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Flow velocity of the cortical vein and its effect on functional brain MRI at 1.5T: preliminary results by cine-MR venography.

The purpose of this study is to demonstrate the effect of altering flow velocity of cerebral cortical veins as the source of the signal change observed in functional magnetic resonance imaging (fMRI) of the brain. 10 healthy volunteers were examined after instructions in self-paced hand grasping. Experiments were performed using a 1.5-Tesla whole body MR scanner with a conventional two-dimensional gradient echo sequence (TR/TE/flip angle 400/60/40, first order flow rephased, reduced band width 8 Hz/pixel). Flow velocity measurements were performed for the cortical veins which corresponded to the activated areas depicted on fMRI. Velocity was estimated from the cine-MR venography (cine-MRV) with a tagging technique. Flow phantom studies were performed to delineate the effect of flow velocity differences upon the subtraction images of fMRI. The cine-MRV revealed increased flow velocity of the cortical veins during activation in seven volunteers, with a mean velocity difference of 15 mm/sec. Flow phantom studies suggested that the increased flow velocity may result in changes of the flow signal profile due to oblique flow displacement. Subtraction of the two images with different flow profiles produces flow signal enhancement. Increased flow velocity of the cortical veins during the activation is an important factor which contributes to the signal of fMRI.

Adult↗

Manganese ion enhances T1-weighted MRI during brain activation: an approach to direct imaging of brain function.

Present techniques for functional MRI rely on detecting changes in hemodynamics that result as a consequence of brain activation. It would be useful if MRI techniques could be developed that enable imaging of a parameter directly related to neuronal activity. Influx of calcium into neurons is necessary for release of neurotransmitters. Divalent manganese ions (Mn2+) can enter cells through voltage-gated calcium channels and Mn2+ is paramagnetic. Mn2+ accumulation in brain due to activation should alter relaxation times offering an approach to sensitize MRI to calcium influx in the brain. To test this idea, T1-weighted MRI was obtained from the rat brain in the presence of a continuous intravenous infusion of 3.6 mumol/min MnCl2. In the anesthetized rat brain, signal enhancement was detected in regions corresponding to ventricles. Activation of the brain with glutamate led to increase in MRI signal intensity in the brain to 238 +/- 23% of the original. This increase in signal was dependent on the presence of MnCl2 and was not due to changes in blood flow. It was necessary to break the blood brain barrier with mannitol to make Mn2+ accessible to the active sites for efficient detection. Enhancement of MRI signal in the brain was also detected with decreasing anesthesia and with somatosensory stimulation. Due to the slow clearance of Mn2+ from the stimulated region of the brain, MRI enhancement could also be detected after stimulation that occurred on awake, behaving rats outside the magnet. These data indicate that MnCl2 shows potential as a MRI contrast agent that is directly sensitive to brain activation.

Animals↗

Computational hyperspectral interferometry for studies of brain function: proof of concept.

Hyperspectral interferometric microscopy uses a unique combination of optics and algorithm design to extract information. Local brain activity rapidly changes local blood flow and red blood cell concentration (absorption) and oxygenation (color). We demonstrate that brain activity evoked during whisker stimulation can be detected with hyperspectral interferometric microscopy to identify the active whisker-barrel cortex in the rat brain. Information about constituent components is extracted across the entire spectral band. Algorithms can be flexibly optimized to discover, detect, quantify, and visualize a wide range of significant biological events, including changes relevant to the diagnosis and treatment of disease.

Animals↗

Functional brain organization in bipolar affective patients during manic phase and after recovery: a digit dichotic listening study.

To study the functional organization of the cerebral hemispheres in patients with bipolar psychosis using a verbal dichotic listening test for pairs of digits 26 patients were tested twice, during the acute expression of manic phase and after recovery. The patient group during the manic phase did not support the expected right-ear advantage of normal subjects on verbal dichotic tests but showed a statistically significant left-ear advantage, which shifted after recovery toward the typical normal asymmetry. Comparing patients during the manic phase and after recovery showed that the left-ear advantage as well as the shift in right-ear advantage after recovery was due to the reduction of left-ear performance. From the over-all neuropsychological findings for these patients mania may be hypothesized to be characterized by overactivation of the right hemisphere. This phaenomenon seems associated with acuteness of the symptoms of the psychotic disorder.

