Usage of fMRI for pre-surgical planning in brain tumor and vascular lesion patients: task and statistical threshold effects on language lateralization.

BACKGROUND AND PURPOSE: Functional magnetic resonance imaging (fMRI) is a non-invasive pre-surgical tool used to assess localization and lateralization of language function in brain tumor and vascular lesion patients in order to guide neurosurgeons as they devise a surgical approach to treat these lesions. We investigated the effect of varying the statistical thresholds as well as the type of language tasks on functional activation patterns and language lateralization. We hypothesized that language lateralization indices (LIs) would be threshold- and task-dependent. MATERIALS AND METHODS: Imaging data were collected from brain tumor patients (n = 67, average age 48 years) and vascular lesion patients (n = 25, average age 43 years) who received pre-operative fMRI scanning. Both patient groups performed expressive (antonym and/or letter-word generation) and receptive (tumor patients performed text-reading; vascular lesion patients performed text-listening) language tasks. A control group (n = 25, average age 45 years) performed the letter-word generation task. RESULTS: Brain tumor patients showed left-lateralization during the antonym-word generation and text-reading tasks at high threshold values and bilateral activation during the letter-word generation task, irrespective of the threshold values. Vascular lesion patients showed left-lateralization during the antonym and letter-word generation, and text-listening tasks at high threshold values. CONCLUSION: Our results suggest that the type of task and the applied statistical threshold influence LI and that the threshold effects on LI may be task-specific. Thus identifying critical functional regions and computing LIs should be conducted on an individual subject basis, using a continuum of threshold values with different tasks to provide the most accurate information for surgical planning to minimize post-operative language deficits.

Association of functional magnetic resonance imaging indices with postoperative language outcomes in patients with primary brain tumors.

OBJECT: Functional MRI (fMRI) has the potential to be a useful presurgical planning tool to treat patients with primary brain tumor. In this study the authors retrospectively explored relationships between language-related postoperative outcomes in such patients and multiple factors, including measures estimated from task fMRI maps (proximity of lesion to functional activation area, or lesion-to-activation distance [LAD], and activation-based language lateralization, or lateralization index [LI]) used in the clinical setting for presurgical planning, as well as other factors such as patient age, patient sex, tumor grade, and tumor volume. METHODS: Patient information was drawn from a database of patients with brain tumors who had undergone preoperative fMRI-based language mapping of the Broca and Wernicke areas. Patients had performed a battery of tasks, including word-generation tasks and a text-versus-symbols reading task, as part of a clinical fMRI protocol. Individually thresholded task fMRI activation maps had been provided for use in the clinical setting. These clinical imaging maps were used to retrospectively estimate LAD and LI for the Broca and Wernicke areas. RESULTS: There was a relationship between postoperative language deficits and the proximity between tumor and Broca area activation (the LAD estimate), where shorter LADs were related to the presence of postoperative aphasia. Stratification by tumor location further showed that for posterior tumors within the temporal and parietal lobes, more bilaterally oriented Broca area activation (LI estimate close to 0) and a shorter Wernicke area LAD were associated with increased postoperative aphasia. Furthermore, decreasing LAD was related to decreasing LI for both Broca and Wernicke areas. Preoperative deficits were related to increasing patient age and a shorter Wernicke area LAD. CONCLUSIONS: Overall, LAD and LI, as determined using fMRI in the context of these paradigms, may be useful indicators of postsurgical outcomes. Whereas tumor location may influence postoperative deficits, the results indicated that tumor proximity to an activation area might also interact with how the language network is affected as a whole by the lesion. Although the derivation of LI must be further validated in individual patients by using spatially specific statistical methods, the current results indicated that fMRI is a useful tool for predicting postoperative outcomes in patients with a single brain tumor.

Characterizing the relationship between functional MRI-derived measures and clinical outcomes in patients with vascular lesions.

