Total Cerebral Tissue Research Articles

Volumetric study of brain MRI in a cohort of patients with neurotransmitter disorders.

Inborn errors of neurotransmitters are rare monogenic diseases. In general, conventional neuroimaging is not useful for diagnosis. Nevertheless, advanced neuroimaging techniques could provide novel diagnosis and prognosis biomarkers. We aim to describe cerebral volumetric findings in a group of Spanish patients with neurotransmitter disorders. Fifteen 3D T1-weighted brain images from the International Working Group on Neurotransmitter related Disorders Spanish cohort were assessed (eight with monoamine and seven with amino acid disorders). Volumes of cortical and subcortical brain structures were obtained for each patient and then compared with those of two healthy individuals matched by sex and age. Regardless of the underlying disease, patients showed a smaller total cerebral tissue volume, which was apparently associated with clinical severity. A characteristic volumetric deficit pattern, including the right Heschl gyrus and the bilateral occipital gyrus, was identified. In severe cases, a distinctive pattern comprised the middle and posterior portions of the right cingulate, the left superior motor area and the cerebellum. In succinate semialdehyde dehydrogenase deficiency, volumetric affection seems to worsen over life. Despite the heterogeneity and limited size of our cohort, we found novel and relevant data. Total volume deficit appears to be a marker of severity, regardless of the specific neurotransmitter disease and irrespective of the information obtained from conventional neuroimaging. Volumetric assessment of individual brain structures could provide a deeper knowledge about pathophysiology, disease severity and specific clinical traits.

Neonatal cerebral morphometry and later risk of persistent inattention/hyperactivity in children born very preterm

Attention problems are among the most prevalent neurobehavioral morbidities affecting very preterm (VPT) born children. The first study aim was to document rates of persistent attention/hyperactivity problems from ages 4 to 9 years in a regional cohort of VPT born children. The second aim was to examine the extent to which persistent problems were related to cerebral white matter abnormality and structural development on neonatal MRI. Data were drawn from a prospective longitudinal study of 110 VPT (≤32 weeks gestation) and 113 full-term (FT) children born from 1998 to 2000. At term equivalent, all VPT and 10 FT children underwent cerebral structural MRI, with scans analyzed qualitatively for white matter abnormalities and quantitatively for cortical and subcortical gray matter, myelinated and unmyelinated white matter, and cerebrospinal fluid volumes. At ages 4, 6, and 9 years, each child's parent and teacher completed the Inattention/Hyperactivity subscale of the Strengths and Difficulties Questionnaire. VPT born children had a fivefold increased risk of persistent attention/hyperactivity problems compared with FT children (13.1% vs. 2.8%; p = .002). No association was found between neonatal white matter abnormalities and later persistent inattention/hyperactivity risk (p ≥ .24). In contrast, measures of cerebral structural development including volumetric estimates of total cerebral tissue and cerebrospinal fluid relative to intracranial volume were associated with an increased risk of persistent attention/hyperactivity problems in VPT born children (p = .001). The dorsal prefrontal region showed the largest volumetric reduction (↓3.2-8.2 mL). These brain-behavior associations persisted and in some cases, strengthened after covariate adjustment for postmenstrual age at MRI, gender, and family socioeconomic status. Just over one in 10 VPT born children are subject to early onset and persistent attention/hyperactivity problems during childhood. These problems appear to reflect, at least in part, neonatal disturbances in cerebral growth and development rather than the effects of white matter injury.

P.7.b.011 First episode psychosis during adolescence: clinical and therapeutic differences from adulthood onset

Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach.Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis.As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes.In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma.

Early adversity and combat exposure interact to influence anterior cingulate cortex volume in combat veterans

ObjectiveChildhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach.MethodAnterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis.ResultsAs previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes.ConclusionsIn the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma.

