Detecting brain growth patterns in normal children using tensor-based morphometry

Previous magnetic resonance imaging (MRI)-based volumetric studies have shown age-related increases in the volume of total white matter and decreases in the volume of total gray matter of normal children. Recent adaptations of image analysis strategies enable the detection of human brain growth with improved spatial resolution. In this article, we further explore the spatio-temporal complexity of adolescent brain maturation with tensor-based morphometry. By utilizing a novel non-linear elastic intensity-based registration algorithm on the serial structural MRI scans of 13 healthy children, individual Jacobian growth maps are generated and then registered to a common anatomical space. Statistical analyses reveal significant tissue growth in cerebral white matter, contrasted with gray matter loss in parietal, temporal, and occipital lobe. In addition, a linear regression with age and gender suggests a slowing down of the growth rate in regions with the greatest white matter growth. We demonstrate that a tensor-based Jacobian map is a sensitive and reliable method to detect regional tissue changes during development.     

Smaller neocortical gray matter and larger sulcal cerebrospinal fluid volumes in neuroleptic-naive women with schizotypal personality disorder

CONTEXT: Structural brain abnormalities, including larger cerebrospinal fluid (CSF) volumes, have been observed in men diagnosed as having schizotypal personality disorder (SPD). OBJECTIVES: To determine whether women with SPD have abnormalities similar to those of men with SPD and to elucidate specific SPD regional volume deficits and symptom correlations. DESIGN: Naturalistic study.Setting and PARTICIPANTS: Thirty neuroleptic-naive women with SPD and 29 female control subjects, both recruited from the community. Participants were group matched for age, parental socioeconomic status, handedness, and IQ. INTERVENTIONS: A new segmentation method was applied to magnetic resonance images to automatically parcel the images into CSF, gray matter, and white matter. The neocortex was manually separated from subcortical and other nonneocortical structures. Voxel-based morphometry was applied to determine global and regional volume deficits. MAIN OUTCOME MEASURES: Left and right neocortical gray matter, white matter, and CSF relative volumes as well as clinical symptoms from the Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire-Brief Version. RESULTS: Smaller left (3.84%) and right (3.83%) neocortical gray matter relative volumes associated with larger left (9.66%) and right (9.61%) sulcal CSF relative volumes were found in women with SPD compared with controls. Voxel-based morphometry showed that the neocortical deficits in SPD were especially prominent in the left superior and middle temporal gyri, left inferior parietal region with postcentral gyrus, and right superior frontal and inferior parietal gyri. In the SPD group, larger lateral ventricle volumes correlated with more severe symptoms on the Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire-Brief Version. CONCLUSIONS: The smaller neocortical gray matter volume and larger sulcal CSF volume provide evidence of the brain basis of this personality disorder and emphasize the communality of brain abnormalities in the schizophrenia spectrum.     

Does an Increase in Sulcal or Ventricular Fluid Predict Where Brain Tissue Is Lost?

Quantitative volumes of cerebrospinal fluid (CSF) and brain tissue were measured on magnetic resonance images (MRIs) of 287 individuals from 5 diagnostic groups: Alzheimer's disease (AD), chronic alcoholics (ALC), individuals positive for human immunodeficiency virus (HIV), schizophrenia subjects (SZ), and normal comparison subjects (NC) older than 50 years of age. Within each group, mean volumes were calculated for ventricular CSF, cortical (sulcal) CSF, cortical gray matter, total white matter, basal ganglia gray matter, and thalamic gray matter. Correlations of CSF measures with brain tissue measures were determined, and multiple regression analyses were performed to try and predict volume of gray matter or white matter region from volume of CSF compartment. Results indicated the following: 1. Enlarged cortical fluid volume significantly predicts cortical gray matter deficits for subjects with AD and those who are ALC and SZ but not for subjects with HIV or NC. 2. Enlarged cortical fluid volume also significantly predicts white matter deficits in all five groups. 3. Enlarged ventricular fluid volume significantly predicts basal ganglia deficits in AD, HIV, and NC but not in SZ or ALC. 4. Enlarged ventricular volume has no predictive value for thalamic volume for any of the groups. This study supports the clinical practice of predicting brain tissue volume loss from CSF enlargement but not for all brain regions in all diagnoses.     

Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes

The goals of this study were to measure if chronic active heavy drinking is associated with brain volume loss in non-treatment seeking men and women, and to assess the effect of positive family history of problem drinking on brain structure in heavy drinkers. Automated image processing was used to analyze high-resolution T1-weighted magnetic resonance images from 49 active heavy drinkers and 49 age- and sex-matched light drinkers, yielding gray matter, white matter and cerebrospinal fluid (CSF) volumes within the frontal, temporal, parietal and occipital lobes. Regional brain volume measures were compared as a function of group, sex and their interaction. Within heavy drinkers, volumes were correlated with measures of alcohol consumption and compared as a function of family history of problem drinking. Deformation morphometry explored localized patterns of atrophy associated with heavy drinking or severity of drinking. We found significant gray matter volume losses, but no white matter losses, in active heavy drinkers compared with light drinkers. Women had greater gray matter and smaller white matter and CSF volumes as a percentage of intracranial vault than men. Within heavy drinkers, smaller gray matter volumes were associated with higher current levels of drinking and older age, while a positive family history of problem drinking was associated with smaller CSF volumes. Community-dwelling heavy drinkers who are not in alcoholism treatment have dose-related gray matter volume losses, and family history of problem drinking ameliorates some structural consequences of heavy drinking.     

Evidence of subtle gray-matter pathologic changes in healthy elderly individuals with nonspecific white-matter hyperintensities

OBJECTIVE: To investigate whether additional "occult" tissue changes can be detected in the normal-appearing white matter and gray matter of otherwise normal elderly individuals with nonspecific white-matter hyperintensities on conventional magnetic resonance images of the brain. METHODS: Conventional and magnetization transfer magnetic resonance images were obtained from 12 otherwise normal elderly subjects with white-matter hyperintensities and 11 age- and sex-matched normal individuals. After automatic tissue segmentation, image coregistration, and masking of T2-visible lesions, we obtained magnetization transfer ratio histograms of the normal-appearing white matter and gray matter. For each histogram, the average magnetization transfer ratio, the peak height, and the peak position were measured. We also calculated the percentages of gray-matter and white-matter volumes normalized over the total volume of the intracranial content and the total normalized brain volumes. RESULTS: Average magnetization transfer ratio (P =.03) and mean peak position (P =.01) of the gray-matter histograms from elderly individuals with white-matter hyperintensities were significantly lower than the corresponding quantities from those without white-matter hyperintensities. The normalized percentages of gray and white matter and normalized brain volume did not differ between the 2 groups. The average gray-matter magnetization transfer ratio was correlated with the average lesion magnetization transfer ratio (r = 0.68; P<.01). CONCLUSIONS: This study shows that brain abnormalities in otherwise normal elderly subjects with nonspecific white-matter hyperintensities extend beyond the macroscopic white-matter lesions visualized on conventional magnetic resonance images.     

Quantitative magnetic resonance imaging differences between Alzheimer disease with and without subcortical lacunes

Previous reports showed that patients with Alzheimer disease (AD) frequently have coexisting vascular-related pathologies, such as cerebral infarcts and white matter lesions. The aim of this study was to determine the effects of subcortical lacunar infarcts on brain structure in patients with AD. Semi-automated tissue segmentation and volumetry of magnetic resonance imaging data were performed in 38 AD patients without lacunes (AD-L), 24 AD patients with subcortical lacunes (AD+L), and 40 age-matched cognitively healthy subjects without lacunes. The following tissue volumes were quantified, expressed as percentage of total intracranial volume: ventricular cerebrospinal fluid (CSF), sulcal CSF, cortical gray matter (GM), subcortical GM, white matter (WM), white matter signal hyperintensities (WMSH), lacunes, and hippocampus. There was no difference in the Mini-Mental State Examination between the two AD groups. AD+L patients compared with AD-L subjects had significantly greater volumes of WMSH and ventricular CSF spaces (as expected) but smaller sulcal CSF spaces and no significant increase in cortical GM atrophy (both unexpected). In the AD groups, ventricular CSF correlated inversely with cortical GM but not with WM; sulcal CSF correlated inversely with cortical GM and WM. Cognitive impairment was associated with sulcal CSF volume but not with volumes of WMSH or lacunes. In conclusion, the presence of subcortical lacunes in those with AD is associated with more WM lesions and ventriculomegaly but not with cortical atrophy.     

