A multi-scanner study of subcortical brain volume abnormalities in schizophrenia

Schizophrenia patients show significant subcortical brain abnormalities. We examined these abnormalities using automated image analysis software and provide effect size estimates for prospective multi-scanner schizophrenia studies. Subcortical and intracranial volumes were obtained using FreeSurfer 5.0.0 from high-resolution structural imaging scans from 186 schizophrenia patients (mean age±SD=38.9±11.6, 78% males) and 176 demographically similar controls (mean age±SD=37.5±11.2, 72% males). Scans were acquired from seven 3-Tesla scanners. Univariate mixed model regression analyses compared between-group volume differences. Weighted mean effect sizes (and number of subjects needed for 80% power at α=0.05) were computed based on the individual single site studies as well as on the overall multi-site study. Schizophrenia patients have significantly smaller intracranial, amygdala, and hippocampus volumes and larger lateral ventricle, putamen and pallidum volumes compared with healthy volunteers. Weighted mean effect sizes based on single site studies were generally larger than effect sizes computed based on analysis of the overall multi-site sample. Prospectively collected structural imaging data can be combined across sites to increase statistical power for meaningful group comparisons. Even when using similar scan protocols at each scanner, some between-site variance remains. The multi-scanner effect sizes provided by this study should help in the design of future multi-scanner schizophrenia imaging studies

Normative data for subcortical regional volumes over the lifetime of the adult human brain

Normative data for volumetric estimates of brain structures are necessary to adequately assess brain volume alterations in individuals with suspected neurological or psychiatric conditions. Although many studies have described age and sex effects in healthy individuals for brain morphometry assessed via magnetic resonance imaging, proper normative values allowing to quantify potential brain abnormalities are needed. We developed norms for volumetric estimates of subcortical brain regions based on cross-sectional magnetic resonance scans from 2790 healthy individuals aged 18 to 94 years using 23 samples provided by 21 independent research groups. The segmentation was conducted using FreeSurfer, a widely used and freely available automated segmentation software. Models predicting subcortical regional volumes of each hemisphere were produced including age, sex, estimated total intracranial volume (eTIV), scanner manufacturer, magnetic field strength, and interactions as predictors. The mean explained variance by the models was 48%. For most regions, age, sex and eTIV predicted most of the explained variance while manufacturer, magnetic field strength and interactions predicted a limited amount. Estimates of the expected volumes of an individual based on its characteristics and the scanner characteristics can be obtained using derived formulas. For a new individual, significance test for volume abnormality, effect size and estimated percentage of the normative population with a smaller volume can be obtained. Normative values were validated in independent samples of healthy adults and in adults with Alzheimer's disease and schizophrenia

The effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI study

INTRODUCTION This project investigated volumetric differences in certain subcortical structures as measured on high-resolution structural Magnetic Resonance Imaging (MRI) scans traced manually. The sample comprised 79 5-year old children, 52 with HIV and 27 uninfected controls. Infected children were all stable on antiretroviral therapy (ART) and were from the Children with HIV early antiretroviral (CHER) cohort who have been followed since birth. The study aimed to investigate the long-term effects of HIV and ART on the developing brain. While high-resolution structural data has been analysed using automated FreeSurfer to determine volume and cortical thickness, manual tracing remains the gold standard. Thus, manual tracing was used to validate automated measures and investigate subtle group differences in selected regions of interest. METHODS Extensive clinical data were available for all participants in the study. MR images were AC-PC transformed and converted to analyse format. Structures were traced using MultiTracer software. Structures selected included the caudate, nucleus accumbens (NA), putamen (Pu), globus pallidus (GP) and corpus callosum (CC). Four of these structures occur bilaterally. Tracing was performed in 79 subjects. Three subjects were excluded due to poor quality images or pathology; 5 HIV-1 infected children were excluded as they were not randomized between treatment groups. Certain subjects were retraced for inter and intrarater reliabilities. The effect and association of ethnicity, age, birthweight and sex as possible confounders were investigated. As the groups were not well matched for ethnicity, all Cape Coloured children were excluded from further analyses. Analysis of variance was used to test the effect on structure size between HIV-1 infected children and controls, as well as between 3 treatment arms (ART deferred until clinical criteria were met, early ART for 40 weeks, early ART for 96 weeks) and uninfected controls. Analysis of covariance was used to control for the possible confounding effects of sex and age. Each structure was tested for possible association with clinical variables (CD4, CD8, CD4/CD8 ratio and CD4%) both at enrolment and time of scanning. Linear regressions were modelled using clinical variables that showed significant correlation with structure size whilst controlling for covariates. Congruence between automated FreeSurfer and manual segmentation were evaluated via Bland-Altman, Pearson r and Cronbach's alpha

