Echo-shifted multislice EPI for high-speed fMRI

The advantages of event-related functional Magnetic Resonance Imaging (fMRI) and the increasing use of fMRI in cognitive experiments are both driving the development of techniques that allow images sensitive to the blood oxygen level-dependent effect to be acquired at ever-higher temporal resolution. Here, we present a technique based on the use of echo shifting (ES) in conjunction with a multislice (MS) echo planar imaging (EPI) readout, which allows T2*-weighted images to be generated with a repetition time per slice that is less than the echo time (TE). Using this ES-MS-EPI approach, it is shown that images with a TE of 40 ms can be acquired with an acquisition time per slice of only 27 ms. The utility of the MS-ES-EPI sequence is demonstrated in a visual-motor, event-related fMRI study in which nine-slice image volumes are acquired continuously at a rate of 4.1 Hz. The sequence is shown to produce reliable activation associated with both visual stimuli and motor actions.     

Functional MRI using super-resolved spatiotemporal encoding

Recently, new ultrafast imaging sequences such as rapid acquisition by sequential excitation and refocusing (RASER) and hybrid spatiotemporal encoding (SPEN) magnetic resonance imaging (MRI) have been proposed, in which the phase encoding of conventional echo planar imaging (EPI) is replaced with a SPEN. In contrast to EPI, SPEN provides significantly higher immunity to frequency heterogeneities including those caused by B₀ inhomogeneities and chemical shift offsets. Utilizing the inherent robustness of SPEN, it was previously shown that RASER can be used to successfully perform functional MRI (fMRI) experiments in the orbitofrontal cortex — a task which is challenging using EPI due to strong magnetic susceptibility variation near the air-filled sinuses. Despite this superior performance, systematic analyses have shown that, in its initial implementation, the use of SPEN was penalized by lower signal-to-noise ratio (SNR) and higher radiofrequency power deposition as compared to EPI-based methods. A recently developed reconstruction algorithm based on super-resolution principles is able to alleviate both of these shortcomings; the use of this algorithm is hereby explored within an fMRI context. Specifically, a series of fMRI measurements on the human visual cortex confirmed that the super-resolution algorithm retains the statistical significance of the blood oxygenation level dependent (BOLD) response, while significantly reducing the power deposition associated with SPEN and restoring the SNR to levels that are comparable with those of EPI.     

Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques

Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high resolution fast low angle shot (FLASH) technique (matrix size 128²). The FLASH technique was applied additionally with a 64² matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64² matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and postior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 128² compared to FLASH 64² and EPI 64², whereas the activated areas proved to be smaller in FLASH 128² functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 128². Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.     

Event-related fMRI with painful electrical stimulation of the trigeminal nerve

Several functional brain imaging studies of pain using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have shown that painful stimulation causes activation of different brain areas. The aim of the present study was to develop and implement painful stimulation of the trigeminal nerve, which can be applied with event-related paradigms by using MRI. Twelve healthy, right-handed volunteers were examined. Painful electrical stimulation of the first trigeminal branch was performed. In an event-related setting with a 1.5 T clinical scanner with EPI capability, the following fMRI parameters were used: 20 slices, 3 mm thickness, isotropic voxel, 306 measurements with 54 randomized events. Statistical postprocessing was performed with SPM99. Activation of the ipsi- and contralateral secondary somatosensory cortex (SII), and the contralateral insular cortex was observed as well as a contralateral thalamic activation (T=4.45, extension 15 voxels). Six of the 12 volunteers revealed also activation of the cingulate cortex. The investigation demonstrates that painful stimulation of the trigeminal nerve activates the contralateral insular cortex, SII, and thalamus, as well as the ipsilateral SII. In contrast to other studies, the cingulate cortex was only activated inconsistently.     

High spatial resolution BOLD fMRI using simultaneous multislice excitation with echo-shifting gradient echo at 7 Tesla

We introduce an accelerated gradient echo (GRE) sequence combining simultaneous multislice excitation (SMS) with echo-shifting technique for high spatial resolution blood oxygen level dependent (BOLD) functional MRI (fMRI). The simulation was conducted to optimize scan parameters. To validate the feasibility of the proposed technique, the visual and motor task experiments were performed at 7.0 Tesla (T). The single-shot EPI sequence was also applied in comparison with the proposed technique. The simulation results showed that an optimized flip angle of 9° provided maximal BOLD contrast for our scanning scheme, allowing low power deposition and SMS acceleration factor of 5. Additionally, parallel acquisition imaging with acceleration factor of 2 was utilized, which allowed a total acceleration factor of 10 in volunteer study. The experiment results showed that geometric distortion-free BOLD images with voxel size of 1.0 × 1.0 × 2.5 mm³ were obtained. Significant brain activation was identified in both visual and motor task experiments, which were in accordance with previous investigations. The proposed technique has potential for high spatial resolution fMRI at ultra-high field because of its sufficient BOLD sensitivity as well as improved acquisition speed over conventional GRE-based techniques.     

