Re-examine tumor-induced alterations in hemodynamic responses of BOLD fMRI: implications in presurgical brain mapping

Background Blood oxygenation level dependent (BOLD) fMRI is used for presurgical functional mapping of brain tumor patients. Abnormal tumor blood supply may affect hemodynamic responses and BOLD fMRI signals. Purpose To perform a multivariate and quantitative investigation of the effect of brain tumors on the hemodynamic responses and its impact on BOLD MRI signal time course, data analysis in order to better understand tumor-induced alterations in hemodynamic responses, and accurately mapping cortical regions in brain tumor patients. Material and Methods BOLD fMRI data from 42 glioma patients who underwent presurgical mapping of the primary motor cortex (PMC) with a block designed finger tapping paradigm were analyzed, retrospectively. Cases were divided into high grade (n = 24) and low grade (n = 18) groups based on pathology. The tumor volume and distance to the activated PMCs were measured. BOLD signal time courses from selected regions of interest (ROIs) in the PMCs of tumor affected and contralateral unaffected hemispheres were obtained from each patient. Tumor-induced changes of BOLD signal intensity and time to peak (TTP) of BOLD signal time courses were analyzed statistically. Results The BOLD signal intensity and TTP in the tumor-affected PMCs are altered when compared to that of the unaffected hemisphere. The average BOLD signal level is statistically significant lower in the affected PMCs. The average TTP in the affected PMCs is shorter in the high grade group, but longer in the low grade tumor group compared to the contralateral unaffected hemisphere. Degrees of alterations in BOLD signal time courses are related to both the distance to activated foci and tumor volume with the stronger effect in tumor distance to activated PMC. Conclusion Alterations in BOLD signal time courses are strongly related to the tumor grade, the tumor volume, and the distance to the activated foci. Such alterations may impair accurate mapping of tumor-affected functional areas when using conventional fixed models.     

BOLD signal in the motor cortex shows a correlation with the blood volume of brain tumors

PURPOSE: To investigate whether and how the blood-oxygenation-level-dependent (BOLD) functional MRI (fMRI) signal is modified by brain tumors. MATERIALS AND METHODS: The BOLD signal depends on the perfusion, which in turn may be affected in the presence of a tumor. Some studies have demonstrated a reduced BOLD signal in the tumor-bearing hemisphere. The BOLD signal variation in the motor cortex area was studied with finger tapping in a brain tumor group and a control group. An a priori volume-of-interest (VOI)-based method was applied that allows quantification of the mean BOLD signal amplitude and extent of activated volume. BOLD signal amplitude and activated volume were correlated with the extent of edema, a mass effect on the central sulcus, tumor volume, distance of tumor to somatosensory cortex, and tumor blood volume. RESULTS: In the tumor group the ipsilateral activated volume was reduced by 21% (P = 0.025) and the mean signal amplitude was reduced by 16% (P = 0.004). The mean BOLD signal amplitude shows a significant correlation with the total intratumoral blood volume (P = 0.014). CONCLUSION: We concluded that the peritumoral perfusion was reduced resulting due to a tumor aspirating perfusion (steal phenomenon).     

健康成人及脑肿瘤患者利手和非利手简单与复杂运动fMRI研究

目的:应用脑血氧水平依赖性功能MRI(BOLD-f MRI)研究健康成年人及脑肿瘤患者运动功能皮层定位并探讨其对脑肿瘤的临床应用价值。方法:10例健康志愿者和32例脑肿瘤患者(术前25例,术后7例)共42例受试者,行利手、非利手的单手握拳(简单运动)或单手对指(复杂运动)运动的脑BOLD-f MRI检查,分析脑肿瘤对运动皮层位置和功能的影响。结果:健康成人运动皮层主要位于对侧躯体感觉运动皮层(SMC),单或双侧辅助运动区(SMA)、运动前区(PMA)和双侧小脑半球。复杂运动或非利手运动时脑功能激活区范围和程度较简单运动或利手运动时增多。累及功能皮层的脑肿瘤患者,可见患侧部分脑功能区激活,但激活区移位、分布弥散。术后脑肿瘤患者功能皮层的位置基本恢复正常。结论:BOLD-f MRI是一种有效而无创的脑功能皮层定位方法,有利于脑肿瘤的精确定位诊断并指导临床治疗。     

