Real-time functional magnetic resonance imaging: methods and applications

Functional magnetic resonance imaging (fMRI) has been limited by time-consuming data analysis and a low signal-to-noise ratio, impeding online analysis. Recent advances in acquisition techniques, computational power and algorithms increased the sensitivity and speed of fMRI significantly, making real-time analysis and display of fMRI data feasible. So far, most reports have focused on the technical aspects of real-time fMRI (rtfMRI). Here, we provide an overview of the different major areas of applications that became possible with rtfMRI: online analysis of single-subject data provides immediate quality assurance and functional localizers guiding the main fMRI experiment or surgical interventions. In teaching, rtfMRI naturally combines all essential parts of a neuroimaging experiment, such as experimental design, data acquisition and analysis, while adding a high level of interactivity. Thus, the learning of essential knowledge required to conduct functional imaging experiments is facilitated. rtfMRI allows for brain-computer interfaces (BCI) with a high spatial and temporal resolution and whole-brain coverage. Recent studies have shown that such BCI can be used to provide online feedback of the blood-oxygen-level-dependent signal and to learn the self-regulation of local brain activity. Preliminary evidence suggests that this local self-regulation can be used as a new paradigm in cognitive neuroscience to study brain plasticity and the functional relevance of brain areas, even being potentially applicable for psychophysiological treatment.     

Ictal imaging using functional magnetic resonance

Magnetic resonance imaging (MRI) can now provide maps of human brain function with high spatial and temporal resolution. This noninvasive technique can also map the coritical activation that occurs during focal seizures, as demonstrated here by the results obtained using a conventional 1.5 T clinical MRI system for the investigation of a 4-year-old boy suffering from frequent partial motor seizures of his right side. FLASH images (TE = 60 ms) were acquired every 10 s over a period of 25 min, and activation images derived by subtracting baseline images from images obtained during clinical seizures. Functional MRI revealed sequential activation associated with specific gyri within the left hemisphere with each of five consecutive clinical seizures, and also during a period that was not associated with a detectable clinical seizure. The activated regions included gyri that were structurally abnormal. These results demonstrate (a) that functional MRI can potentially provide new insights into the dynamic events that occur in the epileptic brain and their relationship to brain structure; and (b) that there is the possibility of obtaining similar information in the absence of clinical seizures, suggesting the potential for studies in patients with interictal electrical disturbances.     

Task-specific deactivation patterns in functional magnetic resonance imaging

In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis and echo-planar functional magnetic resonance imaging to address the relationship of the reference state to the deactivations. We employed two dichotomous covert tasks, orthographic lexical retrieval and pure visual retrieval, to contrast with the reference state (baseline) of silent counting. Our analysis yielded extensive, task-specific landscapes of regional incremental and decremental responses. We have specifically demonstrated that the decremental responses are not due to activation in the reference state. We have also demonstrated that they are not an artifact of a specific part of the image analysis, and propose that they represent a physiological, task specific signal that should be considered an integral component of neural networks representing brain function.     

Integration of structural and functional magnetic resonance imaging improves mild cognitive impairment detection

The identification of mild cognitive impairments (MCI) via either structural magnetic resonance imaging (sMRI) or functional MRI (fMRI) has great potential due to the non-invasiveness of the techniques. Furthermore, these techniques allow longitudinal follow-ups of single subjects via repeated measurements. sMRI- or fMRI-based biomarkers have been adopted separately to diagnose MCI; however, there has not been a systematic effort to integrate sMRI- and fMRI-based features to increase MCI detection accuracy. This study investigated whether the detection of MCI can be improved via the integration of biomarkers identified from both sMRI and fMRI modalities. Regional volume sizes and neuronal activity levels of brains from MCI subjects were compared with those from healthy controls and used to identify biomarkers from sMRI and fMRI data, respectively. In the subsequent classification phase, MCI was automatically detected using a support vector machine algorithm that employed the identified sMRI- and fMRI-based biomarkers as an input feature vector. The results indicate that the fMRI-based biomarkers provided more information for detecting MCI than the sMRI-based biomarkers. Moreover, the integrated feature sets using the sMRI- and fMRI-based biomarkers consistently showed greater detection accuracy than the feature sets based only on the fMRI-based biomarkers. The results demonstrate that integration of sMRI and fMRI modalities can provide supplemental information to improve the diagnosis of MCI relative to either the sMRI or fMRI modalities alone.     

