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PubMed2005

White matter lesion progression, brain atrophy, and cognitive decline: the Austrian stroke prevention study.

White matter lesions progress over time, but the clinical consequences are widely unknown. Three-hundred twenty-nine elderly community-dwelling volunteers underwent serial magnetic resonance imaging scanning and cognitive testing at baseline and at 3- and 6-year follow-up. We measured the changes in white matter lesion and brain parenchymal volumes. After 6 years, the median increase in white matter lesion load was 0.2 cm3 (interquartile range [IQR], 0.0-0.80 cm3) with a maximum of 31.4 cm3. The median loss of brain volume was 2.3% (IQR, 1.13-3.58%). Increasing white matter lesion volume was correlated with loss of brain volume (p < 0.0001) and performance decline in tests of memory (p = 0.022), conceptualization (p = 0.046), and visuopractical skills (p = 0.005). Associations between changes in white matter lesion load and cognitive functioning were no longer significant when adding change in brain volume to the models, suggesting that cognitive decline related directly to loss of brain substance with progression of lesion burden.

Aged↗
PubMed2006

Development of microglia in the cerebral white matter of the human fetus and infant.

Although microglial activation may be an initial beneficial response to a variety of insults, prolonged activation can release toxic substances and lead to cell death. Microglial activation secondary to hypoxia-ischemia and/or infection in immature cerebral white matter is important in the pathogenesis of periventricular leukomalacia (PVL), the major pathological substrate of cerebral palsy in the premature infant. We hypothesize that a transient overexpression in activated microglial density occurs normally in the cerebral white matter of the human fetus during the peak window of vulnerability for PVL. Such an increase could render this region susceptible to insults that cause prolonged microglial activation, as conceptualized in PVL. To examine the developmental profile of microglia in the human fetus and infant brain, immunocytochemistry with microglial specific markers were used in 23 control (non-PVL) cases ranging from 20 to 183 postconceptional (PC) weeks. Tomato lectin, used to identify microglial morphology, revealed that the cerebral white matter of the human fetus and infant is densely populated with intermediate and amoeboid microglia; the latter is indicative of an activated state. Quantitative analysis with CD68 showed increased density of activated microglia in the cerebral white matter of the fetus (<37 PC weeks) relative to the neonate/infant (> or =37 PC weeks) and to the overlying cortex of either age group (P = 0.01). The primary finding of a transient, developmental-dependent overabundance of CD68-activated microglia in the cerebral white matter of the fetus suggests a potential "priming" of this area for diverse brain insults characterized by activation of microglia, particularly PVL. J.

Age Factors↗
PubMed1988

Postnatal development of interstitial (subplate) cells in the white matter of the temporal cortex of kittens: a correlated Golgi and electron microscopic study.

The early postnatal development of interstitial cells (IC) in the white matter of the temporal cortex in kittens was studied. Counts in Nissl-stained preparations show that the number of IC diminishes by about 60% during the second postnatal week. In Golgi preparations, IC are bipolar or bitufted with long, beaded dendrites coursing in the white matter toward the ventricular surface. Ascending, shorter dendrites are thinner, often branch in a short bush, and possess long spines resembling filopodia. The majority of their axons descend in the white matter, emitting numerous recurrent collaterals that become ascending fibers reaching various cortical layers. Most IC resemble inverted pyramidal cells. They appear well developed at the time of birth and continue to develop elaborate axonal complexes in the white matter of older animals. Electron microscopic observations of degenerating IC were detected in all cases studied and their presence was related to the existence of cell death responsible for elimination of a fraction of IC. They were recognized by their dark aspect and by dilations of the endoplasmic reticulum. Synapses contacting degenerating profiles were also observed. It is concluded that IC belong to the population of early generated subplate cells which may have a transient function involved in certain morphogenetic events during the development of the cortical plate. Some persist in the adult where they can be recognized as IC of the white matter.