Multisite fMRI reproducibility of a motor task using identical MR systems

PURPOSE: To estimate between-scanner functional MRI (fMRI) reproducibility in a multisite study. MATERIALS AND METHODS: A total of five identical 1.5T MR systems were used to repeatedly scan five subjects while performing a finger tapping task. A two-way (scanners, subjects) random effects analysis of variance (ANOVA) was used to estimate between-scanner and between-subject variability on two outcome variables: task-related mean blood oxygenation level dependent (BOLD) signal change and volume of activation within a motor region-of-interest (ROI). RESULTS: Between-scanner variability of fMRI data accounted for a small proportion of the total variation in the BOLD signal change (8.34%, P = 0.114) and volume of activation (5.46%, P = 0.203). Between-subject variation accounted for more than half of the total variation for both measurements (57.17% and 54.46%, respectively, P < 0.01). CONCLUSION: These results support the feasibility of multisite studies using identical scanner systems.     

Concurrent fMRI and optical measures for the investigation of the hemodynamic response function.

Functional magnetic resonance imaging (fMRI) signal variations are based on a combination of changes in cerebral blood flow (CBF) and volume (CBV), and blood oxygenation. We investigated the relationship between these hemodynamic parameters in the rodent barrel cortex by performing fMRI concurrently with laser Doppler flowmetry (LDF) or optical imaging spectroscopy (OIS), following whisker stimulation and hypercapnic challenge. A difference between the positions of the maximum blood oxygenation level-dependent (BOLD) and CBV changes was observed in coronal fMRI maps, with the BOLD region being more superficial. A 6.5% baseline blood volume fraction in this superficial region dropped to 4% in deeper cortical layers (corresponding to total hemoglobin baseline volumes Hbt0 = 110 microM and 67 microM, respectively), as inferred from maps of deltaR2*. Baseline volume profiles were used to parameterize the Monte Carlo simulations (MCS) to interpret the 2D OIS. From this it was found that the optical blood volume measurements (i.e., changes in total hemoglobin) equated with CBV-MRI measurements when the MRI data were taken from superficial cortical layers. Optical measures of activation showed a good spatial overlap with fMRI measurements taken in the same plane (covering the right hemisphere surface). Changes in CBV and CBF followed the scaling relationship CBV = CBF(alpha), with mean alpha = 0.38 +/- 0.06.     

健侧C7神经移位术后大脑运动皮层功能重组的功能MRI研究

目的利用功能MRI（fMRI），观察健侧C7神经移位术后大脑运动皮层的变化特征。方法随访经临床和手术证实的因全臂丛神经损伤而接受健侧C7神经移位术者13例，左侧损伤者10例，右侧者3例。根据手部运动功能的恢复情况，将病例分为2组：a组10例，息手不能自主运动。b组3例，患手可以自主运动。另外，选择12名健康志愿者作为对照。所有受检者均接受了fMRI，扫描方法采用平面回波血氧水平依赖（BOLD）序列，利用SPM99软件对图像进行处理分析。结果患者健侧和患侧上肢运动诱发激活区最强信号体素主要出现于对侧半球初级运动皮层（PMC），健侧肢体运动诱发同侧PMC激活者10例，患侧肢体运动诱发同侧PMC激活者7例；a组受检者健侧上肢运动诱发对侧PMC激活区形态正常者9例，手部运动诱发平均激活区大小为3159个体素，肩部运动诱发平均激活区大小为1746个体素。患侧手部和肩部运动诱发对侧PMC激活区扩大者各有6例；b组受检者患肢运动诱发双侧PMC出现激活者1例，对侧PMC激活者2例。结论外周神经损伤可以引起大脑运动皮层的改变；患肢躯体代表区可以在神经损伤以后相当长时期内存在并对运动的心理表达产生应答；健侧C7神经移位术后中枢神经系统重组可能发生在多种水平上，并且可以受到多种因素影响。     

Degree of hippocampal atrophy is related to side of seizure onset in temporal lobe epilepsy