人脑初级视皮层内事件相关型视觉刺激fMRI BOLD响应特性初步研究

基于脑血氧水平依赖(BOLD)对比的功能磁共振成像（fMRI）方法是研究脑功能活动的一种重要的无损伤探测手段，BOLD的机制及它与脑神经活动关系一直是国际上十分活跃的研究领域，尤其是在实验研究方面. 视觉刺激所引起的脑的初级视皮层(V1) 的BOLD响应的时间特性已有较多的研究，但是在这些研究中，有的结论认为BOLD对视觉刺激的响应是线性的，有的结论却是相反的. 我们采用事件关联型核磁共振功能成像（ER-fMRI）方法，研究不同的短暂视觉刺激持续时间下的BOLD响应，得到了视觉刺激下的脑激活图. 同时找出了视觉刺激时间分别是1、2、3、4、5和6 s的V1区的BOLD响应曲线，并初步显示出BOLD响应与刺激持续时间的线性关系.     

High-resolution segmented EPI in a motor task fMRI study

A high-resolution gradient echo, multi-slice segmented echo planar imaging method was used for functional MRI (fMRI) using a motor task at 1.5 Tesla. Functional images with an in-plane resolution of 1 mm and slice thickness of 4 mm were obtained with good white-gray matter contrast. The multi-shot approach, combined with a short total readout period of 82 ms, limits blurring effects for short T(2)(*) tissues (such as gray matter), assuring truly high-resolution images. In all subjects, motor functions were clearly depicted in the contralateral central sulcus over several slices and sometimes activation was detected in the supplementary motor area and/or ipsilateral central sulcus. The average signal change of 11+/-3% was much higher than in standard low-resolution fMRI EPI experiments, as a result of larger relative blood fractions.     

Multiresolution MRI temperature monitoring in a reduced field of view

Purpose

The purpose was to develop a new magnetic resonance imaging technique for fast temperature monitoring with extended volume coverage.

Materials and Methods

The Multiple Resolutions Along Phase-Encode and Slice-Select Dimensions (MURPS) method was implemented in both a two-dimensional (2D) spoiled gradient echo (SPGR) sequence and a multishot echo-planar imaging (EPI) sequence. Both modified sequences were used to acquire image data from three slices with variable phase-encode resolution and slice thickness. In the SPGR sequence, a 2D resonant frequency pulse was also implemented to enable imaging within a reduced field of view, and this was used to monitor (at 1.5 T) the temperature changes in a live rabbit and in gel phantoms heated by focused ultrasound. A modified EPI sequence was tested during heating of a phantom undergoing motion.

Results

The in vivo experiments demonstrated that temperature changes in unexpected locations away from the focal plane, such as near bone structures, could be detected due to the extra volume coverage afforded by the MURPS method. Temperature changes in a moving phantom were resolved using the MURPS EPI sequence with an acquisition rate of three slices every 300 ms.

Conclusion

The MURPS method enables temperature monitoring over multiple slices without loss of temporal resolution compared with single-slice imaging and, if combined with multishot EPI, enables volume temperature monitoring in moving organs.     

Reduced susceptibility effects in perfusion fMRI with single-shot spin-echo EPI acquisitions at 1.5 Tesla

Arterial spin labeling (ASL) perfusion contrast is not based on susceptibility effects and can therefore be used to study brain function in regions of high static inhomogeneity. As a proof of concept, single-shot spin-echo echo-planar imaging (EPI) acquisition was carried out with a multislice continuous ASL (CASL) method at 1.5T. A bilateral finger tapping paradigm was used in the presence of an exogenously induced susceptibility artifact over left motor cortex. The spin-echo CASL technique was compared with a regular gradient-echo EPI sequence with the same slice thickness, as well as other imaging methods using thin slices and spin-echo acquisitions. The results demonstrate improved functional sensitivity and efficiency of the spin-echo CASL approach as compared with gradient-echo EPI techniques, and a trend of improved sensitivity as compared with spin-echo EPI approach in the brain regions affected by the susceptibility artifact. ASL images, either with or without subtraction of the control, provide a robust alternative to blood oxygenation level dependant (BOLD) methods for activation imaging in regions of high static field inhomogeneity.     

