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Optimization of fMRI Processing Parameters for Simutaneous Acquisition of EEG/fMRI in Focal Epilepsy

Forjaz Secca, M; Fernandes, H; Cabral, J; Leal, A
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Conferência ou Objeto de Conferência
Publicado em //2008 Português
Relevância na Pesquisa
26.79%
In the context of focal epilepsy, the simultaneous combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) holds a great promise as a technique by which the hemodynamic correlates of interictal spikes detected on scalp EEG can be identified. The fact that traditional EEG recordings have not been able to overcome the difficulty in correlating the ictal clinical symptoms to the onset in particular areas of the lobes, brings the need of mapping with more precision the epileptogenic cortical regions. On the other hand, fMRI suggested localizations more consistent with the ictal clinical manifestations detected. This study was developed in order to improve the knowledge about the way parameters involved in the physical and mathematical data, produced by the EEG/fMRI technique processing, would influence the final results. The evaluation of the accuracy was made by comparing the BOLD results with: the high resolution EEG maps; the malformative lesions detected in the T1 weighted MR images; and the anatomical localizations of the diagnosed symptomatology of each studied patient. The optimization of the set of parameters used, will provide an important contribution to the diagnosis of epileptogenic focuses...

Optimization of fMRI Processing Parameters for Simutaneous Acquisition of EEG/fMRI in Focal Epilepsy

Forjaz Secca, M; Fernandes, H; Cabral, J; Leal, A
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Conferência ou Objeto de Conferência
Publicado em //2008 Português
Relevância na Pesquisa
26.79%
In the context of focal epilepsy, the simultaneous combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) holds a great promise as a technique by which the hemodynamic correlates of interictal spikes detected on scalp EEG can be identified. The fact that traditional EEG recordings have not been able to overcome the difficulty in correlating the ictal clinical symptoms to the onset in particular areas of the lobes, brings the need of mapping with more precision the epileptogenic cortical regions. On the other hand, fMRI suggested localizations more consistent with the ictal clinical manifestations detected. This study was developed in order to improve the knowledge about the way parameters involved in the physical and mathematical data, produced by the EEG/fMRI technique processing, would influence the final results. The evaluation of the accuracy was made by comparing the BOLD results with: the high resolution EEG maps; the malformative lesions detected in the T1 weighted MR images; and the anatomical localizations of the diagnosed symptomatology of each studied patient. The optimization of the set of parameters used, will provide an important contribution to the diagnosis of epileptogenic focuses...

Magnetic Resonance Imaging of Neuronal Function in the Spinal Cord: Spinal fMRI

Stroman, Patrick W.
Fonte: © 2005. Clinical Medicine & Research Publicador: © 2005. Clinical Medicine & Research
Tipo: Artigo de Revista Científica
Publicado em /08/2005 Português
Relevância na Pesquisa
26.79%
A review of the current literature on magnetic resonance imaging of neuronal function in the spinal cord (spinal fMRI) is presented. The unique challenges of spinal fMRI are identified as being the small cross-sectional dimensions of the spinal cord, magnetic field inhomogeneity caused by the bone and cartilage in the spine, and motion of cerebrospinal fluid, blood, adjacent tissues and organs and of the spinal cord itself. Techniques have been developed to overcome or compensate for these challenges and the result is a fMRI method which is distinct from that used for mapping function in the brain. Evidence that the current spinal fMRI method provides accurate and sensitive maps of neuronal function is also discussed. Studies presented in the literature have demonstrated areas of neuronal activity corresponding with spinal cord neuroanatomy as a result of thermal and electrical stimuli and motor tasks with the hands, arms and legs. Signal intensity changes detected in active areas have also been demonstrated to depend on the intensity of the stimuli with both thermal stimulation and a motor task, providing evidence of the correspondence between spinal fMRI results and neuronal activity in the spinal cord.