Brain Volume Shrinkage Parallels Rise in Antipsychotic Drug Dosage

Brain Volume Shrinkage Parallels Rise in Antipsychotic Drug Dosage

Postnatal Dexamethasone Therapy and Cerebral Tissue Volumes in Extremely Low Birth Weight Infants

Our goal was to relate postnatal dexamethasone therapy in extremely low birth weight infants (birth weight of < or = 1000 g) to their total and regional brain volumes, as measured by volumetric MRI performed at term-equivalent age. Among 53 extremely low birth weight infants discharged between June 1 and December 31, 2003, 41 had high-quality MRI studies; 30 of those infants had not received postnatal steroid treatment and 11 had received dexamethasone, all after postnatal age of 28 days, for a mean duration of 6.8 days and a mean cumulative dose of 2.8 mg/kg. Anatomic brain MRI scans obtained at 39.5 weeks (mean) postmenstrual age were segmented by using semiautomated and manual, pretested, scoring algorithms to generate three-dimensional cerebral component volumes. Volumes were adjusted according to postmenstrual age at MRI. After controlling for postmenstrual age at MRI, we observed a 10.2% smaller total cerebral tissue volume in the dexamethasone-treated group, compared with the untreated group. Cortical tissue volume was 8.7% smaller in the treated infants, compared with untreated infants. Regional volume analysis revealed a 20.6% smaller cerebellum and a 19.9% reduction in subcortical gray matter in the dexamethasone-treated infants, compared with untreated infants. In a series of regression analyses, the reductions in total cerebral tissue, subcortical gray matter, and cerebellar volumes associated with dexamethasone administration remained significant after controlling not only for postmenstrual age but also for bronchopulmonary dysplasia and birth weight. We identified smaller total and regional cerebral tissue volumes in extremely low birth weight infants treated with relatively conservative regimens of dexamethasone. These volume deficits may be the structural antecedents of neuromotor and cognitive abnormalities reported after postnatal dexamethasone treatment.

Evidence that brain tissue volumes are associated with HVA reactivity to metabolic stress in schizophrenia

Background Although liability to psychosis is thought to have its origins in cerebral alterations, expressed as cerebral grey and white matter loss, less is known about the degree to which such vulnerabilities impact on functional parameters, in particular altered stress reactivity. Breier et al. [Breier, A., Davis, O.R., Buchanan, R.W., Moricle, L.A., Munson, R.C., 1993b. Effects of metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship to prefrontal cortex volume. Arch. Gen. Psychiatry 50(7), 541–550] reported that lower prefrontal cortex volume was associated with altered metabolic stress response, but this finding has never been replicated. Methods Thirty-one patients with psychosis underwent structural magnetic resonance imaging scanning and a metabolic stress paradigm (glucoprivic 2-deoxyglucose (2DG) condition versus placebo condition) that yielded information on plasma homovanillic acid (HVA) reactivity. Total cerebral tissue volumes were derived from automated segmentation procedures. Associations between metabolic stress and tissue volumes (as well as their interactions) on the one hand, and plasma HVA level on the other, were investigated using multilevel random regression techniques. Results Analysis revealed a significant increase in plasma HVA over time in the 2DG condition. The increase in HVA in the stress condition was stronger in patients with lower grey and white matter volumes. There was no significant interaction between metabolic stress and CSF volume. Conclusion Lower grey and white matter volumes in schizophrenia are associated with a dysregulated dopaminergic/noradrenergic mediated stress response. These findings may support the hypothesis that alterations in cortico-subcortical connections affect psychosis susceptibility through an altered stress response.

