Fast functional brain imaging using constrained reconstruction based on regularization using arbitrary projections

This work describes a novel method for highly undersampled projection imaging using constrained reconstruction by Tikhonov‐Phillips regularization and its application for high temporal resolution functional MRI (fMRI) at a repetition time of 80 ms. The high‐resolution reference image used as in vivo coil sensitivity is acquired in a separate acquisition using otherwise identical parameters. Activation studies using a standard checkerboard activation paradigm demonstrate the inherent high sensitivity afforded by the possibility to separate activation‐related effects from “physiological noise.”. In this first proof‐of‐principle of the constrained reconstruction based on regularization using arbitrary projections (COBRA) technique, experiments are performed in a single‐slice mode, which allows for a comparison with fast single‐slice echo‐planar imaging (EPI) at equal temporal resolution. The COBRA method can be extended to three‐dimensional (3D) encoding without severe penalty in temporal performance. Analysis of the global signal change demonstrates the excellent reproducibility of COBRA compared to standard EPI. Activation analysis is considerably improved by the possibility to remove electrocardiogram (ECG)‐related and breathing‐related signal fluctuations by physiological correction of each individual breathing and ECG cycle, respectively. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

A comparison of fast MR scan techniques for cerebral activation studies at 1.5 Tesla

To evaluate the sensitivity of fast, gradient-echo MR scan techniques in their ability to detect blood oxygenation level dependent (BOLD) signal changes in task activation studies, three dedicated fast scan techniques, each with whole-brain coverage, were compared during a 3-min finger tapping paradigm on nine normal volunteers on a clinical 1.5 T scanner. Multislice (2D) single-shot spiral, 3D spiral, and multislice (2D) single-shot EPI scan techniques were done with similar temporal and spatial resolutions on each of the volunteers in random order. After image registration and statistical analysis, the sensitivity to detect activation was evaluated for the techniques by calculating t scores and number of activated voxels in predetermined regions of interest, including the contralateral primary sensorimotor cortex, the premotor region, the parietal region, the supplementary motor area, and the ipsilateral cerebellum. Baseline images acquired with the three techniques were qualitatively comparable and had a similar effective spatial resolution of around 5 × 5 × 5 mm³, as determined from autocorrelation analysis. The anatomical coverage was somewhat reduced (4 less slices per volume) with EPI at the identical temporal resolution of 1.76 s for all techniques. The use of multislice 2D spiral scan for motor cortex fMRI experiments provided for a superior overall temporal stability, and an increased sensitivity compared with multislice 2D EPI, and 3D spiral scan. The difference in sensitivity between multislice 2D spiral and EPI scans was small, in particular in the case of a ramp-sampled version of EPI. The difference in performance is attributed mainly to the difference in scan-to-scan stability.     

Improvement of temporal resolution in fMRI using slice phase encode reordered 3D EPI.

A magnetic resonance imaging (MRI) pulse sequence was developed for acquiring high temporal resolution 3D functional magnetic resonance images (fMRI). The technique uses a 3D-acquisition scheme that increases the SNR per unit time. Compared to the previously developed methods, the proposed one does not sacrifice the spatial resolution or require a reduction in the number of acquired slices. The method was tested on six control subjects using a well-known visual activation task. Statistical analysis of the acquired data showed significant activation in the primary visual cortex of each subject. The proposed acquisition method makes use of the periodicity of the applied stimulus. A given kz plane is scanned sequentially using a modified 3D EPI pulse sequence while the stimulus cycle (SC) is applied. The same SC is repeated for each acquisition of a new kz plane sequence. After data acquisition, temporal reordering is done on the data to obtain the proper 3D image sequence. Since the familiarization of the subject with the activation task is an important aspect that might affect the performance of the method, habituation of the primary visual cortex was tested by applying a similar visual stimulus and acquiring data using standard 2D Echo Planar Imaging (EPI). No habituation was observed within a duration of 7 min 12 sec.     

Correction of physiologically induced global off-resonance effects in dynamic echo-planar and spiral functional imaging.

In functional magnetic resonance imaging, a rapid method such as echo-planar (EPI) or spiral is used to collect a dynamic series of images. These techniques are sensitive to changes in resonance frequency which can arise from respiration and are more significant at high magnetic fields. To decrease the noise from respiration-induced phase and frequency fluctuations, a simple correction of the "dynamic off-resonance in k-space" (DORK) was developed. The correction uses phase information from the center of k-space and a navigator echo and is illustrated with dynamic scans of single-shot and segmented EPI and, for the first time, spiral imaging of the human brain at 7 T. Image noise in the respiratory spectrum was measured with an edge operator. The DORK correction significantly reduced respiration-induced noise (image shift for EPI, blurring for spiral, ghosting for segmented acquisition). While spiral imaging was found to exhibit less noise than EPI before correction, the residual noise after the DORK correction was comparable. The correction is simple to apply and can correct for other sources of frequency drift and fluctuations in dynamic imaging.     