Cortical fMRI Activation to Sequences of Tones Alternating in Frequency: Relationship to Perceived Rate and Streaming

Wilson, E. Courtenay; Melcher, Jennifer R.; Micheyl, Christophe; Gutschalk, Alexander; Oxenham, Andrew J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Human listeners were functionally imaged while reporting their perception of sequences of alternating-frequency tone bursts separated by 0, 1/8, 1, or 20 semitones. Our goal was to determine whether functional magnetic resonance imaging (fMRI) activation of auditory cortex changes with frequency separation in a manner predictable from the perceived rate of the stimulus. At the null and small separations, the tones were generally heard as a single stream with a perceived rate equal to the physical tone presentation rate. fMRI activation in auditory cortex was appreciably phasic, showing prominent peaks at the sequence onset and offset. At larger-frequency separations, the higher- and lower-frequency tones perceptually separated into two streams, each with a rate equal to half the overall tone presentation rate. Under those conditions, fMRI activation in auditory cortex was more sustained throughout the sequence duration and was larger in magnitude and extent. Phasic to sustained changes in fMRI activation with changes in frequency separation and perceived rate are comparable to, and consistent with, those produced by changes in the physical rate of a sequence and are far greater than the effects produced by changing other physical stimulus variables...

Low Frequency Fluctuations in the Cardiac Rate as a Source of Variance in the Resting-State fMRI BOLD Signal

Shmueli, Karin; van Gelderen, Peter; de Zwart, Jacco A.; Horovitz, Silvina G.; Fukunaga, Masaki; Martijn Jansma, J.; Duyn, Jeff H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Heart rate fluctuations occur in the low frequency region (< 0.1 Hz) probed in functional magnetic resonance imaging (fMRI) studies of resting-state functional connectivity and most fMRI block paradigms, and may be related to low frequency blood-oxygenation-level-dependent (BOLD) signal fluctuations. To investigate this hypothesis, temporal correlations between cardiac rate and resting-state fMRI signal timecourses were assessed at 3 Tesla. Resting-state BOLD fMRI and accompanying physiological data were acquired and analyzed using cross-correlation and regression. Time-shifted cardiac rate timecourses were included as regressors in addition to established physiological regressors (RETROICOR (Glover et al., 2000) and respiration volume per unit time (Birn et al., 2006b)). Significant correlations between the cardiac rate and BOLD signal timecourses were revealed, particularly negative correlations in gray matter at time-shifts of 6-12 seconds and positive correlations at time shifts of 30-42 seconds (TR = 6 s). Regressors consisting of cardiac rate timecourses shifted by delays of between 0 and 24 seconds explained an additional 1 % of the BOLD signal variance on average over the whole brain across 9 subjects, a similar additional variance to that explained by respiration volume per unit time and RETROICOR regressors...

Energetics of neuronal signaling and fMRI activity

Maandag, Natasja J. G.; Coman, Daniel; Sanganahalli, Basavaraju G.; Herman, Peter; Smith, Arien J.; Blumenfeld, Hal; Shulman, Robert G.; Hyder, Fahmeed
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Energetics of resting and evoked fMRI signals were related to localized ensemble firing rates (ν) measured by electrophysiology in rats. Two different unstimulated, or baseline, states were established by anesthesia. Halothane and α-chloralose established baseline states of high and low energy, respectively, in which forepaw stimulation excited the contralateral primary somatosensory cortex (S1). With α-chloralose, forepaw stimulation induced strong and reproducible fMRI activations in the contralateral S1, where the ensemble firing was dominated by slow signaling neurons (SSN; ν range of 1–13 Hz). Under halothane, weaker and less reproducible fMRI activations were observed in the contralateral S1 and elsewhere in the cortex, but ensemble activity in S1 was dominated by rapid signaling neurons (RSN; ν range of 13–40 Hz). For both baseline states, the RSN activity (i.e., higher frequencies, including the γ band) did not vary upon stimulation, whereas the SSN activity (i.e., α band and lower frequencies) did change. In the high energy baseline state, a large majority of total oxidative energy [cerebral metabolic rate of oxygen consumption (CMRO2)] was devoted to RSN activity, whereas in the low energy baseline state, it was roughly divided between SSN and RSN activities. We hypothesize that in the high energy baseline state...

