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PubMed2003

Characterization of CNS disorders and evaluation of therapy using structural and functional MRI.

Modern drug development requires technologies that allow rapid translation from the preclinical to the clinical stage. It is obvious that non-invasive imaging modalities such as magnetic resonance imaging (MRI) will play a central role in this regard. This article reviews the use of structural and functional MRI readouts for characterization of central nervous system (CNS) disorders and evaluation of the efficacy of potential CNS drugs. Examples comprise dementia of Alzheimer's type, cerebral ischemia, and neuroinflammation covering both clinical and preclinical aspects. In these examples MRI has been used to obtain relevant structural information on brain atrophy, on the location and extent of ischemic brain areas, and on the number and distribution of demyelinated plaques. These structural data are complemented by readouts assessing the functional consequences associated with the pathomorphological changes. In the last decade, MRI has evolved into a standard tool for the development of CNS drugs. With regard to target-specific/molecular imaging applications MRI is limited by its inherently low sensitivity; complementary imaging modalities utilizing optical and radionuclear reporter systems will thus be required.

Animals↗
PubMed1996

Multislice interleaved excitation cycles (MUSIC): an efficient gradient-echo technique for functional MRI.

A method providing improved slice efficiency for gradient-echo imaging requiring long echo times, such as in functional neuromagnetic resonance imaging, is presented. To enhance the volume coverage while maintaining the short imaging time of a conventional single-slice gradient-echo technique, an interleaved multislice excitation is performed during the echo time. This technique allows detection of susceptibility changes, e.g., the acquisition of stimulated human cortical activation maps, on clinical MR instruments at multiple planes within total imaging times of a few seconds. The efficiency of the technique is demonstrated in the detection of temporary changes in T2* in functional MRI experiments of the human visual cortex at magnetic field strengths of 2 Tesla and 3 Tesla. Fourteen 128 x 128 slices can be acquired in 13 s to cover a large volume-of-interest in the same time that would be required for single-slice acquisition using the conventional technique.

Adult↗
PubMed1995

Activation of association auditory cortex demonstrated with functional MRI.

Activations in the temporal lobes previously observed using positron emission tomography and auditory stimuli were partially reproduced with functional MRI and echo-planar imaging at 1.5 T in six volunteers performing tone and phoneme monitoring tasks. Verbal processing compared to a tone recognition task significantly activated a cortical area located in the left anterior temporal region (P < 0.02).

Adult↗
PubMed2005

Gender-specific cerebral activation during cognitive tasks using functional MRI: comparison of women in mid-luteal phase and men.

Previous studies of gender-specific differences in functional imaging during spatial and language tasks have been inconclusive. Furthermore, among women, such differences may occur during mid-luteal phase compared to the rest of the menstrual cycle. In order to examine further gender differences, functional MRI was performed in 12 male volunteers and 12 female volunteers (in the mid-luteal phase) during mental rotation and verb-generation tests. Two-sample t-tests with uncorrected P values of <0.001 for the specific regions of interest (ROIs) revealed cerebral activation differences in both stimuli. During mental rotation tests, higher levels of activation were noted in the right medial frontal, precentral, and bilateral inferior parietal cortex, while in women this occurred in the right inferior and medial temporal, right superior frontal cortex, and left fusiform gyrus. During verb-generation tests, higher levels of activation in men was found in the left medial temporal and precentral cortex. Our results indicate that differences in cerebral activity during cognitive tasks can be shown between men and women in the mid-luteal phase. Gender differences while performing a mental rotation task were more prominent than during a verb-generation task.

Adolescent↗
PubMed2001

Asymmetrical activation of human visual cortex demonstrated by functional MRI with monocular stimulation.

We have demonstrated asymmetric activation patterns in the visual cortices of normal humans who have undergone functional MRI with monocular photic stimulation. The contralateral hemisphere is activated more strongly and to a greater spatial extent than the ipsilateral hemisphere when either eye is stimulated. This asymmetry can be explained by nasotemporal asymmetries which have been described in anatomical studies of the visual system in primates and humans. In part, the representation of the monocular crescent of the temporal hemifield of either eye, which exists only in the crossed projection, may explain this. In addition, within the binocular field, there is a biased crossed projection of nasal retinal ganglion cells which drive the contralateral ocular dominance columns in V1. Finally, the blind spot representation in the ipsilateral visual cortex may also contribute to the observed asymmetries. Our study may in effect provide a functional correlate of the anatomical asymmetries that have been observed in humans and animals.