BACKGROUND AND PURPOSE: Temporal lobe epilepsy (TLE) is associated with pathologic changes in hippocampal physiology and morphology. Our aim was to quantify volume reduction of the right and left hippocampus in patients with TLE and to investigate whether the degree of hippocampal atrophy is related to the side of seizure onset. METHODS: The volume of the right and left hippocampus was estimated for 50 controls and 101 patients with TLE, by applying the unbiased Cavalieri method on MR images. RESULTS: Pairwise comparisons, within a multivariate analysis of variance and adjusted by using the Bonferroni correction, revealed that both right and left hippocampal volumes were, on average, significantly smaller in patients with right-sided seizure onset (R-patients) relative to those of controls (P < .001 and P = .04, respectively). Furthermore, left hippocampal volume was significantly smaller in patients with left-sided seizure onset (L-patients) compared with controls (P < .001), but the right-sided hippocampal volume was not significantly smaller (P = .71). Moreover, a correlation analysis revealed that the strong linear association between the right and left hippocampal volumes existing in the control population (r = 0.73) is partially lost in patients with TLE (r < or = 0.48), and this loss in correlation appears to be more pronounced in L-patients than in R-patients. CONCLUSION: Our MR imaging results suggest that although the major damage in patients with TLE is located in the hippocampus ipsilateral to the side of seizure onset, R-patients are more likely to have bilateral hippocampal volume reduction. These findings support the hypothesis that cerebral hemispheres may not only differ in their functionality organization but also in their vulnerability to a neurologic insult.     

MR volumetry of the entorhinal, perirhinal, and temporopolar cortices in drug-refractory temporal lobe epilepsy

BACKGROUND AND PURPOSE: The occurrence of damage in the entorhinal, perirhinal, and temporopolar cortices in unilateral drug-refractory temporal lobe epilepsy (TLE) was investigated with quantitative MR imaging. METHODS: Volumes of the entorhinal, perirhinal, and temporopolar cortices were measured in 27 patients with unilateral drug-refractory TLE, 10 patients with extratemporal partial epilepsy, and 20 healthy control subjects. All patients with TLE were evaluated for epilepsy surgery and underwent operations. RESULTS: In left TLE, the mean volume of the ipsilateral entorhinal cortex was reduced by 17% (P <.001 compared with control subjects) and that of the ipsilateral temporopolar cortex by 17% (P <.05). In right TLE, the mean ipsilateral entorhinal volume was reduced by 13% (P < or =.01), but only in patients with hippocampal atrophy. Asymmetry ratios also indicated ipsilateral cortical atrophy. When each patient was analyzed individually, the volume of the ipsilateral hippocampus was reduced (> or = 2 SD from the mean of controls) in 63% and that of the entorhinal cortex in 52% of patients with TLE. Furthermore, ipsilateral entorhinal (left: r = 0.625, P <.001; right: r = 0.524, P < or =.01), perirhinal (left: r = 0.471, P <.05), and temporopolar (right: r = 0.556, P <.01) volumes correlated with ipsilateral hippocampal volumes. There was no association, however, with clinically or pathologically identified causes of epilepsy, duration of epilepsy, or age at onset of epilepsy. Mean cortical volumes were unaffected in extratemporal partial epilepsy. CONCLUSION: Subpopulations of patients with unilateral TLE have ipsilateral damage in the entorhinal and temporopolar cortices. The damage is associated with hippocampal damage.     

A comparison between blood oxygenation level-dependent and cerebral blood volume contrast in the rat cerebral and cerebellar somatosensoric cortex during electrical paw stimulation

PURPOSE: To implement and optimize cerebral blood volume (CBV)-weighted functional magnetic resonance imaging (fMRI) in the rat cerebral and cerebellar cortex during electrical paw stimulation. MATERIALS AND METHODS: fMRI of the cerebral and cerebellar cortex was performed during electrical paw stimulation on a 7-T MRI system (MRRS, Guilford, UK) comparing the blood oxygenation level-dependent (BOLD) and CBV-weighted contrast with different ultrasmall particles of iron oxide (USPIO) contrast doses (NC100150, 30 mg Fe/mL; Amersham Health, Oslo, Norway) and different TE. RESULTS: Doses of 15 and 20 mg/kg USPIO at TE = T*2 or TE = 14 msec almost doubled the contrast-to-noise ratio (CNR) of the activated areas in the cerebral cortex without affecting the overall signal-to-noise ratio (SNR) or the incidence of activation (100%). In the cerebellum the SNR decreased significantly with an increasing contrast dose. At a dose of 15 mg/kg, the CNR was slightly smaller than the CNR measured in the BOLD images, but the activation incidence seemed to be doubled. At 20 mg/kg, the CNR was slightly increased, but the activation incidence was lower. At both contrast doses the venous artifacts disappeared. CONCLUSION: A USPIO contrast dose of 20 mg/kg proved to be beneficial for fMRI in the rat, even though it affected the CNR and SNR in the cerebral and the cerebellar cortex differentially.     

