3-dimensional functional imaging of human brain using echo-shifted FLASH MRI

A 3-dimensional MRI method has been developed for functional mapping of the human brain, based on blood oxygenation level dependent (BOLD) contrast mechanisms. The method uses recently introduced principles of echo-shifted FLASH to acquire a single 3D data set in 20 s. The technique was tested on a conventional 1.5 Tesla clinical scanner with a standard head coil using visual stimulation with a 8 Hz flashing white light, or a varying checkerboard pattern. Areas of increased signal intensity were identified in the visual cortex, consistent with the known functional organization.     

False-positive analysis of functional MRI during simulated deep brain stimulation: a phantom study

PURPOSE: To investigate the false-positive activations/deactivations in functional MRI (fMRI) of deep brain stimulation (DBS) using a phantom. MATERIALS AND METHODS: fMRI experiments were performed on a 1.5T scanner using a single-shot gradient-echo echo-planar imaging (GE-EPI) sequence (TR/TE/FA = 6000 msec/60 msec/90 degrees ) on an agar-gel phantom inserted with DBS electrodes. During the experimental blocks, two-second stimuli were delivered during the interscan waiting time (ISWT), which was adjusted by changing the number of slices acquired within the TR (3500 msec with 30 slices and 5160 msec with 10 slices). Data were analyzed using SPM2 software, and the false-positive voxels were detected with five different P-value thresholds. RESULTS: The number of false-positive voxels in experimental conditions had no significant differences from those in control conditions with either long or short ISWT, which increased with the P-value threshold from zero at P < 0.0001 to approximately 40 at P < 0.05. The pattern of increasing number of false-positive reactions along with P-value was similar between all conditions. CONCLUSION: False-positive findings from fMRI with similar experimental design can be well controlled with a statistical threshold of P < 0.001 or tighter. The short ISWT of 3500 msec did not increase false-positive reactions compared to the long ISWT of 5160 msec.     

Diffeomorphic brain mapping based on T1‐weighted images: Improvement of registration accuracy by multichannel mapping

Purpose:

To improve image registration accuracy in neurodegenerative populations.

Materials and Methods:

This study used primary progressive aphasia, aged control, and young control T1‐weighted images. Mapping to a template image was performed using single‐channel Large Deformation Diffeomorphic Metric Mapping (LDDMM), a dual‐channel method with ventricular anatomy in the second channel, and a dual‐channel with appendage method, which utilized a priori knowledge of template ventricular anatomy in the deformable atlas.

Results:

Our results indicated substantial improvement in the registration accuracy over single‐contrast‐based brain mapping, mainly in the lateral ventricles and regions surrounding them. Dual‐channel mapping significantly (P < 0.001) reduced the number of misclassified lateral ventricle voxels (based on a manually defined reference) over single‐channel mapping. The dual‐channel (w/appendage) method further reduced (P < 0.001) misclassification over the dual‐channel method, indicating that the appendage provides more accurate anatomical correspondence for deformation.

Conclusion:

Brain anatomical mapping by shape normalization is widely used for quantitative anatomical analysis. However, in many geriatric and neurodegenerative disorders, severe tissue atrophy poses a unique challenge for accurate mapping of voxels, especially around the lateral ventricles. In this study we demonstrate our ability to improve mapping accuracy by incorporating ventricular anatomy in LDDMM and by utilizing a priori knowledge of ventricular anatomy in the deformable atlas. J. Magn. Reson. Imaging 2013;37:76–84. © 2012 Wiley Periodicals, Inc.     

Functional arterial spin labeling: Optimal sequence duration for motor activation mapping in clinical practice

Purpose:

To determine the minimal optimal functional arterial spin labeling (fASL) sequence duration allowing steady and reproducible motor activation mapping.

Materials and Methods:

Three magnetic resonance imaging (MRI) sessions including fASL and blood oxygenation level‐dependent (BOLD) functional MRI (fMRI) sequences were performed on 12 healthy subjects at 3T with a 32‐channel coil. The raw 7‐minute fASL sequence was truncated to obtain six fASL sequences with durations ranging from 1–6 minutes. All the resulting fASL activations were compared between themselves and with both the 7‐minute fASL and BOLD activations. Quantitative parameters assessed activation location (activated volume, barycenter, and distance between barycenters), activation quantification (activation‐related cerebral blood flow), and intraindividual reproducibility across fMRI sessions. The statistical analysis was based on analysis of variance (ANOVA) and Tukey's multiple comparisons.

