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PubMed2004

Diffusion tensor imaging of early relapsing-remitting multiple sclerosis with histogram analysis using automated segmentation and brain volume correction.

Diffusion tensor magnetic resonance imaging (DTI) reveals measurable abnormalities in normal-appearing brain tissue (NABT) in established multiple sclerosis (MS). However, it is unclear how early this occurs. Recent studies have employed whole brain histogram analysis to improve sensitivity, but concern exists regarding reliability of tissue/cerebrospinal fluid segmentation and possible intersubject brain volume differences, which can introduce partial volume error: To address this, 28 early relapsing-remitting MS subjects [median disease duration 1.6 years; median Expanded Disability Status Scale (EDSS) score 1.5] and 20 controls were compared with whole brain histogram analysis using an automated segmentation algorithm to improve reproducibility. Brain parenchymal volumes (BPV) were estimated for each subject in the analysis. The mean, peak height and peak location were calculated for DTI parameters [fractional anisotropy (FA), mean diffusivity and volume ratio]. An increased FA peak height in MS subject NABT was observed (P = 0.02) accounting for age, gender and BPV. Removing BPV revealed additional abnormalities in NABT. The main conclusions are i) FA peak height is increased in NABT in early MS, ii) partial volume edge effects may contribute to apparent NABT histogram abnormalities, and iii) correction for brain volume differences should reduce potential partial volume edge effects.

Adult↗
PubMed2004

Brain volumes in adult survivors of very low birth weight: a sibling-controlled study.

OBJECTIVES: To establish whether adults who were born very low birth weight (VLBW) show altered volumes of certain brain structures. METHODS: Unmatched case-control study was conducted of 33 individuals from a cohort of VLBW (<1500 g) infants who were born between 1966 and 1977 and 18 of their normal birth weight siblings. Whole brain, gray matter, ventricular, corpus callosum, and hippocampal volumes were measured on structural magnetic resonance imaging scans. RESULTS: VLBW individuals had a 46% increase in total ventricular volume and a 17% reduction in posterior corpus callosum volume. No differences in whole brain, gray matter, or hippocampal volumes were observed. CONCLUSION: Specific differences exist in the volumes of certain brain structures in adults who were born VLBW compared with their normal birth weight siblings.

Adult↗
PubMed2005

Brain volume in pediatric patients with sickle cell disease: evidence of volumetric growth delay?

BACKGROUND AND PURPOSE: Despite the large body of data available about somatic growth delay in patients with sickle cell disease (SCD), virtually nothing is known about the effect of the disease on volumetric growth of the brain. This study was designed to test a hypothesis that children with SCD have a disease-related delay in brain volumetric growth compared with healthy children. METHODS: A cross-sectional study design was used to evaluate 83 children with SCD and 43 age-similar healthy children, including 27 patient siblings. Brain volume was measured by segmenting and classifying MR imaging data, by using at least three separate image sets (T1-, T2-, and proton density-weighted MR images). A linear model was used to compare the various brain volumes with the covariates of group (patient versus control) and age, with age treated as a continuous variable. RESULTS: With age controlled for, no significant difference was noted in total brain volume between patients and control subjects at age 9.5 years. However, patients showed a deficit specifically in gray matter volume (P=.005), without significant differences in white matter or ventricular volume. The deficit in patient gray matter was greater in central gray matter (P <.005) than in cortical gray matter (P <.02). In healthy control subjects, gray matter volume decreased significantly with age (P <.005), probably due to myelination of white matter tracts. In patients with SCD, gray matter volume did not change with age. CONCLUSION: Volumetric growth of brain gray matter may be delayed in children with SCD, suggesting that there may be neurodevelopmental consequences of this disease.

Adolescent↗
PubMed2003

Changes in premorbid brain volume predict Alzheimer's disease pathology.

OBJECTIVE: To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology. METHODS: Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI. RESULTS: Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results. CONCLUSIONS: MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology.

Aged↗
PubMed2002

Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.

