Deficits in gray matter volume are present in schizophrenia but not bipolar disorder

Studies using magnetic resonance (MR) imaging have provided strong evidence that patients with schizophrenia as a group have structural brain abnormalities, including enlarged ventricles and sulci as well as smaller cortical gray matter volumes. This study was undertaken to investigate whether the brain abnormalities found in schizophrenia could be distinguished from those seen in bipolar disorder. The MR scans of 23 patients with schizophrenia were compared to those of 17 healthy community volunteers and 14 patients with bipolar disorder. Images were processed using computer-based image processing techniques to generate quantitative measures of cerebrospinal fluid (CSF), gray matter and white matter volumes. Compared to the community volunteers, the schizophrenia group had larger total CSF volumes while the bipolar group had larger ventricles. Smaller cortical gray matter volumes were found in the schizophrenia group, but not in the bipolar group. The schizophrenia group had regional deficits in gray matter volumes in comparison with both the community volunteers and the bipolar group. These findings suggest that the brain tissue abnormalities found in schizophrenia and bipolar disorder may be distinguishable using MR imaging.     

Lipoprotein profile in canine pancreatitis induced with oleic acid

In the treatment of children with brain tumors, balancing the efficacy of treatment against commonly observed side effects is difficult because of a lack of quantitative measures of brain damage that can be correlated with the intensity of treatment. We quantitatively assessed volumes of brain parenchyma on magnetic resonance (MR) images using a hybrid combination of the Kohonen self-organizing map for segmentation and a multilayer backpropagation neural network for tissue classification. Initially, we analyzed the relationship between volumetric differences and radiologists' grading of atrophy in 80 subjects. This investigation revealed that brain parenchyma and white matter volumes significantly decreased as atrophy increased, whereas gray matter volumes had no relationship with atrophy. Next, we compared 37 medulloblastoma patients treated with surgery, irradiation, and chemotherapy to 19 patients treated with surgery and irradiation alone. This study demonstrated that, in these patients, chemotherapy had no significant effect on brain parenchyma, white matter, or gray matter volumes. We then investigated volumetric differences due to cranial irradiation in 15 medulloblastoma patients treated with surgery and radiation therapy, and compared these with a group of 15 age-matched patients with low-grade astrocytoma treated with surgery alone. With a minimum follow-up of one year after irradiation, all radiation-treated patients demonstrated significantly reduced white matter volumes, whereas gray matter volumes were relatively unchanged compared with those of age-matched patients treated with surgery alone. These results indicate that reductions in cerebral white matter: 1) are correlated significantly with atrophy; 2) are not related to chemotherapy; and 3) are correlated significantly with irradiation. This hybrid neural network analysis of subtle brain volume differences with magnetic resonance may constitute a direct measure of treatment-induced brain damage.     

Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome: Relation to ataxia.

The authors used magnetic resonance imaging to measure gray and white matter volumes in cerebellar hemispheres and 4 vermian regions in 61 normal control (NC) men aged 23–72 years, 25 men with uncomplicated alcoholism (ALC), and 8 men and 1 woman with alcoholic Korsakoff's syndrome (KS). NC and ALC took quantitative gait and balance tests. Gray but not white matter volume declined with normal age in both hemispheres and anterior–superior vermis. ALC had gray but not white matter cerebellar hemisphere volume deficits, whereas KS had deficits in both tissue types. ALC and KS had gray and white matter volume deficits in anterior superior but not posterior inferior vermis. ALC had a 1 SD ataxia deficit, significantly and selectively correlated with white matter volume in anterior superior vermis. Regional distribution but not severity of cerebellar volume deficits is similar in alcoholic individuals whether or not complicated by KS and relates to ataxia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Sentinel lymph node biopsy for melanoma

Serum levels of leptin are decreased in underweight AN patients and increase with weight restoration. To assess the relationship of decreased leptin levels with other hormonal abnormalities in AN and to evaluate the possible role of increasing leptin levels, alone or in combination with other hormones, in the resumption of menses that accompanies weight gain, we studied cross-sectionally sixty-five consecutively enrolled AN patients. Subjects were divided in three groups: (I) underweight and amenorrheic; (II) weight-recovered but still amenorrheic; and (III) weight-recovered and eumenorrheic women. Patients in group I had decreased BMI, serum leptin, estradiol (E2), insulin-like growth factor 1 (IGF-1) and urinary growth hormone (GH) levels and increased sex hormone-binding globulin (SHBG) levels, compared to AN patients in groups II and III. Moreover, although no differences in leptin levels or BMI were observed between amenorrheic and eumenorrheic weight-recovered patients (groups II and III), free E2 and GH levels were higher (P<0.02) in weight-recovered, eumenorrheic women. Thus, it appears that leptin is a necessary, but not a sufficient, factor for the resumption of menses in AN patients.     

