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Numerical calculations of the static magnetic field in three-dimensional multi-tissue models of the human head.

Susceptibility-induced perturbation of the static magnetic field by the human body during magnetic resonance imaging (MRI) leads to undesirable artifacts as well as valuable physiological information, as in functional MRI. The ability to calculate these perturbations for a multi-tissue human body model provides a powerful tool in designing hardware and acquisition methods for reducing the artifacts, and in relating observed image contrast to physiological origins. We have developed a method for calculating the static field in arbitrary 3D magnetic susceptibility distributions and performed calculations in a complete model of the human head and shoulders. The accuracy of our method was validated in regular geometries with known analytical solutions and in comparison with experimental results acquired from the head of the same human subject used for computer modeling. Results are presented in parts per million (ppm) deviation from the applied field strength and are valid for any imaging or spectroscopy system.

Computer Simulation↗

Functional magnetic resonance imaging of human brain activity in a verbal fluency task.

OBJECTIVES: Functional MRI (fMRI) holds the promise of non-invasive mapping of human brain function in both health and disease. Yet its sensitivity and reliability for mapping higher cognitive function are still being determined. Using verbal fluency as a task, the objective was to ascertain the consistency of fMRI on a conventional scanner for determining the anatomic substrate of language between subjects and between sexes. Comparison was made with previous PET studies. METHODS: Using a 1.5 Tesla magnet and an echoplanar pulse sequence, whole brain fMRI was obtained from 12 normal right handed subjects (6 males and 6 females) as they performed a verbal fluency task. RESULTS: A broadly consistent pattern of response was seen across subjects. Areas showing activation changes included the left prefrontal cortex and right cerebellum, in agreement with previous PET 15O-H2O studies. In addition, significantly decreased responses were seen in the posterior cingulate and over an extensive area of mesial and dorsolateral parietal and superior temporal cortices. The male cohort showed a slight asymmetry of parietal deactivation, with more involvement on the right, whereas the female cohort showed a small region of activation in the right orbitofrontal cortex. There were individual task related regional changes in all 12 subjects with the area showing the most significant change being the left prefrontal cortex in all cases. CONCLUSIONS: Magnetic resonance scanners of conventional field strength can provide functional brain mapping data with a sensitivity at least that of PET. Activation was seen in left prefrontal and right cerebellar regions, as with PET. However, decremental responses were seen over a much larger area of the posterior cortex than had been anticipated by prior studies. The ability to see a response in each subject individually suggests that fMRI may be useful in the preinterventional mapping of pathological states, and offers a non-invasive alternative to the Wada test for assessment of hemispheric dominance. There were no gross differences in the pattern of activation between male and female subjects.

Adult↗

Functional brain imaging of young, nondemented, and demented older adults.

Brain imaging based on functional MRI (fMRI) provides a powerful tool for characterizing age-related changes in functional anatomy. However, between-population comparisons confront potential differences in measurement properties. The present experiment explores the feasibility of conducting fMRI studies in nondemented and demented older adults by measuring hemodynamic response properties in an event-related design. A paradigm involving repeated presentation of sensory-motor response trials was administered to 41 participants (14 young adults, 14 nondemented older adults, and 13 demented older adults). For half of the trials a single sensory-motor event was presented in isolation and in the other half in pairs. Hemodynamic response characteristics to the isolated events allowed basic response properties (e.g., amplitude and variance) between subject groups to be contrasted. The paired events further allowed the summation properties of the hemodynamic response to be characterized. Robust and qualitatively similar activation maps were produced for all subject groups. Quantitative results showed that for certain regions, such as in the visual cortex, there were marked reductions in the amplitude of the hemodynamic response in older adults. In other regions, such as in the motor cortex, relatively intact response characteristics were observed. These results suggest caution should be exhibited in interpreting simple main effects in response amplitude between subject groups. However, across all regions examined, the summation of the hemodynamic response over trials was highly similar between groups. This latter finding suggests that, even if absolute measurement differences do exist between subject groups, relative activation change should be preserved. Designs that rely on group interactions between task conditions, parametric manipulations, or group interactions between regions should provide valuable data for making inferences about functional-anatomic changes between different populations.