A novel functional magnetic resonance imaging compatible search-coil eye-tracking system

Measuring eye movements (EMs) using the search-coil eye-tracking technique is superior to video-based infrared methods [Collewijn H, van der Mark F, Jansen TC. Precise recording of human eye movements. Vision Res 1975;15(3):447-50], which suffer from the instability of pupil size, blinking behavior and lower temporal resolution. However, no conventional functional magnetic resonance imaging (fMRI)-compatible search-coil eye tracker exists. The main problems for such a technique are the interaction between the transmitter coils and the magnetic gradients used for imaging as well as the limited amount of space in a scanner. Here we present an approach to overcome these problems and we demonstrate a method to record EMs in an MRI scanner using a search coil. The system described has a spatial resolution of 0.07 degrees (visual angle) and a high temporal resolution (22 kHz). The transmitter coils are integrated into the visual presentation system and the control/analysis unit is portable, which enables us to integrate the eye tracker with an MRI scanner. Our tests demonstrate low noise in the recorded eye traces and scanning with minimal artifact. Furthermore, the induced current in the search coil caused by the RF pulses does not lead to measurable heating. Altogether, this MR-compatible search-coil eye tracker can be used to precisely monitor EMs with high spatial and temporal resolution during fMRI. It can therefore be of great importance for studies requiring accurate fixation of a target, or measurement and study of the subject's oculomotor system.     

Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.

Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.     

Phase vs. magnitude information in functional magnetic resonance imaging time series: toward understanding the noise

Although it has been shown that the phase of the MR signal from the brain is particularly prone to variation due to respiration, the overall physiological information contained in phase time series is not well understood. Here, we explore the different physiological processes contributing to the phase time series noise, identify their spatiotemporal characteristics and examine their relationship to BOLD-related and non-BOLD-related physiological noise in the magnitude time series. This was performed by manipulating the contribution of physiological noise to the total signal variance by modulating the TE and voxel volume, and using a short TR in order to adequately sample physiological signal fluctuations. The phase and magnitude signals were compared both before and after removal of signal fluctuations at the primary respiratory and cardiac frequencies with RETROICOR. We found that the temporal phase noise increased with TE at a faster rate than predicted by 1/TSNR as a result of physiological noise. As suggested by previous studies, the primary contributor to phase physiological noise was respiration-related effects which were manifested at a large scale (>1 cm). Notably, RETROICOR removed respiration-related large-scale artifacts and this resulted in considerable improvements in the temporal phase stability (7–90%). Physiological noise in the magnitude time series after RETROICOR consisted of low-frequency BOLD-related fluctuations (<0.13 Hz) localized to gray matter and the vasculature, and fluctuations in the vasculature correlated with slow (<0.1 Hz) variations in respiration volume and cardiac rhythm. Physiological noise in the phase signal after RETROICOR also occurred in frequencies below 0.13 Hz and was consistent with (1) residual large-scale magneto-mechanical effects correlated with slow variations in respiration volume and cardiac rhythm over time, and (2) local scale (<1 cm) effects localized in gray matter and vasculature most likely due to vascular dephasing mediated by a BOLD susceptibility change. While BOLD-related magnitude noise exhibited a TE dependence similar to BOLD, the ‘BOLD-related’ noise in the phase data increased with increasing TE and thus caused the overall phase noise to increase at a faster rate with TE than predicted by 1/TSNR. Interestingly, the spatial specificity of this effect was more evident for the higher resolution phase data, as opposed to the magnitude data, suggesting that at a higher spatial resolution the phase signal may contain more information on physiological processes than the magnitude signal.     

Off-resonance frequency filtered magnetic resonance imaging

One of the main problems with rapid magnetic resonance imaging (MRI) techniques is the artifacts that result from off-resonance effects. The proposed off-resonance frequency filtered MRI (OFF-MRI) method focuses on the elimination of off-resonance components from the image of the observed object. To maintain imaging speed and simultaneously achieve good frequency selectivity, MRI is divided into two steps: signal acquisition and post-processing.     