Clinical factors related to brain structure in HIV: the CHARTER study

Despite the widening use of combination antiretroviral therapy (ART), neurocognitive impairment remains common among HIV-infected (HIV+) individuals. Associations between HIV-related neuromedical variables and magnetic resonance imaging indices of brain structural integrity may provide insight into the neural bases for these symptoms. A diverse HIV+ sample (n?=?251) was studied through the CNS HIV Antiretroviral Therapy Effects Research initiative. Multi-channel image analysis produced volumes of ventricular and sulcal cerebrospinal fluid (CSF), cortical and subcortical gray matter, total cerebral white matter, and abnormal white matter. Cross-sectional analyses employed a series of multiple linear regressions to model each structural volume as a function of severity of prior immunosuppression (CD4 nadir), current CD4 count, presence of detectable CSF HIV RNA, and presence of HCV antibodies; secondary analyses examined plasma HIV RNA, estimated duration of HIV infection, and cumulative exposure to ART. Lower CD4 nadir was related to most measures of the structural brain damage. Higher current CD4, unexpectedly, correlated with lower white and subcortical gray and increased CSF. Detectable CSF HIV RNA was related to less total white matter. HCV coinfection was associated with more abnormal white matter. Longer exposure to ART was associated with lower white matter and higher sulcal CSF. HIV neuromedical factors, including lower nadir, higher current CD4 levels, and detectable HIV RNA, were associated with white matter damage and variability in subcortical volumes. Brain structural integrity in HIV likely reflects dynamic effects of current immune status and HIV replication, superimposed on residual effects associated with severe prior immunosuppression.     

Apolipoprotein E genotype and subcortical vascular lesions in older depressed patients and control subjects.

BACKGROUND: Several studies have linked geriatric depression with cerebrovascular disease. The apolipoprotein E gene (APOE) epsilon 4 allele has been associated with a variety of late-life neuropsychiatric disorders, including Alzheimer's disease, vascular dementia, and depression. METHODS: The sample consisted of 145 elderly depressive individuals and 100 nondepressed elderly control subjects. After a standardized clinical assessment, all subjects underwent a magnetic resonance imaging brain scan. Volumes of subcortical white and gray matter lesions were determined using a semi-automated method. Apolipoprotein E genotype was determined on blood sample using a standard protocol. A series of linear regression models were developed to assess the relationships between APOE genotype and white and gray matter lesion volumes. RESULTS: Older age, lower Mini-Mental State Examination score, and having any APOE epsilon 4 allele were each correlated with gray-matter lesion volume in depressed patients. Apolipoprotein E genotype was not associated with any lesion volume among control subjects. In a subsequent linear regression model, gray matter lesion volume was associated with older age, having at least one APOE epsilon 4 allele, and white matter lesion volume among depressed patients. CONCLUSIONS: These results are consistent with previous reports linking cerebrovascular disease and APOE genotype. Further studies are needed to replicate this finding in elderly depressive individuals and to explain the relationship between the APOE locus and development of central nervous system vascular pathology.     

Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection

MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79 % initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis.     

Brain development in children with new onset epilepsy: A prospective controlled cohort investigation

Purpose: To characterize prospective neurodevelopmental changes in brain structure in children with new and recent‐onset epilepsy compared to healthy controls. Methods: Thirty‐four healthy controls (mean age 12.9 years) and 38 children with new/recent‐onset idiopathic epilepsy (mean age 12.9 years) underwent 1.5 T magnetic resonance imaging (MRI) at baseline and 2 years later. Prospective changes in total cerebral and lobar gray and white matter volumes were compared within and between groups. Results: Prospective changes in gray matter volume were comparable for the epilepsy and control groups, with significant (p < 0.0001) reduction in total cerebral gray matter, due primarily to significant (p < 0.001) reductions in frontal and parietal gray matter. Prospective white matter volume changes differed between groups. Controls exhibited a significant (p = 0.0012) increase in total cerebral white matter volume due to significant (p < 0.001) volume increases in the frontal, parietal, and temporal lobes. In contrast, the epilepsy group exhibited nonsignificant white matter volume change in the total cerebrum (p = 0.51) as well as across all lobes (all p’s > 0.06). The group by white matter volume change interactions were significant for total cerebrum (p = 0.04) and frontal lobe (p = 0.04). Discussion: Children with new and recent‐onset epilepsy exhibit an altered pattern of brain development characterized by delayed age‐appropriate increase in white matter volume. These findings may affect cognitive development through reduced brain connectivity and may also be related to the impairments in executive function commonly reported in this population.     

Volumetric analysis reveals corticospinal tract degeneration and extramotor involvement in ALS.