CONTEXT: Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder (ADHD), with varying methods, small samples, cross-sectional designs, and without accounting for stimulant drug exposure. OBJECTIVE: To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. MAIN OUTCOME MEASURES: Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls. RESULTS: On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P<.001). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F(2,288) = 11.65) compared with controls (-10.7%, P<.001) and with medicated children with ADHD (-8.9%, P<.001). Volumetric abnormalities persisted with age in total and regional cerebral measures (P =.002) and in the cerebellum (P =.003). Caudate nucleus volumes were initially abnormal for patients with ADHD (P =.05), but diagnostic differences disappeared as caudate volumes decreased for patients and controls during adolescence. Results were comparable for male and female patients on all measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P values were <.05). CONCLUSIONS: Developmental trajectories for all structures, except caudate, remain roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.

Adolescent↗
PubMed1998

Fetal and fetal brain volume estimation in the third trimester of human pregnancy using gradient echo MR imaging.

The Cavalieri method has been applied in combination with gradient echo magnetic resonance imaging (MRI) to investigate the increase in the volume of the fetus and fetal brain in the third trimester of pregnancy. Eighteen women with singleton pregnancies were recruited. Birthweights for the fetuses all lay within the 10-90th centile based on Liverpool data. A regression analysis, weighted using values derived from the coefficient of error predicted for each volume estimate, revealed a linear relationship between total fetal volume and gestational age (R2 = 0.88) and between fetal brain volume and gestational age (R2 = 0.71) during the third trimester. Fetal volume increased by an average of 25.2 ml per day and fetal brain volume increased by an average of 2.3 mL per day. Fetal brain volume is on average a constant proportion (10%, SD = 2%) of total fetal volume throughout the third trimester. Volume data were also obtained for eight fetuses diagnosed as abnormal. The volume of seven of the eight abnormal fetuses fell outside the 95% confidence interval established from the data obtained for the normal fetuses. However, for only three of the eight abnormal fetuses did brain volume fall outside the 95% confidence interval established for normals, possibly due to brain sparing occurring in asymmetrical growth retardation. The volume of the fetus and fetal brain may be readily estimated directly using the Cavalieri method and magnetic resonance imaging. These parameters represent potentially useful information for assessing fetal growth.

Adult↗
PubMed2003

Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study.

Gray matter brain volume decreases have been found in patients with schizophrenia as compared to healthy control subjects measured by using Magnetic Resonance Imaging (MRI). An association has been suggested between decreased gray matter volume and poor outcome in chronically ill patients with schizophrenia. The present longitudinal multi-center study investigated whether gray matter volume at illness onset can predict poor outcome in recent-onset schizophrenia after a follow-up of approximately 2 years. An MRI calibration study was performed since scans of patients with recent-onset psychosis were conducted at three sites with 1.5 T MR scanners from two different manufacturers. Applying a linear scaling procedure on the histogram improved comparability between volume measurements acquired from images from the different scanners. Brain scans were obtained from 109 patients with recent-onset schizophrenia. Volumes of intracranium, total brain, cerebral gray and white matter, third and lateral ventricles, and cerebellum were measured. After a mean follow-up period of approximately 2 years, measurements of symptoms, functioning, need for care, and illness history variables were assessed. No significant correlations were found between the brain volume measures and any of these measures. Gray matter volume at illness onset does not predict outcome after 2 years in recent-onset schizophrenia.

Adolescent↗
PubMed2004

An automated algorithm for the computation of brain volume change from sequential MRIs using an iterative principal component analysis and its evaluation for the assessment of whole-brain atrophy rates in patients with probable Alzheimer's disease.

This article introduces an automated method for the computation of changes in brain volume from sequential magnetic resonance images (MRIs) using an iterative principal component analysis (IPCA) and demonstrates its ability to characterize whole-brain atrophy rates in patients with Alzheimer's disease (AD). The IPCA considers the voxel intensity pairs from coregistered MRIs and identifies those pairs a sufficiently large distance away from the iteratively determined PCA major axis. Analyses of simulated and real MRI data support the underlying assumption of a linear relationship in paired voxel intensities, identify an outlier distance threshold that optimizes the trade-off between sensitivity and specificity in the detection of small volume changes while accounting for global intensity changes, and demonstrate an ability to detect changes as small as 0.04% of brain volume without confounding effects of between-scan shifts in voxel intensity. In eight patients with probable AD and eight age-matched normal control subjects, the IPCA was comparable to the established but partly manual digital subtraction (DS) method in characterizing annual rates of whole-brain atrophy: resulting rates were correlated (Spearman rank correlation = 0.94, P < 0.0005) and comparable in distinguishing probable AD from normal aging (IPCA-detected atrophy rates: 2.17 +/- 0.52% per year in the patients vs. 0.41 +/- 0.22% per year in the controls [Wilcoxon-Mann-Whitney test P = 7.8 x 10(-4)]; DS-detected atrophy rates: 3.51 +/- 1.31% per year in the patients vs. 0.48 +/- 0.29% per year in the controls [P = 7.8 x 10(-4)]). The IPCA could be used in tracking the progression of AD, evaluating the disease-modifying effects of putative treatments, and investigating the course of other normal and pathological changes in brain morphology.