Adolescent↗

Encoding and retrieval in aging and memory loss, a fMRI study.

Mild cognitive impairment (MCI) is a term for nondemented individuals with memory complaints and deficits greater than age-adjusted normal performance. Functional MRI (fMRI) may be a more sensitive method than other techniques to reveal functional abnormalities in individuals with MCI, only a proportion of whom progress to Alzheimer's disease (AD). fMRI was carried out while subjects (four MCI, five age-matched normal controls, and one AD) performed incidental encoding (deep and shallow) and recognition tasks for colored and black and white photographs contrasted to baseline fixation. fMRI revealed interesting dissociations between activation patterns and behavioral performance when comparing the MCI and AD to the NC.

Aging↗

Perfusion magnetic resonance imaging with continuous arterial spin labeling: methods and clinical applications in the central nervous system.

Several methods are now available for measuring cerebral perfusion and related hemodynamic parameters using magnetic resonance imaging (MRI). One class of techniques utilizes electromagnetically labeled arterial blood water as a noninvasive diffusible tracer for blood flow measurements. The electromagnetically labeled tracer has a decay rate of T1, which is sufficiently long to allow perfusion of the tissue and microvasculature to be detected. Alternatively, electromagnetic arterial spin labeling (ASL) may be used to obtain qualitative perfusion contrast for detecting changes in blood flow, similar to the use of susceptibility contrast in blood oxygenation level dependent functional MRI (BOLD fMRI) to detect functional activation in the brain. The ability to obtain blood flow maps using a non-invasive and widely available modality such as MRI should greatly enhance the utility of blood flow measurement as a means of gaining further insight into the broad range of hemodynamically related physiology and pathophysiology. This article describes the biophysical considerations pertaining to the generation of quantitative blood flow maps using a particular form of ASL in which arterial blood water is continuously labeled, termed continuous arterial spin labeling (CASL). Technical advances permit multislice perfusion imaging using CASL with reduced sensitivity to motion and transit time effects. Interpretable cerebral perfusion images can now be reliably obtained in a variety of clinical settings including acute stroke, chronic cerebrovascular disease, degenerative diseases and epilepsy. Over the past several years, the technical and theoretical foundations of CASL perfusion MRI techniques have evolved from feasibility studies into practical usage. Currently existing methodologies are sufficient to make reliable and clinically relevant observations which complement structural assessment using MRI. Future technical improvements should further reduce the acquisition times for CASL perfusion MRI, while increasing the slice coverage, resolution and stability of the images. These techniques have a broad range of potential applications in clinical and basic research of brain physiology, as well as in other organs.

Central Nervous System↗

Direct and fast detection of neuronal activation in the human brain with diffusion MRI.

Using MRI, we found that a slowly diffusing water pool was expanding (1.7 +/- 0.3%) upon activation on the human visual cortex at the detriment of a faster diffusing pool. The time course of this water phase transition preceded the activation-triggered vascular response detected by usual functional MRI by several seconds. The observed changes in water diffusion likely reflect early biophysical events that take place in the activated cells, such as cell swelling and membrane expansion. Although the exact mechanisms remain to clarify, access to such an early and direct physiological marker of cortical activation with MRI will provide opportunities for functional neuroimaging of the human brain.

Adult↗

Validity and power in hemodynamic response modeling: a comparison study and a new approach.

