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.     

Mapa cortical y subcortical del lenguaje. Correlación de la resonancia magnética funcional y tractografía en 3 T con la estimulación intraoperatoria cortical y subcortical en tumores cerebrales localizados en áreas elocuentes

ObjectiveTo describe the detection of cortical areas and subcortical pathways involved in language observed in MRI activation studies and tractography in a 3 T MRI scanner and to correlate the findings of these functional studies with direct intraoperative cortical and subcortical stimulation.Material and methodsWe present a series of 14 patients with focal brain tumors adjacent to eloquent brain areas. All patients underwent neuropsychological evaluation before and after surgery. All patients underwent MRI examination including structural sequences, perfusion imaging, spectroscopy, functional imaging to determine activation of motor and language areas, and 3D tractography. All patients underwent cortical mapping through cortical and subcortical stimulation during the operation to resect the tumor. Postoperative follow-up studies were done 24 hours after surgery.ResultsThe correlation of motor function and of the corticospinal tract determined by functional MRI and tractography with intraoperative mapping of cortical and subcortical motor areas was complete. The eloquent brain areas of language expression and reception were strongly correlated with intraoperative cortical mapping in all but two cases (a high grade infiltrating glioma and a low grade glioma located in the frontal lobe). 3D tractography identified the arcuate fasciculus, the lateral part of the superior longitudinal fasciculus, the subcallosal fasciculus, the inferior fronto-occipital fasciculus, and the optic radiations, which made it possible to mark the limits of the resection. The correlation with the subcortical mapping of the anatomic arrangement of the fasciculi with respect to the lesions was complete.ConclusionThe best treatment for brain tumors is maximum resection without associated deficits, so high quality functional studies are necessary for preoperative planning.     

Effectiveness of four different clinical fMRI paradigms for preoperative regional determination of language lateralization in patients with brain tumors

Introduction

Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) has demonstrated its capability to provide comparable results to gold standard intracarotid sodium amobarbital (Wada) testing for preoperative determination of language hemispheric dominance. However, thus far, no consensus has been established regarding which fMRI paradigms are the most effective for the determination of hemispheric language lateralization in specific categories of patients and specific regions of interest (ROIs).

Methods

Forty-one brain tumor patients who performed four different language tasks—rhyming (R), silent word generation (SWG) sentence completion, and sentence listening comprehension (LC)—for presurgical language mapping by fMRI were included in this study. A statistical threshold-independent lateralization index (LI) was calculated and compared among the paradigms in four different ROIs for language activation: functional Broca’s (BA) and Wernicke’s areas (WA) as well as larger anatomically defined expressive (EA) and receptive (RA) areas.

Results

The two expressive paradigms evaluated in this study are very good lateralizing tasks in expressive language areas; specifically, a significantly higher mean LI value was noted for SWG (0.36?±?0.25) compared to LC (0.16?±?0.24, p?=?0.009) and for R (0.40?±?0.22) compared to LC (0.16?±?0.24, p?=?0.001) in BA. SWG LI (0.28?±?0.19) was higher than LC LI (0.12?±?0.16, p?=?0.01) also in EA. No significant differences in LI were found among these paradigms in WA or RA.

Conclusions

SWG and R are sufficient for the determination of lateralization in expressive language areas, whereas new semantic or receptive paradigms need to be designed for an improved assessment of lateralization in receptive language areas.     

Translocation of Broca's area to the contralateral hemisphere as the result of the growth of a left inferior frontal glioma

We report a case of a patient with a left inferior frontal glioma in whom language functional magnetic resonance imaging (fMRI) paradigms produced activation of Broca's area on the right and Wernicke's area on the left. We propose that tumor invasion of the left frontal operculum led to cortical reorganization and interhemispheric transfer of Broca's area. This case emphasizes the importance of preoperative fMRI in assessing the location of eloquent cortices adjacent to a tumor and in guiding neurosurgical decision-making.     

Developing optimized fMRI protocol for clinical use: comparison of different language paradigms

Purpose:

To compare the potential of five functional magnetic resonance imaging (fMRI) language paradigms in activating language areas in Persian‐speaking volunteers in order to optimize these tasks for clinically useful protocol.

Materials and Methods:

16 healthy right‐handed Persian‐speaking volunteers were studied. Each individual performed five tasks during the fMRI scan: word generation (WG), object naming (ON), word reading (WR), word production (WP), and reverse word reading (RWR). The ability of each task to activate classical language areas was assessed using group analysis. In addition, the lateralization index (LI) for each subject‐task was calculated and compared.