BACKGROUND: Pathologic changes in the motor cortex and corticospinal tracts in ALS may be reflected by abnormal signal intensities on conventional MRI. The sensitivity of these changes in detecting underlying pathology remains unclear. METHOD: The authors used automated image analysis to quantify volumes of cerebral gray and white matter in 16 patients with ALS (eight limb onset, eight bulbar onset) and eight normal controls. Previously they had demonstrated a reduction in N-acetyl aspartate/creatine + phosphocreatine (NAA/[Cr + PCr]) measured by (1)H-MRS in the subcortical white matter in the motor cortex region in the patients with bulbar-onset ALS. To determine whether this resulted from axonal degeneration, they also compared gray and white matter volumes in the patients with limb- and bulbar-onset ALS. RESULTS: There were no differences in the total brain volumes of gray or white matter for the three subject groups (p > 0.23). Comparison of the total ALS group and controls revealed localized deficits in gray matter volume centered on Brodmann areas 8, 9, and 10 bilaterally. Comparison of the patients with limb- and bulbar-onset ALS revealed deficits in the white matter volume in the bulbar-onset group, extending bilaterally from the precentral gyrus into the internal capsule and brainstem, consistent with the course of the corticospinal tract. There was no loss in gray matter volume in the precentral gyri. CONCLUSIONS: The loss of gray matter in the frontal regions (total ALS group) provides further support that ALS is a multisystem disorder. In addition, there is in vivo evidence of axonal degeneration in the subcortical white matter in the motor region in patients with bulbar-onset ALS. This is consistent with a "dying back" process affecting cortical motoneurons in bulbar-onset ALS.     

Brain structural damage in spinocerebellar ataxia type 2. A voxel‐based morphometry study

Voxel‐based morphometry (VBM) enables an unbiased in‐vivo whole‐brain quantitative analysis of differences in gray matter (GM), white matter (WM) and cerebro‐spinal fluid (CSF) volumes. We assessed with VBM 20 spinocerebellar ataxia Type 2 (SCA2) patients with mild or moderate cerebellar deficit and 20 age and sex‐matched healthy controls. SCA2 patients showed a significant (P < 0.05 corrected for multiple comparison) symmetric loss of GM in the cerebellar vermis and hemispheres sparing lobules I,II, Crus II,VII, and X, and of the WM in the peridentate region, middle cerebellar peduncles, dorsal pons, and cerebral peduncles. The CSF volume was increased in the posterior cranial fossa. No GM, WM or CSF volume changes were observed in the supratentorial compartment. A mild (P < 0.05, >0.01) correlation was observed between the GM and WM loss and severity of the neurological deficit. In SCA2 patients with mild to moderate cerebellar deficit, GM and WM volume loss and CSF volume increase are confined to the posterior cranial fossa. © 2008 Movement Disorder Society     

Age-related brain volume reductions in amphetamine and cocaine addicts and normal controls: implications for addiction research

The study evaluated the relationship between age and frontal and temporal lobe volumes in young cohorts of cocaine-dependent (CD), amphetamine-dependent (Am), and normal control subjects. Ten CD, nine Am, and 16 age- and gender-matched control subjects underwent magnetic resonance imaging (MRI). The volume of the frontal and temporal lobes was measured from an identically positioned slab of seven contiguous 3-mm-thick coronal images. Follow-up measures of the gray and white matter subcomponents of these volumes were also obtained. Both CD and Am groups had a significantly smaller temporal lobe volumes, but only the CD group demonstrated a significantly greater decline in temporal lobe volume with age (intracranial volume, education, and race were controlled for in all statistical analyses). Segmenting the brain regions into gray and white matter revealed that the negative correlation between age and temporal lobe volume of CD patients was mostly due to a significant age-related decline in the gray matter subcomponent. Negative trends between age and gray matter volumes were also observed in the Am and normal groups. In the frontal lobes, age was negatively correlated with gray matter volume in the control, CD, and Am groups. Unlike the consistent decreases in gray matter volumes, white matter showed non-significant increases in volume with age. The data suggest that CD patients may have an accelerated age-related decline in temporal lobe gray matter volume and a smaller temporal lobe volume compared to normal controls. In the frontal lobe, age-related gray matter volume reductions occur in all three groups. These age-related cortical gray matter volume reductions may be a biological marker for the risk of addictive behavior, which also decreases with age.     

Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome: a preliminary study

BACKGROUND: As children with velocardiofacial syndrome (VCFS) develop, they are at increased risk for psychopathology; one third will eventually develop schizophrenia. Because VCFS and the concomitant symptomatology result from a known genetic origin, the biological and behavioral characteristics of the syndrome provide an optimal framework for conceptualizing the associations among genes, brain development, and behavior. The purpose of this study was to investigate the effect of the parental origin of the 22q11.2 microdeletion on the brain development of children and adolescents with VCFS. METHODS: Eighteen persons with VCFS and 18 normal control subjects were matched individually for age and sex. Results of DNA polymorphism analyses determined the parental origin of the deletion. Nine persons with VCFS had a deletion on the maternally derived chromosome 22; 9 persons, on the paternally derived chromosome 22. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of gray and white matter brain tissue. RESULTS: Total brain volume was approximately 11% smaller in the VCFS group than in controls. Comparisons between VCFS subgroups (maternal vs paternal microdeletion 22q11.2) indicated a significant 9% volumetric difference in total volume of cerebral gray matter (volume was greater in patients with paternal microdeletion) but not cerebral white matter. Significant age-related changes in gray matter were detected for subjects whose 22q11.2 deletion was on the maternal chromosome. CONCLUSIONS: Children and adolescents with VCFS experience major alterations in brain volumes. Significant reduction in gray matter development is attributable to presence of 22q11.2 microdeletion on the maternal chromosome.     

Age-related brain structural alterations in children with specific language impairment

Previous neuroimaging studies have suggested that children with specific language impairment (SLI) may show subtle anatomical alterations in specific brain regions. We aimed to characterize structural abnormalities in children with SLI using a voxel-wise analysis over the whole brain. Subjects covered a wide age range (5-17 years) in order to assess the dynamic nature of the disorder across childhood. Three-dimensional MRIs were collected from 36 children with SLI and from a comparable group of healthy controls. Global gray and white matter measurements were obtained for each subject, and voxel-based morphometry (VBM) was used to evaluate between-group differences in regional brain anatomy. Possible age-related changes were assessed in separate analyses of younger (below 11 years of age) and older children. SLI patients showed larger global gray and white matter volumes, particularly in the younger subgroup. Voxel-wise analyses of the whole sample showed two regions of increased gray matter volume in SLI: the right perisylvian region and the occipital petalia. Age-group analyses suggested a more extended pattern of volume increases in the younger subjects, which included entorhinal, temporopolar, caudate nucleus, motor-precentral and precuneus gray matter, and white matter of the frontal and temporal lobes. Our results suggest that in the SLI brain there are enduring anatomical alterations that exist across a wide age range, as well as a distributed pattern of abnormalities that appear to normalize with development. They also suggest that the neuroanatomical basis of SLI may be better characterized by considering the dynamic course of the disorder throughout childhood.     

The relationship between P300 amplitude and regional gray matter volumes depends upon the attentional system engaged

Event-related potentials (ERPs) and brain magnetic resonance images (MRIs) were acquired from 28 normal men, age 21–60 years. ERPs were recorded during 3 paradigms designed to elicit automatic or effortful attention, and a combination of both. MRI-derived measures of brain gray matter, white matter and cerebral spinal fluid (CSF) volumes were computed from frontal, parietal and temporal lobes. P300 amplitude correlated significantly with gray matter volumes but not with white matter or CSF volumes. Furthermore, the relationships between P300 amplitude and gray matter volumes reflected functional rather than direct topographical relationships: P300 recorded at Pz during automatically elicited attention correlated significantly with frontal but not parietal lobe gray matter volumes, P300 recorded during effortful attention correlated significantly with parietal but not frontal lobe gray matter volumes, and P300 recorded when both types of attention were invoked correlated significantly with both frontal and parietal gray matter volumes. Startle blinks, also elicited during automatic attention-engaging paradigms, were significantly correlated with frontal but not parietal lobe gray matter volumes. There was no evidence for a direct spatial relationship between P300 amplitude and the gray matter volumes underlying the recording electrode.     

Structural neuroimaging in adolescents with a first psychotic episode

OBJECTIVE: The objective of the present study is to replicate findings in first-episode psychosis reporting a smaller volume in brain structures in a population with adolescent onset. METHOD: Magnetic resonance imaging studies were performed on 23 psychotic adolescents (12-18 years old, 17 males, 6 females) consecutively admitted to an adolescent inpatient unit and on 37 normal controls (13-18 years, 23 males, 14 females) matched for age, sex, and years of education. Diagnosis was made at baseline on the basis of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version and confirmed after 12 months of follow-up. Total brain volume and gray matter, white matter, and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured bilaterally using a segmentation method based on the Talairach grid system. RESULTS: Male patients showed significantly larger volumes than did male controls in overall CSF and left frontal and right parietal sulci CSF. Male patients also showed significantly lower volumes of gray matter in the right and left frontal lobes. No significant volumetric differences were found in females. There were no differences between individuals with a diagnosis of schizophrenia at follow-up and the rest of the patients. CONCLUSIONS: This study suggests that larger CSF and lower gray matter volumes in the frontal lobes may be a nonspecific vulnerability marker for psychosis in male adolescents.     

