animals as a control. No neuroplastic changes in connectivities were found in the primary visual cortex upon forelimb deafferentation. Differences were noted in regions responsible for processing multisensory visual-motor information. This incidental discovery is considered to be significant. It may provide insight into phantom limb epiphenomena., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

The alpha-2-adrenoreceptor agonist, medetomidine, which exhibits dose-dependent sedative effects and is gaining acceptance in small-animal functional magnetic resonance imaging (fMRI), has been studied. Rats were examined on the bench using the classic tail-pinch method with three infusion sequences: 100 microg/kg/h, 300 microg/kg/h, or 100 microg/kg/h followed by 300 microg/kg/h. Stepping the infusion rate from 100 to 300 microg/kg/h after 2.5 h resulted in a prolonged period of approximately level sedation that cannot be achieved by a constant infusion of either 100 or 300 microg/kg/h. By stepping the infusion dosage, experiments as long as 6 h are possible. Functional MRI experiments were carried out on rats using a frequency dependent electrical stimulation protocol-namely, forepaw stimulation at 3, 5, 7, and 10 Hz. Each rat was studied for a four-hour period, divided into two equal portions. During the first portion, rats were started at a 100 microg/kg/h constant infusion. During the second portion, four secondary levels of infusion were used: 100, 150, 200, and 300 microg/kg/h. The fMRI response to stimulation frequency was used as an indirect measure of modulation of neuronal activity through pharmacological manipulation. The frequency response to stimulus was attenuated at the lower secondary infusion dosages 100 or 150 microg/kg/h but not at the higher secondary infusion dosages 200 or 300 microg/kg/h. Parallel experiments with the animal at rest were carried out using both electroencephalogram (EEG) and functional connectivity MRI (fcMRI) methods with consistent results. In the secondary infusion period using 300 microg/kg/h, resting-state functional connectivity is enhanced.

The regions of the body have cortical and subcortical representation in proportion to their degree of innervation. The rat forepaw has been studied extensively in recent years using functional magnetic resonance imaging (fMRI), typically by stimulation using electrodes directly inserted into the skin of the forepaw. Here we stimulate the nerve directly using surgically implanted electrodes. A major distinction is that stimulation of the skin of the forepaw is mostly sensory, whereas direct nerve stimulation reveals not only the sensory system but also deep brain structures associated with motor activity. In this article, we seek to define both the motor and sensory cortical and subcortical representations associated with the four major nerves of the rodent upper extremity. We electrically stimulated each nerve (median, ulnar, radial, and musculocutaneous) during fMRI acquisition using a 9.4-T Bruker scanner (Bruker BioSpin, Billerica, MA). A current level of 0.5 to 1.0 mA and a frequency of 5 Hz were used while keeping the duration constant. A distinct pattern of cortical activation was found for each nerve that can be correlated with known sensorimotor afferent and efferent pathways to the rat forepaw. This direct nerve stimulation rat model can provide insight into peripheral nerve injury.

Functional MRI (fMRI) studies of tasks involving orofacial motion, such as speech, are prone to problems related to motion-induced magnetic field variations. Orofacial motion perturbs the static magnetic field, leading to signal changes that correlate with the task and corrupt activation maps with false positives or signal loss. These motion-induced signal changes represent a contraindication for the implementation of fMRI to study the neurophysiology of orofacial motion. An fMRI experiment of a structured, non-semantic vowel production task was performed using four different voxel volumes and three different slice orientations in an attempt to find a set of acquisition parameters leading to activation maps with maximum specificity. Results indicate that the use of small voxel volumes (2 x 2 x 3 mm(3)) yielded a significantly higher percentage of true positive activation compared to the use of larger voxel volumes. Slice orientation did not have as great an impact as spatial resolution, although coronal slices appeared superior at high spatial resolutions. Furthermore, it was found that combining the strategy of high spatial resolution with an optimum task duration and post-processing methods for separating true and false positives greatly improved the specificity of single-subject, block-design fMRI studies of structured, overt vowel production.