Differential interictal activity of the precuneus/posterior cingulate cortex revealed by resting state functional MRI at 3T in generalized vs. partial seizure

PURPOSE: To characterize, using functional MRI (fMRI), the pattern of active brain regions in the resting state in patients with epilepsy. MATERIALS AND METHODS: We studied 28 patients with epilepsy, divided into a partial seizure (PS; N = 9) and a generalized seizure group (GS; N = 19), and 34 control subjects. Resting state fMRI was performed using a GE 3T scanner by collecting 200 volumes of echo-planar imaging (EPI) images with subjects relaxed, eyes closed. Data were processed using a modification of the method of Fransson (Hum Brain Mapp 2005;26:15-29), which reveals information on regional low-frequency Blood Oxygenation Level Dependent (BOLD) signal oscillations in the resting state without any a priori hypothesis. The significant active areas in brain were identified with both individual and group analysis. RESULTS: Controls showed active regions in the precuneus/posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC)/ventral anterior cingulate cortex (vACC), theregions associated with the brain "default mode." Similar active regions were observed in PS, whereas GS showed no significant activation of precuneus/PCC. CONCLUSION: In GS, the lack of activation in precuneus/PCC may partly account for their more severe interictal deficits, compared to PS, in cognitive functions such as concentration and memory.     

抑郁症患者杏仁核、海马形态功能变化的MR研究

目的 综合形态学测量及功能MR检查对抑郁症患者杏仁核、海马形态及功能进行研究,探讨其变化规律及其机制.方法 60例抑郁症患者[按病情及汉密尔顿抑郁量表(HAMD)分为轻(17分≥HAMD＞8分)、中(24分≥HAMD>17分)及重度组(HAMD>24分),每组20例]及20名健康志愿者行MR形态及fMRI扫描,根据形态图像勾画海马和杏仁核,计算其体积,并进行标准化处理.使用统计参数图(SPM)5软件对功能图像进行后处理,得到受试者脑激活图.体积测量数据采用方差分析及多个试验组与1个对照组均数差别比较的Dunnett-t检验进行分析,并分别对患者组海马、杏仁核体积及信号强度与疾病程度(HAMD评分)进行Pearson相关性分析.结果 抑郁症轻、中及重度组海马体积均小于对照组(左侧2296±202,右侧2283±199),以重度组最为显著(左侧1978±176,Dunnett-t=-10.0,P<0.01;右侧1981±171,Dunnett-t=-9.2,P<0.01),中度组次之(左侧2127±180,Dunnett-t=-3.0,P<0.05;右侧2135±183,Dunnett-t=-3.0,P<0.05),轻度组改变轻微(左侧2207±189,Dunnett-t=-1.4,P>0.05;右侧2210±191,Dunnett-t=-1.6,P>0.05).抑郁症组杏仁核体积依病情由轻到重呈由大至小的趋势,对照组左侧为1762±185,右侧为1749±182.轻度组显著增大(左侧1992±200,Dunnett-t=4.8,P<0.01;右侧1989±191,Dunnett-t=5.0,P<0.01),中度组轻度增大(左侧1889±192,Dunnett-t=2.8,P<0.05;右侧1896±195,Dunnett-t=2.8,P<0.05),重度组显著缩小(左侧1539±178,Dunnett-t=-6.8,P<0.01;右侧1543±180,Dunnett-t=-7.0,P<0.01).功能MR显示抑郁症患者杏仁核、海马对负性图片刺激有着更为显著的脑活动信号,并具有一定的规律,轻度组杏仁核最为显著,中度组信号有所减低,重度组信号最弱,但仍高于对照组.抑郁组海马杏仁核体积、信号强度与疾病程度(HAMD评分)均呈明显的相关性(r值范围为-0.80～-0.90,P值均＜0.05).结论 抑郁症患者海马体积缩小,且这种改变可能与杏仁核有关,杏仁核依病情不同而体积不同;抑郁患者杏仁核、海马对负性图片有着更为显著的脑活动信号.