Comprehensive quantification of signal‐to‐noise ratio and g‐factor for image‐based and k‐space‐based parallel imaging reconstructions

Parallel imaging reconstructions result in spatially varying noise amplification characterized by the g‐factor, precluding conventional measurements of noise from the final image. A simple Monte Carlo based method is proposed for all linear image reconstruction algorithms, which allows measurement of signal‐to‐noise ratio and g‐factor and is demonstrated for SENSE and GRAPPA reconstructions for accelerated acquisitions that have not previously been amenable to such assessment. Only a simple “prescan” measurement of noise amplitude and correlation in the phased‐array receiver, and a single accelerated image acquisition are required, allowing robust assessment of signal‐to‐noise ratio and g‐factor. The “pseudo multiple replica” method has been rigorously validated in phantoms and in vivo, showing excellent agreement with true multiple replica and analytical methods. This method is universally applicable to the parallel imaging reconstruction techniques used in clinical applications and will allow pixel‐by‐pixel image noise measurements for all parallel imaging strategies, allowing quantitative comparison between arbitrary k‐space trajectories, image reconstruction, or noise conditioning techniques. Magn Reson Med 60:895–907, 2008. © 2008 Wiley‐Liss, Inc.     

Blipped‐controlled aliasing in parallel imaging for simultaneous multislice echo planar imaging with reduced g‐factor penalty

Simultaneous multislice Echo Planar Imaging (EPI) acquisition using parallel imaging can decrease the acquisition time for diffusion imaging and allow full‐brain, high‐resolution functional MRI (fMRI) acquisitions at a reduced repetition time (TR). However, the unaliasing of simultaneously acquired, closely spaced slices can be difficult, leading to a high g‐factor penalty. We introduce a method to create interslice image shifts in the phase encoding direction to increase the distance between aliasing pixels. The shift between the slices is induced using sign‐ and amplitude‐modulated slice‐select gradient blips simultaneous with the EPI phase encoding blips. This achieves the desired shifts but avoids an undesired “tilted voxel” blurring artifact associated with previous methods. We validate the method in 3× slice‐accelerated spin‐echo and gradient‐echo EPI at 3 T and 7 T using 32‐channel radio frequency (RF) coil brain arrays. The Monte‐Carlo simulated average g‐factor penalty of the 3‐fold slice‐accelerated acquisition with interslice shifts is <1% at 3 T (compared with 32% without slice shift). Combining 3× slice acceleration with 2× inplane acceleration, the g‐factor penalty becomes 19% at 3 T and 10% at 7 T (compared with 41% and 23% without slice shift). We demonstrate the potential of the method for accelerating diffusion imaging by comparing the fiber orientation uncertainty, where the 3‐fold faster acquisition showed no noticeable degradation. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Improvements in parallel imaging accelerated functional MRI using multiecho echo‐planar imaging

Multiecho echo‐planar imaging (EPI) was implemented for blood‐oxygenation‐level‐dependent functional MRI at 1.5 T and compared to single‐echo EPI with and without parallel imaging acceleration. A time‐normalized breath‐hold task using a block design functional MRI protocol was carried out in combination with up to four echo trains per excitation and parallel imaging acceleration factors R = 1–3. Experiments were conducted in five human subjects, each scanned in three sessions. Across all reduction factors, both signal‐to‐fluctuation‐noise ratio and the total number of activated voxels were significantly lower using a single‐echo EPI pulse sequence compared with the multiecho approach. Signal‐to‐fluctuation‐noise ratio and total number of activated voxels were also considerably reduced for nonaccelerated conventional single‐echo EPI when compared to three‐echo measurements with R = 2. Parallel imaging accelerated multiecho EPI reduced geometric distortions and signal dropout, while it increased blood‐oxygenation‐level‐dependent signal sensitivity all over the brain, particularly in regions with short underlying T*₂. Thus, the presented method showed multiple advantages over conventional single‐echo EPI for standard blood‐oxygenation‐level‐dependent functional MRI experiments. Magn Reson Med 63:959–969, 2010. © 2010 Wiley‐Liss, Inc.     