Animals↗
PubMed1994

Neocortex provides direct synaptic input to interstitial neurons of the intermediate zone of kittens and white matter of cats: a light and electron microscopic study.

The existence of direct synaptic input from the neocortex to intermediate zone and white matter interstitial neurons was examined in both neonate and adult cats. This projection was studied by injecting the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the neocortex and examining whether cortical efferent axons formed synapses in the intermediate zone or white matter. Anterogradely labeled boutons establishing synapses in the intermediate zone and white matter were found at the electron microscopic level after injecting PHA-L into the primary visual, somatosensory, and suprasylvian cortex. Although labeled synapses were found in the intermediate zone of kittens injected at postnatal days 2 and 6, their morphological features appeared immature compared to those found in kittens aged 3 weeks or in adults. Postsynaptic targets of efferent cortical axons were studied in serial sections and shown to be dendritic shafts and spines. This paper shows that cortical efferent axons contribute synapses to interstitial neurons located in the intermediate zone of kittens and white matter of adults. The functional role of the corticointermediate zone/white matter projection remains to be determined.

Animals↗
PubMed2005

Chronic alterations in the cellular composition of spinal cord white matter following contusion injury.

Spinal cord injury (SCI) involves the loss of neurons and glia due to initial mechanical and secondary biochemical mechanisms. Treatment with the sodium channel blocker tetrodotoxin (TTX) reduces acute white matter pathology and increases both axon density and hindlimb function chronically at 6 weeks after injury. We investigated the cellular composition of residual white matter chronically to determine whether TTX also has a significant effect on the numbers and types of cells present. Rats received an incomplete thoracic contusion injury, in the presence or absence of TTX (0.15 nmole) injected focally, beginning at 15 min prior to injury. Six weeks later, cell density was significantly increased in the residual white matter of the dorsal, lateral, and ventral funiculi, both rostral and caudal to the injury site in both TTX-treated and injury control groups. Oligodendrocyte and astrocyte density was similar to normal but large numbers of cells expressing microglia/macrophage markers were present. Labeling with the progenitor markers nestin and NG2 showed that precursor cell density had also doubled or tripled as compared with uninjured controls. Some of these cells were also labeled for antigens that indicate their possible progression along an oligodendrocyte or astrocyte lineage. Our results support the hypothesis that the beneficial effect of TTX in SCI is related to its preservation of axons per se; no effect on chronic white matter cell composition was detected. They highlight the profound changes in cellular composition in preserved white matter chronically at 6 weeks after injury, including the accumulation of endogenous progenitor cells and the persistence of activated macrophages/microglia. The manipulation of these endogenous cells may be used in the future to enhance recovery after SCI.

Animals↗
PubMed2001

Depression in late life, cognitive decline and white matter pathology in two clinico-pathologically investigated cases.

CASE REPORTS: We report two cases of late life depression who became progressively more resistant to treatment, developed cognitive impairment, and began to exhibit neurological abnormalities and evidence of vascular disease. A discussion of the clinical features of the cases is accompanied by reports of neuropathology and neuroimaging findings. Extensive white matter lesions were present on computed tomography in both patients, and basal ganglia infarcts were seen in one. Neuropathology revealed evidence of cerebral atrophy, demyelination and white matter lesions in addition to cerebrovascular and generalised vascular disease. Neither patient exhibited Alzheimer pathology outwith the norm for their age. We believe this to be the first report of neuropathological findings in depression with white matter changes. LITERATURE REVIEW: The pathological basis of white matter lesions and their relationship to depression, its age of onset and clinical features is addressed in relation to the cases described. Pathological investigation of white matter lesions has not previously been carried out in depression and hypotheses regarding their nature in this illness are based on extrapolation from research in a variety of other disorders. The association of depression with vascular risk factors is considered, as is the relationship between depression and cognitive deficits. There is a need for further investigation in this area.

Age of Onset↗
PubMed2003

18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images.