Object working memory deficits predicted by early brain injury and development in the preterm infant

Children born preterm and of very low birth weight are at increased risk of learning difficulties and educational under-achievement. However, little is known about the specific neuropsychological problems facing these children or their neurological basis. Using prospective longitudinal data from a regional cohort of 92 preterm and 103 full-term children, this study examined relations between term MRI measures of cerebral injury and structural brain development and children's subsequent performance on an object working memory task at the age of 2 years. Results revealed clear between-group differences, with preterm children having greater difficulty encoding new information in working memory than term control children. Within the preterm group, task performance at the age of 2 years was related to both qualitative MRI measures of white matter (WM) injury and quantitative measures of total and regional brain volumes assessed at term equivalent. Bilateral reductions in total tissue volumes (%region) of the following cerebral regions were specifically related to subsequent working memory performance: dorsolateral prefrontal cortex, sensorimotor, parietooccipital and premotor. Associations between total cerebral tissue volumes at term (adjusted and unadjusted for intracranial volume) persisted even after the effects of WM injury were taken into account. This suggests that early disturbance in cerebral development may have an independent adverse impact on later working memory function in the preterm infant. These findings add to our understanding of the neuropathological pathways associated with later executive dysfunction in the very preterm infant.

43 Total Cerebral Volume Measurements Following Preterm Birth

Background. Preterm infants have reduced cerebral tissue volumes in adolescence, and relative loss of some brain regions in early childhood, but it is unclear if this is due to perinatal or more prolonged growth failure. We therefore compared total cerebral tissue volume in preterm infants at term equivalent age and term born controls. Methods. Subjects: We studied 89 preterm infants born at median 29.7 weeks GA without parenchymal lesions at median 40.57 weeks, and 20 term born controls (median 40.43 weeks GA). Image acquisition: A 1.5 Tesla MR system was used to acquire T1-weighted volume datasets with a voxel size 1x1x1.6mm, in addition to conventional and diffusion weighted imaging. Image processing: A non-rigid image registration algorithm transformed all images to a reference subject, and transformations were used to propagate region of interest (ROI) labels segmented in the reference anatomy to the corresponding structure in all subjects. The volume change for each ROI relative to the reference was computed, enabling cerebral tissue volume measurements (excluding CSF) to be calculated for each subject. Results. Mean cerebral tissue volume in preterm infants at term was 404.9cm3; and in term controls, 401.1cm3 (p=0.765). Diffuse white matter injury, oxygen requirement at 28 days, and intrauterine growth restriction were not associated with significant reductions in cerebral tissue volume. Conclusions. Despite evidence of regional and later growth failure, total brain tissue volume in preterm infants at term is similar to term born controls.

Amygdala and hippocampal volumes in Turner syndrome: a high-resolution MRI study of X-monosomy

Turner syndrome (TS) results from partial or complete X-monosomy and is characterized by deficits in visuospatial functioning as well as social cognition and memory. Neuroimaging studies have demonstrated volumetric differences in the parietal region of females with TS compared to controls. The present study examined amygdala and hippocampus morphology in an attempt to further understand the neural correlates of psychosocial and memory functioning in TS. Thirty females with TS age 7.6–33.3 years (mean = 14.7 ± 6.4) and 29 age-matched controls (mean age = 14.8 ± 5.9; range = 6.4–32.7) were scanned using high resolution MRI. Volumetric analyses of the MRI scans included whole brain segmentation and manual delineation of the amygdala and hippocampus. Compared to controls, participants with TS demonstrated significantly larger left amygdala gray matter volumes, irrespective of total cerebral tissue and age. Participants with TS also showed disproportionately reduced right hippocampal volumes, involving both gray and white matter. Amygdala and hippocampal volumes appear to be impacted by X-monosomy. Aberrant morphology in these regions may be related to the social cognition and memory deficits often experienced by individuals with TS. Further investigations of changes in medial temporal morphology associated with TS are warranted.

Prediction of total cerebral tissue volumes in normal appearing brain from sub-sampled segmentation volumes.