The response of the rat visual system to flashes of blue light has been studied by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The BOLD temporal response is dependent on the number of flashes presented and demonstrates a refractory period that depends on flash frequency. Activated brain regions included the primary and secondary visual cortex, superior colliculus (SC), dorsal lateral geniculate (DLG), and lateral posterior nucleus (LP), which were found to exhibit differing temporal responses. To explain these differences, the BOLD neurovascular response function was modeled. A second-order differential equation was developed and solved numerically to arrive at region-specific response functions. Included in the model are the light input from the diode (duty cycle), a refractory period, a transient response following onset and cessation of stimulus, and a slow adjustment to changes in the average level of the signal. Constants in the differential equation were evaluated for each region by fitting the model to the experimental BOLD response from a single flash, and the equation was then solved for multiple flashes. The simulation mimics the major features of the data; however, remaining differences in the frequency dependence of the response between the cortical and subcortical regions were unexplained. We hypothesized that these discrepancies were due to regional-specific differences in neuronal response to flash frequency. To test this hypothesis, cortical visual evoked potentials (VEPs) were recorded using the same stimulation protocol as the fMRI. Cortical VEPs were more suppressed than subcortical VEPs as flash frequency increased, supporting our hypothesis. This is the first report that regional differences in neuronal activation to the same stimulus lead to differential BOLD activation.

Regional-specific average time courses of spontaneous fluctuations in blood oxygen level dependent (BOLD) MRI contrast at 9.4T in lightly anesthetized resting rat brain are formed, and correlation coefficients between time course pairs are interpreted as measures of connectivity. A hierarchy of regional pairwise correlation coefficients (RPCCs) is observed, with the highest values found in the thalamus and cortex, both intra- and interhemisphere, and lower values between the cortex and thalamus. Independent sensory networks are distinguished by two methods: data driven, where task activation defines regions of interest (ROI), and hypothesis driven, where regions are defined by the rat histological atlas. Success in these studies is attributed in part to the use of medetomidine hydrochloride (Domitor) for anesthesia. Consistent results in two different rat-brain systems, the sensorimotor and visual, strongly support the hypothesis that resting-state BOLD fluctuations are conserved across mammalian species and can be used to map brain systems., ((c) 2008 Wiley-Liss, Inc.)

It is well understood that the different regions of the body have cortical representations in proportion to the degree of innervation. Our current understanding of the rat upper extremity has been enhanced using functional MRI (fMRI), but these studies are often limited to the rat forepaw. The purpose of this study is to describe a new technique that allows us to refine the sensory and motor representations in the cerebral cortex by surgically implanting electrodes on the major nerves of the rat upper extremity and providing direct electrical nerve stimulation while acquiring fMRI images. This technique was used to stimulate the ulnar, median, radial, and musculocutaneous nerves in the rat upper extremity using four different stimulation sequences that varied in frequency (5 Hz vs. 10 Hz) and current (0.5 mA vs. 1.0 mA). A distinct pattern of cortical activation was found for each nerve. The higher stimulation current resulted in a dramatic increase in the level of cortical activation. The higher stimulation frequency resulted in both increases and attenuation of cortical activation in different regions of the brain, depending on which nerve was stimulated., (Copyright 2007 Wiley-Liss, Inc.)

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.

Functional MRI (fMRI) studies of jaw motion, speech, and swallowing disorders have been hampered by motion artifacts. Tissue motion perturbs the static magnetic field, creating geometric distortions in echo-planar images that lead to many false positives in activation maps. These problems have restricted blood oxygenation level-dependent (BOLD) fMRI studies involving orofacial muscles to event-related designs, which offer weak contrast-to-noise ratios when compared to block designs. Two new approaches are described that greatly reduce false positives in the activation maps created by the distortions in block-design fMRI studies involving jaw and tongue motion during chewing. First, an appropriate task duration of 10-14 s was found to maximize functional contrast while minimizing motion artifacts. Second, three motion-sensitive postprocessing methods were applied successively to examine the temporal and spatial characteristics of responses and identify and remove false positives caused by motion artifacts. These techniques are shown to allow the use of block design in an fMRI study of a jaw motion task. Extension to speech and swallowing tasks is discussed.

