Diffusion tensor MR imaging of the human brain

PURPOSE: To assess intrinsic properties of water diffusion in normal human brain by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation. MATERIALS AND METHODS: Maps of the principal diffusivities of D, of Trace(D), and of diffusion anisotropy indices were calculated in eight healthy adults from 31 multisection, interleaved echo-planar diffusion-weighted images acquired in about 25 minutes. RESULTS: No statistically significant differences in Trace(D) (approximately 2,100 x 10(-6) mm2/sec) were found within normal brain parenchyma, except in the cortex, where Trace(D) was higher. Diffusion anisotropy varied widely among different white matter regions, reflecting differences in fiber-tract architecture. In the corpus callosum and pyramidal tracts, the ratio of parallel to perpendicular diffusivities was approximately threefold higher than previously reported, and diffusion appeared cylindrically symmetric. However, in other white matter regions, particularly in the centrum semiovale, diffusion anisotropy was low, and cylindrical symmetry was not observed. Maps of parameters derived from D were also used to segment tissues based on their diffusion properties. CONCLUSION: A quantitative characterization of water diffusion in anisotropic, heterogeneously oriented tissues is clinically feasible. This should improve the neuroradiologic assessment of a variety of gray and white matter disorders.     

Striatal and extrastriatal imaging of dopamine D2 receptors in the living human brain with [123I]epidepride single-photon emission tomography

The complete sequence of a 36775 bp DNA segment located on the right arm of chromosome XV of Saccharomyces cerevisiae has been determined and analysed. The sequence encodes 26 open reading frames of at least 100 amino acids. Eight of these correspond to known genes, whereas 18 correspond to new genes.     

Addiction is a brain disease, and it matters

Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction has embedded behavioral and social-context aspects that are important parts of the disorder itself. Therefore, the most effective treatment approaches will include biological, behavioral, and social-context components. Recognizing addiction as a chronic, relapsing brain disorder characterized by compulsive drug seeking and use can impact society's overall health and social policy strategies and help diminish the health and social costs associated with drug abuse and addiction.     

Magnetic brain imaging of extinction processes in human classical conditioning

By recording neuromagnetic events during aversive classical conditioning, we examined the extinction of a previously described conditioned response. Averaging over non-reinforced exposures to the conditioned stimulus revealed magnetic activity in the secondary somatosensory and insular cortices, appearing between 110 and 140 ms after the omitted unconditioned electric shock. We suggest this activity to be elicited by the discrepancy between shock expectancy and perceptual processes associated with the omission of the unconditioned stimulus, reflecting one of several brain processes in extinction.     

Echo-planar imaging of the brain

In this review, the clinical utility of echoplanar techniques in MRI of the brain is discussed. Comparison of high-resolution EPI with SE/turbo-SE shows high image quality of EPI in the supratentorial brain. In the infratentorial region, however, susceptibility artifacts limit image quality. For the assessment of neuronal brain activation utilizing the intrinsic contrast of blood (BOLD), EPI has definite advantages over other techniques of functional MRI. Due to its superior temporal resolution and multislice capabilities, EPI allows for analysis of complex neuronal activation patterns. Diffusion imaging benefits from the lack of bulk motion artifacts and serves primarily to detect early stroke. Three methods of perfusion imaging (rel. blood volume, rel. blood flow) are discussed: the susceptibility artifact method (T2*), the relaxitivity method (T1), and the signal-labelling technique (STAR). Perfusion imaging may have a clinical impact in the assessment of brain tumors and cerebral ischemia.     

Intraoperative imaging of the brain

The development of computed imaging techniques has revolutionized contemporary neurosurgical procedures. In a 20-year interval, intraoperative imaging was used in more than 4,000 patients at our center. The selection of the appropriate intraoperative imaging tool was dependent on the neurosurgical procedure performed. In our dedicated operating room suite, intraoperative fluoroscopic imaging was used during transsphenoidal, spinal, and functional procedures, e.g. to treat percutaneous trigeminal neuralgia. A dedicated intraoperative computed tomography scanner was first available in 1981 and was used in more than 1,500 stereotactic or image-guided procedures. During radiosurgical procedures with the Gamma Knife (n = 1,560) a variety of intraoperative imaging tools (MRI, CT, angiography, and digital subtraction angiography) were used to define the target. The output of these imaging tools is currently transferred via fiberoptic ethernet to a wide variety of computer workstations designed to facilitate surgical or radiation dose planning. In addition, intraoperative imaging became increasingly important during vascular neurosurgery. Because of its superior patient accessibility and instrument compatibility. CT is likely to remain the most important imaging tool for conventional intraoperative image-guided stereotactic surgery. In contrast, intraoperative MRI proved to be the superior imaging tool for radiosurgery.     

Three-dimensional visualization and quantification of the benzodiazepine receptor population within a living human brain using PET and MRI

The purpose of this study was to measure feelings following weaning in women planning employment within 1 year postpartum and to examine the effects of factors related to duration and employment on these feelings. No significant differences in feelings of sadness, anger, guilt, and relief were reported by women who weaned due to mother-led reasons or baby-led reasons or in women who did or did not meet their breastfeeding goal. Women who did not feed their babies as planned when employed, however, felt significantly more sadness/depression and guilt compared to women who achieved their planned method of feeding.     