Real-time MR artifacts filtering during continuous EEG/fMRI acquisition

The purpose of this study was the development of a real-time filtering procedure of MRI artifacts in order to monitor the EEG activity during continuous EEG/fMRI acquisition. The development of a combined EEG and fMRI technique has increased in the past few years. Preliminary “spike-triggered” applications have been possible because in this method, EEG knowledge was only necessary to identify a trigger signal to start a delayed fMRI acquisition. In this way, the two methods were used together but in an interleaved manner. In real simultaneous applications, like event-related fMRI study, artifacts induced by MRI events on EEG traces represent a substantial obstacle for a right analysis. Up until now, the methods proposed to solve this problem are mainly based on procedures to remove post-processing artifacts without the possibility to control electrophysiological behavior of the patient during fMRI scan. Moreover, these methods are not characterized by a strong “prior knowledge” of the artifact, which is an imperative condition to avoid any loss of information on the physiological signals recovered after filtering. In this work, we present a new method to perform simultaneous EEG/fMRI study with real-time artifacts filtering characterized by a procedure based on a preliminary analytical study of EPI sequence parameters-related EEG-artifact shapes. Standard EEG equipment was modified in order to work properly during ultra-fast MRI acquisitions. Changes included: high-performance acquisition device; electrodes/cap/wires/cables materials and geometric design; shielding box for EEG signal receiver; optical fiber link; and software. The effects of the RF pulse and time-varying magnetic fields were minimized by using a correct head cap wires-locked environment montage and then removed during EEG/fMRI acquisition with a subtraction algorithm that takes in account the most significant EPI sequence parameters. The on-line method also allows a further post-processing utilization.     

脑功能磁共振成像在人类嗅觉研究中的应用

在人类的5种主要感觉中,嗅觉是最广泛、古老、直接和内在的感觉.这些特性使人们对人类嗅觉的研究异常艰难,以致于直到今天人们对嗅觉的功能仍不清楚,而对大脑的功能机制所知更少.与其他基于物理原理的方法一样,磁共振成像技术的广泛应用极大地推动了整个生命科学的发展.脑功能磁共振成像的优势(高分辨率、高对比度、无损性和无放射性等)为人们研究嗅觉高级中枢以及与嗅觉相关行为的脑机制等提供了强有力的技术手段.文章在简单介绍嗅觉知识的基础上,着重讨论了近十年来,脑功能磁共振成像技术在人类嗅觉研究中所取得的成果.     

脑功能磁共振成像在人类嗅觉研究中的应用

在人类的5种主要感觉中,嗅觉是最广泛、古老、直接和内在的感觉.这些特性使人们对人类嗅觉的研究异常艰难,以致于直到今天人们对嗅觉的功能仍不清楚,而对大脑的功能机制所知更少.与其他基于物理原理的方法一样,磁共振成像技术的广泛应用极大地推动了整个生命科学的发展.脑功能磁共振成像的优势（高分辨率、高对比度、无损性和无放射性等）为人们研究嗅觉高级中枢以及与嗅觉相关行为的脑机制等提供了强有力的技术手段.文章在简单介绍嗅觉知识的基础上,着重讨论了近十年来,脑功能磁共振成像技术在人类嗅觉研究中所取得的成果.     

Functional magnetic resonance imaging of awake monkeys: some approaches for improving imaging quality

