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).     

The influence of gliomas and nonglial space-occupying lesions on blood-oxygen-level-dependent contrast enhancement

BACKGROUND AND PURPOSE: Functional MR (fMR) imaging with blood-oxygen-level-dependent (BOLD) contrast enhancement is increasingly used as a noninvasive tool for presurgical mapping in patients with intracranial tumors. Most physiologic studies of task-related BOLD contrast enhancement have involved healthy volunteers. Therefore, it is not known whether BOLD contrast is evoked in the same way in or adjacent to tumor tissue. The purpose of this study was to study the influence of different intracranial tumors on BOLD contrast enhancement. METHODS: fMR mapping of the sensorimotor cortex was successfully performed in 15 of 21 patients with intracranial space-occupying lesions by using a bimanual motor task. Tumors were located either within the sensorimotor area itself or in adjacent brain areas, inducing changes of signal intensity on T2-weighted images along the pre- or postcentral gyrus. Space-occupying lesions were divided into a group comprising gliomas (seven cases) and a group comprising nonglial space-occupying lesions (three metastases, two cavernomas, one abscess, one arteriovenous malformation, one meningioma). A hemispheric activation index was calculated using the volume of activation on the affected and on the contralateral hemisphere. Hemispheric activation indices of gliomas and nonglial lesions were compared statistically. RESULTS: The activated volume in the hemispheres ipsilateral to the nonglial lesions was 14% larger than in the contralateral hemisphere, whereas in the hemispheres ipsilateral to gliomas, the activated volume decreased by 36% in comparison with the contralateral hemisphere. The difference between nonglial lesions and gliomas was significant (P < .05). CONCLUSION: The generation of BOLD contrast enhancement is reduced near gliomas but is not affected by nonglial tumors.     

Magnocellular and parvocellular visual pathways have different blood oxygen level-dependent signal time courses in human primary visual cortex

PURPOSE: The magnocellular and parvocellular pathways (M and P pathways) are the major pathways of the visual system, with distinct histologic and physiologic properties that may also have different metabolic characteristics. We hypothesize that the differences of the 2 visual pathways would also manifest as differences in the signal time course of blood oxygen level-dependent functional MR imaging (BOLD fMRI). The differences in BOLD signal time course may provide insight into the metabolic requirements of the 2 pathways. METHODS: Eleven fMRI sessions on 6 subjects were performed using stimuli that preferentially activated the 2 pathways. Regions commonly activated by both the M and P stimuli in the primary visual cortex (V1) were determined, and the contrast elicited by the stimulus, time-to-peak (TTP), and the full width at half maximum (FWHM) of the BOLD signal time course were measured. RESULTS: The functional stimuli activated cortical regions described previously in the literature, such as V1, V4, and V5. Within V1, the TTP of the signal time course of the 2 stimuli were statistically different, with the P stimulus generating TTPs that were on average 12% faster than the M stimulus (P = .0037). CONCLUSION: We have demonstrated the ability to functionally differentiate the M and P stimuli in a commonly activated anatomic region. Because the BOLD response is dependent on the ratio of oxyhemoglobin and deoxyhemoglobin in the blood, the difference in the BOLD time course between the 2 stimuli suggests that the oxygen demand of the 2 pathways may be different.     

Functional MRI impulse response for BOLD and CBV contrast in rat somatosensory cortex.

The contrast mechanism in functional MRI (fMRI) results from several vascular processes with different time scales, thus establishing a finite temporal resolution to fMRI experiments. In this work we measured the blood oxygen level-dependent (BOLD) and iron-oxide-derived cerebral blood volume (CBV) impulse response (IR) in a rat model of somatosensory brain activation at 11.7T. A binary m-sequence probe method was used to obtain high-sensitivity single-pixel estimates of the IR, from which two parameters-the full width at half maximum (FWHM) and the time to peak (TTP)-were determined as indices of the temporal resolution of the hemodynamic response (HDR). The results (N = 11) show that the CBV IR (N = 5, subset) is significantly narrower (FWHM = 1.37 +/- 0.11 s), and peaks earlier (TTP = 1.65 +/- 0.15 s) than the BOLD IR (N = 11, FWHM = 1.92 +/- 0.22 s and TTP = 2.18 +/- 0.14 s, respectively). These findings indicate that neurovascular control mechanisms have a temporal resolution better than 1.5 s FWHM, and point to a substantial contribution to BOLD of the dispersive transit of oxygenated hemoglobin across the rat vasculature, bringing important implications for the ultimately attainable temporal resolution of fMRI.     