MRI gradient coil design is a type of nonlinear constrained optimization. A practical problem in transverse gradient coil design using the conjugate gradient descent (CGD) method is that wire elements move at different rates along orthogonal directions (r, phi, z), and tend to cross, breaking the constraints. A momentum-weighted conjugate gradient descent (MW-CGD) method is presented to overcome this problem. This method takes advantage of the efficiency of the CGD method combined with momentum weighting, which is also an intrinsic property of the Levenberg-Marquardt algorithm, to adjust step sizes along the three orthogonal directions. A water-cooled, 12.8 cm inner diameter, three axis torque-balanced gradient coil for rat imaging was developed based on this method, with an efficiency of 2.13, 2.08, and 4.12 mT.m(-1).A(-1) along X, Y, and Z, respectively. Experimental data demonstrate that this method can improve efficiency by 40% and field uniformity by 27%. This method has also been applied to the design of a gradient coil for the human brain, employing remote current return paths. The benefits of this design include improved gradient field uniformity and efficiency, with a shorter length than gradient coil designs using coaxial return paths., (Copyright 2003 Wiley-Liss, Inc.)

Functional magnetic resonance imaging (fMRI) can serve to localize activity in the cerebral cortex. The present study was performed to develop a quantitative means of describing the cortical location activated during voluntary smiling in multiple subjects and to determine whether this location is specific to smiling when compared with other motor tasks. Five human subjects were instructed to smile or to tap the fingers of both hands. Both tasks were performed in a blocked-trial paradigm that consisted of alternating 15-second blocks of a repetitive motor task and 15 seconds of rest. Smiling was also performed as an event-related paradigm in which the subject smiled briefly once every 15 seconds for 20 repetitions that were combined to produce an average response to a single smile. A series of 300 images was acquired using an echo-planar imaging sequence (24-cm field of view; 5-mm slice thickness; repetition time/echo time, 1000/27.2 msec). Each subject's three-dimensional brain images were transformed to Talairach coordinates by stretching or compressing the brain images to fit the standard brain as defined in the Talairach atlas. This allowed data from five subjects to be combined for a numeric description. Functional activation maps acquired by use of the event-related paradigm contained significantly fewer motion artifacts than maps acquired with the blocked-trial paradigm, allowing better visualization of functionally active areas. Three-dimensional Talairach coordinates to describe the locations of peak cortical activity after smiling and finger tapping were established. These coordinates were consistent among subjects. During smiling, statistically significant activation was seen in the motor cortex, primarily along the precentral sulcus; this was inferior and anterior to the region that was associated with finger tapping. This study demonstrates that motion artifacts associated with traditional blocked-trial fMRI protocols can be overcome by employing an event-related paradigm to obtain an average response from a single smile. With the implementation of new imaging paradigms with fMRI, an area of the cerebral cortex has been identified that is specifically activated during voluntary smiling, and remains consistent among subjects. Quantification of fMRI data represents a powerful tool by which to study the cortical response to motor activity and to monitor possible alteration in this activity after injury or surgery. When combined with biofeedback therapy, this technique may help to improve the outcome of facial reanimation procedures in the future.

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.)

Perfusion and blood oxygenation level-dependent (BOLD) signals were simultaneously measured during a finger-tapping task at 3T using QUIPSS II with thin-slice TI(1) periodic saturation, a modified pulsed arterial spin labeling technique that provides quantitative measurement of perfusion. Perfusion and BOLD signal changes due to motor activation were obtained and correlated with the T(1) values estimated from echo-planar imaging (EPI)-based T(1) maps on a voxel-by-voxel basis. The peak perfusion signal occurs in voxels with a T(1) of brain parenchyma while the peak BOLD signal occurs in voxels with a T(1) characteristic of blood and cerebrospinal fluid. The locations of the peak signals of functional BOLD and perfusion only partially overlap on the order of 40%. Perfusion activation maps will likely represent the sites of neuronal activity better than do BOLD activation maps. Magn Reson Med 44:137-143, 2000., (Copyright 2000 Wiley-Liss, Inc.)

Quantitative imaging of perfusion using a single subtraction, second version (QUIPSS II) is a pulsed arterial spin labeling (ASL) technique for improving the quantitation of perfusion imaging by minimizing two major systematic errors: the variable transit delay from the distal edge of the tagged region to the imaging slices, and the contamination by intravascular signal from tagged blood that flows through the imaging slices. However, residual errors remain due to incomplete saturation of spins over the slab-shaped tagged region by the QUIPSS II saturation pulse, and spatial mismatch of the distal edge of the saturation and inversion slice profiles. By replacing the original QUIPSS II saturation pulse with a train of thin-slice periodic saturation pulses applied at the distal end of the tagged region, the accuracy of perfusion quantitation is improved. Results of single and multislice studies are reported.