Aged↗
PubMed2006

Correlations between regional brain volumes and memory performance in anoxia.

This study was aimed at investigating the quantitative relationship between regional brain volumes (hippocampus, amygdala, as well as cerebrum, frontal lobe, parietal lobe, temporal lobe) and performance on anterograde and retrograde memory tests in anoxic patients. We used high-resolution MRI to measure brain volumes in 13 anoxic patients. Neuropsychological testing was conducted contemporaneously with MRI. To control for age and sex, neuroanatomical volume residuals were calculated using regression equations derived from a group of 87 healthy comparison participants. We found that anoxic patients with severe amnesia had hippocampal volumes that were 36% smaller than normal, whereas patients with mild or no amnesia had normal hippocampal volumes. Regional gray matter volumes in severe amnesic anoxics were substantially smaller than expected. Performances on anterograde memory tests were significantly correlated with hippocampal and regional gray matter volume residuals. There was a significant correlation between white matter volume (but not hippocampal volume) and performance on the Visual Retention Test, a multi-dimensional test of cognitive function. There were no significant correlations between neuroanatomical measures and performance on a retrograde memory test. Our results indicate a strong quantitative relationship between performance on anterograde memory tests and hippocampal and regional gray matter volume residuals. Correlations between white matter volume residuals and performance on the VRT were found to be independent of hippocampal volume. Given the strong correlation between hippocampal volume and total gray matter volume residuals, a quantitative, normalized measure of total gray matter volume may provide a good indication of clinical outcome in anoxia.

Adult↗
PubMedDate not supplied

The effects of dehydration on brain volume -- preliminary results.

In adults the cranium is a rigid bony vault of fixed size and therefore the intra-cranial volume is a constant which equals the sum of the volume of the brain, the intra-cranial volume of CSF and the intra-cranial volume of blood. There can be marked changes in the volumes of these three intra-cranial compartments which may influence susceptibility to brain damage after head injury. This is the first study to investigate the relationship between dehydration and changes in the volume of the brain and the cerebral ventricles. Six healthy control subjects underwent magnetic resonance imaging of the brain before and after a period of exercise in an environmental chamber. The subjects lost between 2.1 % and 2.6 % of their body mass due to water loss through sweating. We found a correlation between the degree of dehydration and the change in ventricular volume (r=0.932, p=0.007). The changes in ventricular volume caused by dehydration were much larger than those seen in day-to-day fluctuations in a normally hydrated healthy control subject.

Adolescent↗
PubMed1991

Magnetic resonance imaging (MRI) and model-free estimates of brain volume determined using the Cavalieri principle.

A complete set of parallel (coronal) slices through a fixed human forebrain was generated by magnetic resonance imaging (MRI) and the Cavalieri principle, combined with point counting, was used to estimate brain volume. Alternative sampling schemes for estimating volume were then assessed by taking systematic and simple random selections of slices. Later, the brain was weighed and its fixed volume determined by fluid displacement. For the complete set of n = 28 MRI slices, the volume (1025 ml) was estimated with a coefficient of error (CE) of less than 1%. Decreasing the number of slices by systematic sampling increased the CE but this was still only 5% when just 5-6 slices were analysed. Estimated volumes varied from 947 ml to 1098 ml. Simple random sampling was less efficient (estimated volumes for 5-6 slices were 644-1187 ml). The forebrain actually weighed 1090 g and displaced 1060 ml of fluid. A set of 14 other brains was physically sliced in order to assess sampling errors in the context of observed brain-to-brain variation. It was found that 5-6 slices per brain is enough to yield efficient estimates of mean brain volume. The findings demonstrate the practicability of using MRI to estimate brain volumes unbiasedly and efficiently. The methods have great potential for noninvasive, longitudinal studies on in vivo brains and other organs.