Abstract：

Objective To explore the morphometric and functional alterations of amygdale and hippocampus in patients with depression by anatomical and functional MRI, and try to reveal the pattern and pathogenesis of the changes in depression. Methods Sixty patients (divided equally into mild, moderate and major groups according to patient′s scores of HAMD) and 20 healthy control groups were scanned using T1WI and fMRI. The outlines of hippocampus and amygdale were drawn manually by observer and the volumes were calculated and normalized subsequently. Functional MRI was processed using SPM5 and individual activation map was got subsequently. Dunnett-t test and Pearson correlation analysis were separately used to analyze the morphometric and functional changes and the correlations between cerebral changes and clinical severity. Results The hippocampal volumes of control groups were 2296±202 left for left side and 2283±199 for right side. The hippocampal volumes of depressive patients were smaller than those of control groups, especially for the major group (left 1978±176,Dunnett-t=-10.0,P<0.01,right 1981±171,Dunnett-t=-9.2,P<0.01). The moderate group showed moderate reduced volume(left 2127±180,Dunnett-t=-3.0,P<0.05,right 2135±183,Dunnett-t=-3.0,P<0.05), while the mild ones showed slightly decreased volume (left 2207±189,Dunnett-t=-1.4,P>0.05,right 2210±191,Dunnett-t=-1.6,P>0.05). The amygdale′s volumes of control groups was 1762±185,the right was 1749±182, while those in patient group reduced along with the patient′s condition, i.e., the mild groups (left 1992±200,Dunnett-t=4.8,P<0.01,right 1989±191, Dunnett-t=5.0,P<0.001), the moderate groups (left 1889±192, Dunnett-t=2.8,P<0.05,right 1896±195,Dunnett-t=2.8,P<0.05), and the major groups (left 1539±178,Dunnett-t=-6.8,P<0.01,right 1543±180,Dunnett-t=-7.0,P<0.01).For fMRI study, patient group demonstrated more activation of the amygdale and hippocampus under the stimulations of negative images than controls. Furthermore, the strengthens of activation decreased along with the patient′s condition, i.e., the major ones showed the weakest activation among the patients, though it was higher than that of control group. In patient group, both the volumes and activations of hippocampus and amygdale showed significant negative correlations with HAMD scores(r=-0.80--0.90,P＜0.05). Conclusion The hippocampal volumes of depressive patients reduced, which may be due to the change of the amygdale, and the amygdale′s volumes were changed along with the patient′s condition. There were more activation in the amygdale and hippocampus of depressive patients under the stimulations of negative images.     

The effect of tumour type and distance on activation in the motor cortex

Functional MRI has been widely used to identify the eloquent cortex in neurosurgical/radiosurgical planning and treatment of CNS neoplasms and malformations. In this study we examined the effect of CNS tumours on the blood oxygenation level-dependent (BOLD) activation maps in the primary and supplementary motor cortex. A total of 33 tumour patients and five healthy right-handed adults were enrolled in the study. Patients were divided into four groups based on tumour type and distance from primary motor cortex: (1) intra-axial, near, (2) extra-axial, near, (3) intra-axial, far and (4) extra-axial, far. The intra-axial groups consisted of patients with astrocytomas, glioblastomas and metastatic tumours of mixed histology; all the extra-axial tumours were meningiomas. The motor task was a bilateral, self-paced, finger-tapping paradigm. Anatomical and functional data were acquired with a 1.5 T GE Echospeed scanner. Maps of the motor areas were derived from the BOLD images, using SPM99 software. For each subject we first determined the activation volume in the primary motor area and the supplementary motor area (SMA) and then calculated the percentage difference between the hemispheres. Two factors influenced the activation volumes: tumour type (P<0.04) and distance from the eloquent cortex (P<0.06). Patients in group 1 (intra-axial, near) had the smallest activation area in the primary motor cortex, the greatest percentage difference in the activation volume between the hemispheres, and the largest activation volume in the SMA. Patients in group 4 (extra-axial, far) had the largest activation volume in the primary motor cortex, the least percentage difference in volume between the hemispheres, and the smallest activation volume in the SMA. There was no significant change in the volume of the SMA in any group, compared with controls, suggesting that, although there is a gradual decrease in SMA volume with distance from the primary motor area, the effect on motor reorganisation is minimal. All the tumour patients showed a net loss in total activation volumes (both hemispheres plus SMA) compared with controls. The effect of the tumours on interhemispheric volume differences was: group 1>group 3>group 2>group 4. Within the intra-axial tumours, there was no significant effect of tumour type on the results. We conclude that BOLD–imaged activation volume is affected at least by the interplay of two factors: tumour type and distance from the motor cortex. Further, all tumours may be expected to cause some loss of activation volumes in motor areas. We suggest that, with proper precautions and planning, BOLD functional magnetic resonance imaging (fMRI) maps can be useful in minimising damage to the functional areas.     