Adult↗
PubMed2002

Congenital mirror movement: a study of functional MRI and transcranial magnetic stimulation.

Two male patients (a child and an adult) with congenital mirror movement were studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Bilateral primary sensorimotor cortices were activated during unilateral hand gripping on fMRI when the child patient was 8 years old andthe adult was 37 years old. Bilateral motor evoked potentials were induced from the hand and forearm muscles after TMS of each hemisphere. Bilateral motor responses were also induced from the arm muscles in the adult patient. Bilateral motor responses had short and similar latencies. Contralateral motor responses to TMS were smaller than ipsilateral ones in the hand muscles, while contralateral responses were larger than ipsilateral ones in the arm muscles. Contralateral hand motor responses reduced in amplitude or disappeared with increasing age while in the child patient, mirror movements decreased gradually. Our results suggest that bilateral activation of the primary sensorimotor cortices during intended unilateral hand movement and bilateral motor responses to TMS account, at least in part, for the pathophysiology of congenital mirror movement. Reduction of contralateral hand motor responses may be related to the decrease in mirror movements during development.

Adult↗
PubMed2000

Functional MRI at 1.5 tesla: a comparison of the blood oxygenation level-dependent signal and electrophysiology.

How well does the functional MRI (fMRI) signal reflect underlying electrophysiology? Despite the ubiquity of the technique, this question has yet to be adequately answered. Therefore, we have compared cortical maps generated based on the indirect blood oxygenation level-dependent signal of fMRI with maps from microelectrode recording techniques, which directly measure neural activity. Identical somatosensory stimuli were used in both sets of experiments in the same anesthetized macaque monkeys. Our results demonstrate that fMRI can be used to determine the topographic organization of cortical fields with 55% concordance to electrophysiological maps. The variance in the location of fMRI activation was greatest in the plane perpendicular to local vessels. An appreciation of the limitations of fMRI improves our ability to use it effectively to study cortical organization.

Animals↗
PubMed2006

Functional MRI of task switching in children with Specific Language Impairment (SLI).

The objective of this study was to examine executive functioning in children with Specific Language Impairment (SLI) using functional MRI. Six children with SLI and seven control children participated in this study and received a task-switching paradigm. No specific deficit in executive control was observed at the behavioral level in children with SLI. However, the neuroimaging data did show remarkable differences between the SLI and control children. The children with SLI recruited frontal and cingulate areas, normally associated with executive control, even when the task did not require them in the children without SLI. This might indicate that the task was more demanding for the SLI group and that compensatory mechanisms were engaged for successful task performance.

Analysis of Variance↗
PubMedDate not supplied

Functional MRI: primary motor cortex localization in patients with brain tumors.

PURPOSE: Our goal was (a) to test the ability of functional MRI (fMRI) to localize the hand primary motor cortex in patients with brain neoplasms using a conventional scanner and (b) to compare within the same subject the location and morphology of the activated motor areas in the affected hemisphere with the contralateral ones. METHOD: Seventeen right-handed patients with frontoparietal intra- and extraaxial tumors were studied. Hand motor performance ranged from normal to slight impairment of finger dexterity. The fMRI study was based on a series of FLASH images. Two or three contiguous slices parallel to the bicommissural plane were acquired through the level of frontoparietal cortex. Each patient was requested to perform with each hand a finger-tapping task or a simpler repetitive flexion-extension of the last four fingers. Pseudo-color activation maps were then calculated by a Z-score method and superimposed on high resolution images. RESULTS: Five patients were excluded because of gross motion artifacts. In all other patients, areas of significant signal increase were detected on the precentral gyrus. They had a spot-like appearance, and no substantial side-to-side differences in shape or extension could be observed. In the presence of severe compression of the gyri, a displacement of the activated areas in the affected hemisphere with respect to the contralateral ones was noticeable. CONCLUSION: fMRI localization of the primary motor area using a conventional scanner can be obtained also in patients with brain tumors, although with a lower success rate than in normal volunteer studies, mainly because of subject compliance problems. Areas of significantly increased signal are detectable even in cortex where normal anatomical patterns are lost.

Adolescent↗
PubMed1994

Potential pitfalls of functional MRI using conventional gradient-recalled echo techniques.

The conventional gradient-recalled echo technique, FLASH, has widely been used for functional MRI. FLASH results at 4 T with short TEs of 10-20 ms mimic those at 1.5 T with TEs of 25-50 ms or longer. Under these conditions, large venous vessels dominate the activated area; however, the use of longer TEs at 4 T reveals activation in gray matter areas as well as large vessels. Inflow effects of large vessels can be greatly reduced with centric-reordering of phase-encoding steps and inter-image delay. Finger and toe movement paradigms show that functional activation maps are consistent with classical somatotopic maps, and are specific to the tasks. Navigator-based motion correction generates functional maps with larger activation areas by reducing physiological noise.