Functional MRI of the human motor cortex using single-shot, multiple gradient-echo spiral imaging

In this study, we combined the advantages of a fast multi-slice spiral imaging approach with a multiple gradient-echo sampling scheme at high magnetic field strength to improve quantification of BOLD and inflow effects and to estimate T2* relaxation times in functional brain imaging. Eight echoes are collected with echo time (TE) ranging from 5 to 180 ms. Acquisition time per slice and echo time is 25 ms for a nominal resolution of 4 x 4 x 4 mm3. Evaluation of parameter images during rest and stimulation yields no significant activation on the inflow sensitive spin-density images (rho or I0-maps) whereas clear activation patterns in primary human motor cortex (M1) and supplementary motor area (SMA) are detected on BOLD sensitive T2*-maps. The calculation of relaxation times and rates of the activated areas over all subjects yields an average T2* +/- standard deviation (SD) of 46.1+/-4.5 ms (R2* of 21.8+/-2.2 s(-1)) and an average increase (deltaT2* +/- SD) of 0.93+/-0.47 ms (deltaR2* of -0.4+/-0.14 s(-1)). Our findings demonstrate the usefulness of a multiple gradient echo data acquisition approach in separating various vascular contributions to brain activation in fMRI.     

Functional MRI Using Spin Lock Editing Preparation Pulses

A novel approach for detecting blood oxygenation level-dependent (BOLD) signals in the brain is investigated using spin locking (SL) pulses to selectively edit the effects of extravascular diffusion in field gradients from different sized vascular structures. We show that BOLD effects from diffusion amongst susceptibility gradients will contribute significantly not only to transverse relaxation rates (R₂* and R₂) but also to R_1ρ, the rate of longitudinal relaxation in the rotating frame. Similar to the ability of 180-degree pulses to refocus static dephasing effects in a spin echo, moderately strong SL pulses can also reduce contributions of diffusion in large-scale gradients and the choice of SL amplitude can be used to selectively emphasize smaller scale inhomogeneities (such as microvasculature) and to drastically reduce the influence of larger structures (such as veins). Moreover, measurements over a range of locking fields can be used to derive estimates of the spatial scales of intrinsic gradients. The method was used to detect BOLD activation in human visual cortex. Eight healthy young adults were imaged at 3 T using a single-slice, SL-prepped turbo spin echo (TSE) sequence with spin-lock amplitudes ω₁ = 80 Hz and 400 Hz, along with conventional T₂*-weighted and T₂-prepped sequences. The BOLD signal varied from 1.1 ± 0.4 % (ω₁ = 80 Hz) to 0.7 ± 0.2 % (at 400 Hz), whereas the T₂-weighted sequence measured 1.3 ± 0.3 % and the T₂* sequence measured 1.9 ± 0.3 %. This new R_1ρ functional contrast can be made selectively sensitive to intrinsic gradients of different spatial scales, thereby increasing the spatial specificity of the evoked response.     

In vivo hypoxia characterization using blood oxygen level dependent magnetic resonance imaging in a preclinical glioblastoma mouse model

PurposeHypoxia measurements can provide crucial information regarding tumor aggressiveness, however current preclinical approaches are limited. Blood oxygen level dependent (BOLD) Magnetic Resonance Imaging (MRI) has the potential to continuously monitor tumor pathophysiology (including hypoxia). The aim of this preliminary work was to develop and evaluate BOLD MRI followed by post-image analysis to identify regions of hypoxia in a murine glioblastoma (GBM) model.MethodsA murine orthotopic GBM model (GL261-luc2) was used and independent images were generated from multiple slices in four different mice. Image slices were randomized and split into training and validation cohorts. A 7 T MRI was used to acquire anatomical images using a fast-spin-echo (FSE) T2-weighted sequence. BOLD images were taken with a T2*-weighted gradient echo (GRE) and an oxygen challenge. Thirteen images were evaluated in a training cohort to develop the MRI sequence and optimize post-image analysis. An in-house MATLAB code was used to evaluate MR images and generate hypoxia maps for a range of thresholding and ΔT2* values, which were compared against respective pimonidazole sections to optimize image processing parameters. The remaining (n = 6) images were used as a validation group. Following imaging, mice were injected with pimonidazole and collected for immunohistochemistry (IHC). A test of correlation (Pearson's coefficient) and agreement (Bland-Altman plot) were conducted to evaluate the respective MRI slices and pimonidazole IHC sections.ResultsFor the training cohort, the optimized parameters of “thresholding” (20 ≤ T2* ≤ 35 ms) and ΔT2* (±4 ms) yielded a Pearson's correlation of 0.697. These parameters were applied to the validation cohort confirming a strong Pearson's correlation (0.749) when comparing the respective analyzed MR and pimonidazole images.ConclusionOur preliminary study supports the hypothesis that BOLD MRI is correlated with pimonidazole measurements of hypoxia in an orthotopic GBM mouse model. This technique has further potential to monitor hypoxia during tumor development and therapy.     