Interaction of 4-(n-dimethylaminostyryl)-1-methylpyridinium-n-toluolsulfonate with liposomes: analysis of fluorescence spectra

A previous magnetic resonance imaging study from our laboratory reported significant temporal lobe volume deficits in cortical gray matter, white matter, and anterior hippocampus in chronic alcoholic men relative to controls. In the present study, we reexamined these data and asked whether withdrawal seizure history was predictive of either the hippocampal or the extrahippocampal volume deficits. A review of the medical charts indicated that 11 alcoholics had experienced one or more alcohol-related seizures and 35 were seizure-free; no patient had a seizure disorder unrelated to alcohol. The two alcoholic groups did not differ significantly in age, education, alcohol consumption variables, premorbid intelligence, Memory Quotient, Trail Making, or detection of hidden figures. Although each alcoholic group showed significant bilateral volume deficits of the anterior hippocampus and frontal-parietal and temporal gray matter, relative to controls, the seizure group had significantly smaller temporal lobe white matter volumes than either the control or the seizure-free groups; the latter two groups did not differ from each other. Both alcoholic groups, however, had white matter volume deficits in the frontal-parietal region. Thus, the seizure group accounted for the white matter volume deficits in the temporal lobe previously reported in the full sample of alcoholics. It seems, then, that reduced white matter volume in the temporal lobes may be either a risk factor for or sequela of alcohol withdrawal seizures.     

Differentiation of gray matter and white matter perfusion in patients with unilateral internal carotid artery occlusion

In this study, we investigated differences between gray matter and white matter perfusion in patients with a unilateral occlusion of the internal carotid artery (ICA) with dynamic susceptibility contrast. Seventeen patients and 17 control subjects were studied, using T2*-weighted gradient echo acquisition. Gray and white matter regions were obtained by segmentation of inversion recovery MRI. Lesions were excluded by segmentation of T2-weighted MRI. In the symptomatic hemisphere, cerebral blood volume was increased in white matter (P < .05) but not in gray matter. No cerebral blood flow changes were found. All timing parameters (mean transit time [MTT], time of appearance, and time to peak) showed a significant delay for both white and gray matter (P < .05), but the MTT increase of white matter was significantly larger than for gray matter (P < .05). These findings indicate that differentiation between gray and white matter is essential to determine the hemodynamic effects of an ICA occlusion.     

Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice

This study investigated the effects of different rearing conditions on neural and cognitive development of male rhesus monkeys (Macaca mulatta). Infants raised individually in a nursery from 2 to 12 months of age (NURSERY, n=9) were compared to age-matched infants raised in a semi-naturalistic, social environment (CONTROL, n=11). Various brain regions were measured by MRI. Although overall brain volumes did not differ between NURSERY and CONTROL animals, corpus callosum (CC) size, measured in mid-sagittal sections, was significantly decreased in the NURSERY group. Group differences were most evident in the posterior aspects of the corpus callosum and appeared to result from changes in the number of cross-hemispheric projections rather than from a decrease in cortical gray matter volume. The decrease in corpus callosum size in the NURSERY animals persisted after 6 months of social housing in a peer-group. Rearing group differences were not found in other structures analyzed, including the hippocampus, cerebellum and anterior commissure. In cognitive testing, NURSERY animals had more difficulty acquiring the delayed non-matching to sample (DNMS) task, but showed no deficits in subsequent memory performance when a 2 or 10 min delay was imposed. The NURSERY infant monkeys were also impaired in object, but not in spatial, reversal learning, although there were no differences in a simple object discrimination task. The cognitive deficits exhibited by the NURSERY animals were significantly correlated with the alterations found in the CC. In summary, rearing environment was associated with sustained differences in cross-hemispheric projections, white matter volume and cognitive performance.     