Determination of gradient magnetic field-induced acoustic noise associated with the use of echo planar and three-dimensional,fast spin echo techniques

The purpose of this study was to assess gradient magnetic-field-induced acoustic noise levels associated with the use of echo planar imaging (EPI) and three-dimensional fast spin echo (3D-FSE) pulse sequences. Acoustic noise measurements were obtained from two different high field-strength MR systems (1.5 T, Siemens and General Electric Co.) under ambient noise conditions and the use of EPI and 3D-FSE pulse sequences. Parameters were selected to produce “worst case” acoustic noise levels. Acoustic noise recordings were made at the entrance, the center, and at the exit of the magnet bores with a specially designed microphone that was unperturbed by electromagnetic fields. The highest ambient noise levels (A-weighted scale) were 67 dB (Siemens: the same values were recorded at the center and at the exit) and 78 dB (General Electric Co.; recorded at the exit). The highest acoustic noise levels recorded during activation of the gradient magnetic fields were 114 dB (Siemens) and 115 dB (General Electric Co.) and those occurred at the centers of the MR systems with the use of the EPI technique. Gradient magnetic fields associated with the use of EPI and 3D-FSE techniques produced acoustic noise levels that were within permissible levels recommended by federal guidelines.     

Reducing flow artifacts in echo-planar imaging

Echo-planar imaging (EPI) is very susceptible to flow artifacts. Two ways to improve its flow properties are presented. First, “partial flyback” is proposed to reduce artifacts arising from flow in the readout direction. Near the center of k-space, only the even echoes of the EPI echo-train are used. Partial flyback is shown to improve the readout-flow properties at the expense of a slight worsening of the phase-encode flow and off-resonance properties. We recommend that the flyback region acquire 95% of the energy in k-space. Second, “inside-out” EPI is used to reduce artifacts arising from flow in the phase-encode direction. Data collection begins at the center of k-space, with separate interleaves to acquire the top and bottom halves of k-space. Partial flyback is combined with partial-Fourier EPI and inside-out EPI. Partial-flyback inside-out EPI has worse off-resonance properties than partial-flyback partial-Fourier EPI but demonstrates better flow properties and does not require partial k-space reconstruction.     

Assessment of MR compatibility of a PET insert developed for simultaneous multiparametric PET/MR imaging on an animal system operating at 7 T

The combination of positron emission tomography and MR in one system is currently emerging and opens up new domains in the functional examinations of living systems. This article reports on relevant influences of a positron emission tomography insert on MR imaging. The basic conditions of main magnetic field and RF field homogeneity were measured as well as image quality and signal‐to‐noise ratio when applying the usual MR sequence types including echo‐planar techniques. Moreover, the influence of the positron emission tomography insert on the RF noise level and on RF interferences was measured by comparing results achieved with and without the positron emission tomography insert. The temporal stability of EPI imaging with and without the positron emission tomography insert was assessed. Small but significant decreases in the signal‐to‐noise ratio were revealed when the positron emission tomography insert was present, whereas B₀ and B₁ homogeneity as well as RF noise level were not adversely affected. A higher signal intensity drift was found for EPI imaging studies; however, this can be compensated by post processing. In summary, this study shows that positron emission tomography inserts can be designed for and used within an MR system practically, without substantially affecting the MR image quality. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Single‐shot 3D GRASE with cylindrical k‐space trajectories

Development of GRASE (gradient‐ and spin‐echo) pulse sequences for single‐shot 3D imaging has been motivated by physiologic studies of the brain. The duration of echo‐planar imaging (EPI) subsequences between RF refocusing pulses in the GRASE sequence is determinant of image distortions and susceptibility artifacts. To reduce these artifacts the regular Cartesian trajectory is modified to a circular trajectory in 2D and a cylindrical trajectory in 3D for reduced echo train time. Incorporation of “fly‐back” trajectories lengthened the time of the subsequences and proportionally increased susceptibility artifact but the unipolar readout gradients eliminate all ghost artifacts. The modified cylindrical trajectory reduced susceptibility artifact and distortion artifact while raising the signal‐to‐noise ratio in both phantom and human brain images. Magn Reson Med 60:976–980, 2008. © 2008 Wiley‐Liss, Inc.     

Modeling and suppression of respiration-related physiological noise in echo-planar functional magnetic resonance imaging using global and one-dimensional navigator echo correction.

