Impact of brain tumor location on morbidity and mortality: a retrospective functional MR imaging study.

BACKGROUND AND PURPOSE: fMRI is increasingly used in neurosurgery to preoperatively identify areas of eloquent cortex. Our study evaluated the efficacy of clinical fMRI by analyzing the relationship between the distance from the tumor border to the area of functional activation (LAD) and patient pre- and postoperative morbidity and mortality. MATERIALS AND METHODS: The study included patients with diagnosis of primary or metastatic brain tumor who underwent preoperative fMRI-based motor mapping (n=74) and/or language mapping (n=77). The impact of LAD and other variables collected from patient records was analyzed with respect to functional deficits in terms of morbidity (paresis and aphasia) and mortality. RESULTS: Significant relationships were found between motor and language LAD and the existence of either pre- or postoperative motor (P < .001) and language deficits (P=.009). Increasing age was associated with motor and language deficits (P=.02 and P=.04 respectively). Right-handedness was related to language deficits (P=.05). Survival analysis revealed that pre- and postoperative deficits, grade, tumor location, and LAD predicted mortality. Motor deficits increased linearly as the distance from the tumor to the primary sensorimotor cortex decreased. Language deficits increased exponentially as the distance from the tumor to the language areas decreased below 1 cm. Postoperative mortality analysis showed an interaction effect between motor or language LAD and mortality predictors (grade and tumor location, respectively). CONCLUSIONS: These findings indicate that tumors may affect language and motor function differently depending on tumor LAD. Overall, the data support the use of fMRI as a tool to evaluate patient prognosis and are directly applicable to neurosurgical planning.

Assessment of multiple task activation and reproducibility in patients with benign and low-grade neoplasm.

Twenty-four patients with proven benign and low-grade brain neoplasms each performed two iterations of four fMRI paradigms: language (word generation), primary and association auditory (text listening), upper limb fine motor control (alternating-limb bilateral finger tapping), and primary visual perception (reversing checkerboard). Activation clusters with varying thresholds were generated for each scan and used to calculate reproducibility parameters: Difference in the Center of Mass (COM) location, R(size), and R(overlap). The average difference in the COM, R(size), and R(overlap) values ranged from 1.70 +/- 0.53 mm -10.60 +/- 3.21 mm, 0.6 +/- 0.04-0.90 +/- 0.05 and 0.23 +/- 0.12 -1 +/- 0.16 respectively for all tasks. These values are within the range of, or higher than, previously published reports on fMRI test-retest precision. FMRI is indicated to be a noninvasive tool with acceptable reproducibility measures for assessing the localizations of multiple language and sensorimotor functions in patients scheduled for radiotherapy treatment.

Activation of brain regions vulnerable to Alzheimer's disease: the effect of mild cognitive impairment.

This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, and in the right hippocampus during encoding of novel items, despite comparable task performance to the controls. Reduced fMRI signal change in the MTL supports prior studies implicating the hippocampus for encoding new information. Reduced signal change in the PC converges with recent research on its role in recognition in normal adults as well as metabolic decline in people with genetic or cognitive risk for AD. Our results suggest that a change in function in the PC may account, in part, for memory recollection failure in AD.

Test-retest precision of functional magnetic resonance imaging processed with independent component analysis.

This study was designed to compare the test-retest precision of functional magnetic resonance imaging (fMRI) data processed with independent component analysis (ICA) and the same data analyzed with a conventional model-dependent method (Student's- t mapping). Volunteers underwent two or three iterations of visual and auditory stimuli, while data were collected for fMRI scans. The scan data were separately processed with ICA and with Student's- t mapping (STM). As a measure of test-retest precision, concurrence ratios were calculated for each subject and each task as the number of voxels that were activated by two iterations of a task divided by the average number of voxels activated in each repetition. In 28 test-retest comparisons, the average concurrence ratio was 0.69+/-0.10 for ICA and 0.65+/-0.13 for the conventional method, a statistically insignificant difference. In fMR image data of block stimulus paradigms, ICA had similar test-retest precision to a conventional model-dependent method.

Functional MR imaging assessment of a non-responsive brain injured patient.

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Reliability of functional MR imaging with word-generation tasks for mapping Broca's area.