Establishing norms for age-related changes in proton T1 of human brain tissue in vivo

The goal of this study was to determine the expected normal range of variation in spin-lattice relaxation time (T1) of brain tissue in vivo, as a function of age. A previously validated precise and accurate inversion recovery method was used to map T1 transversely, at the level of the basal ganglia, in a study population of 115 healthy subjects (ages 4 to 72; 57 male and 58 female). Least-squares regression analysis shows that T1 varied as a function of age in pulvinar nucleus (R2 = 56%), anterior thalamus (R2 = 51%), caudate (R2 = 50%), frontal white matter (R2 = 47%), optic radiation (R2 = 39%), putamen (R2 = 36%), genu (R2 = 22%), occipital white matter (R2 = 20%) (all p < 0.0001), and cortical gray matter (R2 = 53%) (p < 0.001). There were no significant differences in T1 between men and women. T1 declines throughout adolescence and early adulthood, to achieve a minimum value in the fourth to sixth decade of life, then T1 begins to increase. Quantitative magnetic resonance imaging provides evidence that brain tissue continues to change throughout the lifespan among healthy subjects with no neurologic deficits. Age-related changes follow a strikingly different schedule in different brain tissues; white matter tracts tend to reach a minimum T1 value, and to increase again, sooner than do gray matter tracts. Such normative data may prove useful for the early detection of brain pathology in patients.     

MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.

Objective: Brain MRI measures were correlated with neuropsychological function in 35 pediatric-onset multiple sclerosis (MS) patients and 33 age- and sex-matched healthy controls. Method: Mean age of MS patients was 16.3 ± 2.3 years with average disease duration of 4.3 ± 3.1 years. Cortical gray matter, thalamic, and global brain volumes were calculated for all participants using a scaling factor computed using normalization of atrophy method to normalize total and regional brain volumes for head size. T1- and T2-weighted lesion volumes were calculated for MS patients. Results: Cognitive impairment (CI) was identified in 29% of the MS cohort. Cognitive deficits predominantly involved attention and processing speed, expressive language, and visuomotor integration. Relative to controls, the MS group showed significantly lower thalamic volume (p p p p     

Regional cerebral blood flow and cerebrospinal fluid amino acid analysis in elderly dementia

Regional cerebral blood flow and amino acid concentration in the cerebrospinal fluid were studied in 12 cases of vascular dementia, 12 cases of Alzheimer's disease, 12 cases of chronic alcoholism, and 12 age-matched healthy controls. In vascular dementia, blood flows were decreased in the cerebral cortex, frontal white matter, thalamus, caudate nucleus, and putamen and alpha-aminobutyric acid and glutamic acid concentrations were increased in the cerebrospinal fluid. In Alzheimer's disease, blood flows were decreased in the frontal cortex, parietal cortex, temporal cortex, and frontal white matter and alanine concentration was increased in the cerebrospinal fluid. In chronic alcoholism, blood flows were decreased in the cerebral cortex, thalamus, and putamen and urea, alanine, and glycine concentrations were increased in the cerebrospinal fluid.     

Cognitive recovery correlates with white-matter restitution after head injury

Longitudinal measurements of local cerebral perfusion (LCBF) and local partition coefficients (L lambda) using xenon-enhanced computed tomography were examined in six patients who had suffered from head injury at a mean age of 30 +/- 9.3 years. They were selected from a larger group with head injury because all were observed longitudinally to make excellent cognitive recovery some years after acute cerebral trauma. Results were compared with similar longitudinal measurements made in six age-matched neurologically normal volunteers. In the index group, cognitive test scores were reduced at the time of the first LCBP measurement but significantly improved to normal at the time of the second. The mean interval between measurements was 2.7 +/- 0.7 years. At the time of the first measurement, all six patients exhibited abnormal volumes of white matter with reduced Hounsfield numbers and LCBF and L lambda values. Abnormalities in volume of white matter and LCBF and L lambda values improved to normal at the time of the second measurement. Perfusion values for frontal cortex, putamen, and thalamus were still slightly reduced but also improved toward normal between measurements. Cognitive recovery correlated best with restoration of white matter integrity, suggesting that following head injury, cognitive impairments may be associated with temporary disconnections of corticothalamic projection systems.     

Abnormalities of auditory evoked magnetic fields and structural changes in the left hemisphere of male schizophrenics--a magnetoencephalographic-magnetic resonance imaging study

Functional and structural changes in 10 DSM-III-R male schizophrenics and 10 healthy volunteers were investigated using magnetoencephalographically (MEG) detected long-latency (N100 m) auditory evoked fields (AEFs) and magnetic resonance imaging (MRI). The AEFs were characterized by single moving equivalent dipoles, which were superimposed on MRIs. There were significant differences in dipole orientations and in AEF latencies in the left hemisphere of schizophrenics, when compared to the controls. The MEG-detected alterations were found to be associated with a bilateral volume reduction of the posterior superior temporal gyrus (pSTG), which was more pronounced in the left hemisphere. Separate analysis of white and gray matter has shown that the pSTG volume reduction resulted from decreased gray matter volumes without white matter changes. Both the functional and the morphological data indicate a left-hemispheric disturbance in our patients.     