Electric current-induced phase alternations have been imaged by fast magnetic resonance image (MRI) technology. We measured the magnetic resonance phase images induced by pulsed current stimulation from a phantom and detected its sensitivity. The pulsed current-induced phase image demonstrated the feasibility to detect phase changes of the proton magnetic resonance signal that could mimic neuronal firing. At the present experimental setting, a magnetic field strength change of 1.7 +/- 0.3 nT can be detected. We also calculated the averaged value of the magnetic flux density BT parallel to B0 produced by electric current I inside the voxel as a function of the wire position. The results of the calculation were consistent with our observation that for the same experimental setting the current-induced phase change could vary with location of the wire inside the voxel. We discuss our findings in terms of possible direct MRI detection of neuronal activity., (Copyright 1999 Academic Press.)

Background and Purpose: In Gilles de la Tourette syndrome, PET scanning and EEG suggest an abnormal organization of the sensorimotor cortex and basal ganglia. The purpose of this study was to use functional MR imaging to study activation in the sensorimotor cortex in patients with Tourette syndrome., Methods: From echo-planar images acquired during intermittent performance of a finger-tapping task, the location of activated pixels was determined by means of conventional signal processing methods. In five patients with Tourette syndrome and five healthy volunteers, the number of activated pixels in the sensorimotor cortices and supplementary motor areas were counted. The area over which the activation was distributed was calculated., Results: In the five patients, the average number of pixels activated during the finger-tapping task in the sensorimoter cortices and supplementary motor area (69.4 pixels) exceeded that in the volunteers (49.2 pixels). The difference was significant. The area over which the pixels was distributed was significantly larger (25.4 vs 13.8 cm2)., Conclusion: Motor function is organized differently in patients with Tourette syndrome than in healthy subjects.

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.

Data acquired using functional magnetic resonance imaging are often contaminated by head motion. As a result, optimal information regarding task-induced (or resting-state) signal changes cannot be extracted. Intensity-based registration methods, including intensity correlation or minimum intensity variance techniques, are widely used to register two or more images. It is shown here that intensity-based registration cannot accurately register two or more images in the presence of local intensity changes arising from functional magnetic resonance, fMRI, signals. In this paper, we present a contour-based technique that can be used not only for a more robust registration, but also to help differentiate between task-induced and motion-induced signal changes. Results obtained using both phantom and human brain images demonstrate advantages of this technique compared with a conventional intensity registration technique.

A magnetization transfer (MT)-prepared echo-planar imaging (EPI) pulse sequence was developed to study motor cortex activation, using a finger tapping paradigm. MT weighting resulted in a reduction of both the activated area and, in the majority of activated pixels, the functional MRI signal, regardless of the correlation coefficient threshold used in generating the activation map. The magnetization transfer ratio (MTR) was higher during task activation than during rest. Because the MT effect is strongly tissue-dependent, these results support the hypothesis that incorporation of MT into functional MRI will help to understand the origin of the functional MRI signal.

We have recently demonstrated using functional magnetic resonance imaging the presence of synchronous low-frequency fluctuations of signal intensities from the resting human brain that have a high degree of temporal correlation (p < 0.0001) both within and across the sensorimotor cortex. A statistically significant overlap between the resting-state functional connectivity map and the task-activation map due to bilateral finger tapping was obtained. Similar results have been obtained in the auditory and visual cortex. Because the pulse sequence used for collecting data was sensitive to blood flow and blood oxygenation, these low-frequency fluctuations of signal intensity may have arisen from variations of both. The objective of this study was simultaneously to determine the contribution of the blood oxygenation level signal and the flow signal to physiological fluctuations in the resting brain using the flow-sensitive alternating inversion recovery pulse sequence. In all subjects, the functional connectivity maps obtained from BOLD had a greater coincidence with task-activation maps than the corresponding functional connectivity maps obtained from blood-flow signals at the same level of statistical significance. Results of this study suggest that while variations in blood flow might contribute to functional connectivity maps, BOLD signals play a dominant role in the mechanism that gives rise to functional connectivity in the resting human brain.