OBJECT: Functional MRI (fMRI) has proven to be an effective component of pretreatment planning in patients harboring a variety of different brain lesions. The authors have recently reported significant relationships concerning distances between brain tumor borders and areas of functional activation (lesion-to-activation distance; LAD) with regard to patient morbidity and mortality. This study further examines the relationship between LAD, focusing on a host of vascular lesions and pre- and posttreatment morbidity. METHODS: This study included a sample population of patients with vascular lesions (n = 106), primarily arteriovenous malformations (AVMs) and cavernomas. These patients underwent pretreatment fMRI-based motor mapping (n = 72) or language mapping (n = 84). The impact of LAD and other variables derived from the patient medical record were analyzed with respect to functional deficits in terms of morbidity (weakness and/or aphasia). RESULTS: In patients with no pretreatment deficits, there was trend for a significant relationship between the Wernicke area LAD and posttreatment language deficits. In patients with or without pretreatment deficits, a trend toward significance was observed between sensorimotor LAD and posttreatment motor deficits. Additionally, lesion type (AVMs or cavernomas) affected posttreatment deficits, with more patients with cavernomas showing posttreatment language deficits than patients with AVMs. However, this difference was not observed for posttreatment motor deficits. CONCLUSIONS: These findings suggest that the proximity of a vascular lesion to sensorimotor and language areas is a relevant parameter in estimating patient prognosis in the perioperative period. Additionally, vascular lesion type and existence of pretreatment deficits play a significant role in outcomes.

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

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

Independent component analysis applied to self-paced functional MR imaging paradigms.

Self-paced functional MR imaging (fMRI) paradigms, in which the task timing is determined by the subject's performance, can offer several advantages over commonly applied paradigms with predetermined stimulus timing. Independent component analysis (ICA) does not require specification of a timed response function, and could be an advantageous method of deriving results from fMRI data sets with varying response timings and durations. In this study normal volunteers (N = 10) each performed two self-paced fMRI motor and arithmetic paradigms. Individual data sets were analyzed with the Infomax spatial ICA algorithm. Conventional regression analysis was performed for comparison purposes. Spatial ICA effectively produced task-related components from each of the self-paced data sets, even in a few cases where regression analysis yielded non-specific functional maps. For the motor paradigm, these components consistently mapped to primary motor areas. ICA of the arithmetic paradigm yielded multiple task-related components that variably mapped to regions of parietal and frontal lobes. Regression analysis generally yielded similar spatial maps. The multiple task-related ICA components that were sometimes produced from each self-paced data set can be challenging to identify and evaluate for significance. These preliminary results indicate that ICA is useful as an exploratory and complementary method to conventional regression analysis for fMRI of self-paced paradigms.

Functional MRI neuroanatomic correlates of the Hooper Visual Organization Test.

The Hooper Visual Organization Test (VOT), a commonly applied neuropsychological test of visual spatial ability, is used for assessing patients with suspected right hemisphere, or parietal lobe involvement. A controversy has developed over whether the inferences of this test metric can be assumed to involve global, lateralized, or regional functionality. In this study, the characteristic visual organization and object naming aspects of the VOT task presentation were adapted to a functional MR imaging (fMRI) paradigm to probe the neuroanatomic correlates of this neuropsychological test. Whole brain fMRI mapping results are reported on a cohort of normal subjects. Bilateral fMRI responses were found predominantly in the posterior brain, in regions of superior parietal lobules, ventral temporal-occipital cortex, and posterior visual association areas, and to a lesser extent, the frontal eye fields bilaterally, and left dorsolateral prefrontal cortex. The results indicate a general brain region or network in which VOT impairment, due to its visuospatial and object identification demands, is possible to be detected. Discussion is made of interpretive limitations when adapting neuropsychological tests to fMRI analysis.

Supplementary motor area activation in patients with frontal lobe tumors and arteriovenous malformations.

