Clinical applicability of functional MRI

Functional MRI (fMRI) has become the most widely used modality for examining human brain function in basic and clinical neuroscience. As compared to the application of fMRI in basic neuroscience research, clinical fMRI presents unique challenges. A growing body of literature supports the feasibility of clinical fMRI, with the best-studied applications being localization of motor cortex and lateralization of language. While it may be tempting to assume that fMRI will supercede prior approaches, it may turn out that fMRI will be used to complement more difficult or invasive methods rather than replace them entirely. This article focuses on fMRI studies in patients and patient populations. Specific considerations for such applications include pathophysiological effects on functional physiology, brain-behavior correlations in the presence of cognitive or sensorimotor deficits, and test-retest reliability for longitudinal studies.     

Intraoperative functional MRI as a new approach to monitor deep brain stimulation in Parkinson's disease

This article deals with technical aspects of intraoperative functional magnetic resonance imaging (fMRI) for monitoring the effect of deep brain stimulation (DBS) in a patient with Parkinson's disease. Under motor activation, therapeutic high-frequency stimulation of the subthalamic nucleus was accompanied by an activation decrease in the contralateral primary sensorimotor cortex and the ipsilateral cerebellum. Furthermore, an activation increase in the contralateral basal ganglia and insula region were detected. These findings demonstrate that fMRI constitutes a promising clinical application for investigating brain activity changes induced by DBS.     

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.     

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.     

fMRI for preoperative neurosurgical mapping of motor cortex and language in a clinical setting

PURPOSE: Identification of the precentral gyrus can be difficult in patients with brain tumors. The purpose of the current study was to evaluate the clinical usefulness of functional MRI (fMRI) in identifying motor cortex and speech areas as a part of preoperative neurosurgical planning. METHOD: fMRI was performed using a 1.5 T MR unit in 41 patients with brain tumors. The motor paradigm was finger tapping and foot movement, whereas the language paradigm consisted of a two word semantic test. Statistical analysis of the data was done using the Kolmogorow-Smirnow test. Plots of signal intensities over time were created. RESULTS: The precentral gyrus was identified in 38 of 41 patients. In two patients, fMRI was not of acceptable quality due to motion artifacts. Speech areas were localized in 33 patients. In a typical clinical setting, the value of the method was graded "high." CONCLUSION: fMRI's efficacy in the preoperative localization of language and motor areas is high. The method should become a routine adjunct for preoperative evaluation of brain tumors in the near future.     

Developing a comprehensive presurgical functional MRI protocol for patients with intractable temporal lobe epilepsy: a pilot study

Our aim was to put together and test a comprehensive functional MRI (fMRI) protocol which could compete with the intracarotid amytal (IAT) or Wada test for the localisation of language and memory function in patients with intractable temporal lobe epilepsy. The protocol was designed to be performed in under 1 h on a standard 1.5 tesla imager. We used five paradigms to test nine healthy right-handed subjects: complex scene-encoding, picture-naming, reading, word-generation and semantic-decision tasks. The combination of these tasks generated two activation maps related to memory in the mesial temporal lobes, and three language-related maps of activation in a major part of the known language network. The functional maps from the encoding and naming tasks showed typical and symmetrical posterior mesial temporal lobe activation related to memory in all subjects. Only four of nine subjects also showed symmetrical anterior hippocampal activation. Language lateralisation was best with the word generation and reading paradigms and proved possible in all subjects. The reading paradigm enables localisation of language function in the left anterior temporal pole and middle temporal gyrus, areas typically resected during epilepsy surgery. The combined results of this comprehensive f MRI protocol are adequate for a comparative study with the IAT in patients with epilepsy being assessed for surgery.     

Presurgical Assessment of the Sensorimotor Cortex Using Resting-State fMRI

BACKGROUND AND PURPOSE:The functional characterization of the motor cortex is an important issue in the presurgical evaluation of brain lesions. fMRI noninvasively identifies motor areas while patients are asked to move different body parts. This task-based approach has some drawbacks in clinical settings: long scanning times and exclusion of patients with severe functional or neurologic disabilities and children. Resting-state fMRI can avoid these difficulties because patients do not perform any goal-directed tasks.MATERIALS AND METHODS:Nineteen patients with diverse brain pathologies were prospectively evaluated by using task-based and resting-state fMRI to localize sensorimotor function. Independent component analyses were performed to generate spatial independent components reflecting functional brain networks or noise. Three radiologists identified the motor components and 3 portions of the motor cortex corresponding to the hand, foot, and face representations. Selected motor independent components were compared with task-based fMRI activation maps resulting from movements of the corresponding body parts.RESULTS:The motor cortex was successfully and consistently identified by using resting-state fMRI by the 3 radiologists for all patients. When they subdivided the motor cortex into 3 segments, the sensitivities of resting-state and task-based fMRI were comparable. Moreover, we report a good spatial correspondence with the task-based fMRI activity estimates.CONCLUSIONS:Resting-state fMRI can reliably image sensorimotor function in a clinical preoperative routine. It is a promising opportunity for presurgical localization of sensorimotor function and has the potential to benefit a large number of patients affected by a wide range of pathologies.