The tools needed for analysis and visualization of three-dimensional human brain functional magnetic resonance image results are outlined, covering the processing categories of data storage, interactive vs batch mode operations, visualization, spatial normalization (Talairach coordinates, etc.), analysis of functional activation, integration of multiple datasets, and interface standards. One freely available software package is described in some detail. The features and scope that a generally useful and extensible fMRI toolset should have are contrasted with what is available today. The article ends with a discussion of how the fMRI research community can cooperate to create standards and develop software that meets the community's needs.

Using magnetic resonance (MR) echo-planar imaging (EPI), we recently demonstrated the presence of low-frequency fluctuations (< 0.1 Hz) in MR signal intensity from the resting human brain that have a high degree of temporal correlation (p < 10(-3)) within and across associated regions of the sensorimotor cortex. These fluctuations in MR signal intensity are believed to arise from fluctuations in capillary blood flow and oxygenation. A substantial overlap between the activation map generated by bilateral finger tapping and temporally-correlated voxels from the sensorimotor cortex obtained during rest was observed. In the work reported here, we investigated whether respiratory hypercapnia, which is known to suspend spontaneous oscillations in regional cerebral blood flow, influences these low-frequency fluctuations. The magnitude of low-frequency fluctuations was reversibly diminished during hypercapnia, resulting in a substantial decrease of the temporal correlation both within and across contralateral hemispheres of the sensorimotor cortex. After the breathing mixture was returned to ambient air, the magnitude and spatial extent of the temporal correlation of low-frequency fluctuations returned to normal. Results of this study support the hypothesis that low-frequency physiological fluctuations observed by MR in the human cortex and spontaneous flow oscillations observed in early studies by laser-Doppler flowmetry (LDF) in the cortex of the rat are identical and are secondary to fluctuations in neuronal activity.

Functional magnetic resonance imaging (fMRI) is capable of detecting task-induced blood oxygenation changes using susceptibility sensitive pulse sequences such as gradient-recalled echo-planar imaging (EPI). The local signal increases seen in the time course are believed to be due to an increase in oxygen delivery that is incommensurate with oxygen demands. To help isolate the sources of functional signal changes, the authors have incorporated various forms of diffusion weighting into EPI pulse sequences to characterize the apparent mobility of the functionally modulated protons. Results suggest that the majority of the functional signal at 1.5 T arises from protons that have apparent diffusion coefficients that are approximately four or five times higher than that of brain tissue. This implies that significant functional signal sources are either protons within the vascular space or protons from the perivascular space that is occupied by cerebrospinal fluid.

Data obtained from functional magnetic resonance imaging are often limited by a low signal-to-noise ratio. The time-course data obtained from activated regions contain both system noise and physiological noise, primarily linked to the heart and respiratory rates, that are superimposed on task induced signals. Time averaging of a practical number of data sets is not very effective in improving the signal-to-noise ratio because neither system nor physiological noise is truly random. In this paper, a method is presented for filtering unwanted physiological fluctuations, including aliased signals that are formed as a result of long repetition time (TR) values. A pulse oximeter was used to obtain cardiac and respiratory information during the scanning period. Finite impulse response band-reject digital filters were designed to remove the physiological fluctuations. For comparison, cross-correlation analyses were performed at the same level of statistical significance on both filtered and unfiltered data. We demonstrate that this method can improve the detection of weak signals without increasing the probability of false positives.

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.

Objective: To develop a procedure for noninvasive measurement of language lateralization with functional magnetic resonance imaging (MRI)., Design: Functional neuroimaging using time-series echo-planar MRI., Setting: University medical center research facility., Subjects: Five healthy, right-handed, young adults., Main Outcome Measures: Number of MRI voxels in left and right hemispheres showing task-related signal increases during two contrasting auditory processing tasks. The nonlinguistic task involved processing of pure tones, while the linguistic task involved processing of single words based on semantic content., Results: The pure-tone processing task activated temporal lobe auditory areas and dorsolateral frontal regions bilaterally. Using this task as a control condition, the semantic processing task resulted in lateralized activity in distributed regions of the left hemisphere. A significant effect of task on intrahemispheric activity pattern was demonstrated in every subject. Results were reproduced in preliminary studies of test-retest reliability., Conclusions: The results demonstrate the lateralized anatomy of semantic linguistic systems in contrast to non-linguistic auditory sensory processors and introduce a task subtraction technique adapted for functional MRI as a noninvasive measure of language lateralization.