Results:

We found that WP, RWR, and WG robustly activated language‐related areas in the dominant hemisphere. ON and WR failed to sufficiently delineate these activation areas. Highest activation intensities in the frontal lobe (including Broca's area) were seen with WP, whereas RWR showed the highest LI among all examined tasks.

Conclusion:

Our results demonstrated that the Persian version of WG and newly presented WP and RWR tasks can be reliably used for localization of language‐related areas in Persian speakers. This type of language evaluation may be used in presurgical planning of neurosurgical procedures in the Persian population. We recommend application of WP and RWR in future researches establishing the optimized protocol for other language speakers. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Functional magnetic resonance imaging for neurosurgical planning in neurooncology

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that is widely available and can be used to determine the spatial relationships between tumor tissue and eloquent brain areas. Within certain limits, this functional information can be applied in the field of neurosurgery as a pre-operative mapping tool to minimize damage to eloquent brain areas. In this article, we review the literature on the use of fMRI for neurosurgical planning. The issues addressed are: (1) stimulation paradigms, (2) the influence of tumors on the blood oxygenation level-dependent (BOLD) signal, (3) post-processing the fMRI time course, (4) integration of fMRI results into neuronavigation systems, (5) the accuracy of fMRI and (6) fMRI compared to intra-operative mapping (IOM).     

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.     

Assessment of the language laterality index in patients with brain tumor using functional MR imaging: effects of thresholding, task selection, and prior surgery

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is used to determine preoperatively the laterality of cortical language representation along with the relationship of language areas to adjacent brain tumors. The purpose of this study was to determine whether changing the statistical threshold for different language tasks influences the language laterality index (LI) for a group of controls, patients with tumor without prior surgery, and patients with tumor and prior surgery.MATERIALS AND METHODS: Seven controls, 9 patients with tumor without prior surgery, and 4 patients with tumor and prior surgery performed verb-generation, phonemic fluency, and semantic fluency language tasks during fMRI. Interhemispheric activation differences between the left and right Broca regions of interest were determined by calculating language LIs. LIs were compared within each group, between groups, and between language tasks. Intraoperative electrocortical mapping or the presence of aphasia during postoperative neurology examinations or both were used as ground truth.RESULTS: The language LI varied as a result of statistical thresholding, presence of tumor, prior surgery, and language task. Although patients and controls followed a similar shape in the LI curve, there was no optimal P value for determining the LI. Three patients demonstrated a shift in the LI between hemispheres as a function of statistical threshold. Verb generation was the least variable task both between tasks and across groups.CONCLUSION: For preoperative patients with tumor, the LI should be examined across a spectrum of P values and a range of tasks to ensure reliability. Our data suggest that the LI may be threshold- and task-dependent, particularly in the presence of adjacent tumor.

Quality of life is an important factor in the decision to undergo neurosurgery. The ability to produce and comprehend language is a significant part of postoperative quality of life. Therefore, the potential of losing language function postoperatively may preclude surgical resection of a tumor.The preoperative assessment of language localization can be useful in planning surgical resection and deciding whether to perform awake cortical mapping. To this end, functional MR imaging (fMRI) has been used to determine the areas of the cortex involved in language functioning in preoperative patients with tumor.^1–5 fMRI is noninvasive and repeatable; and by showing the relationship between functional language cortex and a tumor, it may tailor a surgeon''s approach to the tumor. Currently, intraoperative cortical mapping remains the gold standard for localizing language in patients with tumor, and several studies have demonstrated significant concordance between fMRI and intraoperative electrocorticography.^1,6–9 Additionally, fMRI may reduce overall surgical time by guiding direct cortical stimulation and is particularly useful in cases in which the awake mapping procedure fails due to seizures or issues with the patient''s tolerance for anesthesia.The language laterality index (LI) is a ratio measure using the number of active fMRI voxels that determines hemispheric dominance for language and has been used to determine surgical candidacy for patients with brain tumor.^7,10–14 One potential issue with the LI calculations in fMRI is that the specificity and sensitivity to true neural activity change with the application of different statistical thresholds. As a result, it is expected that language dominance as measured by the LI will vary as the statistical confidence threshold is changed. Theoretically, it is possible for the LI to transfer from 1 hemisphere to the other, depending on the threshold chosen. It has been shown in control subjects that the LI strengthens toward the dominant hemisphere as the statistical threshold increases.¹² No prior studies have examined the LI across a spectrum of P values in patients with tumor. This issue is especially important in evaluating preoperative patients for whom the determination of language dominance is relevant to surgical planning.Using fMRI in patients with tumor presents unique challenges. First, prior studies in angiography and MR imaging have shown that vessels within a glioma lose their ability to autoregulate normally.^15–17 This, in turn, may limit the ability of the blood oxygen level–dependent (BOLD) signal intensity to detect true neural activity in patients with tumor. Previous studies have shown that the volume of BOLD activation is significantly reduced in the tumor hemisphere in comparison with the contralateral control hemisphere in the motor strip.^18–21 Second, the mass effect of large tumors may affect the blood flow of adjacent circulation by compressing veins, thereby causing oxygenated blood to drain from the activated region more quickly, possibly truncating the BOLD signal intensity.^22,23 Finally, susceptibility artifacts from surgical staples, metal used to secure skull flaps, and blood products may also compromise the detection of the BOLD signal intensity, given prior neurosurgery.²⁴In addition to physiologic and technical parameters affecting the measure of laterality, studies suggest that the degree of lateralization may depend on the language task.^7,9,25 In general, paradigms such as verb generation tend to lateralize language better than paradigms like picture naming.^7,11 The verb-generation task has shown the most concordance with intraoperative mapping overall.^7,12,26Accordingly, the goal of our study was multifactorial. We aimed to characterize the LIs measured over a range of statistical thresholds in control subjects and in patients with brain tumors, and we compared the relative distribution of fMRI activity seen by using several paradigms known to lateralize language. We predicted that laterality indices would be more variable in patients with tumor than in control subjects and that the verb-generation paradigm would most consistently lateralize language across groups.     