MR signal intensity of gray matter/white matter contrast and intracranial fat: effects of age and sex

Signal intensity (SI) values of gray- and white-matter brain regions of interest (ROIs) were obtained from T(2)- and proton density-weighted magnetic resonance (MR) images of 58 normal subjects aged 22-82 years (31 females, 52.3+/-18.8 years; 27 males, 54.1+/-18.1 years). Sampled ROIs included the caudate, putamen, thalamus, orbitofrontal gyrus, gyrus rectus, uncus, frontal white matter, anterior and posterior corpus callosum, cranial-cervical junction fat, and retroorbital fat. Effects of age and sex on SI were examined using repeated-measures analysis of covariance. For both T(2)- and proton density-weighted acquisitions, a significant inverse relationship between age and SI was observed for the ratio of all summed gray-matter ROIs divided by summed white-matter ROIs. This relationship was additionally observed for ratios of both subcortical gray/white matter and cortical gray/white matter. Females compared with males had significantly lower cortical gray/white matter ratios on T(2)-weighted scans. Differences in SI were observed between cranial-cervical junction fat and retroorbital fat on both acquisitions, with females showing significantly higher values for cranial-cervical junction fat and males showing higher values for retroorbital fat. Implications for brain morphometry, the use of fat as a reference standard, and other issues in neuroimaging are discussed.     

Microencephaly in children congenitally infected with human immunodeficiency virus – a gross-anatomical morphometric study

A quantitative technique involving serial sectioning and semiautomatic morphometric analysis was used to assess the severity of the reduction in size of the major brain structures in cerebral hemispheres of children congenitally infected with HIV-1. Cerebral hemispheres from 12 children (18–48 months of age) who died of AIDS were sectioned into 5-mm-thick serial slabs and photographed. The cross-sectional areas of grossly recognizable brain structures were digitized, and the volumes were calculated according to Cavalieri’s principle. The results were compared with those of an identically processed group of control brains from non-AIDS children. Analysis of the brain weight showed that there was a significant reduction in supratentorial and infratentorial weight in the AIDS group. The results of the morphometric study revealed that the loss in brain mass was associated with a statistically significant reduction in the total volume of both hemispheres, the entire cortex, white matter, and basal ganglia. Detailed analysis of individual brain structures also showed a significant reduction in volume of all cortical regions and most of the subcortical gray matter (e.g., caudate nucleus, putamen, globus pallidus, claustrum, and thalamus). It appears that in the microencephaly observed as a frequent sequel in pediatric AIDS, the loss of brain tissue is global and includes an almost proportional loss of cortex, subcortical gray matter and white matter. Received: 18 July 1995 / Revised: 17 July 1996 / Accepted: 22 August 1996     

Cortical gray and white brain tissue volume in adolescents and adults with autism.

BACKGROUND: A number of studies have found brain enlargement in autism, but there is disagreement as to whether this enlargement is limited to early development or continues into adulthood. In this study, cortical gray and white tissue volumes were examined in a sample of adolescents and adults with autism who had demonstrated total brain enlargement in a previous magnetic resonance imaging (MRI) study. METHODS: An automated tissue segmentation program was applied to structural MRI scans to obtain volumes of gray, white, and cerebrospinal fluid (CSF) tissue on a sample of adolescent and adult males ages 13-29 with autism (n = 23) and controls (n = 15). Regional differences for brain lobes and brain hemispheres were also examined. RESULTS: Significant enlargement in gray matter volume was found for the individuals with autism, with a disproportionate increase in left-sided gray matter volume. Lobe volume enlargements were detected for frontal and temporal, but not parietal or occipital lobes, in the subjects with autism. Age and nonverbal IQ effects on tissue volume were also observed. CONCLUSIONS: These findings give evidence for left-lateralized gray tissue enlargement in adolescents and adults with autism, and demonstrate a regional pattern of cortical lobe volumes underlying this effect.