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).     

Presurgical planning for tumor resectioning

Since the birth of functional magnetic resonance imaging (fMRI)-a noninvasive tool able to visualize brain function-now 15 years ago, several clinical applications have emerged. fMRI follows from the neurovascular coupling between neuronal electrical activity and cerebrovascular physiology that leads to three effects that can contribute to the fMRI signal: an increase in the blood flow velocity, in the blood volume and in the blood oxygenation level. The latter effect, gave the technique the name blood oxygenation level dependent (BOLD) fMRI. One of the major clinical uses is presurgical fMRI in patients with brain abnormalities. The goals of presurgical fMRI are threefold: 1) assessing the risk of neurological deficit that follows a surgical procedure, 2) selecting patients for invasive intraoperative mapping, and 3) guiding of the surgical procedure itself. These are reviewed here. Unfortunately, randomized trials or outcome studies that definitively show benefits to the final outcome of the patient when applying fMRI presurgically have not been performed. Therefore, fMRI has not yet reached the status of clinical acceptance. The final purpose of this article is to define a roadmap of future research and developments in order to tilt pre-surgical fMRI to the status of clinical validity and acceptance.     

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

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

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。     

T1-weighted functional imaging based on a contrast agent in presurgical mapping

Purpose

To assess the applicability of T1‐weighted images in the presence of a contrast agent for functional mapping free of susceptibility artifacts, in comparison to the blood oxygenation level‐dependent (BOLD) imaging.

Materials and Methods

Six patients and five control subjects were scanned using BOLD and T1‐weighted functional imaging, in the presence of a Gd‐DTPA contrast‐agent (TOFICA). In the control group, low‐ and high‐resolution BOLD images were performed. Functional stimuli included motor and language activations.

Results

Both BOLD and TOFICA methods resulted in activations in the expected anatomical regions. The TOFICA mapping gave less distributed and with higher percent signal changes in comparison with the BOLD images. Gd‐DTPA remained almost constant in the blood for at least 15 min post injection. In one patient with surgical clips, no signal was detected in the left cerebral hemisphere using BOLD imaging, but activation could be mapped using the TOFICA method.

Conclusion

T1‐weighted imaging in the presence of a contrast agent can be used for functional mapping. This method is insensitive to susceptibility artifacts, and is therefore advantageous in the evaluation of presurgical cases and in areas of the brain close to cavities in which the BOLD method cannot reliably be applied. J. Magn. Reson. Imaging 2008;28:1245–1250. © 2008 Wiley‐Liss, Inc.     

Functional MRI in human motor control studies and clinical applications.

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

Assessment of Cortical Visual Impairment in Infants with Periventricular Leukomalacia: a Pilot Event-Related fMRI Study

Objective

We wanted to investigate the usefulness of event-related (ER) functional MRI (fMRI) for the assessment of cortical visual impairment in infants with periventricular leukomalacia (PVL).

Materials and Methods

FMRI data were collected from 24 infants who suffered from PVL and from 12 age-matched normal controls. Slow ER fMRI was performed using a 3.0T MR scanner while visual stimuli were being presented. Data analysis was performed using Statistical Parametric Mapping software (SPM2), the SPM toolbox MarsBar was used to analyze the region of interest data, and the time to peak (TTP) of hemodynamic response functions (HRFs) was estimated for the surviving voxels. The number of activated voxels and the TTP values of HRFs were compared. Pearson correlation analysis was performed to compare visual impairment evaluated by using Teller Acuity Cards (TAC) with the number of activated voxels in the occipital lobes in all patients.

Results

In all 12 control infants, the blood oxygenation level-dependent (BOLD) signal was negative and the maximum response was located in the anterior and superior part of the calcarine fissure, and this might correspond to the anterior region of the primary visual cortex (PVC). In contrast, for the 24 cases of PVL, there were no activated pixels in the PVC in four subjects, small and weak activations in six subjects, deviated activations in seven subjects and both small and deviated activations in three subjects. The number of active voxels in the occipital lobe was significantly correlated with the TAC-evaluated visual impairment (p < 0.001). The mean TTP of the HRFs was significantly delayed in the cases of PVL as compared with that of the normal controls.

