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A method for making group inferences from functional MRI data using independent component analysis.

Independent component analysis (ICA) is a promising analysis method that is being increasingly applied to fMRI data. A principal advantage of this approach is its applicability to cognitive paradigms for which detailed models of brain activity are not available. Independent component analysis has been successfully utilized to analyze single-subject fMRI data sets, and an extension of this work would be to provide for group inferences. However, unlike univariate methods (e.g., regression analysis, Kolmogorov-Smirnov statistics), ICA does not naturally generalize to a method suitable for drawing inferences about groups of subjects. We introduce a novel approach for drawing group inferences using ICA of fMRI data, and present its application to a simple visual paradigm that alternately stimulates the left or right visual field. Our group ICA analysis revealed task-related components in left and right visual cortex, a transiently task-related component in bilateral occipital/parietal cortex, and a non-task-related component in bilateral visual association cortex. We address issues involved in the use of ICA as an fMRI analysis method such as: (1) How many components should be calculated? (2) How are these components to be combined across subjects? (3) How should the final results be thresholded and/or presented? We show that the methodology we present provides answers to these questions and lay out a process for making group inferences from fMRI data using independent component analysis.

Algorithms↗

Recognition and neural plasticity responding to deficient nutrient intake scanned by a functional MRI in the brain of rats with L-lysine deficiency.

Each L-amino acid (AA) in plasma and brain remains unchanged while normal diet is available. Once L-lysine (Lys) deficient diet was offered to rats, Lys in plasma and brain declined, and anorexia occurred. When solutions of AAs were offered, they selected the Lys solution, and their food intake and growth normalized. The single neuron activity in the lateral hypothalamic area of these rats suggested that neural plasticity occurred, specifically responding to Lys, both by iontophoretic application and during ingestion of AA. The recognition site for deficient nutrient intake in the brain of rats with Lys deficiency was identified by non-invasive magnetic resonance imaging (MRI 4.7 tesla, 40 cm bore in diameter) developed to monitor changes in cerebral blood flow and oxygenation in rat brain. Wistar strain young male rats fed with Lys deficient diet for 4 days, were adapted to be settled in the center of the bore. When they received a Lys injection intraperitoneally (0.2 M, 10 mL/kg), a signal intensity decrease in the medial and lateral hypothalamus appeared 30 minutes later in T2 weighted images, reflecting increased oxygenation which lasted for 30 minutes, and then gradually recovered. These changes never occurred in any other areas of the brain of rats with Lys deficiency, i.e., the thalamus, the cortex, the hippocampus, etc. There were no changes in the signal intensity with control injection of saline. In addition, oxygen consumption in the brain of rats without Lys deficiency was not altered by intraperitoneal Lys injection. The present results suggest that in essential AA deficiency, the medial and lateral hypothalamus may play important roles in recognition responses to particular deficient nutrients in order to maintain homeostasis.

Amino Acids↗

Contrast-to-noise ratio in functional MRI of relative cerebral blood volume with sprodiamide injection.

The purpose of this study was to investigate the dependence of contrast-to-noise ratio (CNR) on the dose and rate of sprodiamide injection in magnetic resonance relative cerebral blood volume (rCBV) imaging. rCBV maps for 35 normal volunteers were constructed from dynamic MR image sets acquired with echo-planar spin-echo imaging after intravenous injection of sprodiamide. Doses of .1, .2, and .3 mmol/kg, at rates of 2 ml/second and 5 ml/second, were tested. CNRs and blood/volume ratios of gray to white matter were computed. CNR depended on dose (P < .0001) but was independent of injection rate (P < .69). rCBV ratios of gray to white matter were dose independent (P < .38) and rate independent (P < .97). The dependence of CNR on dose, but not injection rate, has practical implications in optimal protocol design. The independence of gray/white ratios supports the theory underlying the generation of rCBV maps.

Adult↗

Transient relationships among BOLD, CBV, and CBF changes in rat brain as detected by functional MRI.