Mapping of cerebral function in neurosurgery patients aims to predict the efficacy of the neurosurgical treatment, estimate the operation risk, and avoid neurologic deficits. Several techniques have been used to identify brain activity in tissue surrounding the regions planned for resection, including neuronavitaged transcranial magnetic stimulation,¹ magnetoencephalography,² and fMRI,³ each having advantages and drawbacks over the others.The clinical criterion standard for localization of functional brain areas is intraoperative electrical stimulation in the awake patient.⁴ Although electrical stimulation provides unique assistance during surgery, it is an invasive technique that requires expertise of the surgical team and a cooperative and motivated subject. It also adds considerable time to the surgical procedure for an investigation limited to a few cortical areas. Therefore, fMRI has been seen as very promising for clinical applications. However, its integration into preoperative surgical planning has been relatively slow because of several practical constraints: the dedicated experimental setup, long scanning time, and a high cognitive demand on the patient. Moreover, localizing the sensorimotor cortex with fMRI at the individual level can be challenging in some cases when the patient has paresis or paralysis. Furthermore, >1 acquisition is necessary whenever the lesion is bordering on several motor representations.Techniques measuring functional connectivity can address several of the limitations faced by stimulus-driven or task-based fMRI (tb-fMRI). Resting-state fMRI (rs-fMRI) uses slow, spontaneous fluctuations in the blood oxygen level–dependent signal to characterize networks of distant brain regions.⁵ The subject simply “rests” in the scanner without any specific task to perform. rs-fMRI has been successfully applied in groups of healthy volunteers,⁶ provides a means of mapping several functional networks in a single acquisition, appears robust across individuals,⁷ and is less-demanding than tb-fMRI because it requires less cooperation from the patient and can be used in individuals with neurologic deficits or cognitive dysfunction or in children. Additionally, spontaneous activity continues in the primary sensory and motor cortices even when subjects are asleep⁸ or anesthetized.⁹ This feature suggests that complete patient compliance may not be necessary. Resting-state networks have been extensively explored in recent years at the group level in populations of healthy subjects and patients. In the case of neurosurgery patients with brain damage,¹⁰ precise functional network estimation at the individual level is essential for surgery planning and/or intraoperative navigation. The conclusions of previous pioneering studies were limited to the feasibility of rs-fMRI for presurgical mapping by using small patient samples.^11–15In this study, we investigated the sensitivity of extracting the sensorimotor network from rs-fMRI at the individual level in patients with brain damage scheduled for surgery. Because brain lesions can appear at any segment of the motor cortex, we divided our investigations into 3 portions of the somatotypy (foot, hand, and face). rs-fMRI was then compared with tb-fMRI acquired when corresponding body parts were moved.     

BOLD contrast on a 3 T magnet: detectability of the motor areas

To predict the potential and the limitations of functional MRI (fMRI) with a very high field magnet, the detectability and reproducibility of activation were evaluated by comparing the activation induced by a sequential finger movement task at 1.5 T with that at 3 T. The detectability of the premotor area, supplementary motor area (SMA), and ipsilateral sensorimotor area (SM1) showed significant improvement at 3 T. On the other hand, the detectability of contralateral SM1 was not significantly different between 1.5 and 3 T. The degree of activation was proportional to task demand in the ipsilateral SM1 and SMA, whereas that in the contralateral SM1 and SMA was not. FMRI with a 3 T magnet has greater potential for detection of neuronal activation as a functional network. These observations indicated that task demand and static magnetic field strength should be considered in interpretation of fMRI data for clinical usage.     

Whole-brain functional magnetic resonance imaging of cerebral arteriovenous malformations involving the motor pathways

To investigate cortical, basal ganglia and cerebellar activation in patients with arteriovenous malformations (AVMs) involving the motor pathways, we studied ten patients (six male, four female, mean age 30.3 years, range 7.4-44.1) by whole-brain functional magnetic resonance imaging (fMRI) in a 1.5-T scanner with the EPI-BOLD-technique. In seven cases multiple fMRI studies were available, acquired in the course of the multi-session endovascular interventional treatment. Self-paced right- and left-handed finger-tapping tasks were used to invoke activation. In six patients a super-selective amytal test (Wada test) was performed during diagnostic pre-interventional angiography studies. Abnormal cortical activation patterns, with activation of the primary sensorimotor area, the supplementary motor area and/or the cerebellum shifted to unphysiological locations, were found in four patients. In all cases, localization of the AVM could account for the changes from the normal. After endovascular procedures, fMRI demonstrated shifts in the activation pattern in three patients. In the six patients that had undergone fMRI studies and the Wada test, both methods yielded comparable results. The fact that AVMs are structural anomalies for which the brain can partly compensate ('plasticity') was underlined by these results. fMRI is a valuable tool in the pre-therapeutic evaluation and post-interventional follow-up of patients with cerebral AVMs in whom an operation or an endovascular procedure is planned.     