Results:

Four‐minute fASL achieved steady location and quantification of activation with the activated volume corresponding to 81% of the 7‐minute fASL volume and a barycenter located 1.2 mm from the 7‐minute fASL barycenter and 3.0 mm from the BOLD fMRI barycenter. Four‐minute fASL reproducibility was high and statistically equivalent to 7‐minute values.

Conclusion:

A 4‐minute fASL sequence is thus a reliable tool for motor activation mapping and suitable for use in clinical practice. J. Magn. Reson. Imaging 2012; 36:1435–1444. © 2012 Wiley Periodicals, Inc.     

Sex differences in language processing: functional MRI methodological considerations

PURPOSE: To evaluate the influence of both analysis methods and tasks used in the determination of language related sex differences. Previous neuroimaging studies evaluating sex differences in language processing have been inconsistent. MATERIALS AND METHODS: The current study compared FMRI activation between men and women on a variety of language tasks using different types of individual (laterality and activation volume) and group analyses to evaluate the effects of task and methodology. Forty subjects completed five language tasks, 19 men and 21 women. RESULTS: Group analyses revealed greater activation for men compared with women in the left pars orbitalis while women showed greater activation within the right insula. With individual analyses, there were no significant sex differences in laterality using two large regions of interest (ROIs) covering the inferior frontal and temporoparietal regions; however, there were significant sex effects within small, specific ROIs (insula, middle temporal and pars opercularis, triangularis, and orbitalis). When holding the task constant, some methods (for example different ROIs within individual analyses) revealed sex differences while others methods did not, indicating a dependence on methodology. CONCLUSION: The results partly explain why FMRI studies evaluating language related sex effects have been inconsistent.     

Flow velocity of the cortical vein and its effect on functional brain MRI at 1.5t: Preliminary results by Cine-MR venography

The purpose of this study is to demonstrate the effect of altering flow velocity of cerebral cortical veins as the source of the signal change observed in functional magnetic resonance imaging (fMRI) of the brain. 10 healthy volunteers were examined after instructions in self-paced hand grasping. Experiments were performed using a 1.5-Tesla whole body MR scanner with a conventional two-dimensional gradient echo sequence (TR/TE/flip angle 400/60/40, first order flow rephased, reduced band width 8 Hz/pixel). Flow velocity measurements were performed for the cortical veins which corresponded to the activated areas depicted on fMRI. Velocity was estimated from the cine-MR venography (cine-MRV) with a tagging technique. Flow phantom studies were performed to delineate the effect of flow velocity differences upon the subtraction images of fMRI. The cine-MRV revealed increased flow velocity of the cortical veins during activation in seven volunteers, with a mean velocity difference of 15 mm/sec. Flow phantom studies suggested that the increased flow velocity may result in changes of the flow signal profile due to oblique flow displacement. Subtraction of the two images with different flow profiles produces flow signal enhancement. Increased flow velocity of the cortical veins during the activation is an important factor which contributes to the signal of fMRI.     

Further steps toward direct magnetic resonance (MR) imaging detection of neural action currents: optimization of MR sensitivity to transient and weak currents in a conductor.

The characteristics of an MRI technique that could be used for direct detection of neuronal activity are investigated. It was shown that magnitude imaging using echo planar imaging can detect transient local currents. The sensitivity of this method was thoroughly investigated. A partial k-space EPI acquisition with homodyne reconstruction was found to increase the signal change. A unique sensitivity to the position of the current pulse within the imaging sequence was demonstrated with the greatest signal change occurring when the current pulse coincides with the acquisition of the center lines of k-space. The signal change was shown to be highly sensitive to the spatial position of the current conductor relative to the voxel. Furthermore, with the use of optimization of spatial and temporal placement of the current pulse, the level of signal change obtained at this lower limit of current detectability was considerably magnified. It was possible to detect a current of 1.7 microA applied for 20 ms with an imaging time of 1.8 min. The level of sensitivity observed in our study brings us closer to that theoretically required for the detection of action currents in nerves.     