PURPOSE: To study brain MRI findings in patients with 18q- syndrome and to correlate these findings with the results of the molecular breakpoint analysis. MATERIALS AND METHODS: Brain MR images of 17 patients with 18q- syndrome were evaluated. Segregation analysis was performed with 15 microsatellite markers to determine the deletion breakpoints and whether the deletion included the myelin basic protein (MBP) gene. RESULTS: One patient had an interstitial deletion of 18q which spared the MBP gene. He was the only one with normal brain MRI. All 16 patients with deletions including the MBP gene had abnormal white matter in MRI. The main finding was poor differentiation of gray and white matter on T2-weighted images due to increased white matter signal intensity. In addition, measured signal intensity of the white matter was significantly increased in patients compared with controls. CONCLUSIONS: Poor differentiation of gray and white matter on T2-weighted images is the most typical MRI finding of the 18q- syndrome. These results support the postulation that abnormal myelination in 18q- syndrome is due to haploinsufficiency at or near the MBP locus.

Abnormalities, Multiple↗
PubMed2003

Magnetization transfer imaging and magnetic resonance spectroscopy of normal-appearing white matter in late-life major depression.

PURPOSE: To examine the relationships between the damaged macromolecular pool seen on magnetization transfer (MT) imaging and cerebral metabolic changes recorded by magnetic resonance spectroscopy (MRS), in frontal white and gray matter regions of late-life MDD patients. MATERIALS AND METHODS: MT imaging and MRS were performed on eight patients with late-life MDD and eight age-matched healthy controls. MT ratios were calculated using the on-resonance and off-resonance images. Correlations were computed between MT ratios and the ratios of several metabolites, including choline (Cho), myo-inositol (mI), N-acetylaspartate (NAA), and N-acetylaspartylglutamate (NAAG), to creatine (Cr). RESULTS: Statistically significant correlations were found in white matter between the MT ratios and mI/Cr (r = -0.90, N = 7, P = 0.016), and between the MT ratios and (NAA + NAAG)/Cr (r = -0.89, N = 8, P = 0.007). No significant correlations were found in gray matter or between the MT ratios and NAA/Cr or Cho/Cr in white matter. CONCLUSION: Changes in the white matter macromolecular protein pool, observed as reduced MT ratios, may be related to changes in the mI and the total NAA pools. These findings may have implications for the pathophysiology of late-life major depression.

Aged↗
PubMed2002

Oligodendrogenesis is differentially regulated in gray and white matter of jimpy mice.

The factors that regulate oligodendrogenesis have been studied extensively in optic nerve, where oligodendrocyte production and myelination quickly follow colonization of the nerve by progenitor cells. In contrast, oligodendrocyte production in the cerebral cortex begins approximately 1 week after progenitor cell colonization and continues for 3-4 weeks. This and other observations raise the possibility that oligodendrogenesis is regulated by different mechanisms in white and gray matter. The present study examined oligodendrocyte production in the developing cerebral cortex of jimpy (jp) and jimpy(msd) (msd) mice, which exhibit hypomyelination and oligodendrocyte death due to mutations in and toxic accumulations of proteolipid protein, the major structural protein of CNS myelin. Proliferation of oligodendrocyte progenitors and production of myelinating oligodendrocytes was reduced in jp cerebral cortex when compared to wild-type (wt) and msd mice. The incidence of oligodendrocyte cell death was similar in jp and msd cortex, but total dying oligodendrocytes were greater in msd. We confirm previous reports of increased oligodendrocyte production in white matter of both jp and msd mice. The jp mutation, therefore, reduces oligodendrocyte production in cerebral cortex but not in white matter. These data provide additional evidence that oligodendrogenesis is differentially regulated in white matter and gray matter and implicate PLP/DM20 as a modulator of these differences.

Animals↗
PubMed1994

Reactive astrocytes are widespread in the cortical gray matter of amyotrophic lateral sclerosis.