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.     

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.     

Crossed Cerebrocerebellar Language Lateralization: An Additional Diagnostic Feature for Assessing Atypical Language Representation in Presurgical Functional MR Imaging

BACKGROUND AND PURPOSE:Determining language dominance with fMRI is challenging in patients with brain tumor, particularly in cases of suspected atypical language representation. Supratentorial activation patterns must be interpreted with great care when the tumor is in or near the presumed language areas, where tumor tissue or mass effect can lead to false-negative fMRI results. In this study, we assessed cerebrocerebellar language fMRI lateralization in healthy participants and in patients with brain tumors with a focus on atypical language representation.MATERIALS AND METHODS:Twenty healthy participants and 38 patients with a brain tumor underwent fMRI with a verb-generation task. Cerebral and cerebellar language lateralizations were separately classified as left-sided, right-sided, or symmetric. Electrocortical stimulation was performed in 19 patients. With the McNemar test, we evaluated the dependency between language lateralization in the cerebrum and cerebellum, and with Pearson correlation analysis, the relationship between the cerebral and cerebellar lateralization indices.RESULTS:There was a significant dependency between cerebral and cerebellar language activation, with moderate negative correlation (Pearson r = −0.69). Crossed cerebrocerebellar language activation was present in both healthy participants and patients, irrespective of handedness or typical or atypical language representation. There were no discordant findings between fMRI and electrocortical stimulation.CONCLUSIONS:Language lateralization in the cerebellum can be considered an additional diagnostic feature to determine language dominance in patients with brain tumor. This is particularly useful in cases of uncertainty, such as the interference of a brain tumor with cerebral language activation on fMRI and atypical language representation.

Functional MR imaging is a feasible diagnostic neuroimaging tool for determining hemispheric language dominance in patients with brain tumor preoperatively.¹ Nevertheless, it has important limitations when evaluating language lateralization, particularly in patients with brain tumors.^1–3 Activation patterns must be interpreted with great care when the tumor is in or near the presumed language areas, where tumor tissue or mass effect can lead to false-negative fMRI results.²Determining language dominance is additionally challenging in left-handed patients with brain tumor. Left-handers are known to have less well-defined language-lateralization patterns, with more atypical right-sided language lateralization compared with right-handers.^4–6 In patients with brain tumor, the ability of fMRI to confirm Wada-established language lateralization was significantly more specific for right- than for left-handed or ambidextrous patients, presumably due to their higher rate of typical, left-lateralized language representation.⁷ In a study evaluating the role of fMRI confirming language dominance in patients with epilepsy, this technique showed higher posttest probability for language dominance in patients with typical language representation than in patients with atypical language representation.⁸Thus far, studies assessing language lateralization have focused on the supratentorial brain. Prior fMRI studies have shown activation not only in the cerebral hemispheres but also in the cerebellum while performing specific language tasks.^9–11 An example is the verb-generation task, which is preferred to localize language areas in patients with tumor^11–14 and has been properly validated with electrocortical stimulation (ECS).¹⁵ In individuals with left-hemispheric language dominance, this task has been shown to activate the right cerebellum.⁹ Some further studies have provided evidence for a so-called crossed cerebrocerebellar language lateralization pattern in healthy individuals, with both typical, left-sided and atypical, right-sided language lateralization.^10,16 This crossed cerebrocerebellar language lateralization may serve as a useful additional diagnostic feature in determining language hemispheric dominance in patients with brain tumor because the cerebellar language activation is generally undisturbed by the tumor localized in or near the presumed supratentorial language areas. Such an additional diagnostic feature may be especially helpful in patients with potentially atypical language representation, namely left-handers.The purpose of our study was to assess cerebrocerebellar language fMRI lateralization in healthy participants and in patients with brain tumor, with a focus on atypical language representation.     