One of the advantages of event-related functional MRI (fMRI) is that it permits estimation of the shape of the hemodynamic response function (HRF) elicited by cognitive events. Although studies to date have focused almost exclusively on the magnitude of evoked HRFs across different tasks, there is growing interest in testing other statistics, such as the time-to-peak and duration of activation as well. Although there are many ways to estimate such parameters, we suggest three criteria for optimal estimation: 1) the relationship between parameter estimates and neural activity must be as transparent as possible; 2) parameter estimates should be independent of one another, so that true differences among conditions in one parameter (e.g., hemodynamic response delay) are not confused for apparent differences in other parameters (e.g., magnitude); and 3) statistical power should be maximized. In this work, we introduce a new modeling technique, based on the superposition of three inverse logit functions (IL), designed to achieve these criteria. In simulations based on real fMRI data, we compare the IL model with several other popular methods, including smooth finite impulse response (FIR) models, the canonical HRF with derivatives, nonlinear fits using a canonical HRF, and a standard canonical model. The IL model achieves the best overall balance between parameter interpretability and power. The FIR model was the next-best choice, with gains in power at some cost to parameter independence. We provide software implementing the IL model.

Brain↗

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

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

Animals↗

A neural basis for category and modality specificity of semantic knowledge.

Prevalent theories hold that semantic memory is organized by sensorimotor modality (e.g., visual knowledge, motor knowledge). While some neuroimaging studies support this idea, it cannot account for the category specific (e.g., living things) knowledge impairments seen in some brain damaged patients that cut across modalities. In this article we test an alternative model of how damage to interactive, modality-specific neural regions might give rise to these categorical impairments. Functional MRI was used to examine a cortical area with a known modality-specific function during the retrieval of visual and non-visual knowledge about living and non-living things. The specific predictions of our model regarding the signal observed in this area were confirmed, supporting the notion that semantic memory is functionally segregated into anatomically discrete, but highly interactive, modality-specific regions.

Adult↗

Mapping visual cortex in monkeys and humans using surface-based atlases.

We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

Animals↗

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR).

Sleeping and sedated children can respond to visual stimulation with a decrease in blood oxygenation level dependent (BOLD) functional MRI signal response. The contribution of metabolic and hemodynamic parameters to this inverse signal response is incompletely understood. It has been hypothesized that it is caused by a relatively greater increase of oxygen consumption compared to rCBF (regional cerebral blood flow) increase. We studied the rCBF changes during visual stimulation in four sedated children, aged 4-71 months, and four alert adults, with an arterial water spin labeling technique (FAIR) and BOLD fMRI in a 1.5T MR scanner. In the children, FAIR signal decreased by a mean of 0.96% (range 0.77-1.05) of the baseline periods of the non-selective images, while BOLD signal decreased by 2.03% (range 1.99-2.93). In the adults, FAIR and BOLD signal increased by 0.88% (range 0.8-0.99) and 2.63% (range 1.99-2.93), respectively. Thus, in the children, an rCBF increase could not be detected by perfusion MRI, but indications of a FAIR signal decrease were found. An rCBF decrease in the primary visual cortex during stimulation has not been reported previously, but it is a possible explanation for the negative BOLD response. Future studies will have to address if this response pattern is a consequence of age or sleep/sedation.

Adult↗

Age effects on the neural correlates of successful memory encoding.

Event-related functional MRI (fMRI) was used to investigate the neural correlates of memory encoding as a function of age. While fMRI data were obtained, 14 younger (mean age 21 years) and 14 older subjects (mean age 68 years) made animacy decisions about words. Recognition memory for these words was tested at two delays such that older subjects' performance at the short delay was comparable to that of the young subjects at the long delay. This allowed age-associated changes in the neural correlates of encoding to be dissociated from the correlates of differential recognition performance. Activity in left inferior prefrontal cortex and the left hippocampal formation was greater for subsequently recognized words in both age groups, consistent with the findings of previous studies in young adults. In the prefrontal cortex, these 'subsequent memory effects' were, however, left-lateralized in the younger group but bilateral in the older subjects. In addition, for the younger group only, greater activity for remembered words was observed in anterior inferior temporal cortex, as were reversed effects ('subsequent forgetting' effects) in anterior prefrontal regions. The data indicate that older subjects engage much of the same neural circuitry as younger subjects when encoding new memories. However, the findings also point to age-related differences in both prefrontal and temporal activity during successful episodic encoding.

Adolescent↗

New magnetic resonance imaging methods for cerebrovascular disease: emerging clinical applications.

