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Increased water self-diffusion in chronic plaques and in apparently normal white matter in patients with multiple sclerosis.

A new method for measurement of water self-diffusion compensating for zeroth and first order movements was used to study the apparent diffusion coefficient (ADC) in 15 patients with chronic multiple sclerosis (MS) and in two patients with acute MS. Ten healthy volunteers served as controls. A significantly higher ADC was found within chronic plaques compared to the apparently normal white matter of the chronic patients. The ADC was higher in the acute plaques compared to the chronic plaques. The ADC in apparently normal white matter of the chronic patients were significantly higher than in white matter of healthy volunteers. We hypothesize that an increase of the ADC in plaques may be related to an increase in the extracellular space due to oedema and demyelination. The increased ADC in apparently normal white matter suggests that there may be a change in the composition of the white matter of chronic MS patients, perhaps related to oedema and expanded extracellular space.

Adult↗

Age-related white matter atrophy in the human brain.

Aging of the brain involves not only appreciable shrinkage of the cortex and other gray matter structures but above all loss of white matter. This could be due to a decline in the number of myelinated fibers or to a loss of water. To assess the role played by each of these factors we studied brains from 33 neurologically intact subjects at autopsy representing three different age groups: 15-50, 51-70, and 71-93 years. The precentral gyrus, gyrus rectus, and corpus callosum were selected for investigation, with staining for alkaline phosphatase on native cryostat sections to visualize the capillary network, and staining for myelin on semithin sections for nerve fiber visualization. Atrophy was objectified by measuring the number of capillaries, the intercapillary distance, and capillary length, since the capillary network remains constant throughout normal life. A mean difference of 16-20% was found, representing white matter atrophy, between the oldest and youngest age-groups. The cortex of the corresponding gyri, on the other hand, showed a difference of less than 6%. Morphometric investigation of sections stained for myelin showed that the brains with a mean age of 78.7 +/- 6.6 years had 10-15% fewer myelinated fibers. This was only partly offset by an increase in the volume of extracellular space. Our findings show that the age-related decline in brain volume is much more a question of white matter atrophy than of brain cortex atrophy. White matter atrophy could be an indirect indicator of nerve cell loss, since the volume of a nerve cell is much smaller than its myelinated fiber.

Adolescent↗

Relative contents of sodium, potassium, and dry matter in diabetic cataractous lenses.

Cataractous lenses from diabetic patients were pre-operatively divided into 3 groups according to the biomicroscopical appearance of the lenses and biochemical analyses of CNa+, CK+, and dry matter were performed. 1) Immature cataractous lenses without anterior capsular/subcapsular opacity (ac-sco): (N=4) CNa+ = 35 meq/kg lens water, CK+ = 164 meq/kg lens water, dry matter 24%. 2) Immature cataractous lenses with ac-sco: (N=12) CNa+ = 151 meq/kg lens water, CK+ = 62 meq/kg lens water, dry matter 33%. 3) Totally opaque lens: (N=1) CNa+ = 185 meq/kg lens water, CK+ = 12 meq/kg lens water, dry matter 19%. The concentrations of sodium, potassium, and dry matter were equal to the findings in senile non diabetic cataractous lenses.

Aged↗

X-ray microanalytic method for measurement of dry matter and elemental content of individual bacteria.

A method for the determination of dry matter and elemental content of individual bacterial cells is described. The method is based on energy-dispersive X-ray microanalysis in a transmission electron microscope. A theory for area correction of intensity is developed. Escherichia coli in the late exponential phase of growth and early stationary phase (glucose limited) had an average dry matter content of 278 and 154 fg/cell, respectively. Of the elements detected, sodium, magnesium, phosphorus, sulphur, chlorine, potassium, and calcium together made up 15 to 17% of the dry matter content. A phosphorus content of 4.2 to 5.4% of the dry matter was found in these cells. Volume measurements of air-dried cells gave an average of 1.20 to 1.25 micron3. These results emphasize that dry matter content and elemental composition can be measured directly on single cells from complex microbial communities.

Electron Probe Microanalysis↗

Detection of tissue culture-adapted Theiler's virus RNA in spinal cord white matter cells throughout infection.