Implementation and evaluation of a new pulse sequence for rapid acquisition of double inversion recovery images for simultaneous suppression of white matter and CSF

We describe a fast double inversion recovery (DIR) imaging sequence that effectively attenuates signal from both white matter and cerebrospinal fluid (CSF). The pulse sequence uses a novel inversion/excitation scheme and fast spin-echo readout to maximize scan efficiency. The white matter/CSF suppressed images can be acquired from the entire brain in approximately 6 minutes. Evaluation of the fast DIR sequence on patients with multiple sclerosis (MS) demonstrates high lesion conspicuity.     

The human brain age 7-11 years: a volumetric analysis based on magnetic resonance images

Volumetric magnetic resonance image (MRI)-based morphometry was performed on the brains of 30 normal children (15 males and 15 males) with a mean age of 9 years (range 7-11 years). This age range lies in a late but critical phase of brain growth where not volumetric increment will be small but when the details of brain circuity are being fine-tuned to support the operations of the adult brain. The brain at this age is 95% the volume of the adult brain. The brain of the female child is 93% the volume of the male child. For more than 95% of brain structures, the volumetric differences in male and female child brain are uniformly scaled to the volume difference of the total brain in the two sexes. Exceptions to this pattern of uniform scaling are the caudate, hippocampus and pallidum, which are disproportionately larger in female than male child brain, and the amygdala, which is disproportionately smaller in the female child brain. The patterns of uniform scaling are generally sustained during the final volumetric increment in overall brain size between age 7-11 and adulthood. There are exceptions to this uniform scaling of child to adult brain, and certain of these exceptions are sexually dimorphic. Thus, with respect to major brain regions, the cerebellum in the female but not the male child is already at adult volume while the brainstem in both sexes must enlarge more than the brain as a whole. The collective subcortical gray matter structures of the forebrain of the female child are already at their adult volumes. The volumes of these same structures in the male child, by contrast, are greater than their adult volumes and, by implication, must regress in volume before adulthood. The volume of the central white matter, on the other hand, is disproportionately smaller in female than male child brain with respect to the adult volumes of cerebral central white matter. By implication, relative volumetric increase of cerebral central white matter by adulthood must be greater in the female than male brain. The juxtaposed progressive and regressive patterns of growth of brain structures implied by these observations in the human brain have a soundly established precedent in the developing rhesus brain. There is emerging evidence that sexually dimorphic abnormal regulation of these terminal patterns of brain development are associated with gravely disabling human disorders of obscure etiology.     

An image-processing system for qualitative and quantitative volumetric analysis of brain images

In this work, we developed, implemented, and validated an image-processing system for qualitative and quantitative volumetric analysis of brain images. This system allows the visualization and quantitation of global and regional brain volumes. Global volumes were obtained via an automated adaptive Bayesian segmentation technique that labels the brain into white matter, gray matter, and cerebrospinal fluid. Absolute volumetric errors for these compartments ranged between 1 and 3% as indicated by phantom studies. Quantitation of regional brain volumes was performed through normalization and tessellation of segmented brain images into the Talairach space with a 3D elastic warping model. Retest reliability of regional volumes measured in Talairach space indicated errors of < 1.5% for the frontal, parietal, temporal, and occipital brain regions. Additional regional analysis was performed with an automated hybrid method combining a region-of-interest approach and voxel-based analysis, named Regional Analysis of Volumes Examined in Normalized Space (RAVENS). RAVENS analysis for several subcortical structures showed good agreement with operator-defined volumes. This system has sufficient accuracy for longitudinal imaging data and is currently being used in the analysis of neuroimaging data of the Baltimore Longitudinal Study of Aging.     