During the 1990s, novel magnetic resonance imaging (MRI) techniques have emerged that allow the noninvasive and rapid assessment of normal brain functioning and cerebral pathophysiology. Some of these techniques, including diffusion-weighted imaging and perfusion-weighted imaging, have already been used extensively in specialized centers for the evaluation of patients with cerebrovascular disease. Evidence is now rapidly accumulating that both diffusion- and perfusion-weighted imaging, particularly when used in combination with high-speed MR angiography, will lead to improvements in the clinical management of acute stroke patients. Other novel MR techniques, such as spectroscopic imaging, diffusion tensor imaging, and blood oxygenation level-dependent functional MRI, have not yet assumed a definitive role in the diagnostic evaluation of cerebrovascular disease. However, they are promising research tools that provide noninvasive data about infarct evolution as well as mechanisms of stroke recovery. In this article, we review the basic principles underlying these novel MRI techniques and outline their current and anticipated future impact on the diagnosis and management of patients with cerebrovascular disease.

Brain↗

Review and update of MRI for clinicians.

The goal of this review is to provide clinicians with basic information about MRI and its current available uses. Introductory information and updates about MRI for a broad range of topics are presented: mechanics of MRI, selection of MRI for diagnosis; popular uses of MRI (MRA, acute stroke, acute spinal compression fractures, cardiac MR, breast MR); MR spectroscopy, functional MRI, changes in MRI technology; and MRI safety.

Humans↗

Functional neuroimaging in the preoperative evaluation of children with drug-resistant epilepsy.

UNLABELLED: FUNCTIONAL NEUROIMAGING: Although the primary imaging modality in the management of epilepsy is magnetic resonance imaging MRI, functional neuroimaging with positron-emission tomography (PET) and single photon emission computed tomography (SPECT) often provides complementary information and, in a number of situations, provides unique information that cannot be obtained with MRI. The most commonly used PET tracers used for epilepsy evaluation are 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) and [(11)C]flumazenil (FMZ). Recently, interictal PET with alpha-[(11)C]methyl-L: -tryptophan was found to be highly specific for the epileptic focus and can differentiate between epileptogenic and nonepileptogenic lesions in the same patient (e.g., in patients with tuberous sclerosis). DISCUSSION: In this review, we discuss clinical applications of these three PET tracers in drug-resistant temporal and extratemporal lobe epilepsy, selected epilepsy syndromes of childhood, lesional and nonlesional epilepsy, and the challenges of imaging secondary epileptic foci. A brief discussion of SPECT applications in epilepsy is also included. With further development of new tracers highly sensitive and specific for epileptogenic brain regions, the presurgical evaluation of refractory epilepsy will be greatly facilitated. Approximately 0.5 to 1.0% of the population suffer from epilepsy, of which 15-20% are intractable. Infants and children, whose seizures have a focal onset are refractory to anticonvulsants and are prolonged, tend to have the worst cognitive outcome [Meador KJ, Neurology 58 (Suppl 5):S21-S26, 2002]. Seizures themselves affect the developing brain and contribute to an adverse neurologic outcome (Holmes, Pediatric Neurology 33:1-110, 2005). CONCLUSION: Therefore, in treating children with intractable epilepsy, it is important to consider seizure control and to give allowance for normal cognitive development.

Brain Mapping↗

Assessment of pelvic organ descent by use of functional cine-MRI: which reference line should be used?

