3T高场强功能MRI在脑功能区胶质瘤皮质电刺激手术中的应用

目的研究应用3T高场强功能MRI（fMRI）定位脑运动功能区，及在脑胶质瘤直接皮质电刺激手术中的指导作用。方法26例邻近或累及脑运动功能区的胶质瘤患者术前采用双手握拳刺激策略，根据血氧水平依赖（BOLD）原理进行功能成像。经工作站提供的BOLD功能图像分析软件包进行分析，获得脑运动功能区的激活图像，制定手术方案。所有患者均在唤醒麻醉下进行显微外科手术，在术前fMRI指导下利用直接皮质电刺激定位运动区。在保护脑功能不受损的前提下，最大程度地切除胶质瘤。术前、术后均行Karnofsky生活状态（KPS）评分，判断患者的状态。结果26例术前BOLD运动fMRI有23例获得良好的手运动脑功能区激活图像。患者在唤醒麻醉下，在术前fMRI指导下利用直接皮质电刺激快捷、准确定位初级运动皮质区，并且两者具有良好的一致性。同时术前fMRI提供术中未检测到的脑功能区的信息，相互补充。术前KPS评分80．0～90．0分患者21例（平均85．7分）术后恢复至平均95．2分，术前KPS评分40．0～70．0分患者5例（平均68．0分）术后恢复至平均90．0分。结论术前fMRI可活体和无创地描绘出脑运动功能区与肿瘤的功能解剖位置关系，优化手术方案，在唤醒麻醉下指导直接皮质电刺激定位运动区的手术，实现最大程度保护脑功能，并最大程度地切除肿瘤。     

Influence of fMRI on operative planning of brain tumors: Initial experience in a histopathologically variable subset of tumors

Background and purpose

Conventional MR imaging permits subcategorization of brain tumors; however, assessment of relation of the tumor to eloquent cortical centers is limited. Functional MRI (fMRI) is a promising method for visualizing cortical brain centers and for studying their relation to brain tumors which is an essential factor in proper planning of treatment strategy. The aim of this study is to assess and evaluate the value of fMRI in guiding preoperative decision making in patients with brain tumors.

Materials and methods

Both conventional and functional MRI were analyzed in 21 patients with brain tumors, the decision for treatment strategy for each case was determined twice, first with the data provided by the conventional MRI alone, second with the data provided by conventional and functional MRI.

Results

Accurate localization of eloquent cortical centers and as well as detailed assessment of their relation to the brain tumor were feasible in the majority of the examined patients, the data provided by this new technique modified the treatment strategy in seven of them aiming to avoid damage of eloquent brain areas.

Conclusion

fMRI can provide essential data about cortical centers and their relation with the tumor helping in safer preoperative planning.     

Evaluation of a signal intensity mask in the interpretation of functional MR imaging activation maps

BACKGROUND AND PURPOSE: The purpose of this study was to determine the incidence of susceptibility artifacts on functional MR imaging (fMRI) studies and their effect on fMRI readings. We hypothesized that the availability of the signal intensity maps (SIMs) changes the interpretation of fMRI studies in which susceptibility artifacts affected eloquent brain regions. METHODS: We reviewed 152 consecutive clinical fMRI studies performed with a SIM. The SIM consisted of the initial echo-planar images (EPI) in each section thresholded to eliminate signal intensity from outside the brain and then overlaid on anatomic images. The cause of the artifact was then determined by examining the images. Cases with a susceptibility artifact in eloquent brain were included in a blinded study read by four readers, first without and then with the SIM. For each reader, the number of times the interpretation changed on viewing the SIM was counted. RESULTS: Of 152 patients, 44% had signal intensity loss involving cerebral cortex and 18% involving an eloquent brain region. Causes of the artifacts were: surgical site artifact, blood products, dental devices, calcium, basal ganglia calcifications, ICP monitors, embolization materials, and air. When provided with the SIM, readers changed interpretations in 8-38% of patient cases, depending on reader experience and size and location of susceptibility artifact. CONCLUSION: Patients referred for clinical fMRI have a high incidence of susceptibility artifacts, whose presence and size can be determined by inspection of the SIM but not anatomic images. The availability of the SIM may affect interpretation of the fMRI.     