CBF, BOLD, CBV, and CMRO(2) fMRI signal temporal dynamics at 500-msec resolution

PURPOSE: To investigate the temporal dynamics of blood oxygenation level-dependent (BOLD), cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO(2)) changes due to forepaw stimulation with 500-msec resolution in a single setting. MATERIALS AND METHODS: Forepaw stimulation and hypercapnic challenge on rats were studied. CBF and BOLD functional MRI (fMRI) were measured using the pseudo-continuous arterial spin-labeling technique at 500-msec resolution. CBV fMRI was measured using monocrystalline iron-oxide particles following CBF and BOLD measurements in the same animals. CMRO(2) change was estimated via the biophysical BOLD model with hypercapnic calibration. Percent changes and onset times were analyzed for the entire forepaw somatosensory cortices and three operationally defined cortical segments, denoted Layers I-III, IV-V, and VI. RESULTS: BOLD change was largest in Layers I-III, whereas CBF, CBV, and CMRO(2) changes were largest in Layers IV-V. Among all fMRI signals in all layers, only the BOLD signal in Layers I-III showed a poststimulus undershoot. CBF and CBV dynamics were similar. Closer inspection showed that CBV increased slightly first (P < 0.05), but was slow to peak. CBF increased second, but peaked first. BOLD significantly lagged both CBF and CBV (P < 0.05). CONCLUSION: This study provides important temporal dynamics of multiple fMRI signals at high temporal resolution in a single setting.     

听觉性语言刺激的功能磁共振成像研究

目的用MR血氧水平依赖性(BOLD)技术研究听觉语言的功能磁共振成像(fMRI)。资料与方法23例受试者，其中正常志愿者14例，脑肿瘤患者6例，脑外伤软化灶形成患者3例。进行听觉性语言刺激共25次，采用BOLD技术进行相应脑功能区成像。结果所有受试者均能在MRI检查中表现出局部脑功能活动区规律的信号强度-时间变化曲线，并获得较清晰的图像。功能区附近的占位病变可造成局部功能区的移位和缩小等改变。结论BOLD-fMRI在活体人脑听觉语言的功能区定位方面是一种有效的方法。对需实施手术的颅内占位。病变进行BOLD-MRI检查对指导手术有价值。     

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     

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.     

Disparity of activation onset in sensory cortex from simultaneous auditory and visual stimulation: Differences between perfusion and blood oxygenation level-dependent functional magnetic resonance imaging

PURPOSE: To compare the temporal behaviors of perfusion and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in the detection of timing differences between distinct brain areas, and determine potential latency differences between stimulus onset and measurable fMRI signal in sensory cortices. MATERIALS AND METHODS: Inversion recovery (IR) spin-echo echo-planar imaging (EPI) and T2*-weighted gradient-echo EPI sequences were used for perfusion- and BOLD-weighted experiments, respectively. Simultaneous auditory and visual stimulations were employed in an event-related (ER) paradigm. Signal time courses were averaged across 40 repeated trials to evaluate the onset of activation and to determine potential differences of activation latency between auditory and visual cortices and between these scanning methods. RESULTS: Temporal differences between visual and auditory areas ranged from 90-200 msec (root-mean-square (RMS) = 134 msec) and from -80 to 930 msec (RMS = 604 msec) in perfusion and BOLD measurements, respectively. The temporal variability detected with BOLD sequences was larger between subjects and was significantly greater than that in the perfusion response (P < 0.04). The measured time to half maximum (TTHM) values for perfusion imaging (visual, 3260 +/- 710 msec; auditory, 3130 +/- 700 msec) were earlier than those in BOLD responses (visual, 3770 +/- 430 msec; auditory, 3360 +/- 460 msec). CONCLUSION: The greater temporal variability between brain areas detected with BOLD could result from differences in the venous contributions to the signal. The results suggest that perfusion methods may provide more accurate timing information of neuronal activities than BOLD-based imaging.     