The need for anatomical coverage and multi-spectral information must be balanced against examination and processing time to ensure high-quality, feasible imaging protocols for clinical research of cerebral development in normal-appearing brains. The focus of this study was to create and assess models to estimate total cerebral volumes of gray matter, white matter, and cerebrospinal fluid (CSF) from anatomically defined sub-samples of full clinical examinations. Pediatric patients (18F, 11M; aged 1.7 to 18.7, median 5.2 years) underwent a clinical imaging protocol consisting of 3 mm contiguous T1-, T2-, PD-, and FLAIR-weighted images after obtaining informed consent. Magnetic resonance imaging (MRI) sets were registered, RF-corrected, and then analyzed with a hybrid neural network segmentation and classification algorithm to identify normal brain parenchyma. The correlation between the image subsets and the total cerebral volumes of gray matter, white matter and CSF were examined through linear regression analyses. Five sub-sampled sets were defined and assessed in each patient to produce estimation models which were all significantly correlated (p < 0.001) with the total cerebral volumes of gray matter, white matter, and CSF. Volumes were estimated from as little as a single representative slice requiring minimal processing time, 27 min, but with an average estimation error of approximately 6%. Larger sub-samples of approximately three-quarters of the full cerebral volume required much more processing time, 2 h and 4 min, but produced estimates with an average error less than 2%. This study demonstrated that investigators can choose the amount of cerebrum sampled to optimize the acquisition and processing time against the degree of accuracy needed in the total cerebral volume estimates.

Cerebral tissue alterations and daily life stress experience in psychosis

Objective: To examine whether the total volumes of cerebrospinal fluid (CSF), cerebral grey matter and white matter were correlated with the experience of environmental stress in daily life situations. Method: Twenty-seven patients with psychosis underwent magnetic resonance imaging scanning and a random time-sampling self-assessment technique (Experience Sampling Method) to determine subjective daily life stress experiences. Total cerebral tissue volumes were derived from an automated segmentation procedure. Results: CSF volume was positively associated with daily life event-related stress (β=0.016, P=0.002), while the association with total white matter was negative (β=−0.013, P=0.005). The effects were independent of each other and of total cerebral volume and other confounders. No large or significant association was found with grey matter volume. Conclusion: Subjective stress experience in daily life is associated with increased CSF and reduced white matter volumes in patients with psychosis, suggesting functional significance of these cerebral measures.

Cerebral tissue alterations and daily life stress experience in psychosis.

To examine whether the total volumes of cerebrospinal fluid (CSF), cerebral grey matter and white matter were correlated with the experience of environmental stress in daily life situations. Twenty-seven patients with psychosis underwent magnetic resonance imaging scanning and a random time-sampling self-assessment technique (Experience Sampling Method) to determine subjective daily life stress experiences. Total cerebral tissue volumes were derived from an automated segmentation procedure. CSF volume was positively associated with daily life event-related stress (beta=0.016, P=0.002), while the association with total white matter was negative (beta=-0.013, P=0.005). The effects were independent of each other and of total cerebral volume and other confounders. No large or significant association was found with grey matter volume. Subjective stress experience in daily life is associated with increased CSF and reduced white matter volumes in patients with psychosis, suggesting functional significance of these cerebral measures.

Impaired cerebral cortical gray matter growth after treatment with dexamethasone for neonatal chronic lung disease.