The distribution of reactive astrocytes was examined in the cortical gray matter of non-motor and motor regions from cases of familial and sporadic amyotrophic lateral sclerosis (ALS) and compared to that of beta-amyloid deposits. By glial fibrillary acidic protein immunocytochemistry, patches of reactive astrocytes, characterized by multiple reactive astrocytes in a circular or patch-like formation, occurred in 12 of 15 ALS cases examined. These patches of reactive astrocytes were not restricted to the motor cortex but were found in the gray matter in ALS in all examined brain regions, including frontal, temporal, inferior parietal, cingulate, occipital, and motor cortices, from both familial and sporadic ALS cases. Reactive astrocytes were also found in the subpial region and at the gray/white matter junction. Because patches of astrocytes can occur in association with senile plaques, beta-amyloid was localized. By immunostaining, beta-amyloid deposits were observed in five of the 15 ALS cases: three cases had only early plaques, two had both early and classic plaques. The number of ALS cases with both astrocyte patches and amyloid plaques was four of 15, but typically astrocyte patches in ALS occurred without any evidence of an association with beta-amyloid deposits. Therefore, the astrocyte patches in ALS are not the result of beta-amyloid deposition. The widespread occurrence of reactive astrocytes, as patches in the cortical gray matter and in the subpial region and at the gray/white matter junction, is evidence of a widespread pathology in ALS cortex in both familial and sporadic forms of the disease.

Adult↗
PubMed2006

Visual rating of white matter hyperintensities in Parkinson's disease.

Dementia is a common complication of Parkinson's disease (PD), but the cause is incompletely understood. In previous studies, dementia has been associated with an increase in hyperintense lesions in the cerebral white matter. The aim of this study was to explore whether white matter hyperintensities (WMH) on cerebral magnetic resonance imaging (MRI) are associated with dementia in PD. For this study, 35 patients with PD, 16 with dementia (PDD) and 19 without (PDND), and 20 control subjects were recruited. MRI scans of patients and controls were rated for WMH, blind to diagnosis, using the Scheltens visual rating scale. Both bivariate and multivariate statistical analyses were carried out. Cerebrovascular risk factors, education, gender, or age were similar across groups. Compared with the PDND group, the PDD group had significantly higher level of WMH in the deep white matter and in the periventricular areas. WMH in the deep white matter was the only variable that was associated significantly with Mini-Mental State Examination score and explained 38% of the variance in the multivariate linear regression analysis. Our findings suggest that WMH in the deep white matter may contribute to dementia in PD.

Aged↗
PubMed2006

Perinatal white matter injury: the changing spectrum of pathology and emerging insights into pathogenetic mechanisms.

Perinatal brain injury in survivors of premature birth has a unique and unexplained predilection for periventricular cerebral white matter. Periventricular white-matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia; PVL) and diffuses myelination disturbances. Recent neuroimaging studies support that the incidence of PVL is declining, whereas focal or diffuse noncystic injury is emerging as the predominant lesion. Factors that predispose to PVL during prematurity include hypoxia, ischemia, and maternal-fetal infection. In a significant number of infants, PWMI appears to be initiated by perturbations in cerebral blood flow that reflect anatomic and physiological immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical-mediated injury that particularly targets immature stages of the oligodendrocyte lineage. Emerging experimental data supports that pronounced ischemia in the periventricular white matter is necessary, but not sufficient to generate PWMI. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. Injury to oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by disrupting the maturation of myelin-forming oligodendrocytes. Chemical mediators that may contribute to white-matter injury include reactive oxygen species glutamate, cytokines, and adenosine. As our understanding of the pathogenesis of PWMI improves, it is anticipated that new strategies for directly preventing brain injury in premature infants will develop.

Adenosine↗
PubMed1998

Evaluation of 31P metabolite differences in human cerebral gray and white matter.

