White Matter Brain Regions Research Articles

Gray and white matter density changes in monozygotic and same-sex dizygotic twins discordant for schizophrenia using voxel-based morphometry

Global gray matter brain tissue volume decreases in schizophrenia have been associated to disease-related (possibly nongenetic) factors. Global white matter brain tissue volume decreases were related to genetic risk factors for the disease. However, which focal gray and white matter brain regions best reflect the genetic and environmental risk factors in the brains of patients with schizophrenia remains unresolved. 1.5-T MRI brain scans of 11 monozygotic and 11 same-sex dizygotic twin-pairs discordant for schizophrenia were compared to 11 monozygotic and 11 same-sex dizygotic healthy control twin-pairs using voxel-based morphometry. Linear regression analysis was done in each voxel for the average and difference in gray and white matter density separately, in each twin-pair, with group (discordant, healthy) and zygosity (monozygotic, dizygotic) as between subject variables, and age, sex and handedness as covariates. The t-maps (critical threshold value ∣ t∣ > 6.0, P < 0.05) revealed a focal decrease in gray matter density accompanied by a focal increase in white matter density in the left medial orbitofrontal gyrus and a focal decrease in white matter density in the left sensory motor gyrus in twin-pairs discordant for schizophrenia as compared to healthy twin-pairs. Focal changes in left medial (orbito)frontal and left sensory motor gyri may reflect the increased genetic risk to develop schizophrenia. Focal changes in the left anterior hemisphere may therefore be particularly relevant as endophenotype in genetic studies of schizophrenia.

Brain lesion detectability studies with a high resolution PET operating in no-septa and partial-septa configurations

We investigated the effect of partial-septa on the noise equivalent sensitivity and lesion detectability for a high resolution PET camera. For this purpose we used the MDAPET camera to detect small lesions in brain images obtained from the scan of the Hoffman brain phantom. The three-dimensional (3-D) positron emission tomography (PET) acquisition in comparison to two-dimensional (2-D) PET acquisition improves the sensitivity of the system at the cost of higher scatter and accidental coincidence contributions. A partial-septa allowing 3D-acquisition may provide a better alternative. For this work, three small lesion phantoms with diameters of 3, 5 and 8.6 mm were embedded into the Hoffman brain phantom. The activity concentration ratio of the lesions to the surrounding brain gray matter was ranging from 1.5 to 10. For this study, the eight detectors modules of the prototype MDAPET scanner were modified axially to extend from 38.5 mm to 131 mm in order to simulate more closely the performance of a clinical size camera. Data for the hot lesion phantoms and the normal Hoffman brain phantom were taken separately. Then, the two sets of the sinograms data were selectively combined to generate the sinograms data for the desired SUVs. Visual inspection of the lesion images show that we could clearly see the 8.6 mm lesion, with or without septa, at even the lowest activity ratio that we measured. The 5 mm and 3 min lesions were observable at activity ratio of 2.2 and 5.4, respectively. We found that even though the use of septa could increase the noise equivalent count rate and lower the image noise, it does not necessary translate into improvement of the lesion detectability. For partial-septa configurations the white matter regions of brain have less count and the brain images visually looked better; however, images from no-septa data had slightly higher contrast.

In vivo proton magnetic resonance spectroscopy of the normal aging human brain

The effect of age on brain metabolite concentrations was evaluated using localized proton magnetic resonance spectroscopy. This technique allows in vivo measurements of N-acetyl compounds (NA), total creatine (CR), choline-containing compounds (CHO), myo-inositol (MI), glutamate and glutamine (GLX), as well as the percentage of cerebrospinal fluid (CSF) and the brain water content within the brain region studied. Frontal gray matter and frontal white matter brain regions were examined in 36 normal healthy volunteers (19–78 years of age). Using a rigorous absolute quantitation method, with an external reference and atrophy correction, we found relatively stable concentrations of NA, a neuronal marker. In contrast, CR, CHO, MI, and the percentage of CSF increased in the gray matter with age. However, the brain water content decreased significantly with age (r = −0.72; p < 0.0001). No significant age-related changes in metabolite concentrations, CSF or brain water content were observed in the white matter regions. These findings demonstrate that biochemical alterations are associated with aging in the frontal gray matter. There might be an increase in the brain density as indicated by increased metabolite concentrations and decreased brain water content with aging.

Hyperosmolar blood-brain barrier disruption in baboons: an in vivo study using positron emission tomography and rubidium-82.

Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8-to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 +/-2.4 microliter/min/ml (+/- standard deviation) at baseline and increased more than 100% (delta K1=9.4 +/-5.1 microliter/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p< 0.005). Vascular permeability returned to baseline with a halftime of 24.0 +/- 14.3 minutes. The mean brain plasma volume rose by 0.57 +/- 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.

Depletion of acetylated α‐tubulin during microtubule purification from bovine brain gray and white matter regions

We have followed the fate of acetylated alpha-tubulin during microtubule (MT) purification from both gray matter- and white matter-enriched bovine brain regions, using quantitative immunoblot assays employing well characterized monoclonal antibodies specific for acetylated alpha-tubulin and all beta-tubulins. Our results show that crude homogenates from both gray matter and white matter brain regions contain the same proportion of acetylated alpha- to total tubulin. We have found that the acetylated isoform cycles more efficiently with MTs from gray matter than with MTs from white matter. However, the resultant purified MT preparations from both gray and white matter regions are greatly depleted in the acetylated isoform compared to the tubulin in the initial homogenates because most of the acetylated alpha-tubulin from both tissue sources partitions with the cold-insoluble fraction of the initial brain homogenate. A low percentage of the acetylated alpha-tubulin in brain homogenates does become incorporated into MTs initially, but this subpopulation of acetylated alpha-tubulin then becomes associated with a cold- and calcium-insoluble fraction of the MT preparation. These results demonstrate that the standard brain MT and tubulin preparations used by most investigators for in vitro studies are greatly depleted in acetylated alpha-tubulin, and thus provide poor model systems for the analysis of the function of this tubulin isoform.