Clinical applications of functional magnetic resonance imaging

Despite its immediate success as a tool for basic research, the clinical application of functional MRI(fMRI) is still limited. FMRI has proven useful for presurgical functional mapping of the eloquent cortices. Localization of the sensorimotor cortex by fMRI may be of relatively limited value because the sensorimotor cortex can often be readily localized by means of anatomical methods. In contrast, the language cortices may not be localized anatomically and the language dominant hemisphere has been determined by invasive Wada test. Previous reports have shown that fMRI can be a promising alternative to the Wada test. A recent clinical trial has suggested that fMRI can be used to diagnose Alzheimer's disease in its earliest stage, detecting subclinical deterioration of the memory function. FMRI may be useful to predict the future decline of memory in people with genetic risks. Monitoring of the functional recovery of post-stroke brains may be another promising clinical application of fMRI. FMRI has demonstrated functional reorganization of the brain that may be related to the restoration of motor and language functions.     

Language and memory lateralization and localization using different fMRI paradigms in Arabic speaking patients: Initial experience

Purpose

Presurgical assessment of memory in patients with temporal lesions is essential to evaluate the effect of treatment on cognitive functioning (1). In recent years, there has been an increasing interest in the utility of functional MR imaging (fMRI) for presurgical evaluation of memory (2). There is no established fMRI protocol to evaluate memory functions presurgically (3). The identification of language areas in patients undergoing brain surgery is a major clinical challenge, the gold standard for the identification of essential language areas in neurosurgical patients is intraoperative mapping (IOM) by direct cortical stimulation as used by various groups but other techniques, such as functional imaging, are rapidly evolving (4). Language and also memory paradigms designed for patients speaking languages other than Arabic are not totally applicable for examining Arabic speaking and illiterate patients except after some modifications, the aim of this study is to test the applicability of these modified western designed paradigms for lateralization and localization of cortical brain centres concerned with language and memory in Arabic speaking patients.

Materials and methods

Using a 1.5 T Philips scanner, multiple modified western designed language and memory fMRI paradigms were used to assess the eloquent cortical brain areas in Arabic speaking patients of different levels of education having different lesions mainly brain tumors and epilepsy. These modifications consist mainly of providing simpler paradigms in an easy common Arabic language not in high level traditional Arabic, choosing simplified topics for the less educated patients, avoiding any written paradigms and depending on auditory paradigms in easy common Arabic language and simple pictures for illiterate patients. Images were analyzed using Philips extended MR work space release 2.5.3.0. The results were analyzed and compared to each other as regarding the patient cooperation and the ability to give robust fMRI signal.

Results

Multiple fMRI paradigms are efficient in lateralization and localization of cortical centres of language and memory yet they are variable in their ability to give robust fMRI signal clusters, also patients with different levels of education and culture differ in their ability to cooperate with the fMRI paradigms thus also affects the results.

Conclusion

Language and memory fMRI paradigms reported in the western literature are applicable to Arabic speaking patients with brain lesions undergoing an fMRI exam for language and/or memory but need some modifications according to background and level of education to get more robust identification of eloquent language and memory cortical centres.     

Diagnostic benefits of presurgical fMRI in patients with brain tumours in the primary sensorimotor cortex

Objectives  

Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data.     

The effect of prior surgery on blood oxygen level-dependent functional MR imaging in the preoperative assessment of brain tumors

BACKGROUND AND PURPOSE: Blood oxygen level-dependent functional MR imaging (BOLD fMRI) is a clinically useful technique for preoperative mapping of eloquent cortices in patients with brain tumors. The purpose of this study was to determine the effect on BOLD fMRI accuracy of susceptibility artifacts caused by prior surgery by comparing volumes of activation in the primary motor cortex (PMC) of patients with and without prior brain surgery. METHODS: The volumes of fMRI activation of the PMC were measured for the tumor and nontumor sides in patients with (n = 13) and without (n = 30) prior neurosurgery. Statistical comparisons of the volumes were performed by using paired t tests and linear regression analysis. The location and degree of susceptibility artifact were subjectively assessed. RESULTS: No significant difference was found between the mean tumor and nontumor volumes of fMRI activations in patients without prior surgery (P = .51). In patients who had prior surgery, the volume of activation was significantly smaller on the side of the prior operation when compared with the contralateral side (P = .001). The volume of activation on the side of the tumor was also significantly smaller in the patients with prior surgery compared with those without prior surgery (P < .001). Nevertheless, the PMC was identified in all cases, and its location was confirmed intraoperatively. CONCLUSION: Prior surgery is associated with a decrease in the volume of fMRI activation in patients with prior surgery; however, by examining the T2 images, an astute radiologist can recognize this phenomenon, draw the appropriate conclusions, and correctly identify the PMC.     