Intervention Models in Functional Connectivity Identification Applied to fMRI

Sato, João Ricardo; Takahashi, Daniel Yasumasa; Cardoso, Ellison Fernando; Martin, Maria da Graça Morais; Amaro Júnior, Edson; Morettin, Pedro Alberto
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Recent advances in neuroimaging techniques have provided precise spatial localization of brain activation applied in several neuroscience subareas. The development of functional magnetic resonance imaging (fMRI), based on the BOLD signal, is one of the most popular techniques related to the detection of neuronal activation. However, understanding the interactions between several neuronal modules is also an important task, providing a better comprehension about brain dynamics. Nevertheless, most connectivity studies in fMRI are based on a simple correlation analysis, which is only an association measure and does not provide the direction of information flow between brain areas. Other proposed methods like structural equation modeling (SEM) seem to be attractive alternatives. However, this approach assumes prior information about the causality direction and stationarity conditions, which may not be satisfied in fMRI experiments. Generally, the fMRI experiments are related to an activation task; hence, the stimulus conditions should also be included in the model. In this paper, we suggest an intervention analysis, which includes stimulus condition, allowing a nonstationary modeling. Furthermore, an illustrative application to real fMRI dataset from a simple motor task is presented.

High-field fMRI unveils orientation columns in humans

Yacoub, Essa; Harel, Noam; Uğurbil, Kâmil
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90° (vertical stimuli with horizontal motion)...

Lessons from fMRI about mapping cortical columns

Kim, Seong-Gi; Fukuda, Mitsuhiro
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Recently-developed functional magnetic resonance imaging (fMRI) can map small functional structures non-invasively and repeatedly without any depth limitation. However, there has been a persistent concern as to whether the high-resolution fMRI signals actually mark the sites of increased neural activity. To examine this outstanding issue, we used iso-orientation columns of isoflurane-anestheized cats as a biological model and confirmed the neural correlation of fMRI iso-orientation maps by comparing with intrinsic optical imaging maps. Our results suggest that highest fMRI signals indeed indicate the sites of increased neuronal activity. Now fMRI can be used to determine plastic and/or developmental change of functional columnar structure possibly on a layer to layer basis. In this review we focus mainly on what technical aspects should be considered when mapping functional cortical columns, including imaging techniques and experimental design.

NEURAL MECHANISMS OF AUDITORY DISCRIMINATION OF LONG-DURATION TONAL PATTERNS: A NEURAL MODELING AND FMRI STUDY

Ulloa, Antonio; Husain, Fatima T.; Kemeny, Stefan; Xu, Jiang; Braun, Allen R.; Horwitz, Barry
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/2008 Português
Relevância na Pesquisa
26.79%
Language perception comprises mechanisms of perception and discrimination of auditory stimuli. An important component of auditory perception and discrimination concerns auditory objects. Many interesting auditory objects in our environment are of relatively long duration; however, the temporal window of integration of auditory cortex neurons processing these objects is very limited. Thus, it is necessary to make active use of short-term memory in order to construct and temporarily store long-duration objects. We sought to understand the mechanisms by which the brain manipulates long-duration tonal patterns, temporarily stores the segments of those patterns, and integrates them into an auditory object. We extended a previously constructed model of auditory recognition of short-duration tonal patterns by expanding the prefrontal cortically-based short-term memory module of the previous model into a memory buffer with multiple short-term memory submodules and by adding a gating module. The gating module distributes the segments of the input pattern to separate locations of the extended prefrontal cortex in an orderly fashion, allowing a subsequent comparison of the stored segments against the segments of a second pattern. In addition to simulating behavioral data and electrical activity of neurons...