Brain↗
PubMed2005

Echo train shifted multi-echo FLASH for functional MRI of the human brain at ultra-high spatial resolution.

This paper describes the development of a novel technique for functional MRI of the human brain at 0.135 microL resolution for a whole brain section. In comparison with conventional studies at 3 mm isotropic resolution or 27 microL voxel size, the method yields an improvement by a factor of 200. To achieve optimum image quality, the approach is based on a multi-echo fast low-angle shot (FLASH) sequence with unipolar traversals of k-space in the frequency-encoding dimension and echo train shifting to avoid amplitude discontinuities in the phase-encoding dimension. These strategies ensure a smooth point-spread function and eliminate image ghosting artifacts without the need for any phase correction or other post-processing. Signal-to-noise losses due to the considerably reduced voxel sizes are compensated for by single slice acquisitions, optimized bandwidths and an experimental four-channel shoulder coil matched to the posterior portion of the head. Multi-echo FLASH studies of the human brain (2.9 T, seven echoes, 200 Hz/pixel bandwidth, effective echo time 36 ms, acquisition time 6 s) at 300 microm resolution (no interpolation) and 1.5 mm slice thickness revealed robust activations in primary visual areas in response to binocular stimulation. The new method holds promise for refined studies of the columnar organization of specific brain systems and for functional assessments of the gray matter at laminar resolution.

Animals↗
PubMed1999

Model-free functional MRI analysis using Kohonen clustering neural network and fuzzy C-means.

Conventional model-based or statistical analysis methods for functional MRI (fMRI) suffer from the limitation of the assumed paradigm and biased results. Temporal clustering methods, such as fuzzy clustering, can eliminate these problems but are difficult to find activation occupying a small area, sensitive to noise and initial values, and computationally demanding. To overcome these adversities, a cascade clustering method combining a Kohonen clustering network and fuzzy, means is developed. Receiver operating characteristic (ROC) analysis is used to compare this method with correlation coefficient analysis and t test on a series of testing phantoms. Results shown that this method can efficiently and stably identify the actual functional response with typical signal change to noise ratio, from a small activation area occupying only 0.2% of head size, with phase delay, and from other noise sources such as head motion. With the ability of finding activities of small sizes stably this method can not only identify the functional responses and the active regions more precisely, but also discriminate responses from different signal sources, such as large venous vessels or different types of activation patterns in human studies involving motor cortex activation. Even when the experimental paradigm is unknown in a blind test such that model-based methods are inapplicable, this method can identify the activation patterns and regions correctly.

Adult↗
PubMed2001

Functional MRI in a 6-year-old boy with unilateral cortical malformation: concordant representation of both hands in the unaffected hemisphere.

Functional magnetic resonance imaging (fMRI) was performed in a 6-year-old boy with a complex malformation of the right hemisphere who suffered from pharmaco-refractory epilepsy. Clinical examination revealed left-sided hemiparesis and marked mirror movements of the opposite hand both during paretic and non-paretic hand movements. Functional MRI of repetitive unimanual grasping demonstrated that the two hands share a common cortical representation located in the central motor region of the unaffected left hemisphere. The affected right hemisphere did not show any activation during either task. This case study demonstrates the feasibility and usefulness of motor fMRI in young children before they undergo epilepsy surgery.

Brain Mapping↗
PubMedDate not supplied

Functional MRI, drugs, and poststroke recovery.

Stroke is the first cause of disability in industrialized countries. Thus, understanding the mechanisms of poststroke recovery appears to be crucial in improving motor performance and reducing disability in stroke patients. Strategies through which brain restores lost functions after ischemic lesions are numerous. The mechanisms underlying poststroke recovery, known as cerebral plasticity, are so far hypothetical. However, functional magnetic resonance imaging (fMRI) studies recently have provided new insights in to stroke recovery. This article sketches out the mechanisms that are thought to underly recovery and focuses on fMRI experimental studies that have investigated the influence of a number of drugs on functional recovery. Functional MRI is a valuable tool in understanding functional recovery and may help to disclose new therapeutical approaches.

Animals↗
PubMed2005

Reliability of individual functional MRI brain mapping of language.