Proton-decoupled 31P chemical shift imaging of the human brain in normal volunteers

Proton-decoupled, 31P three-dimensional (3-D) chemical shift imaging (CSI) spectra have been acquired from the entire human brain using a new dual tuned resonator. The resonator operates in quadrature mode to provide improved sensitivity, excellent B1 homogeneity and reduced power deposition at both frequencies. Proton-decoupled and fully NOE enhanced, 31P spectra were acquired from normal volunteers using Waltz-4 proton decoupling with continuous wave bi-level excitation applied through a second radio frequency channel. Well resolved peaks in the phosphomonoester (PME) and phosphodiester regions were obtained from nonlocalized FIDs and spectra localized with 3-D CSI without processing for resolution enhancement. pH measurements made over large regions of the brain using the P(i) resonance show no significant variations (6.9 +/- 0.02) for a single individual. The improved spectral resolution and sensitivity of the PME resonances results in more well defined metabolite images of the PME peak region.     

Digital imaging microscopy of living cells

Fluorescence microscopy has undergone a resurgence in interest following the discovery of green-fluorescent protein (GFP) and its increasing use in live-cell imaging. This article describes an enhanced form of epifluorescence microscopy, digital imaging microscopy, that can be used to produce high-resolution three-dimensional images of samples labelled with GFP, or other fluorochromes, using simple instrumentation and image-restoration software.     

Fast spin-echo imaging of the brain and spine

The recent advent and implementation of rapid spin-echo techniques has allowed increased imaging speed while maintaining spin-echo-like contrast. This review explains the basis of fast spin-echo imaging and attempts to elucidate the etiology of the differences between it and spin-echo imaging. Clinical applications and limitations of fast spin-echo imaging in the brain and spine will also be addressed.     

A comparative study of postmortem MR imaging and pathological examination of human brain specimens

OBJECTIVE: To determine typical outcome "benchmarks" for 18 functional tasks in patients undergoing stroke rehabilitation. The benchmarks are intended to serve as points of reference to which the outcomes of patients with similar impairments and degrees of disability can be compared. SUBJECTS: Records from 26,339 stroke patients discharged from 252 inpatient facilities across the United States that submitted 1992 data to the Uniform Data System for Medical Rehabilitation. METHODS: Stroke impairment was detailed as the presence or absence of hemiparesis resulting from stroke and the side(s) of involvement. Within each of five stroke impairment categories, patients were further classified by the Functional Independence Measure-Function-Related Groups (FIM-FRGs) into nine syndromes by degree of disability (admission motor and cognitive FIM scores) and by age. Outcomes were determined for each stroke syndrome at patients' discharge from medical rehabilitation. MAIN OUTCOME MEASURES: Patients' median performance levels on each of the 18 items making up the FIM, length of stay, and community discharge rates. RESULTS: The majority of patients whose admission motor FIM scores were above 37 were able to eat, groom, dress the upper body, and manage bladder and bowel functions independently by discharge. In addition to these tasks, most of those whose motor FIM scores were above 55 were able to dress the lower body, bathe, and transfer onto a chair/bed or toilet. The majority of patients whose initial motor FIM scores were above 62 points and whose cognitive FIM scores were above 30 gained independence in most tasks, including stair climbing and tub transfers. Community discharge rates ranged from 51.6% for the group of patients with the most severe disabilities to 99.2% for the group with the least severe disabilities. CONCLUSION: The clinician can apply these benchmarks to guideline development and quality improvement, and in establishing patient goals.     

Triazolam-induced modulation of muscarinic acetylcholine receptor in living brain slices as revealed by a new positron-based imaging technique

The effect of triazolam, a potent benzodiazepine (BZ) agonist, on muscarinic acetylcholinergic receptor (mAChR) binding was investigated in living brain slices by use of a novel positron-based imaging technique. Fresh rat brain slices were incubated with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB), a mAChR antagonist, in oxygenated Krebs-Ringer solution at 37 degrees C. During incubation, time-resolved imaging of [11C]NMPB binding in the slices was constructed on the storage phosphor screens. Addition of triazolam (1 microM) plus muscimol (30 microM), a GABA(A) receptor agonist, to the incubation mixture decreased the specific binding of [11C]NMPB. Ro15-1788, a BZ receptor antagonist, prevented this effect, indicating that the effect was exerted through the GABA(A)/BZ receptor complex. These results demonstrated that stimulation of the GABA(A)/BZ receptor lowers the affinity of the mAChR for its ligand, which may underlie the BZ-induced amnesia, a serious clinical side effect of BZ. No such effect in the P2-fraction instead implies that the integrity of the neuronal cells and/or their environment is prerequisite for the modulation of mAChR by GABA(A)/BZ stimulation.     