An roc approach for evaluating functional brain mr imaging and postprocessing protocols

A method that can be used to evaluate the performance of MRI methods for detecting discrete regional activations using functional MRI is presented. Computer derived receiver-operator-characteristic (ROC) curves have been used to evaluate quantitatively a range of conditions encountered in functional MRI studies. ROC analysis allows multiple acquisition strategies and multiple postprocessing strategies to be quantitatively and objectively compared. The authors first present this analysis technique and then illustrate its use for assessing the relative performances of different functional MRI data acquisition strategies using different gradient echo, echo-planar imaging protocols. In addition, the authors have used the ROC analysis to evaluate and compare several methods for analyzing functional MRI data to extract regions of activation. This approach to assessing the performance of different methods is of general use and can be applied to evaluate other data acquisition protocols and postprocessing methods.     

In vivo animal functional MRI: improved image quality with a body-adapted mold

PURPOSE: To reduce functional magnetic resonance imaging (fMRI) susceptibility distortion at the air/tissue interphase in animal experiments. MATERIALS AND METHODS: We investigated the applicability of a body-adaptable flexible mold consisting of a fast-setting alginate. This technique was implemented for subcutaneous growing tumors in rats and for the brains of monkeys. RESULTS: The T(2)*-weighted gradient-echo, echo-planar imaging (GE-EPI) data obtained with the body-adapted mold showed a reduction of susceptibility artifacts and improved image quality. With both rat tumor and monkey brain, an optimized match with the anatomical T(1) images was possible. CONCLUSION: The present mold methodology is a rapid, easy, and inexpensive way to reduce magnetic susceptibility during animal GE-EPI.     

Functional Mapping of the Human Somatosensory Cortex with Echo-Planar MRI

The somatotopical organization of the human somatosensory cortex was analyzed with echo-planar imaging at 1.5 Tesla, utilizing deoxyhemoglobin as an endogenous contrast medium. Scrubbing stimulation at a frequency of 3 Hz was applied to one of three cutaneous areas: toes, fingertips, and tongue tip. Parasagittal echo-planar slices were obtained every 2 s. We found focal bands of increased signal intensity (4% on average) during the stimulation, with a rise time of 2–6 s. These activated bands were located on the contralateral postcentral gyrus. The cortical responses from the three stimulation sites were anatomically distinct and organized medially-to-laterally in the order of toes, fingertips, and tongue tip.     

Toward direct mapping of neuronal activity: MRI detection of ultraweak, transient magnetic field changes.

A novel method based on selective detection of rapidly changing DeltaB(0) magnetic fields and suppression of slowly changing DeltaB(0) fields is presented. The ultimate goal of this work is to present a method that may allow detection of transient and subtle changes in B(0) in cortical tissue associated with electrical currents produced by neuronal activity. The method involves the detection of NMR phase changes that occur during a single-shot spin-echo (SE) echo-planar sequence (EPI) echo time. SE EPI effectively rephases all changes in B(0) that occur on a time scale longer than the echo time (TE) and amplifies all DeltaB(0) changes that occur during TE/2. The method was tested on a phantom that contains wires in which current can be modulated. The sensitivity and flexibility of the technique was demonstrated by modulation of the temporal position and duration of the stimuli-evoked transient magnetic field relative to the 180 RF pulse in the imaging sequence-requiring precise stimulus timing. Currently, with this method magnetic field changes as small as 2 x 10(-10) T (200 pT) and lasting for 40 msec can be detected. Implications for direct mapping of brain neuronal activity with MRI are discussed.     

Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation information during brain activation.

Simultaneous acquisition of complementary functional hemodynamic indices reflecting different aspects of brain activity would be a valuable tool for functional brain-imaging studies offering enhanced detection power and improved data interpretation. As such, a new MRI technique is presented that is able to achieve concurrent acquisition of three hemodynamic images based primarily on the changes of cerebral blood volume, blood flow, and blood oxygenation, respectively, associated with brain activation. Specifically, an inversion recovery pulse sequence has been designed to measure VASO (vascular space occupancy), ASL (arterial spin labeling) perfusion, and BOLD (blood-oxygenation-level-dependent) signals in a single scan. The MR signal characteristics in this sequence were analyzed, and image parameters were optimized for the simultaneous acquisition of these functional images. The feasibility and efficacy of the new technique were assessed by brain activation experiments with visual stimulation paradigms. Experiments on healthy volunteers showed that this technique provided efficient image acquisition, and thus higher contrast-to-noise ratio per unit time, compared with conventional techniques collecting these functional images separately. In addition, it was demonstrated that the proposed technique was able to be utilized in event-related functional MRI experiments, with potential advantages of obtaining accurate transient information of the activation-induced hemodynamic responses.     