书写痉挛脑功能成像磁共振研究

目的：利用功能磁共振成像,研究书写痉挛患者皮质异常功能活动,探讨其病因。方法：分别对10名书写痉挛患者和10名健康志愿者进行书写任务期间的功能磁共振成像,对数据经过分析处理,获得患者组和正常对照组两个任务的平均脑激活图并进行比较。结果：与正常对照组相比较,患者组初级感觉运动区和辅助运动区表现为与书写任务相关的明显激活,而双侧的后顶叶皮质激活在两个不同任务期间均较正常减弱。结论：书写痉挛患者存在运动和感觉皮质的异常活动,反应了其运动皮质的去抑制和感觉处理过程的障碍,并且感觉处理过程的异常可能在其病因过程中起重要作用。     

运动皮层区域病变的功能磁共振成像研究及应用

功能磁共振成像是近年来新兴的脑功能成像技术。对运动皮层区域病变的研究是其主要临床应用之处,尤其在该区域占位性病变的术前定位,病变与脑功能区的内在联系及运动皮层的可塑性研究等方面得到了较大的发展。本文就fMRI在运动区域病变中的临床应用及进展方面作一综述。     

Location of hand function in the sensorimotor cortex: MR and functional correlation.

PURPOSETo determine the location of hand function in the sensorimotor cortex using MR and positron emission tomography imaging studies.METHODSAnatomic and physiological methods were used for this study. Anatomic study was based on the MR analysis of 22 subjects. The length of the sensorimotor cortex was measured in the axial and sagittal planes. Physiologic study was based on the positron emission tomography studies of 4 subjects. Each of the studies was correlated with MR.RESULTSWe found that the superior genu of the central sulcus corresponds to hand function in the sensorimotor cortex. This level may prove useful for any clinical correlations or for surgery.CONCLUSIONSFrom this study, the hand function area in the sensorimotor cortex is easily understood with its characteristic shape in axial MR scan. The comparison of MR and positron emission tomography data clearly show anatomic correlations. This may be applied to the functional mapping of the pathologic studies in the sensorimotor cortex regions.     

Neural correlates of simple unimanual discrete and continuous movements: a functional imaging study at 3 T

Introduction The cerebral and cerebellar network involved in unimanual continuous and discrete movements was studied in blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) at 3 T. Methods Seven healthy right-handed volunteers were scanned (1) while drawing a circle with the tip of the right index finger (continuous motor task), and (2) while drawing a triangle with the tip of the right index finger (discrete motor task). Results In both motor tasks, extensive activations were observed in the sensorimotor (M1/S1), parietal, prefrontal, insular, lateral occipital (LOC) and anterior cerebellar cortices. Subcortical activations within red, thalamic and lentiform nuclei were also detected. However, discrete movements were specifically followed by the recruitment of the left orbitofrontal cortex, right dentate nucleus and the second cerebellar homunculus (HVIII), and bilateral and stronger activation of the sensorimotor cortical areas, whereas continuous movements specifically activated the right prefrontal cortex and the lateral hemispherical part of the neocerebellum (crus 1). Conclusion We confirm the findings of previous studies showing partly distinct neural networks involved in monitoring continuous and discrete movements, but we found new differential neural relays within the prefrontal, insular and neocerebellar cortices.     

Preoperative assessment of language areas in epileptic patients using functional MR imaging

ObjectiveTo determine the role of functional magnetic resonance imaging (fMRI) in assessing hemispheric language dominance in patients with epilepsy who are candidates for surgical treatment.Patients and methodsThis study was conducted on (14) consecutively enrolled epileptic patients (12 males, 2 females; mean age, 21 years; range 16–58 years) who were prospectively examined by the neurologist. Eleven (78.6%) patients were dominantly right handed, three (21.4%) were dominantly left handed. All of them underwent language assessment with fMRI and the results were compared with the intraoperative direct electrical stimulation mapping recordings.ResultsIn all the 14 epilepsy cases, language mapping data was concordant between fMRI and intraoperative direct electrocortical stimulation recordings for language dominance. However, fMRI mapping allowed for discrete, focal localization of regions involved in language processes whereas electrical recordings only delineated hemispheric dominance.ConclusionfMRI is considered as a powerful pre-surgical planning tool that has the potential to replace invasive and costly conventional methods. FMRI maps can easily be uploaded and used intra-operatively during stereotactic neurosurgery for accurate localization of complex brain functions.     