A major source of noise in functional magnetic resonance imaging (fMRI) arises from modulations in the local magnetic field in the head due to motion of the subject's chest through the respiratory cycle, and this physiologic noise can nullify the gains in statistical power expected by the use of higher magnetic fields for fMRI. In particular, fMRI data acquired using echo-planar imaging (EPI) are very sensitive to these spatially and temporally varying respiration-induced frequency offsets. In this study, accurate 3D magnetic field maps in the head were measured and used to determine the frequency offsets at the two extremes of the respiratory cycle. From these maps, spatially dependent frequency variations from about -1.0 Hz to +1.5 Hz were measured in the brain through the respiratory cycle. Simulations of a typical axial EPI fMRI experiment acquired in the presence of this measured field variation were performed, demonstrating regional image intensity variations between 1 and 5% in single pixel time series. The inadequacy of either global or 1D navigator echo corrections to measure and suppress respiratory-induced noise in fMRI time series is demonstrated. The nature of the spatial variations observed suggests that 2D approaches should be considered.     

Functional MRI during the execution of a motor task in patients with multiple sclerosis and fatigue

Purpose

This study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue.

Materials and methods

We enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.5 T) was performed with conventional sequences and an echoplanar imaging (EPI) sequence for functional MRI (fMRI). The motor task consisted of sequential finger tapping performed with the right hand. Statistical maps of motor activation were obtained. Comparison between the two subgroups of patients and between patients and controls was performed with analysis of variance (ANOVA) statistical analysis (p<0.05).

Results

Compared with controls, patients without fatigue showed greater activation of the primary sensorimotor cortex bilaterally, of the right supplementary motor cortex, of the left premotor cortex, of the left cerebellum and of the superior parietal lobule bilaterally. Compared with patients without fatigue, patients with fatigue demonstrated greater activation of the right premotor area, of the putamen and the dorsolateral prefrontal cortex.

Conclusions

Patients with fatigue have greater activation of the motor-attentional network when performing a simple motor task.     

Single‐shot echo‐planar imaging with Nyquist ghost compensation: Interleaved dual echo with acceleration (IDEA) echo‐planar imaging (EPI)

Echo planar imaging (EPI) is most commonly used for blood oxygen level‐dependent fMRI, owing to its sensitivity and acquisition speed. A major problem with EPI is Nyquist (N/2) ghosting, most notably at high field. EPI data are acquired under an oscillating readout gradient and hence vulnerable to gradient imperfections such as eddy current delays and off‐resonance effects, as these cause inconsistencies between odd and even k‐space lines after time reversal. We propose a straightforward and pragmatic method herein termed “interleaved dual echo with acceleration (IDEA) EPI”: two k‐spaces (echoes) are acquired under the positive and negative readout lobes, respectively, by performing phase encoding blips only before alternate readout gradients. From these two k‐spaces, two almost entirely ghost free images per shot can be constructed, without need for phase correction. The doubled echo train length can be compensated by parallel imaging and/or partial Fourier acquisition. The two k‐spaces can either be complex averaged during reconstruction, which results in near‐perfect cancellation of residual phase errors, or reconstructed into separate images. We demonstrate the efficacy of IDEA EPI and show phantom and in vivo images at both 3 T and 7 T. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Simultaneous sampling of event-related BOLD responses in auditory cortex and brainstem.

Event-related functional magnetic resonance imaging (fMRI) was applied to investigate blood oxygen level dependent (BOLD) responses in the human auditory system. Auditory fMRI is hindered by the disturbing acoustical noise of echo planar imaging (EPI). A sparse acquisition technique was used in which the delayed hemodynamic response was imaged at discrete sampling time-points after a brief auditory stimulus. Long repetition times (10 heartbeats (HBs)) were used to avoid interactions between the activation due to the sound stimulation and scanner noise. In addition, only a single slice was acquired, to ensure that the scanner noise was minimal in duration and intensity. The image acquisition was triggered by the HB to prevent artifacts from cardiac-related brainstem motion. An image was acquired every 10th HB. Significant hemodynamic BOLD time-course responses were measured from the primary and secondary auditory cortices, as well as the inferior colliculi in the brainstem. No systematic differences were found between the cerebral cortex and the brainstem in terms of activation amplitude or in onset time of the hemodynamic response. Apparently, the slow dynamic nature of the BOLD response signal is similar across spatially separated auditory brain regions, suggesting a corresponding design of vessels and capillaries.     

Continuous arterial spin labeling perfusion measurements using single shot 3D GRASE at 3 T.