The use of individual brain mapping for a single case study implicitly assumes that the pattern of activation obtained in a single session represents the subject's functional neuroanatomy. It is therefore essential to estimate the potential variability of brain activation in individuals. To this purpose, the authors compared the pattern of activation determined by statistical parametric mapping (SPM 99) in 9 subjects who repeated 3 verbal tasks in 3 separate sessions. In each subject for each task, the authors examined the intersession variability of the volume of activation in a set of regions classically implicated in language processing. Their results show that reproducibility of functional MRI brain mapping for language within subject varies as a function of the activation task and the region of interest for language.

Adult↗
PubMedDate not supplied

Intraoperative functional MRI using a real-time neurosurgical navigation system.

A 42-year-old-man had focal left hand motor seizures. MR studies demonstrated a right posterior frontal brain tumor. Functional MRI was performed, localizing the motor cortex posterior to the lesion. The functional images were integrated with a neurosurgical navigation computer. A real-time intraoperative display of the anatomic and functional images was produced, registered to a neurosurgical probe. Excellent correlation was demonstrated between the functional maps and invasive electrophysiologic mapping performed at the time of craniotomy.

Adult↗
PubMed2003

The roles of functional MRI in MR-guided neurosurgery in a combined 1.5 Tesla MR-operating room.

BACKGROUND AND PURPOSE: During MR-guided neurosurgical procedures performed in a combined 1.5 Tesla MR-operating room (MR-OR), we have successfully implemented and validated a functional MRI (fMRI) scheme for efficiently localizing eloquent functional areas and assessing their proximity to a lesion volume immediately prior to the craniotomy. METHODS: The fMRI examination consists of a dynamical blood oxygenation level dependent (BOLD) MR imaging technique and a task paradigm that is designed to activate the brain area of interest. The functional imaging technique was based on gradient-echo (GE) echo-planar imaging (EPI) (TR/TE = 2000-3000/40-50 msec). The motor task paradigm involves a periodic movement task, such as alternating between thumb and the other four fingers as a finger-tapping task, while the language involved a covert repeat of a series of words given as a task stimulus. While patient is performing the task, a dynamical fMRI was performed concurrently covering the volume of interest every 2 or 3 sec. Also, we have used a temporal series averaging (TSA) method for correcting the background drift in the raw fMRI signal, and developed a scheme for presenting fMRI results to neurosurgeons in an intuitive 3-dimensional volume-rendered display format. RESULTS: By using the fMRI scheme, we have successfully performed sixteen fMRI examinations immediately prior to neurosurgery in the combined MR-OR on the same surgical table to localize various eloquent functional areas of interests. TSA was successful in reducing the background drift in the fMRI time course data, and the 3-dimensional volume-rendered display was proven effective in presenting the resulting brain activations to neurosurgeons. More importantly, in three representative cases (one biopsy and two tumor resections) presented, the information provided by fMRI have indeed contributed significantly in making the optimal surgical decisions prior to craniotomy. CONCLUSIONS: Intra-operative fMRI can be an indispensable tool for determining the location of a neighboring eloquent functional area of concern in reference to a targeted lesion. Information provided by fMRI has helped in improving the outcome and clinician confidence of all surgeries performed.

Adolescent↗
PubMed2001

Functional MRI detection of pharmacologically induced memory impairment.

To examine alterations in brain activation associated with pharmacologically induced memory impairment, we used functional MRI (fMRI) to study the effects of lorazepam and scopolamine on a face-name associative encoding paradigm. Ten healthy young subjects were scanned on four occasions, 2 weeks apart; they were administered i.v. saline during two placebo-scanning sessions and then alternately administered i.v. lorazepam (1 mg) or scopolamine (0.4 mg) in a double-blind, randomized, cross-over design. Both the extent and magnitude of activation within anatomic regions of interest (ROIs) were examined to determine the reproducibility of activation in the placebo sessions and the regional specificity of the pharmacologic effects. Activation within all ROIs was consistent across the two placebo scans during the encoding of novel face-name pairs (compared with visual fixation). With the administration of either lorazepam or scopolamine, significant decreases were observed in both the extent and magnitude of activation within the hippocampal, fusiform, and inferior prefrontal ROIs, but no significant alterations in activation in the striate cortex were found. Both medications impaired performance on postscan memory measures, and significant correlations between memory performance and extent of activation were found in hippocampal and fusiform ROIs. These findings suggest that pharmacologic effects can be detected with fMRI by using a reproducible experimental paradigm and that medications that impair memory also diminish activation in specific brain regions thought to subserve complex memory processes.

Adult↗