Functional magnetic resonance imaging (fMRI) at high magnetic field strength can suffer from serious degradation of image quality because of motion and physiological noise, as well as spatial distortions and signal losses due to susceptibility effects. Overcoming such limitations is essential for sensitive detection and reliable interpretation of fMRI data. These issues are particularly problematic in studies of awake animals. As part of our initial efforts to study functional brain activations in awake, behaving monkeys using fMRI at 4.7 T, we have developed acquisition and analysis procedures to improve image quality with encouraging results.We evaluated the influence of two main variables on image quality. First, we show how important the level of behavioral training is for obtaining good data stability and high temporal signal-to-noise ratios. In initial sessions, our typical scan session lasted 1.5 h, partitioned into short (<10 min) runs. During reward periods and breaks between runs, the monkey exhibited movements resulting in considerable image misregistrations. After a few months of extensive behavioral training, we were able to increase the length of individual runs and the total length of each session. The monkey learned to wait until the end of a block for fluid reward, resulting in longer periods of continuous acquisition. Each additional 60 training sessions extended the duration of each session by 60 min, culminating, after about 140 training sessions, in sessions that last about 4 h. As a result, the average translational movement decreased from over 500 μm to less than 80 μm, a displacement close to that observed in anesthetized monkeys scanned in a 7-T horizontal scanner.Another major source of distortion at high fields arises from susceptibility variations. To reduce such artifacts, we used segmented gradient-echo echo-planar imaging (EPI) sequences. Increasing the number of segments significantly decreased susceptibility artifacts and image distortion. Comparisons of images from functional runs using four segments with those using a single-shot EPI sequence revealed a roughly twofold improvement in functional signal-to-noise-ratio and 50% decrease in distortion. These methods enabled reliable detection of neural activation and permitted blood-oxygenation-level-dependent-based mapping of early visual areas in monkeys using a volume coil.In summary, both extensive behavioral training of monkeys and application of segmented gradient-echo EPI sequence improved signal-to-noise ratio and image quality. Understanding the effects these factors have is important for the application of high field imaging methods to the detection of submillimeter functional structures in the awake monkey brain.     

Simultaneous magnetic resonance imaging of diffusion anisotropy and diffusion gradient

The theory of diffusion gradient-weighted MRI (DGWI) is presented in this paper. The Bloch-Torrey equation was modified to include the effect of intravoxel spatial-location variation of water diffusion (diffusion gradient) on MRI signal, in addition to the effect of intravoxel spatial-direction variation of water diffusion (diffusion anisotropy). An analytical solution for a diffusion-encoding spin-echo pulse sequence was derived. Unlike water diffusion which attenuates the image signal intensity, this newly derived solution relates the spatial gradient of the water diffusion with the phase of the image signal. This novel MRI technique directly measures both the water diffusion and its spatial gradient, and thus offers a noninvasive imaging tool to simultaneously investigate the intravoxel inhomogeneity and anisotropy of tissue structures. In addition, as demonstrated with our preliminary data, this new method may be utilized to delineate the interfaces of tissues with different diffusion. This method is an extension of the successful diffusion tensor MRI (DTI), but requires no additional data acquisition. In addition to the measured diffusion tensor, this new method provides measurements of the spatial derivatives of the three principal diffusivities of the tensor, thereby providing additional information for improving white matter fiber tractography.     

New technical developments in magnetic resonance imaging of epilepsy

Within the last several years a number of technical developments have been made in magnetic resonance imaging (MRI) that can potentially impact clinical and research MR imaging applications in epilepsy. These include developments in instrumentation and in pulse sequences. Advances in instrumentation include higher capacity gradient systems and multiple receiver coils as directed to brain imaging. Advances in pulse sequence include use of fast or turbo-spin-echo techniques, variants of echo-planar imaging, and sequences such as fluid-attenuation inversion recovery (FLAIR) targeted to specific applications of brain imaging. The purpose of this paper is to review several of these developments.     

Surface-based functional magnetic resonance imaging analysis of partial brain echo planar imaging data at 1.5 T

Surface-based functional magnetic resonance imaging (fMRI) analysis is more sensitive and accurate than volume-based analysis for detecting neural activation. However, these advantages are less important in practical fMRI experiments with commonly used 1.5-T magnetic resonance devices because of the resolution gap between the echo planar imaging data and the cortical surface models. We expected high-resolution segmented partial brain echo planar imaging (EPI) data to overcome this problem, and the activation patterns of the high-resolution data could be different from the low-resolution data. For the practical applications of surface-based fMRI analysis using segmented EPI techniques, the effects of some important factors (e.g., activation patterns, registration and local distortions) should be intensively evaluated because the results of surface-based fMRI analyses could be influenced by them. In this study, we demonstrated the difference between activations detected from low-resolution EPI data, which were covering whole brain, and high-resolution segmented EPI data covering partial brain by volume- and surface-based analysis methods. First, we compared the activation maps of low- and high-resolution EPI datasets detected by volume- and surface-based analyses, with the spatial patterns of activation clusters, and analyzed the distributions of activations in occipital lobes. We also analyzed the high-resolution EPI data covering motor areas and fusiform gyri of human brain, and presented the differences of activations detected by volume- and surface-based methods.     