BACKGROUND AND PURPOSE: Functional MR (fMR) imaging of word generation has been used to map Broca's area in some patients selected for craniotomy. The purpose of this study was to measure the reliability, precision, and accuracy of word-generation tasks to identify Broca's area. METHODS: The Brodmann areas activated during performance of word-generation tasks were tabulated in 34 consecutive patients referred for fMR imaging mapping of language areas. In patients performing two iterations of the letter word-generation tasks, test-retest reliability was quantified by using the concurrence ratio (CR), or the number of voxels activated by each iteration in proportion to the average number of voxels activated from both iterations of the task. Among patients who also underwent category or antonym word generation or both, the similarity of the activation from each task was assessed with the CR. In patients who underwent electrocortical stimulation (ECS) mapping of speech function during craniotomy while awake, the sites with speech function were compared with the locations of activation found during fMR imaging of word generation. RESULTS: In 31 of 34 patients, activation was identified in the inferior frontal gyri or middle frontal gyri or both in Brodmann areas 9, 44, 45, or 46, unilaterally or bilaterally, with one or more of the tasks. Activation was noted in the same gyri when the patient performed a second iteration of the letter word-generation task or second task. The CR for pixel precision in a single section averaged 49%. In patients who underwent craniotomy while awake, speech areas located with ECS coincided with areas of the brain activated during a word-generation task. CONCLUSION: fMR imaging with word-generation tasks produces technically satisfactory maps of Broca's area, which localize the area accurately and reliably.

Frequencies contributing to functional connectivity in the cerebral cortex in "resting-state" data.

BACKGROUND AND PURPOSE: In subjects performing no specific cognitive task ("resting state"), time courses of voxels within functionally connected regions of the brain have high cross-correlation coefficients ("functional connectivity"). The purpose of this study was to measure the contributions of low frequencies and physiological noise to cross-correlation maps. METHODS: In four healthy volunteers, task-activation functional MR imaging and resting-state data were acquired. We obtained four contiguous slice locations in the "resting state" with a high sampling rate. Regions of interest consisting of four contiguous voxels were selected. The correlation coefficient for the averaged time course and every other voxel in the four slices was calculated and separated into its component frequency contributions. We calculated the relative amounts of the spectrum that were in the low-frequency (0 to 0.1 Hz), the respiratory-frequency (0.1 to 0.5 Hz), and cardiac-frequency range (0.6 to 1.2 Hz). RESULTS: For each volunteer, resting-state maps that resembled task-activation maps were obtained. For the auditory and visual cortices, the correlation coefficient depended almost exclusively on low frequencies (<0.1 Hz). For all cortical regions studied, low-frequency fluctuations contributed more than 90% of the correlation coefficient. Physiological (respiratory and cardiac) noise sources contributed less than 10% to any functional connectivity MR imaging map. In blood vessels and cerebrospinal fluid, physiological noise contributed more to the correlation coefficient. CONCLUSION: Functional connectivity in the auditory, visual, and sensorimotor cortices is characterized predominantly by frequencies slower than those in the cardiac and respiratory cycles. In functionally connected regions, these low frequencies are characterized by a high degree of temporal coherence.

Combining independent component analysis and correlation analysis to probe interregional connectivity in fMRI task activation datasets.

A new approach in studying interregional functional connectivity using functional magnetic resonance imaging (fMRI) is presented. Functional connectivity may be detected by means of cross correlating time course data from functionally related brain regions. These data exhibit high temporal coherence of low frequency fluctuations due to synchronized blood flow changes. In the past, this fMRI technique for studying functional connectivity has been applied to subjects that performed no prescribed task ("resting" state). This paper presents the results of applying the same method to task-related activation datasets. Functional connectivity analysis is first performed in areas not involved with the task. Then a method is devised to remove the effects of activation from the data using independent component analysis (ICA) and functional connectivity analysis is repeated. Functional connectivity, which is demonstrated in the "resting brain," is not affected by tasks which activate unrelated brain regions. In addition, ICA effectively removes activation from the data and may allow us to study functional connectivity even in the activated regions.

Whole-brain functional MR imaging activation from a finger-tapping task examined with independent component analysis.

BACKGROUND AND PURPOSE: Independent component analysis (ICA), unlike other methods for processing functional MR (fMR) imaging data, requires no a priori assumptions about the hemodynamic response to the task. The purpose of this study was to analyze the temporal characteristics and the spatial mapping of the independent components identified by ICA when the subject performs a finger-tapping task. METHODS: Ten healthy subjects performed variations of the finger-tapping task conventionally used to map the sensorimotor cortex. The scan data were processed with ICA, and the temporal configuration of the components and their spatial localizations were studied. The locations with activation were tabulated and compared with locations known to be involved in the organization of motor functions in the brain. RESULTS: Components were identified that correlated to varying degrees with the conventional boxcar reference function. One or more of these components mapped to the sensorimotor cortex, supplementary motor area (SMA), putamen, and thalamus. By means of ICA components, sensorimotor cortex, supplementary motor area, and superior cerebellar activation were identified bilaterally in 100% of the subjects; thalamus activation was contralateral to the active hand in 80%; and putamen activation was contralateral to the active hand in 60%. CONCLUSION: ICA processing of multislice fMR imaging data acquired during finger tapping identifies the sensorimotor cortex, SMA, cerebellar, putamen, and thalamic activation. ICA appears to be a method that provides information on both the temporal and spatial characteristics of activation. Multiple task-related components can be identified by ICA, and specific activation maps can be derived from each separate component.