The transient relationship between arterial cerebral blood flow (CBF(A)) and total cerebral blood volume (CBV(T)) was determined in the rat brain. Five rats anesthetized with urethane (1.2 g/kg) were examined under graded hypercapnia conditions (7.5% and 10% CO(2) ventilation). The blood oxygenation level-dependent (BOLD) contrast was determined by a gradient-echo echo-planar imaging (GE-EPI) pulse sequence, and CBV(T) changes were determined after injection of a monocrystalline iron oxide nanocolloid (MION) contrast agent using an iron dose of 12 mg/kg. The relationship between CBV(T) and CBF(A) under transient conditions is similar to the power law under steady-state conditions. In addition, the transient relationship between CBV(T) and CBF(A) is region-specific. Voxels with > or =15% BOLD signal changes from hypercapnia (7.5% CO(2) ventilation) have a larger power index (alpha = 3.26), a larger maximum possible BOLD response (M = 0.85), and shorter T(*)(2) (32 ms) caused by deoxyhemoglobin, compared to voxels with <15% BOLD signal changes (alpha = 1.82, M = 0.16, and T(*)(2) = 169 ms). It is suggested that the biophysical model of the BOLD signal can be extended under the transient state, with a caution that alpha and M values are region-specific. To avoid overestimation of the cerebral metabolic rate of oxygen changes seen using fMRI, caution should be taken to not include voxels with large veins and a large BOLD signal.

Animals↗

New devices to deliver somatosensory stimuli during functional MRI.

A new class of devices are described for improving investigation of somatosensory neuronal activation using fMRI. Dubbed magnetomechanical vibrotactile devices (MVDs), the principle of operation involves driving wire coils with small oscillatory currents in the large static magnetic field inherent to MRI scanners. The resulting Lorentz forces can be oriented to generate large vibrations that are easily converted to translational motions as large as several centimeters. Representative data demonstrate the flexibility of MVDs to generate different well-controlled vibratory and tactile stimuli to activate special proprioceptive and cutaneous somatosensory afferent pathways. The implications of these data are discussed with respect to the literature on existing devices for producing sensorimotor activation, as well as expanding the scope of current fMRI investigations.

Adult↗

A functional MRI technique combining principles of echo-shifting with a train of observations (PRESTO).

We present a fast MRI technique sensitized to microscopic susceptibility effects. The method combines elements of echo-shifted gradient-recalled MR imaging (TE > TR) with the acquisition of multiple k-space lines within a single TR-period. The sequence results in a much reduced imaging time as compared with conventional gradient-echo MRI methods. The feasibility of the method is demonstrated for susceptibility bolus tracking in the cat brain using an imaging time of 153 ms. The relative cerebral blood volume maps created with this method are comparable with those obtained with conventional methods.

Animals↗

A new method for proton detection of H2(17)O with potential applications for functional MRI.

A method is presented for the sensitive detection of minute amounts of H2(17)O. The method is based on the increase of the T2 of the water protons following an irradiation of the 17O resonance frequency, due to the partial or full decoupling of the 1H-17O spin-spin interaction. It is demonstrated that when 17O concentrations are low, full decoupling is achieved, and at short echo times the increase in the amplitude of the proton echo signal is proportional to the 17O content of the sample. The potential of the method for indirect 17O imaging is substantiated by a simple one dimensional projection of cylindrical phantoms containing various 17O concentrations. Using interleaved sequences with and without 17O decoupling, errors due to time dependent effects are minimized.

Deuterium Oxide↗

Limitations of temporal resolution in functional MRI.

In fMRI, images can be collected in a very short time; therefore, high temporal resolution is possible in principle. However, the temporal resolution is limited by a blurred intrinsic hemodynamic response and a finite signal-to-noise ratio. To determine the upper limit of temporal resolution in a single area during repeated tasks, motor cortex activity was investigated during visually instructed finger movements. Without averaging, a sequence of four single-finger movements with an execution time of approximately 2 s can be resolved when the delay time between consecutive sequences is at least 3 s. The hemodynamic response time is constant for each subject, but not among different subjects. The temporal resolution can be better when the signal from spatially distinct regions is examined. For a series of experiments involving a visually instructed delayed cued finger movement task with a well-defined, independently determined, variable delay time, time courses in the motor area are distinct from each other in two experiments if the difference in delay time is as little as 2 s. The activation in the visual area due to the presentation of the task serves here as an internal time reference. By comparing a set of fMRI time courses in multiple distinct areas, serial neural processing may be investigated.

Brain↗

Functional MRI of brain activation induced by scanner acoustic noise.

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.

Acoustic Stimulation↗

Partial Fourier reconstruction for three-dimensional gradient echo functional MRI: comparison of phase correction methods.