Preoperative mapping of cortical motor function: prospective comparison of functional magnetic resonance imaging and [15O]-H2O-positron emission tomography in the same co-ordinate system

BACKGROUND: Two of the most widely accepted approaches to map eloquent cortical areas preoperatively are positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). As yet, no study has compared these two modalities within the same frame of reference in tumour patients. AIM: We employed [15O]-H2O-PET and fMRI in patients undergoing presurgical evaluation and compared the results with those obtained by direct electrical cortical stimulation (DECS). METHODS: Twenty-five patients with tumours of different aetiology near the central region were investigated. fMRI and PET were processed using the same methods, i.e. statistical parametric mapping (SPM) without anatomical normalization, and transformed into the same frame of reference. RESULTS: fMRI activity was found in more cranial and lateral sections, i.e. closer to the brain surface, in comparison with PET, which demonstrated parenchymal activation. The mean localization difference between fMRI and PET was 8.1 +/- 4.6 mm (range, 2-18 mm). fMRI and [15O]-H2O-PET could reliably identify the central sulcus, as demonstrated by DECS. CONCLUSIONS: fMRI and [15O]-H2O-PET demonstrate comparable results and are sensitive and reliable tools to map the central region, especially in cases of infiltrating brain tumours. However, fMRI is more prone to artefacts, such as the visualization of draining veins, which may explain the more cranial and lateral activation visualized by fMRI, whereas PET depicts capillary perfusion changes and therefore shows activation closer to the parenchyma.     

The quality of functional MR images in patients with brain tumors: influences of neurological disorders and tumor location.

The aim of our study was to investigate the influence of neurological disorders, and the influence of tumor and perifocal edema location on functional magnetic resonance imaging (fMRI) quality. fMRI quality tended to be better the closer the tumor and the perifocal edema were located to the pmc. Hemipareses and seizures had no significant influence on fMRI quality. Therefore, hemiparetic patients do not have to be excluded beforehand. The evaluation of time courses is essential before using z-maps to localize eloquent brain regions preoperatively.     

Klinischer Einsatz der funktionellen MRT bei chronischer Epilepsie

Functional magnetic resonance imaging (fMRI) is frequently used in the presurgical diagnostic procedure of epilepsy patients, in particular for lateralization of speech and memory and for localization of the primary motor cortex to delineate the epileptogenic lesion from eloquent brain areas. fMRI is one of the non-invasive procedures in the presurgical diagnostic process, together with medical history, seizure semiology, neurological examination, interictal and ictal EEG, structural MRI, video EEG monitoring and neuropsychology. This diagnostic sequence leads either to the decision for or against elective epilepsy surgery or to the decision to proceed with invasive diagnostic techniques (Wada test, intra-operative or extra-operative cortical stimulation). It is difficult to evaluate the contribution of the fMRI test in isolation to the validity of the entire diagnostic sequence. Complications such as memory loss and aphasia in temporal lobe resections or paresis after frontal lobe resections are rare and rarely of disastrous extent. This further complicates the evaluation of the clinical relevance of fMRI as a predictive tool. In this article studies which investigated the concordance between fMRI and other diagnostic gold standards will be presented as well as the association between presurgical fMRI and postsurgical morbidity.     

Intraoperative,real-time,functional MRI

Functional MRI (fMRI) methods have been demonstrated to noninvasively identify motor-sensory, visual, and other areas of eloquent cortex for guiding surgical intervention. Typically, fMRI data are acquired preoperatively during a conventional surgical planning MRI examination. Unlike direct cortical stimulation at the time of surgery, however, preoperative fMRI methods do not account for the potential movement of tissues (relative to the time of functional imaging) that may occur in the surgical suite as a direct result of the intervention. Recently, an MRI device has been demonstrated for use in the surgical suite that has the potential to reduce the extent of cortical exposure required for the intervention. However, the invasive requirements of cortical mapping may supersede the invasive requirements of the surgical intervention itself. Consequently, we demonstrate here a modification to the intraoperative MRI device that facilitates a noninvasive, real-time, functional MR examination in the surgical suite.     