Acute Disease↗

Functional brain imaging using a long intravenous half-life gadolinium-based contrast agent.

PURPOSE: We describe a technique for functional MR imaging (fMRI) with high spatial and temporal resolution using a long intravascular half-life gadolinium-based contrast agent, MS-325. METHODS: All fMRI measurements used a rat model of sensory cortex activation with forepaw electrical stimulation under alpha-chloralose anesthesia. Standard blood oxygen level-dependent (BOLD) fMRI measurement was initially performed. MS-325 was then intravenously administered and a MS-325 fMRI measurement was performed by using a 3D gradient-echo sequence. RESULTS: We found that a dose of 0.1 mmol/kg MS-325 produced adequate signal intensity changes in rat sensory cortex to demonstrate activations. Using a boxcar stimulation pattern with a standard correlation analysis, the locations of the most significantly activated voxels (ie, highest Z score) in the MS-325 and BOLD fMRI measurements were not significantly different. CONCLUSIONS: MS-325 fMRI has the advantage of using a T1-weighted sequence, rather than the highly T2*-weighted sequences used in other common fMRI techniques. This could reduce the susceptibility artifacts associated with fMRI.

Animals↗

Long-term treatment of male F344 rats with deprenyl: assessment of effects on longevity, behavior, and brain function.

L-Deprenyl (selegiline) was chronically administered to male Fischer 344 rats via their drinking water beginning at 54 weeks of age (estimated daily dose: 0.5 mg/kg/day). Beginning at 84 weeks of age, the rats were behaviorally evaluated using a sensorimotor battery, a motor-learning task, and the Morris water maze. At 118 weeks of age, cerebellar noradrenergic function was evaluated in the surviving rats using in vivo electrochemistry. The rats were then sacrificed to measure brain monoamine oxidase activity and perform quantitative autoradiography to evaluate the effect of chronic deprenyl treatment on beta-adrenergic receptors in the cerebellum, alpha 2-adrenergic receptors several brain regions, and D1 and D2 dopamine receptors in the striatum. Deprenyl treatment reduced brain monoamine oxidase B activity by 85%, but had no effect on brain monoamine oxidase A. A clear effect of chronic deprenyl treatment upon longevity was not observed. Several measures of CNS function were altered in the deprenyl-treated animals: 1) spatial learning in the Morris water maze was improved; 2) electrochemical signals recorded following local application of NE were reduced, and the responsiveness to the reuptake blocker nomifensine was enhanced, in the cerebellum; 3) beta-adrenergic receptor binding affinity was increased in the cerebellum; 4) alpha 2-adrenergic receptor density was increased in the inferior colliculus; and 5) striatal D1 dopamine receptor density was reduced but binding affinity was enhanced. In contrast, chronic deprenyl treatment did not cause changes in: 1) sensorimotor function, as evaluated by balance beam, inclined screen, or wire hang tasks; 2) motor learning; 3) alpha 2-adrenergic receptor density in any region examined except for the inferior colliculus, or binding affinity in any region examined; or 4) striatal D2 dopamine receptor number or affinity. Thus, long-term oral administration of deprenyl extended the functional life span of rats with respect to cognitive, but not motor, performance.

Animals↗

Magnetic resonance imaging of human brain function.