Purpose: To measure the rate of enhancement in immature intervertebral disks in comparison with that of mature disks after intravenous administration of gadolinium-containing contrast media., Methods: Four rabbits were imaged with MR for 120 minutes after the injection of gadopentetate dimeglumine, gadoteridol, or gadodiamide. Contrast enhancement was measured in the lumbar intervertebral disks on each image. The rate and magnitude of enhancement in the immature and mature disks were compared., Results: Contrast enhancement was detected in intervertebral disks with all three contrast media. Enhancement was significantly greater in immature than in mature animals., Conclusion: Greater enhancement in immature disks is consistent with a lower concentration of fixed negative charges in the glycosaminoglycans of the disk.

A recursive algorithm suitable for functional magnetic resonance imaging (FMRI) calculations is presented. The correlation coefficient of a time course of images with a reference time series, with the mean and any linear trend projected out, may be computed with 22 operations per voxel, per image; the storage overhead is four numbers per voxel. A statistical model for the FMRI signal is presented, and thresholds for the correlation coefficient are derived from it. Selected images from the first real-time functional neuroimaging experiment (at 3 Tesla) are presented. Using a 50-MHz workstation equipped with a 14-bit analog-to-digital converter, each echo planar image was acquired, reconstructed, correlated, thresholded, and displayed in pseudocolor (highlighting active regions in the brain) within 500 ms of the RF pulse.

Purpose: To compare MR contrast enhancement of intervertebral disk tissue after intravenous administration of equimolar doses of an ionic and of a nonionic gadolinium complex., Methods: Contrast enhancement was measured on MR in lumbar intervertebral disks for 120 minutes after intravenous injection of gadoteridol or gadopentetate dimeglumine, 0.3 mmol/kg. MR studies were performed with each contrast medium in four rabbits. Contrast enhancement was measured in intervertebral disks as a function of time and contrast medium., Results: With both contrast media, enhancement of normal intervertebral disks was detected. Enhancement of disks was significantly greater with gadoteridol than with gadopentetate dimeglumine., Conclusion: The enhancement of cartilage is influenced by the molecular structure of the gadolinium complex. The negative charge of gadopentetate dimeglumine may give it a slower rate of diffusion into disk cartilage than a nonionic complex.

In this study, Blood Oxygenation Level Dependent (BOLD) contrast in the detection of human brain activation was compared between spin-echo and gradient-echo echo-planar sequences at 1.5 T. Time course series of spin-echo and gradient-echo images containing the primary motor cortex were collected during rest (no finger movement) and activation (finger movement). Each time course series was collected using a different TE. Resting and active state signal intensities at each TE were measured in identical regions in the motor cortex. From these data, resting and active state R2 (1/T2) and R2* (1/T2*) values were obtained. Across four subjects, brain activation produced an average R2 change of -0.16 +/- 0.02/s (+/- SE), and an average R2* change of -0.55 +/- 0.08/s. The average delta R2*/delta R2 ratio was 3.52 +/- 0.56. The average gradient-echo/spin-echo ratio of activation-induced signal changes at the TE for maximal BOLD contrast for each sequence (TE approximately T2* and T2) was calculated to be 1.87 +/- 0.40.

Purpose: To determine the dose of contrast medium and the imaging strategy sufficient to detect diffusion of low-molecular-weight gadolinium-containing contrast media into normal intervertebral disks., Methods: In 11 rabbits, sequential MR images were obtained of the spine for 120 minutes after intravenous injection of gadopentetate dimeglumine in doses of 0.1 to 2.8 mmol/kg. Images were inspected for evidence of contrast enhancement. Signal intensity was measured and plotted as a function of time and dose., Results: Contrast enhancement was detected by inspection of images and by measurement in animals receiving doses of 0.3 mmol/kg and larger., Conclusions: Diffusion of gadolinium-containing chelates into the intervertebral disk can be detected with clinically used doses of commercially available contrast medium. Therefore, with MR and a gadolinium-containing contrast medium, diffusion into intervertebral disks can be studied.