Systemic theophylline augments the blood oxygen level-dependent response to forepaw stimulation in rats

BACKGROUND AND PURPOSE: Functional MR imaging with blood oxygen level-dependent (BOLD) contrast enhancement is believed to rely on changes in cerebral blood flow and deoxyhemoglobin level to estimate the location and degree of neural activation. We studied the relationship between neural activation and the observed BOLD response by using theophylline, an antagonist of the inhibitory neurotransmitter adenosine and a potent inhibitor of the vasodilatory response to neural activation. METHODS: Using a rat model with electrical forepaw stimulation, we performed fMRI measurements before and after the systemic injection of either theophylline (0.1 mmol/kg) or an equivalent volume of saline. Changes in the BOLD response were quantified by determining the number of activated voxels and the amplitude of the BOLD response for each animal in the theophylline and saline groups. RESULTS: The theophylline group had a significantly Tincreased BOLD response (70-150% increased activated voxel count and 60-65% increased BOLD response amplitude) at 45 and 60 minutes after systemic injection compared with baseline. The response of the saline-injected control group did not change significantly. CONCLUSION: The administration of systemic theophylline significantly augmented the BOLD response due to either an elevation of resting deoxyhemoglobin levels or the neuroexcitatory effect of theophylline. This effect potentially could be used in human fMRI studies to increase the sensitivity of the BOLD response.     

急性期脑卒中患者和健康成人食指被动运动BOLD-fMRI

目的：对比分析急性期脑梗死患者与健康成人各运动相关脑区激活程度和方法的差异,探讨急性期脑梗死后运动功能变化的模式。方法：对12例基底节区急性期缺血性脑梗死患者（实验组）和与之相匹配的12例健康成人（对照组）进行食指被动运动BOLD-fMRI检查,然后应用SPM对功能图像进行处理分析,并选取初级感觉运动区（SM1）、次级感觉运动区（SM2）、运动前区（PM）、补充运动区（SMA）、扣带回运动区（CMA）及小脑作为兴趣区,观察两组受试者各运动相关脑区的激活情况,并对对侧SM1区的激活体积、激活率进行定量分析。结果：对照组主要激活对侧SM1区（激活体积中位数1006k,四分位间距1142k,激活率100％）,其它运动相关脑区激活次数较少,且激活体积相对较小;患者组主要激活对侧SM1区（激活体积中位数15k,四分位间距71k,激活率58．3％）,其它运动相关脑区偶尔或无激活。患者组对侧SM1激活率、激活体积均比对照组低（P〈0．05）。结论：BOLD-fMRI是一种研究脑梗死患者运动功能的有效方法。     

Fuzzy clustering of gradient-echo functional MRI in the human visual cortex. Part II: Quantification

Fuzzy cluster analysis (FCA) is a new exploratory method for analyzing fMRI data. Using simulated functional MRI (fMRI) data, the performance of FCA, as implemented in the software package Evident, was tested and a quantitative comparison with correlation analysis is presented. Furthermore, the fMRI model fit allows separation and quantification of flow and blood oxygen level dependent (BOLD) contributions in the human visual cortex. In gradient-recalled echo fMRI at 1.5 T (TR = 60 ms, TE = 42 ms, radiofrequency excitation flip angle [?] = 10^°–60^°) total signal enhancement in the human visual cortex, ie, flow-enhanced BOLD plus inflow contributions, on average varies from 5% to 10% in or close to the visual cortex (average cerebral blood volume [CBV] = 4%) and from 10% to 20% in areas containing medium-sized vessels (ie, average CBV = 12% per voxel), respectively. Inflow enhancement, however, is restricted to intravascular space (= CBV) and increases with increasing radiofrequency (RF) flip angle, whereas BOLD contributions may be obtained from a region up to three times larger and, applying an unspoiled gradient-echo (GRE) sequence, also show a flip angle dependency with a minimum at approximately 30^°. This result suggests that a localized hemodynamic response from the microvasculature at 1.5 T maybe extracted via fuzzy clustering. In summary, fuzzy clustering of fMRI data, as realized in the Evident software, is a robust and efficient method to (a) separate functional brain activation from noise or other sources resulting in time-dependent signal changes as proven by simulated fMRI data analysis and in vivo data from the visual cortex, and (b) allows separation of different levels of activation even if the temporal pattern is indistinguishable. Combining fuzzy cluster separation of brain activation with appropriate model calculations allows quantification of flow and (flow-enhanced) BOLD contributions in areas with different vascularization.