Functional MRI in human motor control studies and clinical applications.

Functional magnetic resonance imaging (fMRI) has been a useful tool for the noninvasive mapping of brain function associated with various motor and cognitive tasks. Because fMRI is based on the blood oxygenation level dependent (BOLD) effect, it does not directly record neural activity. With the fMRI technique, distinguishing BOLD signals created by cortical projection neurons from those created by intracortical neurons appears to be difficult. Two major experimental designs are used in fMRI studies: block designs and event-related designs. Block-designed fMRI presupposes the steady state of regional cerebral blood flow and has been applied to examinations of brain activation caused by tasks requiring sustained or repetitive movements. By contrast, the more recently developed event-related fMRI with time resolution of a few seconds allows the mapping of brain activation associated with a single movement according to the transient aspects of the hemodynamic response. Increasing evidence suggests that multiple motor areas are engaged in a networked manner to execute various motor acts. In order to understand functional brain maps, it is important that one understands sequential and parallel organizations of anatomical connections between multiple motor areas. In fMRI studies of complex motor tasks, elementary parameters such as movement length, force, velocity, acceleration and frequency should be controlled, because inconsistency in those parameters may alter the extent and intensity of motor cortical activation, confounding interpretation of the findings obtained. In addition to initiation of movements, termination of movements plays an important role in the successful achievement of complex movements. Brain areas exclusively related to the termination of movements have been, for the first time, uncovered with an event-related fMRI technique. We propose the application of fMRI to the elucidation of the pathophysiology of movement disorders, particularly dystonia, which exhibits involuntary co-contraction of agonist and antagonist muscles and manifests abnormal posture or slow repetition of movements.     

Cortical intraoperative stimulation in brain tumors as a tool to evaluate spatial data from motor functional MRI

RATIONALE AND OBJECTIVE: The purpose of this prospective, double-blind study was to correlate motor functional MRI (fMRI) with cortical brain mapping by intraoperative stimulation using 3D reconstructed images of the surface of the brain, and to validate the spatial data of fMRI in patients with brain tumors. METHODS: Fourteen patients with tumors of the rolandic region underwent functional MR mapping of the hand region and subsequently cortical mapping before tumor resection. Data obtained with fMRI and brain mapping were not known previously by the neurosurgeon and by the neuroradiologist, respectively (double-blind study). RESULTS: In each case, the results of direct cortical mapping matched those obtained with fMRI, both positively and negatively, although the extent of the functional activations was larger than the area required to elicit the corresponding movement during intraoperative brain mapping. CONCLUSION: fMRI can be used before surgery to assess motor functional area in patients with rolandic tumors. More studies are needed to validate during surgery the real extent of fMRI activations.     

Fusion von MRT-, fMRT- und intraoperativen MRT-Daten Methode und klinische Bedeutung am Beispiel neurochirurgischer Interventionen

The aim of this work was to realize and clinically evaluate an image fusion platform for the integration of preoperative MRI and fMRI data into the intraoperative images of an interventional MRI system with a focus on neurosurgical procedures. A vertically open 0.5 T MRI scanner was equipped with a dedicated navigation system enabling the registration of additional imaging modalities (MRI, fMRI, CT) with the intraoperatively acquired data sets. These merged image data served as the basis for interventional planning and multimodal navigation. So far, the system has been used in 70 neurosurgical interventions (13 of which involved image data fusion--requiring 15 minutes extra time). The augmented navigation system is characterized by a higher frame rate and a higher image quality as compared to the system-integrated navigation based on continuously acquired (near) real time images. Patient movement and tissue shifts can be immediately detected by monitoring the morphological differences between both navigation scenes. The multimodal image fusion allowed a refined navigation planning especially for the resection of deeply seated brain lesions or pathologies close to eloquent areas. Augmented intraoperative orientation and instrument guidance improve the safety and accuracy of neurosurgical interventions.     