Conclusion

Determining the characteristics of both the BOLD response and the ER fMRI activation may play an important role in the cortical visual assessment of infants with PVL.     

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

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

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

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

Differences in the BOLD fMRI response to direct and indirect cortical stimulation in the rat.

Functional MRI (fMRI) exploits a relationship between neuronal activity, metabolism, and cerebral blood flow to functionally map the brain. We have developed a model of direct cortical stimulation in the rat that can be combined with fMRI and used to compare the hemodynamic responses to direct and indirect cortical stimulation. Unilateral electrical stimulation of the rat hindpaw motor cortex, via stereotaxically positioned carbon-fiber electrodes, yielded blood oxygenation level-dependent (BOLD) fMRI signal changes in both the stimulated and homotypic contralateral motor cortices. The maximal signal intensity change in both cortices was similar (stimulated = 3.7 +/- 1.7%; contralateral = 3.2 +/- 1.0%), although the response duration in the directly stimulated cortex was significantly longer (48.1 +/- 5.7 sec vs. 19.0 +/- 5.3 sec). Activation of the contralateral cortex is likely to occur via stimulation of corticocortical pathways, as distinct from direct electrical stimulation, and the response profile is similar to that observed in remote (e.g., forepaw) stimulation fMRI studies. Differences in the neuronal pool activated, or neurovascular mediators released, may account for the more prolonged BOLD response observed in the directly stimulated cortex. This work demonstrates the combination of direct cortical stimulation in the rat with fMRI and thus extends the scope of rodent fMRI into brain regions inaccessible to peripheral stimulation techniques.     

脑肿瘤患者术前手运动区的功能MRI

目的：探讨应用功能ＭＲＩ（ｆＭＲＩ）研究脑肿瘤患者手运动区（ＨＲＡ）的结构和功能变化特征。材料和方法：２２例位于或邻近实级运动皮质肿瘤患者采用单次激发ＧＲＥ－ＥＰＩ序列采集Ｔ＾＊２Ｗ图像,共３个周期即６个时相,每个周期包括手指对掌运动激发的１０幅活动图像和１０幅静止图像。经离线工作站重建获取减影后的差别图像,设定ＲＯＩ,描绘动态时间－信号强度曲线,测量信号强度（ＳＩ）上升百分率。结果：８例ＨＲＡ呈局限分布,１４例呈弥漫分布。肿瘤实体的边缘与ＨＲＡ活动中心的最短距离为０．３￣２．８ｃｍ。有５例患者在肿瘤内见到高信号区。肿瘤侧ＳＩ上升百分率为１．５％￣３％,正常侧ＳＩ上升百分率为２．５％￣１０％,结论：对位于或邻近初级运动皮质脑肿瘤患者,功能ＭＲＩ为术前手术计划的制定提供了一种非侵袭性而有效的方法。如果肿瘤实体的边     

Direct Impact of Motor Cortical Stimulation on the Blood Oxygen-level Dependent Response in Rats

Purpose:Neuropathic pain is a complex and distressing chronic illness in modern medicine. Since 1990s, motor cortex stimulation (MCS) has emerged as a potential treatment for chronic neuropathic pain; however, the precise mechanisms underlying analgesia induced by MCS are not completely understood. The purpose of the present study was to investigate the blood oxygen-level dependent (BOLD) response in the brain during MCS.Methods:We inserted a bipolar tungsten electrode into the primary motor cortex (M1) of adult male Wistar rats. Functional magnetic resonance imaging (fMRI) scans were implemented simultaneously with the electrical stimulation of M1 and the BOLD signals taken from the fMRI were used as an index to reflect the response against MCS.Results:Our results demonstrated that the bilateral M1, ipsilateral caudate-putamen, and ipsilateral primary somatosensory cortex to the stimulation spot were activated after the onset of MCS. The BOLD signal time courses were analysed in these regions and similar temporal characteristics were found.Conclusion:By conducting direct cortical stimulation of the rodent brain to investigate its instant effect using fMRI, we identified encephalic regions directly involved in the instant motor cortical stimulation effects in healthy rat models. This result may be essential in establishing a foundation for further research on the underlying neuropathways associated with the MCS effects.     

Simultaneous sampling of event-related BOLD responses in auditory cortex and brainstem.