Differential permeability and quantitative MR imaging of a human lung carcinoma brain xenograft in the nude rat

This study characterized agent differential permeability, three-dimensional tumor volume, and survival in an LX-1 human small cell lung carcinoma intracerebral xenograft model in the nude rat. The percent accessible tissue space (distribution volume) and the permeability x capillary surface product for aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), dextran 10 (M(r) 10,000), and dextran 70 (M(r) 70,000) were measured between 8 and 16 days after inoculation of tumor. Magnetic resonance imaging and histology were used to quantitate intracerebral tumor volume (mm3). Accessible tissue space (ml/g) and permeability x capillary surface product in intracranial tumor, surrounding brain, and subcutaneous tumor decreased with increasing molecular weight of the agent, regardless of the number of days after inoculation. Accessible tissue space in intracranial tumor increased between 8 and 16 days for all agents except dextran 70. There was little change in the subcutaneous tumor or other tissues with time. Tumor volume calculations from imaging studies correlated with volumetric measurements from histological sections (r2 = 98.5%) and illustrated natural tumor progression (9 to 225 mm3). These results provide a basis for therapeutic design based on differential permeability of specific agents and the ability to quantitatively measure brain tumor volume for accessing tumor response.     

Psychoneuroendocrinology and brain imaging in depression

During ripening of grape (Vitis labruscana L. cv Concord) berries, abundance of several proteins increased, coordinately with hexoses, to the extent that these became the predominant proteins in the ovary. These proteins have been identified by N-terminal amino acid-sequence analysis and/or function to be a thaumatin-like protein (grape osmotin), a lipid-transfer protein, and a basic and an acidic chitinase. The basic chitinase and grape osmotin exhibited activities against the principal grape fungal pathogens Guignardia bidwellii and Botrytis cinerea based on in vitro growth assays. The growth-inhibiting activity of the antifungal proteins was substantial at levels comparable to those that accumulate in the ripening fruit, and these activities were enhanced by as much as 70% in the presence of 1 m glucose, a physiological hexose concentration in berries. The simultaneous accumulation of the antifungal proteins and sugars during berry ripening was correlated with the characteristic development of pathogen resistance that occurs in fruits during ripening. Taken together, accumulation of these proteins, in combination with sugars, appears to constitute a novel, developmentally regulated defense mechanism against phytopathogens in the maturing fruit.     

Neurotransmission and the ontogeny of human brain

The early appearance of neurotransmitters in brain tissue refers to their regulative functions on the neuronal circuits. Many neurotransmitters have direct effects on neuronal outgrowth and differentiation during brain development, which precede their role in synaptic information coding. Both the neurotrophic and neurotoxic properties of excitatory amino acids (EAAs) have focused special interest on glutamatergic neurotransmission during brain development. Therefore, this work intends to review and discuss developmental alterations of the EAA neurotransmitter system in the human brain, their relation to human brain maturation and implications for pathological processes during early human brain development.     

Functional imaging of the brain using computed tomography

Data from rapid-sequence CT scans of the same cross section, obtained following bolus injection of contrast material, were analyzed by functional imaging. The information contained in a large number of images can be compressed into one or two gray-scale images which can be evaluated both qualitatively and quantitatively. The computational techniques are described and applied to the generation of images depicting bolus transit time, arrival time, peak time, and effective width.     

AFM imaging and elasticity measurements on living rat liver macrophages

The authors investigated the morphology and the elastic properties of living cultured rat liver macrophages (Kupffer cells) with an atomic force microscope (AFM). Continuous imaging and elasticity mapping of individual cells in physiological buffer was carried out for several hours without damaging the cells as judged by their persistent undisturbed morphology. Dynamic events such as protrusive activity were observed in time course. The importance of the cytoskeleton for the mechanical properties of the cell has been investigated by measuring the cell's elasticity as a function of position. Chemical disassembly of the actin network by applying 10 microgram/ml cytochalasin B decreased the cell's average elastic modulus seven-fold within less than 40 minutes. Treating the cells with 0.1 micrograms/ml latrunculin A resulted in a two-fold decrease in the elastic modulus merely in the perinuclear region after 40 minutes, whereas other parts of the cell were not affected.     

Quantitative imaging of TATA-binding protein in living yeast cells

We describe the quantitative monitoring of TATA-binding protein (TBP) localization and expression in living Saccharomyces cerevisiae cells. We replaced the endogenous TBP with a green fluorescent protein (GFP) x TBP fusion, which was imaged quantitatively by laser scanning confocal microscopy (LSCM). When GFP x TBP expression was altered by using various promoters, the levels measured by LSCM correlated well with the levels determined by immunoblot of whole cell extract protein. These results show that GFP x TBP imaging not only offers a method of measurement equivalent to a more conventional technique but also provides real-time quantitation in living cells and subcellular localization information. Time-lapse confocal imaging of GFP x TBP in mitotic yeast cells revealed that it remains localized to the nucleus and displays an asymmetric distribution (1:0.7) between mother and daughter cells. Based on this and data from a mutant which underexpresses GFP x TBP, we suggest that intracellular levels of TBP are near rate-limiting for growth and viability.