Combining fMRI and SNP Data to Investigate Connections Between Brain Function and Genetics Using Parallel ICA

Liu, Jingyu; Pearlson, Godfrey; Windemuth, Andreas; Ruano, Gualberto; Perrone-Bizzozero, Nora I.; Calhoun, Vince
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/2009 Português
Relevância na Pesquisa
26.79%
There is current interest in understanding genetic influences on both healthy and disordered brain function. We assessed brain function with functional magnetic resonance imaging (fMRI) data collected during an auditory oddball task—detecting an infrequent sound within a series of frequent sounds. Then, task-related imaging findings were utilized as potential intermediate phenotypes (endophenotypes) to investigate genomic factors derived from a single nucleotide polymorphism (SNP) array. Our target is the linkage of these genomic factors to normal/abnormal brain functionality. We explored parallel independent component analysis (paraICA) as a new method for analyzing multimodal data. The method was aimed to identify simultaneously independent components of each modality and the relationships between them. When 43 healthy controls and 20 schizophrenia patients, all Caucasian, were studied, we found a correlation of 0.38 between one fMRI component and one SNP component. This fMRI component consisted mainly of parietal lobe activations. The relevant SNP component was contributed to significantly by 10 SNPs located in genes, including those coding for the nicotinic α-7cholinergic receptor, aromatic amino acid decarboxylase, disrupted in schizophrenia 1...

Modulation of spontaneous fMRI activity in human visual cortex by behavioral state

Bianciardi, Marta; Fukunaga, Masaki; van Gelderen, Peter; Horovitz, Silvina G.; de Zwart, Jacco A.; Duyn, Jeff H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
The phenomenon of spontaneous fMRI activity is increasingly being exploited to investigate the connectivity of functional networks in human brain with high spatial-resolution. Although mounting evidence points towards a neuronal contribution to this activity, its functional role and dependence on behavioral state remain unclear. In this work, we used BOLD fMRI at 7 T to study the modulation of spontaneous activity in occipital areas by various behavioral conditions, including resting with eyes closed, eyes open with visual fixation, and eyes open with fixation and focal visual stimulation. Spontaneous activity was separated from evoked activity and from signal fluctuations related to cardiac and respiratory cycles. We found that spontaneous activity in visual areas was substantially reduced (amplitude (44%) and coherence (25%)) with the fixation conditions relative to the eyes-closed condition. No significant further modulation was observed when the visual stimulus was added. The observed dependence on behavioral condition suggests that part of spontaneous fMRI signal fluctuations represents neuronal activity. Possible mechanisms for the modulation of spontaneous activity by behavioral state are discussed. The observed linear superposition of spontaneous fMRI activity with focal evoked activity related to visual processing has important implications for fMRI studies...

Improving fMRI sensitivity by normalization of basal physiologic state

Lu, Hanzhang; Yezhuvath, Uma S.; Xiao, Guanghua
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/2010 Português
Relevância na Pesquisa
26.79%
The power of fMRI in assessing neural activities is hampered by inter-subject variations in basal physiologic parameters, which may not be related to neural activation but has a modulatory effect on fMRI signals. Therefore, normalization of fMRI signals with these parameters is useful in reducing variations and improving sensitivity of this important technique. Recently, we have shown that basal venous oxygenation is a significant modulator of fMRI signals and individuals with higher venous oxygenation tend to have lower fMRI signals. In this study, we aim to test the utility of venous oxygenation normalization in distinguishing subject groups. A “model” condition was used in which two visual stimuli with different flashing frequencies were used to stimulate two subject groups, respectively, thereby simulating the situation of control and patient groups. It was found that visual-evoked BOLD signal is significantly correlated with baseline venous T2 (p=0.0003) and inclusion of physiologic modulator in the regression analysis can substantially reduce p values of group-level statistical tests. When applied to voxel-wise analysis, the normalization process can allow the detection of more significant voxels. The utility of other basal parameters...