A functional MRI study of language networks in left medial temporal lobe epilepsy

Purpose

The purpose of this study was to investigate the abnormality of language networks in left medial temporal lobe epilepsy (MTLE) using fMRI.

Materials and methods

Eight patients with left MTLE and 15 healthy subjects were evaluated. An auditory semantic judgment (AJ) paradigm was used. The fMRI data were collected on a 3T MR system and analyzed by AFNI (analysis of functional neuroimages) to generate the activation map.

Results

Behavioral data showed that the reaction time of the left MTLE patients was significantly longer than that of controls on the AJ task (t = −3.396, P < 0.05). The left MTLE patients also exhibited diffusively decreased activation in the AJ task. Right hemisphere dominance of Broca's and Wernicke's areas was demonstrated in left MTLE patients.

Conclusions

Long-term activation of spikes in left MTLE patients results in language impairment, which is associated with an abnormality of the brain neural network.     

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.     

Resting-State Seed-Based Analysis: An Alternative to Task-Based Language fMRI and Its Laterality Index

BACKGROUND AND PURPOSE:Language is a cardinal function that makes human unique. Preservation of language function poses a great challenge for surgeons during resection. The aim of the study was to assess the efficacy of resting-state fMRI in the lateralization of language function in healthy subjects to permit its further testing in patients who are unable to perform task-based fMRI.MATERIALS AND METHODS:Eighteen healthy right-handed volunteers were prospectively evaluated with resting-state fMRI and task-based fMRI to assess language networks. The laterality indices of Broca and Wernicke areas were calculated by using task-based fMRI via a voxel-value approach. We adopted seed-based resting-state fMRI connectivity analysis together with parameters such as amplitude of low-frequency fluctuation and fractional amplitude of low-frequency fluctuation (fALFF). Resting-state fMRI connectivity maps for language networks were obtained from Broca and Wernicke areas in both hemispheres. We performed correlation analysis between the laterality index and the z scores of functional connectivity, amplitude of low-frequency fluctuation, and fALFF.RESULTS:Pearson correlation analysis between signals obtained from the z score of fALFF and the laterality index yielded a correlation coefficient of 0.849 (P < .05). Regression analysis of the fALFF with the laterality index yielded an R² value of 0.721, indicating that 72.1% of the variance in the laterality index of task-based fMRI could be predicted from the fALFF of resting-state fMRI.CONCLUSIONS:The present study demonstrates that fALFF can be used as an alternative to task-based fMRI for assessing language laterality. There was a strong positive correlation between the fALFF of the Broca area of resting-state fMRI with the laterality index of task-based fMRI. Furthermore, we demonstrated the efficacy of fALFF for predicting the laterality of task-based fMRI.