Dynamics and nonlinearities of the BOLD response at very short stimulus durations

In designing a functional imaging experiment or analyzing data, it is typically assumed that task duration and hemodynamic response are linearly related to each other. However, numerous human and animal studies have previously reported a deviation from linearity for short stimulus durations (<4 s). Here, we investigated nonlinearities of blood-oxygenation-level-dependent (BOLD) signals following visual stimulation of 5 to 1000 ms duration at two different luminance levels in human subjects. It was found that (a) a BOLD response to stimulus durations as short as 5 ms can be reliably detected; this stimulus duration is shorter than employed in any previous study investigating BOLD signal time courses; (b) the responses are more nonlinear than in any other previous study: the BOLD response to 1000 ms stimulation is only twice as large as the BOLD response to 5 ms stimulation although 200 times more photons were projected onto the retina; (c) the degree of nonlinearity depends on stimulus intensity; that is, nonlinearities have to be characterized not only by stimulus duration but also by stimulus features like luminance. These findings are especially of most practical importance in rapid event-related functional magnetic resonance imaging (fMRI) experimental designs. In addition, an 'initial dip' response--thought to be generated by a rapid increase in cerebral metabolic rate of oxygen metabolism (CMRO2) relative to cerebral blood flow--was observed and shown to colocalize well with the positive BOLD response. Highly intense stimulation, better tolerated by human subjects for short stimulus durations, causes early CMRO2 increase, and thus, the experimental design utilized in this study is better for detecting the initial dip than standard fMRI designs. These results and those from other groups suggest that short stimulation combined with appropriate experimental designs allows neuronal events and interactions to be examined by BOLD signal analysis, despite its slow evolution.     

EEG quality during simultaneous functional MRI of interictal epileptiform discharges

This article concerns the evaluation of the quality of interictal epileptiform EEG discharges recorded throughout simultaneous echo planar imaging (EPI). BOLD (blood oxygen level dependent) functional MRI (fMRI) images were acquired continuously on a patient with intractable epilepsy. EEG was sampled simultaneously, during and after imaging, with removal of pulse and imaging artifacts by subtraction of channel-specific running averages. Contiguous EEG epochs recorded with and without fMRI (fMRI+ve vs. fMRI−ve) were next randomized and presented to two blinded observers. Epileptiform discharges were identified retrospectively, and comparison was made in terms of the number of identified events, their amplitude, and spatiotemporal distribution. A spectral analysis was also performed on the EEG. In the randomized comparison of EEG segments, 80 (fMRI+ve) vs. 69 (fMRI−ve) discharges were noted with good interobserver agreement (69%). There were no significant differences in amplitude or spatio-temporal distribution. Comparison of the events detected and measured by two expert observers demonstrated that the Interictal Epileptiform Discharge (IED) characteristics were indistinguishable with and without scanning. We review briefly the existing literature on EEG recording quality for combined EEG/fMRI.     

Influence of baseline hematocrit on between-subject BOLD signal change using gradient echo and asymmetric spin echo EPI

The dependence of BOLD signal change (BSC) on baseline hematocrit is in the process of being characterized, primarily using conventional Gradient Echo (GE) echo planar imaging (EPI). We describe the first empiric exploration of this relationship using, in addition to GE, Spin Echo (SE) and two Asymmetric Spin Echo EPI sequences (ASE10 and ASE20), which are less susceptible to large vessel noise. Motor cortex BSC was measured (N = 17) and regressed against hematocrit and hemoglobin concentration using linear and non-linear functions. GE measurements of BSC yielded a positive linear relationship (r(2) = 0.240, p = 0.0459) whereas a positive non-linear relationship was observed using ASE10 (r(2) = 0.571, p = 0.0146). Results suggest that between-subjects BSC is significantly dependent on baseline hematocrit. The nature of dependence, and implications for quantitative studies vary with the vessel size selectivity of the imaging sequence, and with the effect of hematocrit on blood viscosity in the imaged vessels.     