BACKGROUND AND AIMS: So far there is no agreement between clinical and radiological measurements and reference points for the quantification of pelvic organ descent in women. The aim of this study was to find out which of three reference lines on functional cine-magnetic resonance imaging (MRI) correlates best with the respective clinical diagnoses. METHODS: We retrospectively evaluated the functional cine-MRI studies of 41 asymptomatic volunteers. Our golden standard was the results of the clinical examination using the International Continence Society (ICS)-score. On MRI, we measured the distance of the bladder-neck, distal edge of cervix/posterior fornix, and the most ventrocaudal point of the ventral rectal wall, respectively, to the pubococcygeal line (PCL), the horizontal tangent of the inferior rim of the pubic bone, and the line drawn through the long axis of the pubic bone. The results were correlated with the respective clinical findings using descriptive analysis alone. RESULTS: The volunteers either showed a Stage 0 (16 cases), Stage I (12 cases), or a Stage II (13 cases) organ descent on clinical examination with 10 women (24.4%) having a pathological ICS-score in the anterior, 15 women (36.1%) in the superior, and 4 women (9.8%) in the posterior compartment. On functional MRI the best correlation with the clinical results was achieved using the PCL for the anterior compartment (22.0%), the PCL with an offset of +3 cm for the superior (36.6%), and the hymenal line (HL) for the posterior compartment (9.8%). CONCLUSIONS: Organ descent on functional cine-MRI cannot be described using only one reference line. In order to optimize clinical exploitation of functional MRI of the pelvic floor a consensus regarding imaging protocols and evaluation criteria should be aimed for.

Cervix Uteri↗

Influence of 1.5-Tesla intraoperative MR imaging on surgical decision making.

To determine the frequency that high-field magnetic resonance (MR) imaging sequences influenced surgical decision making during intraoperative MR-guided surgery. From January 1997 to February 2001, 346 MR-guided procedures were performed using a 1.5-Tesla MR system (NT-ACS, Philips Medical Systems). This system can perform functional MR imaging (fMRI), diffusion weighted imaging (DWI), MR spectroscopy (MRS), MR angiography (MRA), and MR venography (MRV) in addition to T1-weighted, T2-weighted, and turbo FLAIR (fluid-attenuated inversion recovery) imaging. FMRI was used to determine areas of brain activation for language, motor function, and memory. DWI was utilized after tumor resection to exclude cerebral ischemia or infarction. MRS was obtained to identify areas of elevated choline that were suspected to correlate with tumor presence. MRA and MRV localized vascular structures adjacent to tumors prior to resection. The intraoperative procedures performed included 140 brain biopsies of which 82 utilized a trajectory guide and prospective stereotaxy. MRS was used in 42 biopsies (30%), of which 29 had turbo spectroscopic imaging (TSI) and 21 had single voxel spectroscopy (SVS). In all biopsy cases, diagnostic tissue was obtained. There were 103 tumor resections of which 18 (17%) had MRS. Functional MRI was used in 17 cases; 3 biopsies (2%) and 14 planned resections (14%). Speech function was localized in 3 cases, memory function in 3, and motor function in 11. In one case where the motor function of the tongue was intimately involved with a low-grade glioma, resection was not attempted. DWI was used in less than 10% of tumor resections. MRA and MRV were performed in 3 (3%) and 2 (2%) of tumor resections, respectively. The imaging capabilities (i.e., fMRI, DWI, MRA, MRV) associated with high-field intraoperative MR influenced surgical decision making primarily for tumor resections. MRS influenced target selection during brain biopsy.

Biopsy↗

Functional neuroimaging and childhood autism.

Childhood autism is now widely viewed as being of developmental neurobiological origin. Yet, localised structural and functional brain correlates of autism have to be established. Structural brain-imaging studies performed in autistic patients have reported abnormalities such as increased total brain volume and cerebellar abnormalities. However, none of these abnormalities fully account for the full range of autistic symptoms. Functional brain imaging, such as positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional MRI (fMRI) have added a new perspective to the study of normal and pathological brain functions. In autism, functional studies have been performed at rest or during activation. However, first-generation functional imaging devices were not sensitive enough to detect any consistent dysfunction. Recently, with improved technology, two independent groups have reported bilateral hypoperfusion of the temporal lobes in autistic children. In addition, activation studies, using perceptive and cognitive paradigms, have shown an abnormal pattern of cortical activation in autistic patients. These results suggest that different connections between particular cortical regions could exist in autism. The purpose of this review is to present the main results of rest and activation studies performed in autism.

Autistic Disorder↗