Magnetic resonance imaging and epilepsy: Neurosurgical decision making

Advances in magnetic resonance imaging (MRI) techniques have had an important impact on the decision-making process leading to surgical resection for chronic seizures. The MRI is now obtained relatively early in the work-up, and, when it shows abnormality, it assumes a crucial role in the detection of specific surgically remediable syndromes. These syndromes, when diagnosed by MR and other confirmatory studies such as electroencephalography (EEG), positron emission tomography (PET), magnetoencephalography (MEG), and neuropsychological testing, define the essential part of the surgical plan; that is, removal of the disease substrate. The availability of a host of MR techniques enable us to investigate epilepsy not only as a structural pathology but as physiological pathology reflected in abnormal blood flow, metabolism, and synaptic transmission. The mainstay of surgical treatment is the removal of the anatomic pathology, but other MR techniques may be helpful in the delineation of dual pathology in lesional cases, in appreciation of the full extent of microscopic pathology in developmental lesions, and in the imposition of restrictions on the resection based upon functional mapping. Finally, functional and anatomic maps obtained preoperatively can be related directly to the spatial coordinates of the exposed brain in the operating room using MRI-based frameless stereotactic methods. The final outcome, then, is the removal of the disease substrate without injury to adjacent, functionally salient cortical regions.     

Techniques of non-orthogonal magnetic resonance imaging and its clinical application

A technique to obtain non-orthogonal magnetic resonance (MR) images in the body has been developed using a simple three-dimensional model (3-DM). Images were obtained with multiple non-orthogonal planes, without subjecting patients to uncomfortable oblique positions. Eighty-two patients were studied using non-orthogonal planes. Euler angle determinations (EAD) were developed for different anatomical locations as well as for multiple clinical situations. One or all three Euler angles were changed using the EAD to define any plane of orientation relative to reference orthogonal frame. In a series of 12 patients for postoperative evaluation of Mustard and Senning procedure, the demonstration of anastomotic site was superior with angled coronal planes when compared to the routine coronal views in 83% of the studies. With the use of EAD, acquisition time for non-orthogonal planes can be reduced. 3-DM aids in the understanding of the Euler angles and leads to multiple non-orthogonal planes.     

Magnetic resonance imaging: application in musculoskeletal infection

Forty-two patients with clinically suspected osteomyelitis were examined using magnetic resonance imaging (MRI). Twenty-seven patients (64%) had previous surgery or fracture, and 15 (36%) were referred for differentiation of acute osteomyelitis from bone tumors or other pathologic conditions. MRI was compared with computed tomography in 12 cases and with 111In-labeled leukocytes scans in 22. With MRI, 92% of proved infections were detected, and bone and soft-tissue changes were more evident than with routine radiographs, tomography, or computed tomography. In patients with negative cultures and no previous surgery or fracture, it was difficult for MRI to differentiate operative changes from infection. In these patients, 111In-labeled leukocyte images were more specific than MRI.     

A novel acquisition-reconstruction algorithm for surface magnetic resonance imaging

In U-shaped, hand-size magnetic resonance surface scanners, imaging is performed along only one spatial direction, with the application of just one gradient (one-dimensional imaging). Lateral spatial resolution can be obtained by magnet displacement, but, in this case, resolution is very poor (on the order of some millimeters) and cannot be useful for high-resolution imaging applications. In this article, an innovative technique for acquisition and reconstruction of images produced by U-shaped, hand-size MRI surface scanners is presented. The proposed method is based on the acquisition of overlapping strips and an analytical reconstruction technique; it is capable of arbitrarily improving spatial lateral resolution without either using a second magnetic field gradient or making any assumptions about the imaged sample extension. Numerical simulations on synthetic images are reported demonstrating the method functionalities. The presented method also makes it possible to use U-shaped, hand-size MRI surface scanners for high-resolution biomedical applications, such as the imaging of skin lesions.