The appearance of histological lesions and the localization of viral RNA in the central nervous system of mice infected with tissue culture-adapted Theiler's murine encephalomyelitis virus (WW strain) (TMEV-WW) was studied. Viral RNA was detected by autoradiography after in situ hybridization, using a (3)H-labeled DNA probe complementary to virion RNA, which was applied to deparaffinized sections of central nervous system tissues from infected mice. Subjacent histological sections of tissues were used to assess the location and extent of lesions. Lesions were first observed at 20 days post-inoculation and appeared to enlarge throughout infection. They consisted of infiltrates of mononuclear cells and lymphocytes in spinal cord white matter and leptomeninges; at 78 days post-inoculation severe necrotizing and demyelinative myelitis and gliosis were observed. In contrast to the pathogenesis of brain-derived TMEV-WW-infected mice, no lesions were found in the central nervous system gray matter of mice infected with tissue culture-adapted TMEV-WW at any time post-infection. Tissue culture-adapted viral RNA was found in the cells of spinal cord white matter throughout infection; only one neuron in close proximity to the injection site was found to contain viral RNA shortly after infection. At early times after infection, spinal cord white matter cells containing viral RNA were found before development of inflammatory lesions; at later days post-inoculation, positive cells were found within, at the periphery of, or at a distance from lesions. The number of infected cells and the amount of viral RNA per cell appeared to remain constant from 20 to 78 days post-inoculation despite the increasing intensity of the inflammatory response. The nearly exclusive spinal cord white matter tropism of tissue culture-adapted TMEV-WW appeared to directly correlate with the disease-inducing potential of this virus.

Animals↗

An attenuated variant of the GDVII strain of Theiler's virus does not persist and does not infect the white matter of the central nervous system.

The DA strain of Theiler's virus causes a persistent and demyelinating infection of the white matter of spinal cord, whereas the GDVII strain causes a fatal gray-matter encephalomyelitis. Studies with recombinant viruses showed that this difference in phenotype is controlled mainly by the capsid. However, conflicting results regarding the existence of determinants of persistence in the capsid of the GDVII strain have been published. Here we show that a GDVII virus whose neurovirulence has been attenuated by an insertion in the 5' noncoding region does not persist in the central nervous systems of mice. Furthermore, this virus infects the gray matter efficiently, but not the white matter. These results confirm the absence of determinants of persistence in the GDVII capsid. They suggest that the DA capsid controls persistence by allowing the virus to infect cells in the white matter of the spinal cord.

Animals↗

Temporal evolution of water diffusion parameters is different in grey and white matter in human ischaemic stroke.

OBJECTIVES: Our purpose was to investigate whether differences exist in the values and temporal evolution of mean diffusivity ( ) and fractional anisotropy (FA) of grey and white matter after human ischaemic stroke. METHODS: Thirty two patients with lesions affecting both grey and white matter underwent serial diffusion tensor magnetic resonance imaging (DT-MRI) within 24 hours, and at 4-7 days, 10-14 days, 1 month, and 3 months after stroke. Multiple small circular regions of interest (ROI) were placed in the grey and white matter within the lesion and in the contralateral hemisphere. Values of [grey], [white], FA[grey] and FA[white] were measured in these ROI at each time point and the ratios of ischaemic to normal contralateral values ( R and FAR) calculated. RESULTS: and FA showed different patterns of evolution after stroke. After an initial decline, the rate of increase of [grey] was faster than [white] from 4-7 to 10-14 days. FA[white] decreased more rapidly than FA[grey] during the first week, thereafter for both tissue types the FA decreased gradually. However, FA[white] was still higher than FA[grey] at three months indicating that some organised axonal structure remained. This effect was more marked in some patients than in others. R[grey] was significantly higher than R[white] within 24 hours and at 10-14 days (p<0.05), and FAR[white] was significantly more reduced than FAR[grey] at all time points (p<0.001). CONCLUSIONS: The values and temporal evolution of and FA are different for grey and white matter after human ischaemic stroke. The observation that there is patient-to-patient variability in the degree of white matter structure remaining within the infarct at three months may have implications for predicting patient outcome.