Pathogenesis of HIV in the Central Nervous System

HIV can infect the brain and impair central nervous system (CNS) function. Combination antiretroviral therapy (cART) has not eradicated CNS complications. HIV-associated neurocognitive disorders (HAND) remain common despite cART, although attenuated in severity. This may result from a combination of factors including inadequate treatment of HIV reservoirs such as circulating monocytes and glia, decreased effectiveness of cART in CNS, concurrent illnesses, stimulant use, and factors associated with prescribed drugs, including antiretrovirals. This review highlights recent investigations of HIV-related CNS injury with emphasis on cART-era neuropathological mechanisms in the context of both US and international settings

Magnetic resonance imaging study of corpus callosum abnormalities in patients with different subtypes of schizophrenia

Background. Reductions in the size of the corpus callosum (CC) have been described for schizophrenia patients, but little is known about the possible regional differences in schizophrenia subtypes (paranoid, disorganised, undifferentiated, residual).  Methods. We recruited 58 chronically schizophrenic patients with different subtypes, and 31 age-and-gender matched healthy controls. The callosum was extracted from a midsagittal slice from T1 weighted magnetic resonance images, and areas of the total CC, its five subregions, CC length and total brain volume were compared between schizophrenia subtypes and controls. Five subregions were approximately matched to fibre pathways from cortical regions.  Results. Schizophrenia patients had reduced CC total area and length when compared with controls. Disorganised and undifferentiated schizophrenics had a smaller prefrontal area, while there was no significant difference for the paranoid and residual groups. The premotor/supplementary motor area was smaller in all schizophrenia subtypes. The motor area was smaller only in the disorganised group. A smaller sensory area was found in all subtypes except the residual group. Parietal, temporal and occipital areas were smaller in the paranoid and undifferentiated groups. Total brain volume was smaller in all schizophrenia subtypes compared with controls, but did not reach statistical significance.  Conclusion. These findings suggest that the heterogeneity of symptoms may lead to the different CC morphological characteristics in schizophrenia subtypes

Reproducibility of hippocampal atrophy rates measured with manual, FreeSurfer, AdaBoost, FSL/FIRST and the MAPS-HBSI methods in Alzheimer's disease

The purpose of this study is to assess the reproducibility of hippocampal atrophy rate measurements of commonly used fully-automated algorithms in Alzheimer disease (AD). The reproducibility of hippocampal atrophy rate for FSL/FIRST, AdaBoost, FreeSurfer, MAPS independently and MAPS combined with the boundary shift integral (MAPS-HBSI) were calculated. Back-to-back (BTB) 3D T1-weighted MPRAGE MRI from the Alzheimer's Disease Neuroimaging Initiative (ADNI1) study at baseline and year one were used. Analysis on 3 groups of subjects was performed – 562 subjects at 1.5 T, a 75 subject group that also had manual segmentation and 111 subjects at 3 T. A simple and novel statistical test based on the binomial distribution was used that handled outlying data points robustly. Median hippocampal atrophy rates were −1.1%/year for healthy controls, −3.0%/year for mildly cognitively impaired and −5.1%/year for AD subjects. The best reproducibility was observed for MAPS-HBSI (1.3%), while the other methods tested had reproducibilities at least 50% higher at 1.5 T and 3 T which was statistically significant. For a clinical trial, MAPS-HBSI should require less than half the subjects of the other methods tested. All methods had good accuracy versus manual segmentation. The MAPS-HBSI method has substantially better reproducibility than the other methods considered