Event-related functional magnetic resonance imaging (fMRI) was applied to investigate blood oxygen level dependent (BOLD) responses in the human auditory system. Auditory fMRI is hindered by the disturbing acoustical noise of echo planar imaging (EPI). A sparse acquisition technique was used in which the delayed hemodynamic response was imaged at discrete sampling time-points after a brief auditory stimulus. Long repetition times (10 heartbeats (HBs)) were used to avoid interactions between the activation due to the sound stimulation and scanner noise. In addition, only a single slice was acquired, to ensure that the scanner noise was minimal in duration and intensity. The image acquisition was triggered by the HB to prevent artifacts from cardiac-related brainstem motion. An image was acquired every 10th HB. Significant hemodynamic BOLD time-course responses were measured from the primary and secondary auditory cortices, as well as the inferior colliculi in the brainstem. No systematic differences were found between the cerebral cortex and the brainstem in terms of activation amplitude or in onset time of the hemodynamic response. Apparently, the slow dynamic nature of the BOLD response signal is similar across spatially separated auditory brain regions, suggesting a corresponding design of vessels and capillaries.     

Asynchrony in Peritumoral Resting-State Blood Oxygen Level–Dependent fMRI Predicts Meningioma Grade and Invasion

BACKGROUND AND PURPOSE:Meningioma grade is determined by histologic analysis, with detectable brain invasion resulting in a diagnosis of grade II or III tumor. However, tissue undersampling is a common problem, and invasive parts of the tumor can be missed, resulting in the incorrect assignment of a lower grade. Radiographic biomarkers may be able to improve the diagnosis of grade and identify targets for biopsy. Prior work in patients with gliomas has shown that the resting-state blood oxygen level–dependent fMRI signal within these tumors is not synchronous with normal brain. We hypothesized that blood oxygen level–dependent asynchrony, a functional marker of vascular dysregulation, could predict meningioma grade.MATERIALS AND METHODS:We identified 25 patients with grade I and 11 patients with grade II or III meningiomas. Blood oxygen level–dependent time-series were extracted from the tumor and the radiographically normal control hemisphere and were included as predictors in a multiple linear regression to generate a blood oxygen level–dependent asynchrony map, in which negative values signify synchronous and positive values signify asynchronous activity relative to healthy brain. Masks of blood oxygen level–dependent asynchrony were created for each patient, and the fraction of the mask that extended beyond the contrast-enhancing tumor was computed.RESULTS:The spatial extent of blood oxygen level–dependent asynchrony was greater in high (grades II and III) than in low (I) grade tumors (P < 0.001) and could discriminate grade with high accuracy (area under the curve = 0.88).CONCLUSIONS:Blood oxygen level–dependent asynchrony radiographically discriminates meningioma grade and may provide targets for biopsy collection to aid in histologic diagnosis.

The 2016 World Health Organization guidelines for meningiomas were notable for the inclusion of brain invasion as a criterion sufficient for assignment to “high-grade” status (ie, grade II or III) and may explain the greater incidence of high-grade meningiomas since 2016.¹ In addition to brain invasion, a meningioma is considered grade II or III if it demonstrates an elevated mitotic index and ≥3 aggressive histologic features or demonstrates a loss of meningothelial differentiation.² While roughly 80% of all meningiomas are grade I, with excellent prognosis following surgical resection, the remaining 20% are grade II or III and more likely to recur.³ Furthermore, grade I tumors have a 10-year survival of 83%, compared with 61% for grade II and III tumors,⁴ making the accurate determination of meningioma grade important for both prognostic and treatment purposes.Histologic assessment remains the criterion standard for grading meningiomas; however, an accurate noninvasive prediction of tumor grade could benefit both clinicians and patients by improving preoperative planning and patient counseling and potentially guiding difficult management decisions. Furthermore, routine surgical biopsy may undersample regions that have histologic features, such as invasion, that are diagnostic for grade II or III meningioma, resulting in possible misdiagnosis. Identifying radiographic features that correlate with tumor invasion would, therefore, be useful for guiding biopsy location. Prior studies using standard-of-care structural imaging have attempted to predict meningioma grade by evaluating a mix of objective radiographic features, such as mean voxel intensity, and subjective radiographic features, such as the presence of hyperostosis.⁵ Peritumoral edema detected by T2-FLAIR has also been associated with higher-grade meningiomas.^6,7 Additionally, histogram analysis of diffusion tensor imaging has also been shown to correlate with tumor grade and tumor subtype in meningiomas.⁸ However, it would be beneficial to develop a single, simple, visual criterion that could be easily applied by radiologists and surgeons to predict meningioma grade with high accuracy.Prior work using resting-state blood oxygen level—dependent (BOLD) fMRI in diffuse glioma has revealed that the BOLD signal in and around the tumor is temporally asynchronous with radiographically normal parts of the brain.⁹ BOLD asynchrony maps provide a quantitation of this phenomenon and are generated by comparing each voxel with the mean global signal intensity of both the contralesional hemisphere and the contrast-enhancing tumor. Stereotactically localized biopsies collected from peritumoral regions have demonstrated that the degree of BOLD asynchrony correlates with local tumor burden.¹⁰ Furthermore, the spatial extent of the asynchrony can discriminate IDH wild-type and IDH-mutated gliomas with high fidelity.¹¹Meningiomas have also been shown to cause disruptions in vascular function observable with resting-state BOLD fMRI.¹¹ We, therefore, hypothesized that brain invasion, a common feature of high-grade meningiomas, would be detectable using BOLD asynchrony maps derived from resting-state BOLD fMRI and that the spatial extent of BOLD asynchrony could be used to discriminate meningioma grade. Furthermore, we evaluated whether combining the spatial features of BOLD asynchrony and T2-FLAIR hyperintensity could improve tumor grading accuracy over either measure alone.     