BACKGROUND AND PURPOSE: Some patients who undergo surgical resection of portions of the supplementary motor area (SMA) have severe postoperative motor and language deficits, whereas others have no deficits. We tested the hypothesis that in some patients with lesions affecting the SMA, the contralateral SMA exhibits some of the activation normally associated with the ipsilateral SMA. METHODS: Functional MR imaging studies in seven healthy volunteers and 19 patients with frontal lobe tumors or arteriovenous malformations were reviewed retrospectively. The hemisphere in which the SMA activation predominated was tabulated for right and left motor tasks. The relative hemispheric dominance in the SMA for the right and left motor tasks was compared in the healthy and patient groups and with the location of the lesion in the patient group. RESULTS: None of the control subjects performing a right hand motor task activated predominantly the right SMA. Fifty percent of the patients with lesions overlapping the left SMA performing the right motor task activated predominantly the right SMA. Fifty-seven percent of control subjects performing the left hand motor task activated the left SMA predominantly. One hundred percent of patients with lesions overlapping the right frontal SMA performing the left motor task activated the left SMA predominantly. Differences between patients and controls were statistically significant. CONCLUSION: A lesion that contacts or overlaps the SMA is associated with an increased functional MR imaging response within the contralateral SMA.

Role of the corpus callosum in functional connectivity.

BACKGROUND AND PURPOSE: Regional cerebral blood flow fluctuates synchronously in corresponding brain regions between the hemispheres. This synchrony implies neuronal connections between brain regions. The synchrony of blood flow changes is defined operationally as functional connectivity. Our purpose was to measure functional connectivity in patients with corpus callosal agenesis, in whom the interhemispheric connectivity is hypothetically diminished. METHODS: In three patients with agenesis of the corpus callosum, functional MR imaging was performed while patients performed text-listening and finger-tapping tasks. Functional images were also acquired while the patients performed no specific task (resting state). Regions of activation temporally correlated with the performance of the tasks were identified by cross-correlating the task data with a reference function. Voxel clusters (seed voxels) that corresponded to regions of activation in the task-activation data set were selected in the resting data set. All the voxels in the resting 3D data set that had a correlation coefficient exceeding 0.4 were identified. The number of these voxels in the ipsilateral and contralateral hemispheres was tabulated. RESULTS: In all patients, technically adequate functional MR and functional connectivity MR maps were obtained. For both tasks, activation was found in both hemispheres. For all of the seed voxels, significantly more functionally connected voxels were found in the ipsilateral hemisphere than in the contralateral hemisphere. For most seed voxels, no functionally connected voxels were found in the contralateral hemisphere. CONCLUSION: Interhemispheric functional connectivity in the motor and auditory cortices is diminished in patients with agenesis of the corpus callosum compared with that of healthy subjects.

Power spectrum ranked independent component analysis of a periodic fMRI complex motor paradigm.

Independent component analysis (ICA) has been demonstrated to be an effective data-driven method for analyzing fMRI data. However, a method for objective differentiation of task-related components from those that are artifactually non-relevant is needed. We propose a method of constant-cycle (periodic) fMRI task paradigm combined with ranking of spatial ICA components by the magnitude contribution of their temporal aspects to the fundamental task frequency. Power spectrum ranking shares some similarity to correlation with an a priori hemodynamic response, but without a need to presume an exact timing or duration of the fMRI response. When applied to a complex motor task paradigm with auditory cues, multiple task-related activations are successfully identified and separated from artifactual components. These activations include sensorimotor, auditory, and superior parietal areas. Comparisons of task-related component time courses indicate the temporal relationship of fMRI responses in functionally involved regions. Results indicate the sensitivity of ICA to short-duration hemodynamics, and the efficacy of a power spectrum ranking method for identification of task-related components.

Functional MR imaging: paradigms for clinical preoperative mapping.

Clinical applications of functional MR imaging include mapping of brain functions in relationship to intracranial tumors, seizure foci, or vascular malformations to determine the risk for performing surgical excision, the need for intraoperative mapping during excision, and selecting the optimal surgical approach to a lesion. A variety of paradigms are used to produce a blood-oxygen-level-dependent response in various brain regions, which can be identified with functional MR imaging. The paradigms used include active motor, language, or cognitive tasks, and passive tactile, auditory, or visual stimuli. Activation usually indicates the location of eloquent cortex. Lack of function in a region cannot be assumed when functional MR imaging shows absence of activation within the region.

Preoperative mapping of the supplementary motor area in patients harboring tumors in the medial frontal lobe.