Implementations of clinical functional magnetic resonance imaging using character-based paradigms for the prediction of Chinese language dominance

PURPOSE: Recently, functional MRI (fMRI) using word generation (WG) tasks has been shown to be effective for mapping the Chinese language-related brain areas. In clinical applications, however, patients' performance cannot be easily monitored during WG tasks. In this study, we evaluated the feasibility of a word choice (WC) paradigm in the clinical setting and compared the results with those from WG tasks. METHOD: Intrasubject comparisons of fMRI with both WG and WC paradigms were performed on six normal human subjects and two tumor patients. Subject responses in the WC paradigm, based on semantic judgments, were recorded. Activation strength, extent, and laterality were evaluated and compared. RESULTS: Our results showed that fMRI with the WC paradigm evoked weaker neuronal activation than that with the WG paradigm in Chinese language-related brain areas. It was sufficient to reveal language laterality for clinical use, however. In addition, it resulted in less nonlanguage-specific brain activation. CONCLUSION: Results from the patient data demonstrated strong evidence for the necessity of incorporating response monitoring during fMRI studies, which suggested that fMRI with the WC paradigm is more appropriate to be implemented for the prediction of Chinese language dominance in clinical environments.     

Mapping functionally related regions of brain with functional connectivity MR imaging

BACKGROUND AND PURPOSE: In subjects who are performing no prescribed cognitive task, functional connectivity mapped with MR imaging (fcMRI) shows regions with synchronous fluctuations of cerebral blood flow. When specific tasks are performed, functional MR imaging (fMRI) can map locations in which regional cerebral blood flow increases synchronously with the performance of the task. We tested the hypothesis that fcMRI maps, based on the synchrony of low-frequency blood flow fluctuations, identify brain regions that show activation on fMRI maps of sensorimotor, visual, language, and auditory tasks. METHODS: In four volunteers, task-activation fMRI and functional connectivity (resting-state) fcMRI data were acquired. A small region of interest (in an area that showed maximal task activation) was chosen, and the correlation coefficient of the corresponding resting-state signal with the signal of all other voxels in the resting data set was calculated. The correlation coefficient was decomposed into frequency components and its distribution determined for each fcMRI map. The fcMRI maps were compared with the fMRI maps. RESULTS: For each task, fcMRI maps based on one to four seed voxel(s) produced clusters of voxels in regions of eloquent cortex. For each fMRI map a closely corresponding fcMRI map was obtained. The frequencies that predominated in the cross-correlation coefficients for the functionally related regions were below 0.1 Hz. CONCLUSION: Functionally related brain regions can be identified by means of their synchronous slow fluctuations in signal intensity. Such blood flow synchrony can be detected in sensorimotor areas, expressive and receptive language regions, and the visual cortex by fcMRI. Regions identified by the slow synchronous fluctuations are similar to those activated by motor, language, or visual tasks.     

Recent developments in optimal experimental designs for functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) is one of the leading brain mapping technologies for studying brain activity in response to mental stimuli. For neuroimaging studies utilizing this pioneering technology, there is a great demand of high-quality experimental designs that help to collect informative data to make precise and valid inference about brain functions. This paper provides a survey on recent developments in experimental designs for fMRI studies. We briefly introduce some analytical and computational tools for obtaining good designs based on a specified design selection criterion. Research results about some commonly considered designs such as blocked designs, and m-sequences are also discussed. Moreover, we present a recently proposed new type of fMRI designs that can be constructed using a certain type of Hadamard matrices. Under certain assumptions, these designs can be shown to be statistically optimal. Some future research directions in design of fMRI experiments are also discussed.     

Functional MRI of the brain: localisation of eloquent cortex in focal brain lesion therapy

The aim of this study was to assess the feasibility of functional MRI (fMRI) in a clinical environment on a large patient group, and to evaluate the pretherapeutic value of localisation of eloquent cortex. Forty patients with focal brain lesions of different origin were studied using fMRI. Functional information was obtained using motor, somatosensory, auditory and phonological stimuli depending on the localisation of the lesions. To obtain information about the spatial accuracy of fMRI, the results were compared with postoperative electrocortical stimulation. Two patients with secondary trigeminal neuralgia were scanned using a motor protocol and were implanted with an extradural plate electrode. Imaging was successful in 40 of 42 patients (including the 2 with trigeminal neuralgia). These patients were analysed for strength of activation, the relation of the lesion to activation sites and the presence of mass effect. The correlation between these data and surgical findings provided significant additional clinical information. Functional MRI can be accurately performed in patients with focal brain lesions using a dedicated approach. Functional MRI offers important clinical information as a contribution to a decrease in posttherapeutic morbidity. The accuracy of the technique can be confirmed by other modalities, including invasive cortical electrostimulation. Received 19 November 1997; Revision received 23 February 1998; Accepted 3 March 1998     