Functional arterial spin labeling: Optimal sequence duration for motor activation mapping in clinical practice

Purpose:

To determine the minimal optimal functional arterial spin labeling (fASL) sequence duration allowing steady and reproducible motor activation mapping.

Materials and Methods:

Three magnetic resonance imaging (MRI) sessions including fASL and blood oxygenation level‐dependent (BOLD) functional MRI (fMRI) sequences were performed on 12 healthy subjects at 3T with a 32‐channel coil. The raw 7‐minute fASL sequence was truncated to obtain six fASL sequences with durations ranging from 1–6 minutes. All the resulting fASL activations were compared between themselves and with both the 7‐minute fASL and BOLD activations. Quantitative parameters assessed activation location (activated volume, barycenter, and distance between barycenters), activation quantification (activation‐related cerebral blood flow), and intraindividual reproducibility across fMRI sessions. The statistical analysis was based on analysis of variance (ANOVA) and Tukey's multiple comparisons.

Results:

Four‐minute fASL achieved steady location and quantification of activation with the activated volume corresponding to 81% of the 7‐minute fASL volume and a barycenter located 1.2 mm from the 7‐minute fASL barycenter and 3.0 mm from the BOLD fMRI barycenter. Four‐minute fASL reproducibility was high and statistically equivalent to 7‐minute values.

Conclusion:

A 4‐minute fASL sequence is thus a reliable tool for motor activation mapping and suitable for use in clinical practice. J. Magn. Reson. Imaging 2012; 36:1435–1444. © 2012 Wiley Periodicals, Inc.     

Reproducibility of single-subject fMRI language mapping with AMPLE normalization

Purpose:

To evaluate the reproducibility of presurgical functional MRI (fMRI) language mapping based on test–retest scans, comparing traditional activation t‐maps to relative activation maps normalized by activation mapping as percentage of local excitation (AMPLE).

Materials and Methods:

Language fMRI scans were performed by 12 healthy volunteer subjects undergoing a standard clinical presurgical mapping protocol in multiple independent scan sessions. Objective relative AMPLE activation maps were generated automatically by normalizing statistical t‐value maps to the local peak activation amplitude within each functional brain region. The spatial distribution of activation was quantified and compared across mapping algorithms, subjects, scanners, and pulse sequences.

Results:

The spatial distribution of traditional blood oxygen level‐dependent (BOLD) t‐value statistical activation maps was highly variable in test–retest scans of single subjects, whereas AMPLE normalized maps were highly reproducible in terms of the location, hemispheric laterality, and spatial extent of relative activation. AMPLE map reproducibility was good regardless of scanner, field strength, or pulse sequence used, but reproducibility was best for scans acquired on the same scanner using the same pulse sequence.

Conclusion:

Reproducibility of the spatial pattern of BOLD activation makes relative amplitude fMRI mapping a useful normalization tool for clinical imaging of language function, where reproducibility and quantitative measurements are critical concerns. J. Magn. Reson. Imaging 2012;36:569–580. © 2012 Wiley Periodicals, Inc.