31P NMR is commonly used to study brain energetics in health and disease. Due to sensitivity constraints, the NMR measurements are typically made in volumes that do not contain pure gray or white matter. For accurate evaluation of abnormalities in brain metabolite levels, it is necessary to consider the differences in normal levels of 31P metabolites in gray and white matter. In this study, voxels from a three-dimensional spectroscopic image acquisition were analyzed for their dependence on tissue type to assess differences in metabolite levels between gray and white matter. Specifically, gray matter was found to have significantly higher ratios of phosphocreatine (PCr) to gamma-ATP and PCr to the total 31P metabolite signal, whereas pH and the ratio of PCr to inorganic phosphate (Pi) were found to differ insignificantly between gray and white matter. Thus, tissue type can be an important factor to consider for alterations in bioenergetics by 31P NMR spectroscopic studies of the brain.

Adenosine Triphosphate↗
PubMed2002

Mineral matter distribution on coal surface and its effect on coal wettability.

Coal is an organic sedimentary rock composed of organic macerals and mineral matter. As it is demonstrated in this paper the discrete mineralogical nature of coal largely influences the wetting of the coal surface by water. Both advancing and receding contact angles were measured using the captive-bubble technique with an automatic bubble shape analysis software. The distribution and amount of mineral inclusions on the coal surface were determined by scanning electron microscopy and examined using the image analysis system. To determine the amount and size distribution of mineral grains, the coal surface layer, on which the contact angles were measured, was separated from the larger piece used in the measurements by microslicing. The separated surface layer was subjected to a low-temperature ashing followed by particle size analysis. As expected, a significant scatter of contact angle values was obtained for the same coal samples. Increasing the amount of mineral matter on the coal surface reduced the value of both advancing and receding contact angles. Also, the scatter of contact angle values increased with the increasing mineral matter content from about 1 to 50 wt%. The results reveal that an important factor in analysis of contact angle variation on coal surfaces is the size of the hydrophilic mineral inclusions. Both the advancing and the receding contact angles decrease with increasing size of the mineral grains. Additionally, the scatter of contact angle values increase with increasing size of the mineral matter grains. Finally, the results of fractal dimension analysis of mineral matter grains distributed over the coal surface indicate that there is no significant effect from the shape of hydrophilic mineral inclusions on both advancing and receding contact angles.

Journal Article↗
PubMed1995

Numerically optimized experiment design for measurement of grey/white matter metabolite T2 in high-resolution spectroscopic images of brain.

T2 relaxation measurements for choline (Cho), total creatine (Cr = creatine + phosphocreatine), and N-acetylaspartate (NAA) were made separately in eight healthy volunteers using an average of forty 0.5 cc volumes (20 from grey matter and 20 from white matter) in spectroscopic images with a 32 x 32 resolution and a 240 mm field of view. In grey matter, the means and standard deviations of the T2 values were 186 +/- 23, 149 +/- 10, and 232 +/- 15 ms for Cho, Cr, and NAA, respectively, and in white matter, the mean T2 values were 178 +/- 16, 143 +/- 8, and 228 +/- 16 ms, respectively, with no significant differences between grey and white matter. The high-resolution measurements of T2 values were possible because of experimental planning based on the minimization of predicted fitting uncertainties. Explicit expressions were derived to estimate the uncertainties in T2 values, and it was found that two spectroscopic images with echo times of 50 and 250 ms, respectively, would yield sufficient precision for T2 measurements. The derivation of the expressions, a discussion of their behavior, and the experimental planning and verification are presented.

Aspartic Acid↗
PubMed1999

MRI-Based topographic parcellation of human cerebral white matter and nuclei II. Rationale and applications with systematics of cerebral connectivity.