BACKGROUND: Previously the exclusive domain of the technology of positron emission tomography, functional MRI is now proving capable of mapping functional regions of the human cortex in near real time during specific task activations or in response to any hemodynamic stress. Of particular interest is the opportunity to observe secondary cortical responses, activation due to imagined tasks, memory function, time-resolved pathways through cortical regions, and activation in sub-cortical structures. METHODS AND RESULTS: One method of functional MRI uses blood oxygenation changes, which can be imaged continuously while functional centers are being stimulated. Image intensity can become darker if there is more deoxygenated blood and brighter if more oxygenated blood enters the brain. This concepts works in all perfused tissues in the body, and allows use of the blood oxygenation mechanism to image neuronal activation. A second method takes advantage of the fact that the protons within the MRI slice are always partially saturated by the rapid rate of imaging. As blood flow delivers unsaturated blood water protons into an imaged slice, these arterially-delivered protons will appear very bright in the image. Visualization of this effect is accomplished by simple image subtraction or by comparison of intensity changes as a function of the paradigm application frequency. Using either approach leads directly to a functional map. CONCLUSIONS: At present, clinical applications are rapidly moving toward routine non-invasive mapping of distortions of the functional motor and somatosensory cortex and other cortical regions as a result of brain tumors. Other clinical applications include the observation of the effect of degenerative diseases such as multiple sclerosis. Alzheimer's disease, stroke, migraine, epilepsy, and other diseases causing neuronal loss and Parkinsonism. Functional MRI and its applications will continue to grow exponentially throughout the decade.

Brain↗

Anatomical and functional brain imaging in adult attention-deficit/hyperactivity disorder (ADHD)--a neurological view.

In this review, we discuss current structural and functional imaging data on ADHD in a neurological and neuroanatomical framework. At present, the literature on adult ADHD is somewhat sparse, and so results from imaging have to therefore be considered mainly from the childhood or adolescence perspective. Most work has considered the impairment of executive functions (motor execution, inhibition, working memory), and as such a number of attention networks and their anatomical correlates are discussed in this review (e.g. the cerebello-(thalamo-)-striato-cortical network seems to play a pivotal role in ADHD pathology from childhood to adulthood). The core findings in ADHD imaging are alterations in the architecture and function of prefrontal cortex and cerebellum. The dorsal part of anterior cingulated cortex (dACC) is an important region for decision making, and executive control is impaired in adult ADHD. Finally, dysfunction of basal ganglia is a consistent finding in childhood and adulthood ADHD, reflecting dysregulation of fronto-striatal circuitry. The cerebellum, and its role in affect and cognition, is also persistently implicated in the pathology of ADHD.

Aged↗

Radiotherapeutic effects on brain function: double dissociation of memory systems.

OBJECTIVE: The neurocognitive sequelae of therapeutic cranial irradiation are not well characterized in adults with primary brain tumors. To address this problem, we prospectively examined neuropsychological findings during two phases of radiation effects. BACKGROUND: Investigations of radiation effects have revealed variable outcomes that range from no radiation-associated morbidity to severe cognitive impairment, but have relied on case reports or retrospective studies of late-delayed changes in white matter or in cognition. No reliable radiographic or neurocognitive tools exist to describe the multiple phases of radiation effects. METHOD: Twenty adult patients (median age, 39 years) from a university hospital were treated with radiotherapy (RT) for low-grade primary brain tumors. Prospective longitudinal neuropsychological studies were compared at baseline (after surgery and before irradiation) and at 3, 6, and 12 months after RT to examine early-delayed effects, including verbal memory changes in 20 patients and visual memory changes in 11 patients. We also examined cognitive changes during the late-delayed phase for up to 3 years after RT and determined whether early-delayed memory deficit predicted late-delayed memory deficit in a small subset of patients. A comprehensive neuropsychological battery was used, including verbal and visual memory tests designed to compare learning, storage, and retrieval. RESULTS: Patients demonstrated normal verbal memory at baseline, decrement, and then rebound in verbal retrieval. Deficit at baseline and recovery up to 1 year after RT defined visual memory. Together, these observations constitute a double dissociation of memory functions. No changes over time were observed in other neurocognitive tests or in fatigue or mood measures. Time-dependent patterns of each long-term memory test were examined in relation to lesion site in individual patients. CONCLUSIONS: The double dissociation of memory functions after RT may provide markers for the damaging and facilitative early-delayed effects of RT. Late-delayed effects were not predicted based on early-delayed changes in a small sample.

Adult↗