Brain surgery demands preservation of eloquent areas, including the language functional areas. Many studies have illustrated that fMRI is a noninvasive imaging technique that facilitates the lateralization of language function in individual patients.^1–3 The hemispheric language laterality index (LI) is estimated by evaluating the asymmetry in the activation of language areas in the right and left hemispheres of the human brain during a particular task.⁴ The ease of integrating fMRI with other MR imaging techniques allows the correct identification of pathology and its landmark with respect to language areas.^5–7During the acquisition of language fMRI, the subject is instructed to perform particular tasks designed to elicit a response from language functional areas. However, not all subjects, such as those with low intelligence quotients and pediatric patients, will be able to cooperate with the task-based fMRI. Resting-state fMRI (rsfMRI) is gradually evolving as an alternative to task-based fMRI. The rsfMRI technique extracts the low-frequency fluctuations in the blood oxygen level–dependent (BOLD) signal when subjects are instructed to lie relaxed inside the scanner.^7,8Tie et al⁹ extracted language networks from rsfMRI and evaluated the effectiveness of the automatic identification of language components by using independent component analysis. The study separated the activation patterns corresponding to the language network components from individual rsfMRI data. Another study adopted rsfMRI connectivity analysis to examine the degree of hemispheric dominance for language processing in healthy controls and patients with temporal lobe epilepsy.¹⁰ Functional connectivity (FC) analysis of the frontal cortex in the control group revealed a strong correlation with the LI. The authors found a good correlation between the LI and the epileptogenic mesial temporal lobe. Similarly, Pravatà et al¹¹ studied the correlation between the strength of FC between language networks and language performance in healthy controls and patients with epilepsy. They demonstrated an overall reorganization and reduction of the connectivity pattern within the language network of patients with intractable epilepsy. These studies evaluated the FC of language networks rather than regional abnormalities in the low-frequency fluctuations.In rsfMRI, the parameters FC, amplitude of low-frequency fluctuation (ALFF), and fractional amplitude of low-frequency fluctuation (fALFF) are used to examine the network-related and regional characteristics of low-frequency oscillations. FC analysis evaluates the correlation between the time courses of voxels in a seed region with every other region within the brain. The regions with strong correlations will be shown as an FC map.^7,12 ALFF and fALFF are rsfMRI metrics that help in identifying regional BOLD signal changes of rsfMRI fluctuations. ALFF quantifies the amplitude of the low-frequency fluctuations of rsfMRI BOLD signals. fALFF corresponds to the power spectrum of the low-frequency band with respect to all frequencies detectable with the applied time of repetition of the study.^13,14 Different studies reported the clinical application of these metrics.^13,15,16 However, none of the studies considered the accuracy of these metrics in determining the LI.^9–11The objective of our study was to determine the potential of rsfMRI to evaluate language lateralization in comparison with task-based fMRI. In the current study, we evaluated the z scores of FC, ALFF, and fALFF obtained via rsfMRI and assessed the correlations of each of these metrics with the LI of task-based fMRI from individual seed regions. We hypothesized that the metrics of seed-based rsfMRI analysis are strongly correlated with the LI obtained by using task-based fMRI. If this hypothesis is proved, then rsfMRI can be used instead of task-fMRI in patients who cannot perform the task.     

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     

中文语言活动区功能磁共振研究

目的　利用BOLD功能磁共振 ,初步探索国人说汉语时大脑语言相关功能区。方法　对 2 2名正常中国人 ,说中文句子状态下进行BOLD磁共振脑功能成像 ,探索其大脑语言活动皮层相关功能区。结果　说中文时激活的脑区包括 :两侧运动区 ,左右侧额下回 ,左右侧颞上回 ,左侧岛叶及左右侧小脑半球。结论　BOLD功能磁共振可显示中文大脑活动相关皮层 ,是无创性研究人类语言的有力武器     

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。     

American Society of Functional Neuroradiology–Recommended fMRI Paradigm Algorithms for Presurgical Language Assessment

INTRODUCTION:Functional MR imaging is increasingly being used for presurgical language assessment in the treatment of patients with brain tumors, epilepsy, vascular malformations, and other conditions. The inherent complexity of fMRI, which includes numerous processing steps and selective analyses, is compounded by institution-unique approaches to patient training, paradigm choice, and an eclectic array of postprocessing options from various vendors. Consequently, institutions perform fMRI in such markedly different manners that data sharing, comparison, and generalization of results are difficult. The American Society of Functional Neuroradiology proposes widespread adoption of common fMRI language paradigms as the first step in countering this lost opportunity to advance our knowledge and improve patient care.LANGUAGE PARADIGM REVIEW PROCESS:A taskforce of American Society of Functional Neuroradiology members from multiple institutions used a broad literature review, member polls, and expert opinion to converge on 2 sets of standard language paradigms that strike a balance between ease of application and clinical usefulness.ASFNR RECOMMENDATIONS:The taskforce generated an adult language paradigm algorithm for presurgical language assessment including the following tasks: Sentence Completion, Silent Word Generation, Rhyming, Object Naming, and/or Passive Story Listening. The pediatric algorithm includes the following tasks: Sentence Completion, Rhyming, Antonym Generation, or Passive Story Listening.DISCUSSION:Convergence of fMRI language paradigms across institutions offers the first step in providing a “Rosetta Stone” that provides a common reference point with which to compare and contrast the usefulness and reliability of fMRI data. From this common language task battery, future refinements and improvements are anticipated, particularly as objective measures of reliability become available. Some commonality of practice is a necessary first step to develop a foundation on which to improve the clinical utility of this field.