Partial Fourier (PF) methods take advantage of data symmetry to allow for either faster image acquisition or increased image resolution. Faster acquisition and increased spatial resolution are advantageous for fMRI because of increased temporal resolution and/or reduced partial volume effects, respectively. Standard PF methods, which use a phase reference obtained from a low resolution image, are adequate for the reconstruction of time-stationary images acquired using either spin echoes or short TE gradient echoes. In fMRI, however, multiple images are acquired using long TE gradient echoes, which introduces possible phase drifts in the fMRI data and high spatial frequencies in the phase reference. This work investigates several techniques developed to reconstruct fMRI data obtained with PF acquisitions. PF methods that account for both high-frequency spatial variations and time-dependent drifts in the phase reference are discussed and are quantitatively evaluated using receiver operator characteristic curve analysis.

Brain Mapping↗

Functional MRI of CO2 induced increase in cerebral perfusion.

The sensitivity of MR gradient echo imaging towards CO2 induced changes in cerebral blood flow was investigated in 10 normal subjects. The subjects were inhaling 5% and 7% CO2 and the experiments were carried out at 1.5 T (n = 6) and 2.0 T (n = 5), allowing a comparison of field strengths. Additional experiments were carried out using a higher spatial resolution. The largest signal increases were noted in areas corresponding to larger vessels, but significant changes were also conspicuous in deeper cortical and central grey matter. The changes appeared linearly related to the arterial CO2 tension, within the range of PaCO2 studied. In white matter, the changes were not statistically significant.

Administration, Inhalation↗

DENSE: displacement encoding with stimulated echoes in cardiac functional MRI.

Displacement encoding with stimulated echoes (DENSE) was developed for high-resolution myocardial displacement mapping. Pixel phase is modulated by myocardial displacement and data spatial resolution is limited only by pixel size. 2D displacement vector maps were generated for the systolic action in canines with 0.94 x 1.9 mm nominal in-plane resolution and 2.3 mm/pi displacement encoding. A radial strain of 0.208 was measured across the free left ventricular wall over 105 ms during systole. DENSE displacement maps require small first-order gradient moments for encoding. DENSE magnitude images exhibit black-blood contrast which allows for better myocardial definition and reduced motion-related artifacts.

Animals↗

Human prefrontal cortex is not specific for working memory: a functional MRI study.

Lesion studies in monkeys have provided evidence that lateral prefrontal cortex is necessary for working memory, the cognitive processes involved in the temporary maintenance and manipulation of information. Monkey electrophysiological studies, however, have also observed prefrontal neuronal activity associated with cognitive processes that are nonmnemonic. We tested the hypothesis that the same regions of human prefrontal cortex that demonstrate activity during working memory tasks would also demonstrate activity during tasks without working memory demands. During echoplanar fMRI imaging, subjects performed a three-condition experiment (working memory task, nonworking memory task, rest). In the working memory task, subjects observed serially presented stimuli and determined if each stimulus was the same as that presented two stimuli back. The nonworking memory task in Experiment 1 required subjects to identify a single predetermined stimulus; in Experiment 2, subjects were required to make a button press to every stimulus. In all subjects in both experiments, the working memory task exhibited greater prefrontal cortical activity compared to either nonworking memory task. In these same prefrontal regions, greater activation was also observed during both nonworking memory tasks compared to rest. We conclude that human lateral prefrontal cortex supports processes in addition to working memory. Thus, reverse inference of the form "if prefrontal cortex is active, working memory is engaged" is not supported.

Adult↗

Functional MRI of human brain during breath holding by BOLD and FAIR techniques.

BOLD (blood oxygenation level-dependent) and FAIR (flow-sensitive alternating inversion recovery) imaging techniques were used to investigate the oxygenation and hemodynamic responses of human brain during repeated challenges of breath holding and prolonged single breath holding. The effects of different breathing techniques on BOLD and FAIR image contrasts were carefully examined. With a periodic breath-holding paradigm of 30 s, global changes in gray matter were observable both in T*2-weighted and FAIR images. T*2-weighted images showed 1-4% relative signal intensity increases, while FAIR images demonstrated relative cerebral blood flow (CBF) increase up to 30-70%. The activated pixels depicted in FAIR images were about three times less than those seen in T*2-weighted images. With prolonged breath holding, it was observed that signal intensities in T*2-weighted and FAIR images were dependent on the breathing techniques used. Breath holding after expiration gave rise to immediate signal intensity increases in T*2-weighted and FAIR images, whereas breath holding performed after deep inspiration signals showed a biphasic change both in flow and T*2-weighted. T*2-weighted and FAIR signals showed a transient decrease before rising above the baseline level.

Adult↗