Aged↗

Diffusion tensor magnetic resonance imaging at 3.0 tesla shows subtle cerebral grey matter abnormalities in patients with migraine.

BACKGROUND AND OBJECTIVE: Diffusion tensor (DT) magnetic resonance imaging (MRI) has the potential to disclose subtle abnormalities in the brain of migraine patients. This ability may be increased by the use of high field magnets. A DT MRI on a 3.0 tesla scanner was used to measure the extent of tissue damage of the brain normal appearing white (NAWM) and grey matter in migraine patients with T2 visible abnormalities. METHODS: Dual echo, T1 weighted and DT MRI with diffusion gradients applied in 32 non-collinear directions were acquired from 16 patients with migraine and 15 sex and age matched controls. Lesion load on T2 weighted images was measured using a local thresholding segmentation technique, and brain atrophy assessed on T1 weighted images using SIENAx. Mean diffusivity and fractional anisotropy histograms of the NAWM and mean diffusivity histograms of the grey matter were also derived. RESULTS: Brain atrophy did not differ between controls and patients. Compared with healthy subjects, migraine patients had significantly reduced mean diffusivity histogram peak height of the grey matter (p=0.04). No diffusion changes were detected in patients' NAWM. In migraine patients, no correlation was found between T2 weighted lesion load and brain DT histogram derived metrics, whereas age was significantly correlated with grey matter mean diffusivity histogram peak height (p=0.05, r=-0.52). CONCLUSIONS: DT MRI at high field strength discloses subtle grey matter damage in migraine patients, which might be associated with cognitive changes in these patients.

Adult↗

Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression.

BACKGROUND: Reduced hippocampal volume and increased prevalence of subcortical white matter lesions are associated with both recurrent early onset depression (EOD) and late onset depression (LOD). It is not clear whether these two factors differentially affect the age of onset of first depression. Therefore, we wished to investigate the relationship between age of first depression onset and hippocampal volume, with adjustment for subcortical white matter lesions. METHODS: MRI brain scans were used to compare hippocampal volumes and white matter lesions between age matched female patients (>60 years) with recurrent EOD and LOD and healthy controls. RESULTS: When comparing the three groups and adjusting for age, the Mini-Mental State Examination score, total brain volume and total hippocampal volume were significantly smaller in patients with EOD compared with controls (5.6 vs 6.1 ml; p = 0.04). The prevalence of larger subcortical white matter lesions was higher in patients with LOD compared with patients with EOD (47% vs 8%; p = 0.002). Patients with LOD did not differ in hippocampal volume from patients with EOD or from controls. CONCLUSIONS: In late life depression, age of first depression onset may distinguish between different independent neuropathological mechanisms. A small hippocampus volume may be a neuroanatomical marker of EOD depression and larger subcortical white matter lesions could be an intermediate between cerebrovascular disease and LOD.

Age of Onset↗

Asymmetrical extra-hippocampal grey matter loss related to hippocampal atrophy in patients with medial temporal lobe epilepsy.

BACKGROUND: Structural neuroimaging studies have consistently shown a pattern of extra-hippocampal atrophy in patients with left and right drug-refractory medial temporal lobe epilepsy (MTLE). However, it is not yet completely understood how extra-hippocampal atrophy is related to hippocampal atrophy. Moreover, patients with left MTLE often exhibit more intense cognitive impairment, and subtle brain asymmetries have been reported in patients with left MTLE versus right MTLE but have not been explored in a controlled study. OBJECTIVES: To investigate the association between extra-hippocampal and hippocampal atrophy in patients with MTLE, and the effect of side of hippocampal atrophy on extra-hippocampal atrophy. METHODS: Voxel-based morphometry analyses of magnetic resonance images of the brain were performed to determine the correlation between regional extra-hippocampal grey matter volume and hippocampal grey matter volume. The results from 36 patients with right and left MTLE were compared, and results from the two groups were compared with those from 49 healthy controls. RESULTS: Compared with controls, patients with MTLE showed a more intense correlation between hippocampal grey matter volume and regional grey matter volume in locations such as the contralateral hippocampus, bilateral parahippocampal gyri and frontal and parietal areas. Compared with right MTLE, patients with left MTLE exhibited a wider area of atrophy related to hippocampal grey matter loss, encompassing both the contralateral and ipsilateral hemispheres, particularly affecting the contralateral hippocampus. CONCLUSIONS: Our results suggest that left hippocampal atrophy is associated with a larger degree of extra-hippocampal atrophy. This may help to explain the more intense cognitive impairment usually observed in these patients.