The use of fMRI in the presurgical assessment of language function, especially in patients with brain tumors, vascular malformations, or epilepsy, has become standard throughout numerous institutions in North America, Europe, and other parts of the world, and the reliance on this technology is increasing.¹ fMRI offers a valuable noninvasive means of assessing language function lateralization and localization, which complements, or in some cases, obviates intraoperative electrocortical stimulation (ECS) mapping.^2,3 The Organization of Human Brain Mapping Committee on Best Practice in Data Analysis and Sharing has recently published a white paper that addresses fMRI research reproducibility through transparency of trial design, tools used for data manipulation, and reporting.⁴Beyond research reporting standards, the American Society of Functional Neuroradiology (ASFNR) perceives the need for increased standardization in clinical practice in an attempt to enhance the communicability of how we assess our patients and the meaningfulness of our imaging findings and reports. Functional MR imaging involves numerous processing steps, which vary among manufacturers of fMRI systems, and this complexity is compounded by institution-unique methods for patient training, paradigm choice, and postprocessing. Data sharing is necessary for research integrity and scientific transparency, but current practice variability obscures reproducibility and hinders adequate interinstitutional sharing of information. This widespread variability thereby limits collective progression, particularly in the presurgical assessment of language function—one of the most important applications of fMRI in clinical practice.Since April 2013, the ASFNR has hosted a monthly teleconference in which clinical fMRI practitioners from across North America have presented presurgical mapping cases from their various practices for educational purposes. This recurring teleconference has highlighted the existing practice variability between institutions. However, it has also offered a regularly occurring, accessible line of communication that has provided impetus for converging practice parameters with a view toward enhanced validation of imaging methodologies, data sharing, and knowledge growth. Consequently, the ASFNR Clinical Practice Committee decided that to strengthen the value of preoperative fMRI language assessment, an ASFNR-approved set of standardized language paradigms should be developed.Because language can be represented across phonologic, orthographic, semantic, pragmatic, and discourse dimensions and 1 task cannot simultaneously activate all of these aspects, multiple tasks are recommended to provide a more sensitive and specific map of language function that will aid in surgical planning.^5,6 There are a number of desirable features for a standardized fMRI task battery: 1) The ideal fMRI language task paradigm set needs to be appropriately challenging for the patient to produce ample activation without being so difficult as to overwhelm a neurologically compromised or otherwise challenged individual; 2) the tasks need to provide an appropriate balance of sensitivity and specificity for language-related activation; and 3) there needs to be the ability to provide both reliable interhemispheric language lateralization as well as intrahemispheric localization of both expressive and receptive language sites, such as the Broca or Wernicke area, with respect to intracerebral lesions.Language Paradigm Review ProcessMembers of an ASFNR Language Paradigm Taskforce were invited to join this project following discussions with the ASFNR Clinical Practice Committee and Executive Committee in an attempt to form a group of interested participants with expertise in the field, a historical perspective of how fMRI has evolved to its current state, and insight into how fMRI must continue to change to further the field.As a first step, the members of the taskforce discussed their own institution''s paradigm choices, practice parameters, and the value of combining results from multiple paradigms. From these discussions, project goals and scope were distilled, including the concept of deriving standardized recommendations that all institutions would hopefully adopt. Initially, the group decided to limit the first iteration of standard paradigms to visually presented paradigms for adult patients with a seventh-grade-equivalent or greater reading ability. Subsequently, it became clear that there was a clinical need to address the pediatric population and adults with limited reading ability, and recommendations for these populations were assessed and developed.The entire ASFNR membership was polled as to how many language-assessment fMRIs per month were performed at their various institutions to determine the most commonly used language paradigms. The poll attempted to gauge the willingness of ASFNR members to adopt a common set of language paradigms. Poll results were assessed by the taskforce, and an attempt was made to balance current practice preferences across the nation with evidence-based data regarding the variable strengths and weaknesses of various language paradigms. The goal was to choose complementary paradigms that would be reasonably applicable to the greatest number of patients. By balancing current practice and scientific evidence, we hoped to motivate adoption of the standardized task battery by making the required change as simple as possible for the practicing members of the society while at the same time being guided by the scientific evidence. This goal necessitated a literature review for each of the most commonly used language paradigms.Two-hundred fifty-nine requests for surveys were sent out with 6 e-mail addresses failing. Fifty-three of 253 responded (21%). Figure 1 depicts the number of fMRIs performed per month for language assessment at different institutions. Fifty-seven percent (30/53) of the responders reported being very likely to adopt language paradigm algorithms, and only 8% (4/53) reported being unlikely to adopt ASFNR recommendations (Fig 2).Open in a separate windowFig 1.fMRIs performed per month for language assessment at different institutions (about one-third of responders do 6+ per month).Open in a separate windowFig 2.Fifty-seven percent (30/53) of responders reported being very likely to adopt language paradigm algorithms, and only 8% (4/53) reported being unlikely to adopt ASFNR recommendations.Results of the ASFNR poll produced 3 tiers of commonly used paradigms across the nation (Fig 3). In the poll, Silent Word Generation (SWG) and Sentence Completion (SC) stood out as the most frequently employed tasks while Verb Generation, Object Naming, Rhyming, and Reading Comprehension seemed to coalesce in a second-tier group. Because SWG and SC were the most commonly used paradigms and also had support in the literature for being reliable and useful, these tasks were favored to form the core of the standard language task battery. However, because a combination of language paradigms has been shown to increase sensitivity and specificity, a third task was considered desirable.^7,8 Nevertheless, converging on a single choice for that third task proved to be more difficult because the taskforce wanted to maintain flexibility for the radiologist to tailor an examination to the patient''s specific clinical scenario.^9,10Open in a separate windowFig 3.The most commonly used language paradigms were sorted into 3 tiers with the total number of imagers by using the paradigms represented on the y-axis. The first tier included SWG and Sentence Completion. The second tier included Verb Generation, Object Naming, Rhyming, and Reading Comprehension. The third tier included Antonym Generation, Semantic Decision, Noun-Verb Semantic Association, Category Naming, and other.Once the paradigm recommendations were decided upon, the taskforce then converged on the specific scanning parameters and stimuli for the paradigms such that the tasks would be vendor-neutral.ASFNR RecommendationsFollowing an analysis of the poll results as well as literature review regarding each of the paradigm tasks mentioned in the poll, the ASFNR taskforce developed language algorithms for both adults and pediatric subjects (Figs 4 and ​and55).Open in a separate windowFig 4.Adult algorithm for presurgical language fMRI.Open in a separate windowFig 5.Pediatric algorithm for presurgical language fMRI.The default adult algorithm includes SC, SWG, and Rhyming. However, to satisfy the need to customize the analysis to the specific clinical scenario, the radiologist may choose to drop Rhyming and repeat the SC or SWG task as a means of confirming and correlating activations between time courses. SC most often offers more robust language area activation than SWG; thus, it would be the most appropriate task to repeat. In patients who may have difficulty adequately performing the SC or SWG tasks, the radiologist may choose either the Object Naming (ON) or Passive Story Listening (PSL) tasks. This also allows customization in that ON is primarily an expressive task and PSL is primarily receptive.The default pediatric algorithm includes SC, Rhyming, and Antonym Generation (AG), but for those patients unable to adequately perform Rhyming, the PSL task should be used instead. In general, this pediatric algorithm should apply to most patients 5–11 years of age, but each patient''s ability to adequately perform tasks should be assessed before the scan.In addition to the language-specific tasks, breath hold fMRI may enhance the fMRI language task battery by identifying areas of potentially false-negative activation. By elevating blood carbon dioxide levels, a breath hold task measures cerebrovascular reactivity throughout the brain. It can therefore help demonstrate potential neurovascular uncoupling or confounding susceptibility artifacts as regions of absent or reduced blood oxygen level–dependent (BOLD) signal in response to breath holding, thereby clarifying regions of false-negative language activation. Due to atypical postprocessing requirements for this task, inclusion of the breath holding task is not considered to be a required component of the language task battery but is nonetheless recommended if available at an institution, to assess potential loss of sensitivity to the BOLD signal, which would influence the confidence level of the interpretation.     