OBJECT: Injury to the supplementary motor area (SMA) is thought to be responsible for transient motor and speech deficits following resection of tumors involving the medial frontal lobe. Because direct intraoperative localization of SMA is difficult, the authors hypothesized that functional magnetic resonance (fMR) imaging might be useful in predicting the risk of postoperative deficits in patients who undergo resection of tumors in this region. METHODS: Twelve patients who had undergone fMR imaging mapping while performing speech and motor tasks prior to excision of their tumor, that is, based on anatomical landmarks involving the SMA, were included in this study. The distance between the edge of the tumor and the center of SMA activation was measured and was correlated with the risk of incurring postoperative neurological deficits. In every patient, SMA activation was noted in the superior frontal gyrus on preoperative fMR imaging. Two speech and two motor deficits typical of SMA injury were observed in three of the 12 patients. The two speech deficits occurred in patients with tumors involving the dominant hemisphere, whereas one of the motor deficits occurred in a patient with a tumor in the nondominant hemisphere. The risk of developing a postoperative speech or motor deficit was 100% when the distance between the SMA and the tumor was 5 mm or less. When the distance between SMA activation and the lesion was greater than 5 mm, the risk of developing a motor or a speech deficit was 0% (p = 0.0007). CONCLUSIONS: Early data from this study indicated that fMR imaging might be useful in localizing the SMA and in determining the risk of postoperative deficits in patients who undergo resection of tumors located in the medial frontal lobe.

Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm.

OBJECT: Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms. METHODS: Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case. CONCLUSIONS: Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

Characterizing instantaneous phase relationships in whole-brain fMRI activation data.

Typically, fMRI data is processed in the time domain with linear methods such as regression and correlation analysis. We propose that the theory of phase synchronization may be used to more completely understand the dynamics of interacting systems, and can be applied to fMRI data as a novel method of detecting activation. Generalized synchronization is a phenomenon that occurs when there is a nonlinear functional relationship present between two or more coupled, oscillatory systems, whereas phase synchronization is defined as the locking of the phases while the amplitudes may vary. In this study, we developed an application of phase synchronization analysis that is appropriate for fMRI data, in which the phase locking condition is investigated between a voxel time series and the reference function of the task performed. A synchronization index is calculated to quantify the level of phase locking, and a nonparametric permutation test is used to determine the statistical significance of the results. We performed the phase synchronization analysis on the data from five volunteers for an event-related finger-tapping task. Functional maps were created that provide information on the interrelations between the instantaneous phases of the reference function and the voxel time series in a whole-brain fMRI activation data set. We conclude that this method of analysis is useful for revealing additional information on the complex nature of the fMRI time series.

Comparison of independent component analysis and conventional hypothesis-driven analysis for clinical functional MR image processing.

BACKGROUND AND PURPOSE: With independent component analysis (ICA), regions of activation can be identified on functional MR (fMR) images without a priori knowledge of expected hemodynamic responses. The purpose of this study was to compare the results of fMR imaging data processed with spatial ICA with results obtained with conventional hypothesis-driven analysis. METHODS: Eleven patients with focal cerebral lesions and one with agenesis of the corpus callosum were enrolled. Each patient performed text-listening, finger-tapping, and word-generation tasks. Conventional activation maps were generated by fitting time courses of each voxel to a boxcar reference function. Maps were created from the same image data with ICA techniques. To compare the maps, a concurrence ratio (CR) (number of voxels activated on both maps to number of voxels activated on either map) was calculated. RESULTS: In the ICA analysis, maps with appropriate spatial and temporal features for auditory, sensorimotor, or language cortices were identified in most patients. Images processed with ICA resembled images processed with conventional means. In patients who moved or performed the task incorrectly, ICA produced a map that resembled the expected activation pattern but differed from the conventional image. CRs averaged 70% for all comparisons in the 12 patients. CONCLUSION: fMR imaging maps for auditory, sensorimotor, and language tasks produced with ICA and conventional techniques were similar in most cases. Differences were consistent with the particular characteristics of the method. In data sets corrupted by motion or incorrect task performance, ICA may produce more accurate maps.