Brain↗
PubMed2005

Assessment of in vivo MR imaging compared to physical sections in vitro--a quantitative study of brain volumes using stereology.

The object of the present study was to compare stereological estimates of brain volumes obtained in vivo by magnetic resonance imaging (MRI) to corresponding volumes from physical sections in vitro. Brains of ten domestic pigs were imaged using a 3-T scanner. The volumes of different brain compartments were obtained from MR images by two observers and from physical sections using the Cavalieri estimator in combination with point counting. Paired t tests revealed no significant differences between the two methods for any of the five compartments considered, except for the basal gray compartment. However, although intraobserver difference of MRI estimates was acceptable, the interobserver difference was not. A statistical highly significant difference of 11-41% was observed between observers for volume estimates of all compartments considered. The study demonstrates that quantitative MRI is susceptible to observer dependent interpretation of images.

Algorithms↗
PubMed1978

[Index of brain volume and space occupied by the CSF--A parameter for the diagnosis of hydrocephalus via computerised tomography (author's transl)].

Cranial computerised tomography allows to calculate, from the volume elements of all layers, the volume of the brain and of the outer and inner spaces occupied by the cerebrospinal fluid. The ratio between the volume of the brain and of the spaces occupied by the CSF is represented by an index figure known as brain--liquor space index. Success of therapy is objectivated by a change of the index as determined by control examinations.

Adolescent↗
PubMed2001

Temporal changes in brain volume and cognition in a randomized treatment trial of vascular dementia.

OBJECTIVE: To measure changes in brain and ischemic volume over time by magnetic resonance imaging (MRI) as part of a randomized treatment trial of vascular dementia. METHODS: Participants who met criteria for vascular dementia underwent comprehensive neurological and neuropsychological testing on entrance, during, and at completion of the 1-year study. For those centers who had easily available MRI, MRI of the brain was to be performed on entry and completion of the study. Image analysis was performed on all balanced and T2-weighted MR films to determine ventricular, sulcal, ischemic, and hemispheric brain volumes. RESULTS: Of the 105 patients who met the criteria for vascular dementia, 40 had a baseline MRI study that met protocol requirements and was of excellent image quality. The baseline ventricular volume in these 40 patients with high-quality MR correlated with most measures of cognitive and behavioral function, including the total Alzheimer's Disease Assessment Score (ADAS) (r = 0.51, P = .0024), as well as activities of daily living (r = 0.61, P = .0002). The baseline ischemic brain volume correlated well only with the gait and postural stability scale (r = 0.74, P = .009). Of the 40 participants, 25 had MRI studies at baseline and at completion of the study that were comparable and of excellent image quality. For these 25 patients, the mean ventricular volumes increased by 9% over the study year (P = .001) and the mean ischemic brain volume increased by 18% (P = .01). Temporal changes in the sulcal and nonischemic brain volume did not reach significance. None of the 14 clinical score measures changed significantly between baseline and completion of the study in these 25 patients. CONCLUSION: In summary, ventricular volume correlated well with cognitive measures in patients with vascular dementia and was a more sensitive marker for change during the study year than the clinical scales used in this study. This study also points out the practical limitations of brain imaging as a surrogate measure of clinical outcome in multicenter randomized treatment trials of brain disease.

Activities of Daily Living↗
PubMed2002

Quantitative genetic modeling of regional brain volumes and cognitive performance in older male twins.

As part of an ongoing longitudinal twin study, data from both MRI brain scanning and from neuropsychological testing were obtained from 139 male-male twin pairs (72 monozygotic [MZ] and 67 dizygotic [DZ]), 69-80 years old at the time of examination. For descriptive purposes, we examined the MZ and DZ intraclass correlations (ICC) of four lobar brain volumes (frontal, temporal, parietal, and occipital), two cerebrospinal fluid (CSF) volumes (lateral ventricle and temporal horn of the lateral ventricles), and two measures of cognitive functioning (verbal memory and executive function). We found that for lobar brain and CSF space volumes, the MZ ICC were significantly greater than zero (r=0.37-0.77) and greater than the corresponding DZ correlations (r=0.02-0.49). Similarly, within-pair correlations for the two neuropsychological factors were statistically significant and significantly larger in MZ twin pairs than in DZ pairs, suggesting the presence of genetic variance. Bivariate genetic analysis revealed that while close to 60% of individual differences in neuropsychological performance were due to genetic influences, less than 50% of genetic effects were in common with those influencing brain volumes. These data may shed light on the genetic liability for brain diseases that affect the elderly.