Functional connectivity MR imaging of the language network in patients with drug-resistant epilepsy

BACKGROUND AND PURPOSE:Subtle linguistic dysfunction and reorganization of the language network were described in patients with epilepsy, suggesting the occurrence of plasticity changes. We used resting state FC-MRI to investigate the effects induced by chronic epilepsy on the connectivity of the language-related brain regions and correlated it with language performance.MATERIALS AND METHODS:FC-MRI was evaluated in 22 right-handed patients with drug-resistant epilepsy (11 with LE and 11 with RE) and in 12 healthy volunteers. Neuropsychological assessment of verbal IQ was performed. Patients and controls underwent BOLD fMRI with a verb-generation task, and language function was lateralized by an LI. Intrinsic activity fluctuations for FC analysis were extracted from data collected during the task. Six seeding cortical regions for speech in both hemispheres were selected to obtain a measure of the connectivity pattern among the language networks.RESULTS:Patients with LE presented atypical language lateralization and an overall reduced connectivity of the language network with respect to controls. In patients with both LE and RE, the mean FC was significantly reduced within the left (dominant) hemisphere and between the 2 hemispheres. In patients with LE, there was a positive correlation between verbal IQ scores and the left intrahemispheric FC.CONCLUSIONS:In patients with intractable epilepsy, FC-MRI revealed an overall reduction and reorganization of the connectivity pattern within the language network. FC was reduced in the left hemisphere regardless of the epileptogenic focus side and was positively correlated with linguistic performance only in patients with LE.