人脑视皮质功能MRI的初步研究及临床应用

目的：本实验应用功能磁共振成像（fMRI）的回波平面（EPI）技术,着重研究了人脑视皮质的血氧水平依赖（BOLD）的功能磁共振成像。方法：本实验包括对36名正常健康志愿者及17例具有枕区病变患者的fMRI研究。在刺激和静止2种对比条件下采集枕区的回波平面图像。结果：主要视皮质位于双侧距状裂两侧 ,属于布劳德曼（Brodmann)17区。3例具有距状裂附近病变的患者的视皮质由于病变的占位效应而发生移位。结论：fMRI可用于在活体上脑上研究各功能区活动。视觉刺激下的fMRI可对人脑视皮质初步定位。由于病变占位效应的影响,病变周围的功能活动区常发生变形或移位。     

简单型书写痉挛患者异常皮质活动的功能磁共振成像研究

目的:利用功能磁共振成像,研究简单型书写痉挛患者的皮质异常功能活动,探讨其病因基础。材料和方法:分别对10名简单型书写痉挛患者和10名健康右利手志愿者进行手指写、执笔写任务期间的功能磁共振成像。使用AFNI软件,对数据经过预处理及反卷积分析等处理,获得患者组和正常组两个任务的平均脑激活图并进行比较。结果:与正常组之间相比较,患者组初级感觉运动区和辅助运动区表现为与执笔写任务相关的更明显的激活,而双侧的后顶叶皮质激活在两个不同任务期间均较正常减弱。结论:简单型书写痉挛患者存在运动和感觉皮质的异常活动,反映了其运动皮质的去抑制和感觉处理过程的障碍,并且感觉处理过程的异常可能在其病因过程中起重要作用。     

Spontaneous brain activity in mild cognitive impairment revealed by amplitude of low-frequency fluctuation analysis: a resting-state fMRI study

Spontaneous low-frequency fluctuations (LFF) in the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal have been shown to reflect cerebral spontaneous neural activity. The objective of this study was to explore brain functional changes in patients with mild cognitive impairment (MCI) by measuring the amplitude of the BOLD signals. Eighteen amnestic MCI patients and 20 healthy elderly individuals underwent the fMRI scan. The amplitude of LFF (ALFF) was calculated using REST software. MCI patients showed decreased ALFF in the right hippocampus and parahippocampal cortex, left lateral temporal cortex and right ventral medial prefrontal cortex and increased ALFF in the left temporal-parietal joint (TPJ) and inferior parietal lobule. The ALFF value in the right hippocampus and parahippocampal cortex was positively correlated with the scores of Mini-Mental State Exam. Reduced medial temporal lobe activity may implicate the underlying memory impairment mechanisms in MCI. Increased TPJ and inferior parietal lobule activity may indicate the compensatory mechanism in MCI patients. These findings suggest that ALFF analysis could provide a useful tool in the fMRI study of MCI.     

Clinical applications of functional MRI at 1.0 T: motor and language studies in healthy subjects and patients

In this article we describe clinical applications of functional MRI (fMRI) at 1.0 T. All experiments were performed on a commercially available 1.0-T system (Magnetom Impact Expert, Siemens AG, Erlangen, Germany) using a blood oxygen level-dependent (BOLD)-sensitive multi-slice EPI technique (TE 66 ms, 4 mm slice thickness, 210 mm field of view, 64 × 64 acquisition matrix). Different paradigms for localization of the motor cortex and for language lateralization were tested in healthy subjects and patients. Methodological considerations concerning the development of the paradigms are also described. In all healthy subjects, motor activation elicited BOLD signal changes in the sensorimotor cortex, permitting identification of primary motor and sensory cortical areas. Furthermore, focal activation of different cortical areas by a language task was possible in 6 of 10 subjects. Nineteen motor studies were performed in 18 patients with supratentorial lesions, in most cases prior to neurosurgical procedures. In 14 studies, fMRI results demonstrated the localization of the motor hand areas relative to the lesion. The results proved valuable for preoperative planning and contributed to therapeutical decisions. We conclude that functional MRI for clinically relevant applications, such as localization of motor and language function, is feasible even at a field strength of 1.0 T without dedicated equipment. Received: 5 May 1998; Revision received: 1 July 1998; Accepted: 13 July 1998     

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.     

Functional connectivity in the motor cortex of resting human brain using echo-planar mri

An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (<0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10^?3) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.