Adolescent↗

Magnetisation transfer ratio of normal brain white matter: a normative database spanning four decades of life.

OBJECTIVES: To establish a normative database for magnetisation transfer ratio (MTR) measurements in the white matter of healthy adult brains. Such MTR values were evaluated for regional variation and evidence of differences associated with aging, sex, and handedness. METHODS: Forty one healthy volunteers, ranging in age from 16 to 55 years, underwent axial brain magnetisation transfer (MT) imaging on a 1.5 Tesla magnetic resonance scanner. Calculated MT images allowed evaluation of MTR from specific regions within the corpus callosum, cerebral hemispheres, and pons. RESULTS: Highest values were noted in the corpus callosum. No significant sex differences were seen for any region studied. Small but significant age related reductions in MTR were noted in the corpus callosum and other cerebral white matter regions studied. Comparing MTR values between young (16-35 years) and older (36-55 years) age groups, this was most apparent in the corpus callosum (40.82% units in the young group v 40.28% units in the older group, P < 0.05) and frontal white matter (39.65% units in the young group v 39.18% units in the older group, P < 0.005). In addition, values for MTR were analysed for evidence of hemispheric asymmetry. MTR values were higher in the left hemisphere for all regions studied, reaching significance in the centrum semiovale (37.75% units v 37.57% units, P < 0.05) and parieto-occipital white matter (37.67% units v 37.43% units, P < 0.05). No relation between such interhemispheric MTR differences and handedness was noted. CONCLUSIONS: Magnetisation transfer imaging shows significant age related changes in normal brain white matter. In addition to regional variations in MTR in the normal brain, there seem to be small but significant variations in MTR between the cerebral hemispheres. It is important to consider such normal variations when evaluating MTR in pathological states.

Adolescent↗

Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study.

PURPOSE: To evaluate differences in white matter diffusion properties as a function of age in healthy children and adolescents. MATERIALS AND METHODS: Echo-planar diffusion-tensor magnetic resonance (MR) imaging was performed in 33 healthy subjects aged 5-18 years who were recruited from a functional imaging study of normal language development. Results of neurologic, psychologic, and structural MR imaging examinations were within the normal range for all subjects. The trace of the apparent diffusion coefficient and fractional anisotropy in white matter were correlated as a function of age by using Spearman rank correlation. RESULTS: Statistically significant negative correlation of the trace of the apparent diffusion coefficient with age was found throughout the white matter. Significant positive correlation of fractional anisotropy with age was found in the internal capsule, corticospinal tract, left arcuate fasciculus, and right inferior longitudinal fasciculus. CONCLUSION: Diffusion-tensor MR imaging results indicate that white matter maturation assessed at different ages involves increases in both white matter density and organization during childhood and adolescence. The trace of the apparent diffusion coefficient and fractional anisotropy may reflect different physiologic processes in healthy children and adolescents.

Adolescent↗

White matter and cerebral metabolite changes in children undergoing treatment for acute lymphoblastic leukemia: longitudinal study with MR imaging and 1H MR spectroscopy.