Evaluation of preprocessing steps to compensate for magnetic field distortions due to body movements in BOLD fMRI

Barry, Robert L.; Williams, Joy M.; Klassen, L. Martyn; Gallivan, Jason P.; Culham, Jody C.; Menon, Ravi S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is currently the dominant technique for non-invasive investigation of brain functions. One of the challenges with BOLD fMRI, particularly at high fields, is compensation for the effects of spatiotemporally varying magnetic field inhomogeneities (ΔB0) caused by normal subject respiration, and in some studies, movement of the subject during the scan to perform tasks related to the functional paradigm. The presence of ΔB0 during data acquisition distorts reconstructed images and introduces extraneous fluctuations in the fMRI time series that decrease the BOLD contrast-to-noise ratio. Optimization of the fMRI data-processing pipeline to compensate for geometric distortions is of paramount importance to ensure high quality of fMRI data. To investigate ΔB0 caused by subject movement, echo-planar imaging scans were collected with and without concurrent motion of a phantom arm. The phantom arm was constructed and moved by the experimenter to emulate forearm motions while subjects remained still and observed a visual stimulation paradigm. These data were then subjected to eight different combinations of preprocessing steps. The best preprocessing pipeline included navigator correction...

FMRI activity patterns in human LOC carry information about object exemplars within category

Eger, Evelyn; Ashburner, John; Haynes, John-Dylan; Dolan, Raymond J; Rees, Geraint
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/2008 Português
Relevância na Pesquisa
26.79%
The lateral occipital complex (LOC) is a set of areas in human occipito-temporal cortex responding to objects as opposed to low-level control stimuli. Conventional fMRI analysis methods based on regional averages could not detect signals discriminative of different types of objects in this region. Here, we examined fMRI signals using multivariate pattern recognition (support vector classification), to systematically explore the nature of object-related information available in fine-grained activity patterns in LOC. Distributed fMRI BOLD signals from LOC allowed for above chance discrimination not only of the category, but also of within-category exemplars of everyday man-made objects, and such exemplar-specific information generalised across changes in stimulus size and viewpoint, particularly in posterior subregions. Object identity could also be predicted from responses of the early visual cortex, even significantly across the changes in size and viewpoint used here. However, a dissociation was observed between these two regions of interest in the degree of discrimination for objects relative to size: In the early visual cortex two different sizes of the same object were even better discriminated than two different objects (in accordance with measures of pixelwise stimulus similarity)...

Sparse logistic regression for whole brain classification of fMRI data

Ryali, Srikanth; Supekar, Kaustubh; Abrams, Daniel A.; Menon, Vinod
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Multivariate pattern recognition methods are increasingly being used to identify multiregional brain activity patterns that collectively discriminate one cognitive condition or experimental group from another, using fMRI data. The performance of these methods is often limited because the number of regions considered in the analysis of fMRI data is large compared to the number of observations (trials or participants). Existing methods that aim to tackle this dimensionality problem are less than optimal because they either over-fit the data or are computationally intractable. Here, we describe a novel method based on logistic regression using a combination of L1 and L2 norm regularization that more accurately estimates discriminative brain regions across multiple conditions or groups. The L1 norm, computed using a fast estimation procedure, ensures a fast, sparse and generalizable solution; the L2 norm ensures that correlated brain regions are included in the resulting solution, a critical aspect of fMRI data analysis often overlooked by existing methods. We first evaluate the performance of our method on simulated data and then examine its effectiveness in discriminating between well-matched music and speech stimuli. We also compared our procedures with other methods which use either L1-norm regularization alone or support vector machine based feature elimination. On simulated data...

Alcohol induced region-dependent alterations of hemodynamic response: implications for the statistical interpretation of pharmacological fMRI studies

Luchtmann, M.; Jachau, K.; Tempelmann, C.; Bernarding, J.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Worldwide, ethanol abuse causes thousands of fatal accidents annually as well as innumerable social dysfunctions and severe medical disorders. Yet, few studies have used the blood oxygenation level dependent functional magnetic resonance imaging method (BOLD fMRI) to map how alcohol alters brain functions, as fMRI relies on neurovascular coupling, which may change due to the vasoactive properties of alcohol. We monitored the hemodynamic response function (HRF) with a high temporal resolution. In both motor cortices and the visual cortex, alcohol prolonged the time course of the HRF, indicating an overall slow-down of neurovascular coupling rather than an isolated reduction in neuronal activity. However, in the supplementary motor area, alcohol-induced changes to the HRF suggest a reduced neuronal activation. This may explain why initiating and coordinating complex movements, including speech production, are often impaired earlier than executing basic motor patterns. Furthermore, the present study revealed a potential pitfall associated with the statistical interpretation of pharmacological fMRI studies based on the general linear model: if the functional form of the HRF is changed between the conditions data may be erroneously interpreted as increased or decreased neuronal activation. Thus...