Correlation between temporal response of fMRI and fast reaction time in a language task

Correlation between behavioral parameters and fMRI responses can provide an advanced understanding of the neuronal processes. A lexical decision task was employed to examine the correlation between the reaction time (RT) and the temporal parameters in event-related BOLD responses. Word frequency was manipulated in the experiment. RTs for high-frequency, low-frequency and pseudowords were measured during fMRI (417 +/- 9 ms, 631 +/- 22 ms and 658 +/- 15 ms, respectively). For high-frequency words, RTs were significantly shorter than that for low-frequency and pseudowords (p < 0.0005). In the left inferior frontal region, the FWHM of the fMRI responses was significantly correlated with RT (p < 0.001), which may correspond to areas with sustained activation during the whole processing.     

Compensation of susceptibility-induced signal loss in echo-planar imaging for functional applications

Functional magnetic resonance imaging favors the use of multi-slice gradient-recalled echo-planar imaging due to its short image acquisition times, whole brain coverage and sensitivity to BOLD contrast. However, despite its advantages, gradient-recalled echo-planar imaging also is sensitive to static magnetic field gradients arising primarily from air-tissue interfaces. This can lead to image artifacts such as voxel shifts and complete signal loss. A method to recover signal loss by adjusting the refocusing gradient amplitude in the slice-select direction, preferably axially, is proposed. This method is implemented as an automated computer algorithm that partitions echo-planar images into regions of recoverable signal intensities using a histogram analysis and determines each region's proper refocusing gradient amplitude. As an example, different refocusing gradient amplitudes are interleaved in a fMRI acquisition to maximize the signal to noise ratio and obtain functional activation in normal and dropout regions. The effectiveness of this method is demonstrated by recovering signal voids in the orbitofrontal cortex, parahippocampal/amygdala region, and inferior visual association cortex near the cerebellum.     

Functional MR imaging of visual and motor cortex stimulation at high temporal resolution using a flash technique on a standard 1.5 tesla scanner

Functional magnetic resonance imaging (fMRI) was performed on a conventional 1.5 T scanner by means of a modified FLASH-technique at temporal resolutions of 80 and 320 ms. The method's stability was assessed by phantom measurements and by investigation of three volunteers resulting in a low amplitude (3%) periodic (4 s) signal modulation for the in vivo measurements, which was not observable in the phantom experiments. fMRI activation studies of motor and visual cortices of four adjacent slices were carried out on 12 healthy right-handed volunteers. Stimulation was performed by a triggered single white light flash or single finger-to-thumb opposition movement, respectively. Event-related response of visual and motor activation was traced over 10.24 s with a temporal resolution of 320 ms for the four slice measurements. Brain activation maps were calculated by correlation of measured signal time courses with a time-shifted boxcar function. Activation was quantified by calculation of percentual signal change in relation to the baseline. Observed signal magnitudes were about 5–7% in visual and about 8–12% in primary motor cortex. While photic response was delayed by about 2 s, motor stimulation showed an instantaneous increase of the MR signal. MR signal responses for both stimuli had decayed completely after about 5 s. Our results show that event-related fMRI enables mapping of brain function at sufficient spatial resolution with a temporal resolution of up to 80 ms on a conventional scanner.     

Failure to direct detect magnetic field dephasing corresponding to ERP generation

Functional magnetic resonance imaging (fMRI) has become the method of choice for mapping brain activity in human subjects and detects changes in regional blood oxygenation and volume associated with local changes in neuronal activity. While imaging based on blood oxygenation level dependent (BOLD) contrast has good spatial resolution and sensitivity, the hemodynamic signal develops relatively slowly and is only indirectly related to neuronal activity. An alternative approach termed magnetic source magnetic resonance imaging (msMRI) is based on the premise that neural activity may be mapped by magnetic resonance imaging (MRI) with greater temporal resolution by detecting the local magnetic field perturbations associated with local neuronal electric currents. We used a hybrid ms/BOLD MRI method to investigate whether msMRI could detect signal changes that occur simultaneously at the time of the production of well-defined event-related potentials, the P300 and N170, in regions that previously have been identified as generators of these electrical signals. Robust BOLD activations occurred after some seconds, but we were unable to detect any significant changes in the T2*-weighted signal in these locations that correlated temporally with the timings of the evoked response potentials (ERPs).