We describe a system for parcellation of the human cerebral white matter and nuclei, based upon magnetic resonance images. An algorithm for subdivision of the cerebral central white matter according to topographic criteria is developed in the companion manuscript. In the present paper we provide a rationale for this system of parcellation of the central white matter and we extend the system of cerebral parcellation to include principal subcortical gray structures such as the thalamus and the basal ganglia. The volumetric measures of the subcortical gray and white matter parcellation units in 20 young adult brains are computed and reported here as well. In addition, with the comprehensive system for cerebral gray and white matter structure parcellation as reference, we formulate a systematics of forebrain connectivity. The degree to which functionally specific brain areas correspond to topographically specific areas is an open empirical issue. The resolution of this issue requires the development of topographically specific anatomic analyses, such as presented in the current system, and the application of such systems to a comprehensive set of functional-anatomic correlation studies in order to establish the degree of structural-functional correspondence. This system is expected to be applied in both cognitive and clinical neuroscience as an MRI-based topographic systematics of human forebrain anatomy with normative volumetric reference and also as a system of reference for the anatomic organization of specific neural systems as disrupted by focal lesions in lesion-deficit correlations.

Adult↗
PubMed2002

Microstructural but not macrostructural disruption of white matter in women with chronic alcoholism.

The results of in vivo neuroimaging studies assessing whether and where brain white matter damage occurs in alcoholic women is controversial. To address this controversy, we examined regional white matter macrostructure and microstructure, the latter of which may be more sensitive to the detection of subtle fiber disruption than gross measures of size. Accordingly, we used conventional magnetic resonance imaging (MRI) to quantify regional callosal size and diffusion tensor imaging (DTI) to examine intravoxel coherence (fractional anisotropy, FA) and intervoxel coherence (C) of white matter of the genu and splenium of the corpus callosum and of the centrum semiovale in 12 detoxified alcoholic women and 18 control women. Additional analyses examined sex differences in FA and C in alcoholic women compared with alcoholic men. Despite absence of group differences in regional areas of callosal macrostructure, the alcoholic women had lower FA and C in genu and centrum semiovale than the control group of women. These measures also correlated with total lifetime consumption of alcohol and performance on a test of visual search in the alcoholic women. Sex comparisons revealed similar extents of FA abnormality in the genu and centrum semiovale in alcoholic men and women and differential effects in other DTI measures, with abnormalities present in splenium FA and C in the men and abnormalities present in centrum C in the women. These results provide in vivo evidence for disruption of white matter microstructure in alcoholic women not necessarily detectable with coarser measures of white matter mass and perhaps antedating its appearance.

Adult↗
PubMed2002

Voxel-based morphometry reveals increased gray matter density in Broca's area in male symphony orchestra musicians.

Broca's area is a major neuroanatomical substrate for spoken language and various musically relevant abilities, including visuospatial and audiospatial localization. Sight reading is a musician-specific visuospatial analysis task, and spatial ability is known to be amenable to training effects. Musicians have been reported to perform significantly better than nonmusicians on spatial ability tests, which is supported by our findings with the Benton judgement of line orientation (JOL) test (P < 0.001). We hypothesised that use-dependent adaptation would lead to increased gray matter density in Broca's area in musicians. Voxel-based morphometry (VBM) and stereological analyses were applied to high-resolution 3D MR images in male orchestral musicians (n = 26) and sex, handedness, and IQ-matched nonmusicians (n = 26). The wide age range (26 to 66 years) of volunteers permitted a secondary analysis of age-related effects. VBM with small volume correction (SVC) revealed a significant (P = 0.002) region of increased gray matter in Broca's area in the left inferior frontal gyrus in musicians. We observed significant age-related volume reductions in cerebral hemispheres, dorsolateral prefrontal cortex subfields bilaterally and gray matter density in the left inferior frontal gyrus in controls but not musicians; a positive correlation between JOL test score and age in musicians but not controls; a positive correlation between years of playing and the volume of gray matter in a significant region identified by VBM in under-50-year-old musicians. We suggest that orchestral musical performance promotes use-dependent retention, and possibly expansion, of gray matter involving Broca's area and that this provides further support for shared neural substrates underpinning expressive output in music and language.

Adult↗