Aged↗
PubMed2001

Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study.

BACKGROUND: We sought to determine whether the brain dysmorphology previously observed cross-sectionally in people with schizophrenia progresses over time and whether such progression is related to the severity of the illness course. SUBJECTS AND METHODS: Men with chronic schizophrenia (n = 24) and control men (n = 25) received 2 brain magnetic resonance imaging scans, on average 4 years apart. Changes in brain volume were adjusted for head-repositioning error and expressed as slopes (cubic centimeters per year). Clinical course severity for the schizophrenic patients was assessed using the mean of time 1 and time 2 Brief Psychiatric Rating Scale (BPRS) scores and the percentage of time the patient was hospitalized during the interscan interval. RESULTS: Schizophrenic patients exhibited faster volume decline than control subjects in right frontal gray matter and bilateral posterior superior temporal gray matter, as well as faster cerebrospinal fluid volume expansion in right frontal sulci, left lateral ventricle, and bilateral prefrontal and posterior superior temporal sulci. Faster rates of frontal sulcal expansion were related to greater BPRS total and positive symptom scores and longer time hospitalized. Prefrontal gray matter decline and sulcal expansion were associated with greater BPRS negative symptom scores and longer time hospitalized. Temporal lobe gray matter decline was associated with greater BPRS total and negative symptom scores. CONCLUSIONS: This controlled study revealed that patients with chronic schizophrenia exhibited accelerated frontotemporal cortical gray matter decline and cortical sulcal and lateral ventricular expansion. Further, greater clinical severity was associated with faster rates of frontotemporal brain volume changes. These observations are consistent with a progressive pathophysiological process but need to be replicated in a larger sample.

Adult↗
PubMed2003

A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging.

OBJECTIVE: To investigate the effect of age on global and regional brain volumes and rates of atrophy, and to compare directly results based on cross-sectional and longitudinal data. METHODS: Thirty-nine healthy control subjects (age range, 31-84 years) underwent serial magnetic resonance imaging assessments. Measurements included the whole-brain, temporal lobe, hippocampal, and ventricular volumes at baseline and for repeat scans. RESULTS: We found significant decreases in cross-sectional whole-brain (P<.001), temporal lobe (P<.001), and hippocampal (P =.003) volumes and a significant increase in ventricular volume (P<.001) with increasing age. Cross-sectional and longitudinal estimates of atrophy rates were similar. We also found directional evidence of acceleration in atrophy rates with increasing age in all analyses, with the most marked changes occurring after 70 years of age. This increase in rates after 70 years of age was particularly marked in the ventricles (P<.001) and the hippocampi (P =.01). CONCLUSIONS: We found a significant age-associated decrease in global and regional brain volumes. Some evidence indicates that this decline in brain volumes may be due to a nonlinear acceleration in rates of atrophy with increasing age. A better understanding of this process may help to discriminate normal age-related changes from neurodegenerative diseases.

Adult↗
PubMed1997

Normal brain volume measurements using multispectral MRI segmentation.

The performance of a supervised k-nearest neighbor (kNN) classifier and a semisupervised fuzzy c-means (SFCM) clustering segmentation method are evaluated for reproducible measurement of the volumes of normal brain tissues and cerebrospinal fluid. The stability of the two segmentation methods is evaluated for (a) operator selection of training data, (b) reproducibility during repeat imaging sessions to determine any variations in the sensor performance over time, (c) variations in the measured volumes between different subjects, and (d) variability with different imaging parameters. The variations were found to be dependent on the type of measured tissue and the operator performing the segmentations. The variability during repeat imaging sessions for the SFCM method was < 3%. The absolute volumes of the brain matter and cerebrospinal fluid between subjects varied quite large, ranging from 9% to 13%. The intraobserver and interobserver reproducibility for SFCM were < 4% for the soft tissues and 6% for cerebrospinal fluid. The corresponding results for the kNN segmentation method were higher compared to the SFCM method.

Adult↗