Single shot 3D GRASE is less sensitive to field inhomogeneity and susceptibility effects than gradient echo based fast imaging sequences while preserving the acquisition speed. In this study, a continuous arterial spin labeling (CASL) pulse was added prior to the single shot 3D GRASE readout and quantitative perfusion measurements were carried out at 3 T, at rest and during functional activation. The sequence performance was evaluated by comparison with a CASL sequence with EPI readout. It is shown that perfusion measurements using CASL GRASE can be performed safely on humans at 3 T without exceeding the current RF power deposition limits. The maps of resting cerebral blood flow generated from the GRASE images are comparable to those obtained with the 2D EPI readout, albeit with better coverage in the orbitofrontal cortex. The sequence proved effective for functional imaging, yielding time series of images with improved temporal SNR with respect to EPI and group activation maps with increased significance levels. The method was further improved using parallel imaging techniques to provide increased spatial resolution and better separation of the gray-white matter cerebral blood flow maps.     

Integrated RF coil with stabilization for fMRI human cortex

Functional brain imaging of the human cortex is limited by poor contrast to noise ratio (CNR) and image degradation due to subject motion during the acquisition period. The work described here combines the use of closely coupled phased array receiver coils with a stabilization system to address these needs. Several phased array designs are evaluated and compared with the conventional “birdcage” design. Coil performance is reported in terms of relative SNR and fMRI results. Relative improvements of up to 360% are obtained for the occipital region and 180% in the temporal region. More modest gains of 10–30% were obtained for a “dome”-shaped birdcage volume coil covering the entire cortex.     

Influence of acoustic masking noise in fMRI of the auditory cortex during phonetic discrimination

The application of functional magnetic resonance imaging (fMRI) to study activation of auditory cortex suffers from one significant confounding factor, namely, that of the acoustic noise generated by the gradient system, which is an integral part of the imaging process. Earlier work has shown that it is indeed possible to distinguish cortical activation resulting from presentation of auditory stimuli despite the presence of background noise from the gradient system. The influence of acoustic noise from the gradient system of the MRI scanner on the blood oxygen level-dependent (BOLD) response during functional activation of the auditory cortex has been investigated in six healthy subjects with no hearing difficulties. Experiments were performed using gradient-echo echoplanar imaging (EPI) and a verbal, auditory discrimination paradigm, presented in a block-wise manner, in which carefully aligned consonant-vowel syllables were presented at a rate of 1 Hz. For each volunteer the experiment was repeated three times with all parameters fixed, except slice number, which was 4, 16, or 64. The positioning of the central four slices in each experiment was common. Thus, the fraction of TR during which the stimulus is on but no imaging is being performed, varies from almost zero, in the case of 64 slices, to over 8 seconds, in the case of four slices. Only the central four slices were of interest; additional slices simply generated acoustic noise and were discarded. During the four-slice experiment, all subjects showed a robust BOLD response in the superior temporal gyrus covering the primary and secondary auditory cortex. The spatial extent and the z-scores of the activated regions decreased with longer duration of gradient noise from the scanner. For a phonetic discrimination task, the results indicate that presentation of the stimulus during periods free from scanner noise leads to a more pronounced BOLD response.     

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.     

Functional MR Imaging of Working Memory in the Human Brain

Objective

In order to investigate the functional brain anatomy associated with verbal and visual working memory, functional magnetic resonance imaging was performed.

Materials and Methods

In ten normal right handed subjects, functional MR images were obtained using a 1.5-T MR scanner and the EPI BOLD technique. An item recognition task was used for stimulation, and during the activation period of the verbal working memory task, consonant letters were used. During the activation period of the visual working memory task, symbols or diagrams were employed instead of letters. For the post-processing of images, the SPM program was used, with the threshold of significance set at p < .001. We assessed activated brain areas during the two stimulation tasks and compared the activated regions between the two tasks.

Results

The prefrontal cortex and secondary visual cortex were activated bilaterally by both verbal and visual working memory tasks, and the patterns of activated signals were similar in both tasks. The superior parietal cortex was also activated by both tasks, with lateralization to the left in the verbal task, and bilaterally without lateralization in the visual task. The inferior frontal cortex, inferior parietal cortex and temporal gyrus were activated exclusively by the verbal working memory task, predominantly in the left hemisphere.

Conclusion

The prefrontal cortex is activated by two stimulation tasks, and this is related to the function of the central executive. The language areas activated by the verbal working memory task may be a function of the phonological loop. Bilateral prefrontal and superior parietal cortices activated by the visual working memory task may be related to the visual maintenance of objects, representing visual working memory.