Image processing strategies for functional magnetic resonance imaging (FMRI) data sets acquired using a gradient-recalled echo-planar imaging sequence are considered. The analysis is carried out using the mathematics of vector spaces. Data sets consisting of N sequential images of the same slice of brain tissue are analyzed in the time-domain and also, after Fourier transformation, in the frequency domain. A technique for thresholding is introduced that uses the shape of the response in a pixel compared with the shape of a reference waveform as the decision criterion. A method is presented to eliminate drifts in data that arise from subject movement. The methods are applied to experimental FMRI data from the motor-cortex and compared with more conventional image-subtraction methods. Several finger motion paradigms are considered in the context of the various image processing strategies. The most effective method for image processing involves thresholding by shape as characterized by the correlation coefficient of the data with respect to a reference waveform followed by formation of a cross-correlation image. Emphasis is placed not only on image formation, but also on the use of signal processing techniques to characterize the temporal response of the brain to the paradigm.

Purpose: Several magnetic resonance imaging (MRI) "tools" for ophthalmologic research have recently been developed in this laboratory, including improved gradient and radiofrequency coils and pulse sequences for high-resolution and diffusion imaging (100-microns resolution)., Methods: These tools have been applied to the in vivo measurement of the relaxation parameters (T1 and T2) and the water diffusion coefficients (Dx and Dy) in the rabbit eye lens, both normal and cataractous. Maps of these parameters in the lens have been computer generated., Results: In the normal lens, water diffusion is highly anisotropic and tends to be parallel to the surface. In the trauma-induced cataractous lens, an increase in spin-spin relaxation times (T2) consistent with edema and alteration of diffusion patterns was observed in a study conducted 2 weeks postsurgery. A partial reversal was observed 6 weeks postsurgery. The histologic data on the enucleated lens at 6 weeks showed a loss of normal lens architecture. Images are shown that display other small structures of the anterior segment with great clarity., Conclusions: An extension of this work, now underway, is the study of the formation of various types of cataract in animal models. It is hypothesized that these methods can be extended to humans as a quantitative alternative for the assessment of cataracts.

We used a new radiofrequency surface coil and complementary software in eyelid magnetic resonance imaging. This custom-designed coil allows visualization of the eyelid structures in submillimeter resolution, providing detailed delineation of such structures as the orbital septum, levator aponeurosis, Müller's muscle, and orbital septa. The effect of Whitnall's ligament on the levator aponeurosis can be observed as a "tenting" of the aponeurosis; the change in vector force is persistent in upgaze and downgaze. This technology will allow accurate dynamic studies of eyelid anatomy in patients with various anatomically based eyelid diseases, before and after surgery, making it possible to test in vivo longstanding theories of normal and pathologic eyelid physiology.

Using gradient-echo echo-planar MRI, a local signal increase of 4.3 +/- 0.3% is observed in the human brain during task activation, suggesting a local decrease in blood deoxyhemoglobin concentration and an increase in blood oxygenation. Images highlighting areas of signal enhancement temporally correlated to the task are created.

Fifteen patients (17 feet) with symptoms suggestive of plantar interdigital neuroma underwent magnetic resonance (MR) imaging at 1.5 T with a solenoid forefoot coil with an 8-cm field of view. Surgery was subsequently performed on six feet. Fifteen interdigital masses were identified with MR imaging. Five of these, in feet that underwent surgery, were pathologically confirmed neuromas. In the remaining foot that underwent surgery, flexor tendon injury with probable inflammatory reaction was demonstrated with MR imaging but was interpreted as indeterminate for neuroma. No neuronal was identified at surgery, which otherwise confirmed the MR imaging findings. Neuromas were most conspicuous on T1-weighted images as foci of decreased signal intensity well demarcated from adjacent fat tissue. The lesions were poorly seen on T2-weighted images, where they appeared isointense or slightly hypointense to fat tissue in all cases. Prominent regions of increased signal intensity, presumably representing fluid in intermetatarsal bursae, were seen proximal to 10 of the 15 masses found with MR imaging.

To determine whether orientation in the static field may be responsible for the frequent occurrence of increased signal intensity within normal tendons at magnetic resonance (MR) imaging, seven healthy volunteers were imaged by means of a 1.5-T unit and standard clinical pulse sequences. The wrist, ankle, and shoulder regions were evaluated with local coils. Imaging was performed with tendon orientations ranging from 0 degree to 90 degrees in relation to the constant magnetic induction field (B0). Markedly increased intratendinous signal intensity was observed at the "magic angle" of 55 degrees, intermediate signal intensity was observed at 45 degrees and 65 degrees, and no signal intensity was observed at 0 degree and 90 degrees. Signal intensity was evident only when a short echo time was used. The authors believe that tendon orientation greatly affects tendon signal intensity in vivo. Increased signal intensity due to the magic angle effect may be misdiagnosed as tendinous degeneration, tendinitis, or frank tear.