DPARSF: A MATLAB Toolbox for “Pipeline” Data Analysis of Resting-State fMRI

Chao-Gan, Yan; Yu-Feng, Zang
Fonte: Frontiers Research Foundation Publicador: Frontiers Research Foundation
Tipo: Artigo de Revista Científica
Publicado em 14/05/2010 Português
Relevância na Pesquisa
26.79%
Resting-state functional magnetic resonance imaging (fMRI) has attracted more and more attention because of its effectiveness, simplicity and non-invasiveness in exploration of the intrinsic functional architecture of the human brain. However, user-friendly toolbox for “pipeline” data analysis of resting-state fMRI is still lacking. Based on some functions in Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST), we have developed a MATLAB toolbox called Data Processing Assistant for Resting-State fMRI (DPARSF) for “pipeline” data analysis of resting-state fMRI. After the user arranges the Digital Imaging and Communications in Medicine (DICOM) files and click a few buttons to set parameters, DPARSF will then give all the preprocessed (slice timing, realign, normalize, smooth) data and results for functional connectivity, regional homogeneity, amplitude of low-frequency fluctuation (ALFF), and fractional ALFF. DPARSF can also create a report for excluding subjects with excessive head motion and generate a set of pictures for easily checking the effect of normalization. In addition, users can also use DPARSF to extract time courses from regions of interest.

Development of an apparatus and methodology for conducting functional magnetic resonance imaging (fMRI) with pharmacological stimuli in conscious rhesus monkeys

Murnane, Kevin Sean; Howell, Leonard Lee
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Functional magnetic resonance imaging (fMRI) is a technique with significant potential to advance our understanding of multiple brain systems. However, when human subjects undergo fMRI studies they are typically conscious whereas pre-clinical fMRI studies typically utilize anesthesia, which complicates comparisons across studies. Therefore, we have developed an apparatus suitable for imaging conscious rhesus monkeys. In order to minimize subject stress and spatial motion, each subject was acclimated to the necessary procedures over several months. The effectiveness of this process was then evaluated, in fully trained subjects, by quantifying objective physiological measures. These physiological metrics were stable both within and across sessions and did not differ from when these same subjects were immobilized using standard primate handling procedures. Subject motion and blood oxygenation level dependent (BOLD) fMRI measurements were then evaluated by scanning subjects under three different conditions: the absence of stimulation, presentation of a visual stimulus, or administration of intravenous (i.v.) cocaine (0.3 mg/kg). Spatial motion differed neither by condition nor along the three principal axes. In addition, maximum translational and rotational motion never exceeded one half of the voxel size (0.75 mm) or 1.5 degrees...

Evaluation of Novel Drugs using fMRI in Early Phase Clinical Trials: Safety Monitoring

George, Edward; Becerrra, Lino; Upadhyay, Jaymin; Schmidt, Ulrich; Borsook, David
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.79%
Recent advances in functional Magnetic Resonance Imaging (fMRI) have allowed for the possibility to help with dose ranging as well as potential drug efficacy and side-effect profiles. The problem that is being addressed in this article relates to the absence of any current guidelines or standards for fMRI that meet established standards of care. Given the potential use of fMRI in drug development, it would seem essential that guidelines are adopted to be used where patients are exposed to novel drugs in particular, but to any drug where immediate access to the patient is limited. When used in phase I trials or very soon after initial Phase I qualification, MRI mandates certain safety standards as subjects are laying positioned in the bore of a magnet with limited opportunity for direct observation or communication, or immediate access in an emergency; these limits can be more pronounced during fMRI acquisition. In developing novel approaches to testing new drugs using fMRI, we suggest that safety guidelines merit discussion and definition. This process could lead to the adoption of standards in the testing of novel agents. Some of these issues are well understood and can be adopted from experiences using sedation in the scanner, while others are unique to the application of the technology in early phase trials.