PURPOSE: To assess the development of white matter and cerebral metabolite changes during and after treatment in children with acute lymphoblastic leukemia. MATERIALS AND METHODS: Twenty-three children (10 boys, mean age of 6.3 years; 13 girls, mean age of 6.6 years) with acute lymphoblastic leukemia were examined prospectively with magnetic resonance (MR) imaging and MR spectroscopy at 0, 8, and 20 weeks and 1, 2, and 3 years after diagnosis. White matter changes were diagnosed on the basis of hyperintense abnormalities on T2-weighted MR images. Single-voxel hydrogen 1 MR spectroscopy results from the right frontoparietal region of 21 children who received intravenous high-dose methotrexate were analyzed for cerebral metabolite changes. Multilevel models were used to assess the change in metabolites from baseline levels at subsequent follow-up. RESULTS: At 20 weeks, MR spectroscopy showed a significant reduction (P <.05) of mean N-acetylaspartate to choline ratio and increase in mean choline to creatine ratio (P <.05) in the children given high-dose methotrexate. This decline in N-acetylaspartate to choline ratio subsequently reversed and increased, possibly because of normal age-related brain maturation. Seventeen of 21 (81%) children showed metabolite changes at MR spectroscopy, while five of 22 (23%) showed white matter changes at MR imaging at 20 weeks. One more child developed white matter changes at 32 weeks. The associated changes resolved or reduced with time. CONCLUSION: MR spectroscopy demonstrated metabolite changes in the brain after high-dose methotrexate treatment in the absence of structural white matter abnormalities at MR imaging. MR spectroscopy might thus be a more sensitive method of monitoring the effects of high-dose methotrexate in the brain.

Adolescent↗

Intraoperative diffusion-tensor MR imaging: shifting of white matter tracts during neurosurgical procedures--initial experience.

PURPOSE: To prospectively evaluate the location of white matter tracts with diffusion-tensor imaging (DTI) during neurosurgical procedures. MATERIALS AND METHODS: Ethical committee approval and signed informed consent were obtained. A 1.5-T magnetic resonance imager with an adapted rotating surgical table that is placed in a radiofrequency-shielded operating theater was used for pre- and intraoperative imaging. DTI was performed by applying an echo-planar imaging sequence with six diffusion directions in 38 patients (20 female patients, 18 male patients; age range, 7-77 years; mean age, 45.6 years) who were undergoing surgery (35 craniotomy and three burr hole procedures). Color-encoded maps of fractional anisotropy were generated by depicting white matter tracts. A rigid registration algorithm was used to compare pre- and intraoperative images. RESULTS: Intraoperative DTI was technically feasible in all patients, and no major image distortions occurred in the areas of interest. Pre- and intraoperative color-encoded maps of fractional anisotropy could be registered; these maps depicted marked and highly variable shifting of white matter tracts during neurosurgical procedures. In the 27 patients who underwent brain tumor resection, white matter tract shifting ranged from an inward shift of 8 mm to an outward shift of 15 mm (mean shift +/- standard deviation, outward shift of 2.5 mm +/- 5.8). In 16 (59%) of 27 patients, outward shifting was detected; in eight (30%), inward shifting was detected. In eight patients who underwent temporal lobe resections for drug-resistant epilepsy, shifting was only inward and ranged from 2 to 14 mm (9 mm +/- 3.3). In two of the three patients who underwent burr hole procedures, outward shifting occurred. CONCLUSION: Intraoperative DTI can depict shifting of major white matter tracts that is caused by surgical intervention.

Adolescent↗

Gray matter heterotopias: MR characteristics and correlation with developmental and neurologic manifestations.

Magnetic resonance (MR) images and clinical records of 20 patients with gray matter heterotopias were retrospectively reviewed to correlate MR characteristics of the heterotopias with clinical findings. On the basis of the MR images, patients were divided into three groups: those with subependymal heterotopias (eight patients), focal subcortical gray matter heterotopias (six patients), and diffuse subcortical heterotopias (six patients). Patients with subependymal heterotopias had a significantly higher prevalence of normal development than patients in the other two groups (P = .02). When all patients with gray matter heterotopias were considered, patients with thick heterotopias and those with overlying cortical gyral anomalies, which correlated with one another, had a significantly higher prevalence of developmental delay (P = .002). Patients with thick focal gray matter heterotopias had a substantially increased prevalence of motor dysfunction. In three cases, gray matter heterotopias were associated with infoldings of dysplastic cortex containing blood vessels or cerebrospinal fluid. If not properly analyzed, these anomalies can be mistaken for vascular or cystic tumors.

Adolescent↗

Cerebral white matter: technical development and clinical applications of effective magnetization transfer (MT) power concepts for high-power, thin-section, quantitative MT examinations.