MR relaxation times in human brain: measurement at 4 T

PURPOSE: To determine the values for relaxation times in human brain for magnetic resonance (MR) imaging at 4 T. MATERIALS AND METHODS: T1 measurements were made with a progressive saturation sequence, an implementation of the Look-Locker sequence, and an inversion-recovery (IR) interleaved echo-planar imaging (IEPI) sequence. T2 measurements were made with a standard spin-echo (SE) sequence and an SE IEPI sequence. RESULTS: The T1 measurements yielded values of 1,724 msec +/- 51 for gray matter, 1,043 msec +/- 27 for white matter, and 4,550 msec +/- 800 msec for cerebrospinal fluid. The deep gray matter regions had T1 values of 1,458 +/- 38 (caudate nucleus) and 1,372 +/- 60 (putamen). The T2 measurements yielded results of 63 msec +/- 6.2 for gray matter and 49.8 msec +/- 2.2 for white matter. CONCLUSION: The T1 values measured at 4 T show a higher value than predicted from extrapolation at lower field strengths. The T2 measurements showed a slight decrease in values over those measured at lower-field strength. The gain in signal-to-noise ratio from the higher field strength may be substantially offset by these altered relaxation time values to a degree that is sequence dependent.     

Hypoxemic episodes of patients in a postanesthesia care unit

The incidence, degree, and duration of acute hypoxemia were evaluated with continuous arterial hemoglobin oxygen saturation monitoring by pulse oximetry in 100 postoperative patients during 40 percent oxygen administration by aerosol face tent from postanesthetic recovery room admission to discharge. Saturations were recorded by pulse oximeters (Nellcor-N 200) with desaturations of < or = 92 percent for > or = 30 s considered significant. On recovery room admission, 15 percent of patients were experiencing episodes of desaturation. Low admission saturations correlated positively with patient age and body weight, American Society of Anesthesiologists class, patients having received general anesthesia, and with greater volumes of intraoperative intravenous fluids, particularly > 1,500 ml. Later desaturations to 86.7 +/- 4.6 percent (72 to 91 percent) at 32 +/- 54 min after admission for 5.2 +/- 12.6 min occurred in 25 percent of patients and correlated positively with peripheral surgical procedures, low oxygen saturation on admission, duration of anesthesia, and volume of intraoperative intravenous fluids. Desaturation durations were longer for female subjects and correlated positively with body weight and intravenous fluid volume. Significant arterial hemoglobin oxygen desaturations occurred despite prophylactic oxygen administration by aerosol face tent during short-term postoperative recovery room care.     

High-altitude cerebral edema evaluated with magnetic resonance imaging: clinical correlation and pathophysiology

CONTEXT: Because of its onset in generally remote environments, high-altitude cerebral edema (HACE) has received little scientific attention. Understanding the pathophysiology might have implications for prevention and treatment of both this disorder and the much more common acute mountain sickness. OBJECTIVES: To identify a clinical imaging correlate for HACE and determine whether the edema is primarily vasogenic or cytotoxic. DESIGN: Case-comparison study. SETTING: Community hospitals accessed by helicopter from mountains in Colorado and Alaska. PATIENTS: A consecutive sample of 9 men with HACE, between 18 and 35 years old, 8 of whom also had pulmonary edema, were studied after evacuation from high-altitude locations; 5 were mountain climbers and 4 were skiers. The control group, matched for age, sex, and altitude exposure, consisted of 3 subjects with high-altitude pulmonary edema only and 3 who had been entirely well at altitude. Four patients with HACE were available for follow-up imaging after complete recovery. MAIN OUTCOME MEASURES: Magnetic resonance imaging (MRI) of the brain during acute, convalescent, and recovered phases of HACE, and once in controls, immediately after altitude exposure. RESULTS: Seven of the 9 patients with HACE showed intense T2 signal in white matter areas, especially the splenium of the corpus callosum, and no gray matter abnormalities. Control subjects demonstrated no such abnormalities. All patients completely recovered; in the 4 available for follow-up MRI, the changes had resolved entirely. CONCLUSIONS: We conclude that HACE is characterized on MRI by reversible white matter edema, with a predilection for the splenium of the corpus callosum. This finding provides a clinical imaging correlate useful for diagnosis. It also suggests that the predominant mechanism is vasogenic (movement of fluid and protein out of the vascular compartment) and, thus, that the blood-brain barrier may be important in HACE.     

Cortical gray matter volume deficits in schizophrenia: a replication

We sought to replicate an earlier finding of widespread deficit in cortical gray matter in schizophrenia by testing new samples of 22 schizophrenic patients and 27 controls between the ages of 21-46 years. Brain values for both patients and controls were standardized against age and head size norms derived from a larger control group (n = 73) spanning a wider age range (21-70). Compared to the new age-matched controls, the new schizophrenic sample showed a deficit in gray matter volume affecting the cortex as a whole and enlargement of the lateral and third ventricles. Thus, widespread cortical gray matter deficit is a replicable feature of the brain dysmorphology of schizophrenia in young to middle-aged men.