The many fibrous tissues of the wrist and hand have short T2s, and, because of the small size of the tissues, their magnetic resonance (MR) imaging necessitates use of the high spatial resolution obtainable with fields of view as small as 2 cm x 2 cm x 1 mm. The authors demonstrate that the use of a local xyz gradient coil, positioned off-center in a clinical MR imager to facilitate patient positioning, permits acquisition of high-resolution images in spin-echo (SE) and gradient-recalled-echo (GRE) sequences with echo time (TE) as short as 6 msec (SE) or 3 msec (GRE). The authors compare this method for obtaining high-resolution images with the alternative method of using normal gradient strengths and increased pulse duration. The effects on image quality of TE, bandwidth, gradient strength, and chemical shift artifacts are presented. Images obtained with the local gradient coil of the carpal tunnel, carpal bones, and proximal interphalangeal joint in healthy volunteers are shown.

A flexible iterative algorithm is presented for optimizing gradient and radio frequency coils for MRI. It is based on a model using discrete current elements and direct Biot-Savart calculation of the fields. An error function is defined over a region of interest (ROI) and is minimized by conjugate gradient descent. The choice of error function allows optimization of the field uniformity, the inductance, and the efficiency of the coil in any combination. Neither the coil nor the ROI is restricted to any particular geometry. A 40-turn cylindrical z-gradient coil of radius a and length 4a, designed for ROI of radius 0.7a and length 2a has an average error in the gradient fields generated of 0.85%, an inductance of 0.014a mH/cm, and an efficiency of 6.65a-2 Gcm/A. A 16-turn birdcage-like RF coil of radius 5 cm, designed for a ROI of radius 4 cm has an average error of 0.79%.

Calculations and experiments that provide support for our previously stated theorem are presented: If two coils simultaneously receiving magnetic resonance signals from the same anatomic region exhibit zero mutual inductance, there can be no correlation of the noise. It is shown that correlation does not exist even in the presence of mutual inductance unless the two signal paths have amplifiers prior to signal combination. It is further found that in the presence of mutual inductance with ideal amplifiers (0 dB noise figure) in the two signal paths, there is no correlation of noise. In order to satisfy the condition of zero mutual inductance, it may be necessary to employ a decoupling circuit external to the body. A novel coil assembly, which was used in the experiments, places a single-turn surface coil in the median plane between the two loops of a counter rotating current coil. The signal-to-noise ratio can be improved by combining signals. This is in analogy to quadrature receiving coils, where the mutual inductance is zero because vector reception fields are perpendicular. In the present geometry, vector reception fields are collinear, but are parallel and antiparallel on the two sides of the coil assembly, resulting in zero mutual inductance.

The tarsal tunnel syndrome may be caused by extrinsic or intrinsic pressure on the posterior tibial nerve or its terminal branches. The specific symptoms depend on the extent of nerve involvement, and compression distal or proximal to the tarsal tunnel may result in variants of the syndrome. To define better the capability of MR imaging for evaluating this entity, we performed MR imaging on three normal subjects and correlated the images with cryomicrotome sections. Six patients with symptoms suggestive of tarsal tunnel syndrome also were studied with MR. In all normal subjects, MR images showed the flexor retinaculum and the structures passing deep to the retinaculum: the tibialis posterior tendon, flexor digitorum longus tendon, flexor hallucis longus tendon, and the posterior tibial neurovascular bundle. The medial calcaneal sensory branch(es) and the medial and lateral plantar nerves also were delineated. Mechanical causes of compression were shown in all six symptomatic patients. The pathologic entities included two neurilemomas, tenosynovitis involving all three tendons, a ganglion cyst arising from the flexor hallucis longus tendon sheath, posttraumatic fibrosis, and post-traumatic fibrosis with associated posttraumatic neuroma. The MR findings were confirmed surgically in five cases. MR imaging can accurately depict the contents of the tarsal tunnel and the courses of the terminal branches of the posterior tibial nerve. In our small series, MR imaging accurately showed the lesions responsible for tarsal tunnel syndrome.