The specific aim of this study was to quantify at term the influence of postnatal systemic dexamethasone treatment for neonatal chronic lung disease on subsequent brain growth and development in premature infants without evidence of severe intraventricular hemorrhage or white matter injury. Eighteen premature (23 to 31 weeks) infants, 7 treated with dexamethasone and 11 not treated, were studied at term, ie, 38 to 41 postconceptional weeks, by an advanced quantitative volumetric 3-dimensional magnetic resonance imaging (MRI) technique to quantify cerebral tissue volumes. Fourteen healthy term infants also were studied for comparison. A sequence of image processing algorithms was used to segment each of the MRI slices into the following separate tissue classes: cerebral cortical gray matter, basal ganglia/thalami, unmyelinated white matter, myelinated white matter, and cerebrospinal fluid, all classified based on magnetic resonance signal intensity and anatomic location. A final summing of voxels for each tissue class was performed to compute absolute volumes in milliliters. Cerebral cortical gray matter volume in premature infants treated with dexamethasone was reduced 35% when compared with gray matter volume in premature infants not treated with dexamethasone (mean +/- standard deviation, 130.3 +/- 54.0 vs 200.6 +/- 35.1 mL, respectively). Subcortical gray matter volumes (basal ganglia and thalami) and myelinated and unmyelinated white matter volumes were not significantly different among the treated and untreated groups. However, premature infants treated with dexamethasone exhibited a reduction (30%) in total cerebral tissue volume compared with total cerebral tissue volume in both the premature infants not treated with dexamethasone and the control term infants (312.7 +/- 43.7 vs 448.2 +/- 50.2 and 471.6 +/- 36.4 mL respectively). This latter finding relates primarily to the decrease in cerebral cortical gray matter volume. The data suggest an impairment in brain growth, principally affecting cerebral cortical gray matter, secondary to systemic dexamethasone therapy. Although the premature infants who received dexamethasone were smaller with more severe respiratory disease, these findings are consistent with growing evidence of a potential deleterious effect of dexamethasone on neonatal brain and subsequent neurodevelopmental outcome. This apparent deleterious effect should be taken into consideration by clinicians when weighing the potential risks and benefits of this therapy for low birth weight infants with neonatal chronic lung disease.

Affective symptoms in the prodrome of first onset psychoses

Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach.Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis.As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes.In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma.

Age-related changes in glucose transporter-one mRNA structure and function.

To determine the molecular mechanisms of age-related changes in the expression of glucose transporter 1 (GLUT-1) mRNA in cerebral tissue, male Fischer 344 rats at 4, 12, and 24 months of age were studied. The GLUT-1 mRNA in cerebral tissue was not significantly different among the various age groups. The in vitro translatability of GLUT-1 mRNA of 24-month-old rats (0.867 +/- 0.066 arbitrary units) was significantly lower than that in 4-month-old (1.403 +/- 0.153) P < 0.01 or 12-month-old rats (1.387 +/- 0.122) P < 0.01. The poly (A) tail length of GLUT-1 mRNA decreased from 200-350 nt in 4-month-old rats to only 50-100 nt in 24-month-old rats. Twelve-month-old rats also showed reduced poly (A) tail lengths. The poly (A) tail of G3PDH mRNA was not altered with age. The changes in GLUT-1 mRNA translatability did not correlate with GLUT-1 content in total cerebral tissue homogenate or in isolated cerebral microvessels, suggesting that GLUT-1 protein turnover is altered with age. It is concluded that aging is associated with significant changes in the structure and function of GLUT-1 mRNA.

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Survival in patients with fulminant hepatic failure (FHF) treated medically, rather than surgically, ranges from 12%-67% (mean 39%), depending on the cause of the disease (1). The major cause of mortality is increased intracranial pressure (ICI’) from brain edema (2). For patients with a poor prognosis (3), orthotopic liver transplantation may be the definitive treatment (41, even though, only a few years ago, some considered this treatment ineffective by the time patients reached Grade 4 encephalopathy (5). ICI’ monitoring allows physicians to use specific therapy to control intracranial hypertension. Continuous measurement of ICI’ perioperatively in the management of FHF has been associated with a survival rate of 54%74% in a series of six to 23 patients (6-9), which is generally higher than with medical means (l), and was as high as 92% for the selected group who had undergone liver transplantation (6). Such invasive monitoring, however, is especially risky in FHF patients with coagulopathy, in whom the incidence of bleeding from ICI’ monitoring ranges from 5%-22% (6,8) with a mortality rate of 60% (6). Although the use of ICI’ monitoring for FHF has become more routine (8), not all centers support the use of this invasive monitoring. We describe a patient with FHF and brain edema who underwent liver transplantation and whose cerebral perfusion was monitored noninvasively by transcranial Doppler (TCD) imaging, as well as invasively by ICI’. The noninvasive technique provided adequate information when cerebral perfusion was low, comparable with the invasive technique, and allowed intracranial hypertension to be diagnosed and treated effectively.