Repetition time in echo planar functional MRI.

To date, surprisingly little attention has been directed toward determining the optimum TR in a functional imaging experiment. A survey of the literature reveals a wide range of TRs, but little justification for a specific TR. Long-TR functional imaging experiments provide maximum signal-to-noise ratio (SNR) in the raw images; allow for the collection of a large number of slice locations; and decrease the size of the data set acquired, simplifying storage and handling. This work, however, demonstrates that long-TR imaging sacrifices statistical power when the paradigm timing is held fixed. That is, for a fixed-run duration consisting of multiple activation/control blocks, shorter TR acquisitions (on the order of 1000 ms) provide better discrimination between the activated and nonactivated brain tissue regions than do long-TR acquisitions (on the order of 4000 ms). Results are shown for modeling the functional imaging experiment and for three different paradigms performed on normal subjects.     

Cortical mapping by functional magnetic resonance imaging in patients with brain tumors

The aim of our study was to establish the effectiveness of the functional MRI (fMRI) technique in comparison with intraoperative cortical stimulation (ICS) in planning cortex-saving neurosurgical interventions. The combination of sensory and motor stimulation during fMRI experiments was used to improve the exactness of central sulcus localization. The study subjects were 30 volunteers and 33 patients with brain tumors in the rolandic area. Detailed topographical relations of activated areas in fMRI and intraoperative techniques were compared. The agreement in the location defined by the two methods for motor centers was found to be 84%; for sensory centers it was 83%. When both kinds of activation are taken into account this agreement increases to 98%. A significant relation was found between fMRI and ICS for the agreement of the distance both for motor and sensory centers (p=0.0021–0.0024). Also a strong dependence was found between the agreement of the location and the agreement of the distance for both kinds of stimulation. The spatial correlation between fMRI and ICS methods for the sensorimotor cortex is very high. fMRI combining functional and structural information is very helpful for preoperative neurosurgical planning. The sensitivity of the fMRI technique in brain mapping increases when using both motor and sensory paradigms in the same patient.     

Biexponential modeling of multigradient-echo MRI data of the brain.

Functional MRI (fMRI) using fast multigradient-echo acquisition methods allows the quantitative determination of the relevant parameter T2*. Previously, the TE-dependent signal decay has been modeled with a monoexponential function despite the complex composition of the brain. In this study, biexponential modeling was used to evaluate the relaxation of brain parenchyma and blood separate from that of cerebrospinal fluid. Single-shot multigradient-echo data acquired with spiral or EPI techniques were analyzed. In phantom experiments the biexponential method proved to be accurate. Compared to the biexponential procedure, the monoexponential model overestimated T2* (72.2 msec vs. 65.3 msec) and underestimated DeltaT2* (2.96 msec vs. 3.19 msec) during visual stimulation. The biexponential method may allow intrinsic correction for partial volume effects due to cerebrospinal fluid. The activation-induced parameter changes are detected with a sensitivity equal to that of a monoexponential method. The resulting T2* and DeltaT2* values describe the experimental data more accurately.     

Comparison of functional MRI image realignment tools using a computer-generated phantom.

This study discusses the development of a computer-generated phantom to compare the effects of image realignment programs on functional MRI (fMRI) pixel activation. The phantom is a whole-head MRI volume with added random noise, activation, and motion. It allows simulation of realistic head motions with controlled areas of activation. Without motion, the phantom shows the effects of realignment on motion-free data sets. Prior to realignment, the phantom illustrates some activation corruption due to motion. Finally, three widely used realignment packages are examined. The results showed that the most accurate algorithms are able to increase specificity through accurate realignment while maintaining sensitivity through effective resampling techniques. In fact, accurate realignment alone is not a powerful indicator of the most effective algorithm in terms of true activation.