PURPOSE: To evaluate white matter disorders with magnetization transfer (MT) techniques. MATERIALS AND METHODS: In 46 healthy volunteers and 46 clinical patients, MT Z spectra were obtained with various continuous-wave-equivalent MT powers (B1CW) and frequency offsets. RESULTS: With B1CW of 270 Hz and 4,000-Hz frequency offset, the MT ratio of normal callosal white matter was 59.2% +/- 1.5 (standard deviation), with less than 5% contribution from direct saturation and spin locking. A small statistically significant (P < .01) regional variation in normal white matter was seen. Plaques in MS patients had a broad (or wide) range of MT ratios; normal appearing white matter had a slightly reduced MT ratio. Vasogenic edema had a minimal effect on MT ratio, and radiation necrosis showed prominent reductions in MT ratio. CONCLUSION: High MT power techniques can expand the dynamic range of MT ratios, maintain a relatively pure MT effect, and be used effectively in MT imaging to evaluate white matter disorders.

Brain↗

Thermodynamics of living matter: physical foundations of biology.

All major functions of life are exerted by reversible conformational changes of living matter, the genetically coded, giant molecules of proteins, polynucleotides, and biological membranes. Only thermodynamics can answer the questions why these reversible actions occur, why they are inevitable, and what the physical foundations may be on which biology rests. Classical Gibbs-Helmholtz thermodynamics was found to be inapplicable to the interpretation of reactions in living matter, because copious flows of heat without exchange of work obscure the subtle bond-forming or bond-breaking energy transformations that are driving the actions of living matter. An alternative thermodynamic formulation that is universally applicable was developed and applied to numerical examples: formation of a diatomic molecule from the elements, and two conformational changes, a protein folding and the winding of a polynucleotide helix. The subtle energy transformations, bond-forming or bond-breaking, that were causing the two reactions of living matter to proceed in vitro forward or in reverse have been identified as the thermal work function delta Wto(T) and the chemical bond energy delta Ho0. Since the chemical bond energies and the heat capacities delta CoP(T) between reaction temperature and the absolute zero, unchangeable attributes of matter, were the only ingredients used for the treatment, the complexity of the reactions has been reduced--as far as effects and ultimate causes are concerned--to the simplicity of low temperature physics, a solid physical foundation for all biological and medical sciences.

Animals↗

Cerebral white matter blood flow is constant during human non-rapid eye movement sleep: a positron emission tomographic study.

This study aimed to identify brain regions with the least decreased cerebral blood flow (CBF) and their relationship to physiological parameters during human non-rapid eye movement (NREM) sleep. Using [(15)O]H(2)O positron emission tomography, CBF was measured for nine normal young adults during nighttime. As NREM sleep progressed, mean arterial blood pressure and whole brain mean CBF decreased significantly; arterial partial pressure of CO(2) and, selectively, relative CBF of the cerebral white matter increased significantly. Absolute CBF remained constant in the cerebral white matter, registering 25.9 +/- 3.8 during wakefulness, 25.8 +/- 3.3 during light NREM sleep, and 26.9 +/- 3.0 (ml.100 g(-1).min(-1)) during deep NREM sleep (P = 0.592), and in the occipital cortex (P = 0.611). The regression slope of the absolute CBF significantly differed with respect to arterial partial pressure of CO(2) between the cerebral white matter (slope 0.054, R = - 0.04) and frontoparietal association cortex (slope - 0.776, R = - 0.31) (P = 0.005) or thalamus (slope - 1.933, R = - 0.47) (P = 0.004) and between the occipital cortex (slope 0.084, R = 0.06) and frontoparietal association cortex (P = 0.021) or thalamus (P < 0.001), and, with respect to mean arterial blood pressure, between the cerebral white matter (slope - 0.067, R = - 0.10) and thalamus (slope 0.637, R = 0.31) (P = 0.044). The cerebral white matter CBF keeps constant during NREM sleep as well as the occipital cortical CBF, and may be specifically regulated by both CO(2) vasoreactivity and pressure autoregulation.

Adult↗