MR imaging plays a crucial role in the preoperative assessment of patients with intractable epilepsy. Structural MR imaging is routinely used for the detection of epileptogenic brain lesions, whereas fMRI localizes brain functions on the cerebral cortex and establishes their spatial relationship with lesions. One of the most frequent applications of fMRI is presurgical mapping of language functions and identification of the dominant hemisphere for speech.^1,2Subtle linguistic dysfunction affects up to one-third of adults with chronic epilepsy,^3–5 even in the absence of a direct injury to the brain language network. Functional neuroimaging has demonstrated different patterns of activation and reorganization of the language network in patients with epilepsy compared with healthy subjects. Using fMRI, Brázdil et al⁶ described a different activation pattern of the Broca area in a group of patients with left mesial-temporal epilepsy. In addition, task-evoked BOLD activity within the language network was found to be less unbalanced toward the dominant hemisphere in patients with epilepsy, compared with the healthy controls, especially in patients with early seizure onset.² Taken as a whole, these results suggest the possibility that epilepsy may induce functional changes across remote cortical regions, including those specialized for speech.In addition to task-evoked fMRI studies, resting state FC-MRI can reveal the cortical connectivity among language-network regions by evaluating correlations of spontaneous BOLD signal-intensity fluctuations.^7–10 FC-MRI has attracted growing interest and new applications and can be reasonably considered a marker of neural connectivity.¹¹ Most important, FC-MRI seems particularly suited for clinical populations because subjects lie in the scanner without any imposed task, thus eliminating the need for complying with task instructions.¹² Similarly, FC analysis of intrinsic brain activity, typically performed on resting state data, can be performed on task-related data by subtracting the contribution of the BOLD activation response.^12,13Recently, Waites et al¹⁴ found a decreased resting state FC-MRI connectivity among language regions and an increased connectivity between the left inferior frontal gyrus and part of the DMN in a group of patients with left temporal lobe epilepsy compared with controls. These observations further confirm the influence of epilepsy on language-network activity and possibly account for subtle language impairments that may affect patients with epilepsy. However, we have little information about potential hemispheric differences in these patients; and most important, the changes in FC associated with verbal performance have not been studied previously, to our knowledge.In the present retrospective analysis, we investigated the FC pattern among language-network nodes in a group of patients (n = 22) with either left- or right-lateralized drug-resistant epilepsy and in a group of matched healthy subjects (n = 12). First, we evaluated the pattern of cortical activation during a conventional block-designed verb-generation task assessing the degree of language function lateralization across hemispheres. We then used FC-MRI to investigate the pattern of functional connectivity among 6 regions of the language network in the 2 hemispheres. Finally, we investigated the correlation between the pattern of FC-MRI and the neuropsychological evaluation of language performance.     

Changes in thalamus connectivity in mild cognitive impairment: evidence from resting state fMRI

Purpose

The subcortical region such as thalamus was believed to have close relationship with many cerebral cortexes which made it especially interesting in the study of functional connectivity. Here, we used resting state functional MRI (fMRI) to examine changes in thalamus connectivity in mild cognitive impairment (MCI), which presented a neuro-disconnection syndrome.

Materials and methods

Data from 14 patients and 14 healthy age-matched controls were analyzed. Thalamus connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions.

Results

We found that functional connectivity between the left thalamus and a set of regions was decreased in MCI; these regions are: bilateral cuneus, middle occipital gyrus (MOG), superior frontal gyrus (SFG), medial prefrontal cortex (MPFC), precuneus, inferior frontal gyrus (IFG) and precentral gyrus (PreCG). There are also some regions showed reduced connectivity to right thalamus; these regions are bilateral cuneus, MOG, fusiform gyrus (FG), MPFC, paracentral lobe (PCL), precuneus, superior parietal lobe (SPL) and IFG. We also found increased functional connectivity between the left thalamus and the right thalamus in MCI.

Conclusion

The decreased connectivity between the thalamus and the other brain regions might indicate reduced integrity of thalamus-related cortical networks in MCI. Furthermore, the increased connectivity between the left and right thalamus suggest compensation for the loss of cognitive function. Briefly, impairment and compensation of thalamus connectivity coexist in the MCI patients.