Hidden Markov event sequence models: toward unsupervised functional MRI brain mapping

RATIONALE AND OBJECTIVES: Most methods used in functional MRI (fMRI) brain mapping require restrictive assumptions about the shape and timing of the fMRI signal in activated voxels. Consequently, fMRI data may be partially and misleadingly characterized, leading to suboptimal or invalid inference. To limit these assumptions and to capture the broad range of possible activation patterns, a novel statistical fMRI brain mapping method is proposed. It relies on hidden semi-Markov event sequence models (HSMESMs), a special class of hidden Markov models (HMMs) dedicated to the modeling and analysis of event-based random processes. MATERIALS AND METHODS: Activation detection is formulated in terms of time coupling between (1) the observed sequence of hemodynamic response onset (HRO) events detected in the voxel's fMRI signal and (2) the "hidden" sequence of task-induced neural activation onset (NAO) events underlying the HROs. Both event sequences are modeled within a single HSMESM. The resulting brain activation model is trained to automatically detect neural activity embedded in the input fMRI data set under analysis. The data sets considered in this article are threefold: synthetic epoch-related, real epoch-related (auditory lexical processing task), and real event-related (oddball detection task) fMRI data sets. RESULTS: Synthetic data: Activation detection results demonstrate the superiority of the HSMESM mapping method with respect to a standard implementation of the statistical parametric mapping (SPM) approach. They are also very close, sometimes equivalent, to those obtained with an "ideal" implementation of SPM in which the activation patterns synthesized are reused for analysis. The HSMESM method appears clearly insensitive to timing variations of the hemodynamic response and exhibits low sensitivity to fluctuations of its shape (unsustained activation during task). Real epoch-related data: HSMESM activation detection results compete with those obtained with SPM, without requiring any prior definition of the expected activation patterns thanks to the unsupervised character of the HSMESM mapping approach. Along with activation maps, the method offers a wide range of additional fMRI analysis functionalities, including activation lag mapping, activation mode visualization, and hemodynamic response function analysis. Real event-related data: Activation detection results confirm and validate the overall strategy that consists in focusing the analysis on the transients, time-localized events that are the HROs. CONCLUSION: All the experiments performed on synthetic and real fMRI data demonstrate the relevance of HSMESMs in fMRI brain mapping. In particular, the statistical character of these models, along with their learning and generalizing abilities are of particular interest when dealing with strong variabilities of the active fMRI signal across time, space, experiments, and subjects.     

Functional magnetic resonance imaging of the human brain based on signal enhancement by extravascular protons (SEEP fMRI).

Functional magnetic resonance imaging (fMRI) studies of the human brain were carried out at 3 Tesla to investigate an fMRI contrast mechanism that does not arise from the blood oxygen-level dependent (BOLD) effect. This contrast mechanism, signal enhancement by extravascular protons (SEEP), involves only proton-density changes and was recently demonstrated to contribute to fMRI signal changes in the spinal cord. In the present study it is hypothesized that SEEP fMRI can be used to identify areas of neuronal activity in the brain with as much sensitivity and precision as can be achieved with BOLD fMRI. A detailed analysis of the areas of activity, signal intensity time courses, and the contrast-to-noise ratio (CNR), is also presented and compared with the BOLD fMRI results. Experiments were carried out with subjects performing a simple finger-touching task, or observing an alternating checkerboard pattern. Data were acquired using a conventional BOLD fMRI method (gradient-echo (GE) EPI, TE = 30 ms), a conventional method with reduced BOLD sensitivity (GE-EPI, TE = 12 ms), and SEEP fMRI (spin-echo (SE) EPI, TE = 22 ms). The results of this study demonstrate that SEEP fMRI may provide better spatial localization of areas of neuronal activity, and a higher CNR than conventional BOLD fMRI, and has the added benefit of lower sensitivity to field inhomogeneities.