Mapping functionally related regions of brain with functional connectivity MR imaging.

BACKGROUND AND PURPOSE: In subjects who are performing no prescribed cognitive task, functional connectivity mapped with MR imaging (fcMRI) shows regions with synchronous fluctuations of cerebral blood flow. When specific tasks are performed, functional MR imaging (fMRI) can map locations in which regional cerebral blood flow increases synchronously with the performance of the task. We tested the hypothesis that fcMRI maps, based on the synchrony of low-frequency blood flow fluctuations, identify brain regions that show activation on fMRI maps of sensorimotor, visual, language, and auditory tasks. METHODS: In four volunteers, task-activation fMRI and functional connectivity (resting-state) fcMRI data were acquired. A small region of interest (in an area that showed maximal task activation) was chosen, and the correlation coefficient of the corresponding resting-state signal with the signal of all other voxels in the resting data set was calculated. The correlation coefficient was decomposed into frequency components and its distribution determined for each fcMRI map. The fcMRI maps were compared with the fMRI maps. RESULTS: For each task, fcMRI maps based on one to four seed voxel(s) produced clusters of voxels in regions of eloquent cortex. For each fMRI map a closely corresponding fcMRI map was obtained. The frequencies that predominated in the cross-correlation coefficients for the functionally related regions were below 0.1 Hz. CONCLUSION: Functionally related brain regions can be identified by means of their synchronous slow fluctuations in signal intensity. Such blood flow synchrony can be detected in sensorimotor areas, expressive and receptive language regions, and the visual cortex by fcMRI. Regions identified by the slow synchronous fluctuations are similar to those activated by motor, language, or visual tasks.

Functional MR imaging activation after finger tapping has a shorter duration in the basal ganglia than in the sensorimotor cortex.

BACKGROUND AND PURPOSE: Repetitive motor tasks that produce sustained neuronal activity in the sensorimotor cortex produce transient neuronal activity in subcortical regions. We tested the hypothesis that a reference function modeling a transient hemodynamic response would more reliably detect activation in the basal ganglia than would a conventional reference function, which models a sustained hemodynamic response. METHODS: Functional MR imaging data were acquired in eight subjects performing an alternating-hand finger-tapping task. Postprocessing was performed by cross-correlation to two types of reference functions: one that models a sustained hemodynamic response to finger tapping and one that models an initial transient hemodynamic response. Activation in the sensorimotor cortex, supplementary motor area, cerebellum, thalamus, and corpus striatum was tabulated for each reference function. RESULTS: With the conventional boxcar reference function, activation was detected in the sensorimotor cortex, supplementary motor area, and cerebellum, but intermittently in the corpus striatum in all subjects. With the reference function for a transient response, activation in the corpus striatum was not detected in all subjects. CONCLUSION: In the corpus striatum, activation is detected more frequently with a reference function that models a transient response. Activated cortical and subcortical regions can be mapped with an alternating-hand finger-tapping paradigm and a combination of reference functions.

Functional differentiation of medial temporal and frontal regions involved in processing novel and familiar words: an fMRI study.

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, approximately 1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior-posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: patterns of functional MRI activation.

Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match-mismatch) about word pairs (category-exemplar, category-function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD.

The clinical applications of functional MR imaging.

Functional MR imaging, similar to positron-emission tomography, shows the regions in which cerebral blood flow changes as neurons are active in the performance of cognitive tasks. Blood flow increases (activation) exceed that needed to supply oxygen for the increased metabolic needs for the increased neuronal activity. Therefore, in regions with activation, the deoxyhemoglobin concentration in the capillary blood decreases below levels found in the brain where neurons are not active.

Single-shot, motion insensitive cardiac imaging on a standard clinical system.

The overall goal of this study was the development and application of a less motion sensitive, single-shot MRI technique for use on a standard clinical system in a dynamic imaging setting, such as cardiac scanning. Time encoding, a single-shot line scanning technique, has been used to produce single-shot, small field-of-view cardiac images without the use of presaturation pulses. The major advantages of this method are: (1) as a line scanning technique, time encoding is minimally sensitive to motion when compared with 2D Fourier methods, and (2) aliasing will not occur if the object being imaged extends beyond the field of view.