Automated brain tissue assessment in the elderly and demented population: construction and validation of a sub-volume probabilistic brain atlas

OBJECTIVES: To develop an automated imaging assessment tool that accommodates the anatomic variability of the elderly and demented population as well as the registration errors occurring during spatial normalization. METHODS: 20 subjects with Alzheimer's disease (AD), mild cognitive impairment, or normal cognition underwent MRI brain imaging and had their 3D volumetric datasets manually partitioned into 68 regions of interest (ROI) termed sub-volumes. Gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) voxel counts were then made in the subject's native space for comparison against automated volumetric measures within three sub-volume probabilistic atlas (SVPA) models. The three SVPAs were constructed using 12 parameter affine (12 p), 2nd order (2nd), and 6th order (6th) transforms derived from registering the manually partitioned scans into a Talairach compatible AD population-based target. The three SVPA automated measures were compared to the manually derived measures in the 20 subjects' native space with a "jack-knife" procedure in which each subject was assessed by an SVPA they did not contribute toward constructing. RESULTS: The mean left and right GM ratio (GM ratio = [GM + CSF] / CSF) "r values" for the 3 SVPAs compared to the manually derived ratios across the 68 ROIs were 0.85 for the 12p SVPA, 0.88 for the 2nd SVPA, and 0.89 for the 6th SVPA. The mean left and right WM ratio (WM ratio = [WM + CSF] / CSF) "r values" for the 3 SVPAs being 0.84 for the 12p SVPA, 0.86 for the 2nd SVPA, and 0.88 for the 6th SVPA. CONCLUSION: We have constructed, from an elderly and demented cohort, an automated brain volumetric tool that has excellent accuracy compared to a manual gold standard and is capable of regional hypothesis testing and individual patient assessment compared to a population.     

Influence of activity level on the outcome of treatment of lateral ankle ligament rupture

Background  Few studies of treatment of lateral ankle ligament rupture have given careful consideration to the activity levels of patients. In the present study, we investigated whether a patient’s activity level influences the outcome of the treatment of lateral ankle ligament rupture and whether treatment should be determined according to activity level. Methods  A total of 115 consecutive patients with lateral ankle ligament rupture were treated with short-term cast immobilization followed by functional bracing. We divided preinjury activity levels and activity levels at follow-up into four classes according to the International Knee Documentation Committee standards. Follow-up examination 1 year after injury included clinical assessment (anterior drawer test, range of motion, maximum circumference of the calf, tenderness, swelling), reinjury assessment, and functional evaluation by means of the Karlsson scoring system. Results  We found significant differences in ankle stability and reinjuries between the four groups classified by their preinjury activity level. The number of patients with ankle instability and reinjury was significantly higher in the high-activity group than in the low-activity groups. We also found significant difference between groups classified by activity level at follow-up with regard to the Karlsson score. Conclusions  The outcome of treatment of lateral ankle ligament rupture is significantly influenced by the patient activity level, and treatment may need to be determined according to this activity level.     

Mapping brain abnormalities in boys with autism

Children with autism spectrum disorder (ASD) exhibit characteristic cognitive and behavioral differences, but no systematic pattern of neuroanatomical differences has been consistently found. Recent neurodevelopmental models posit an abnormal early surge in subcortical white matter growth in at least some autistic children, perhaps normalizing by adulthood, but other studies report subcortical white matter deficits. To investigate the profile of these alterations in 3D, we mapped brain volumetric differences using a relatively new method, tensor‐based morphometry. 3D T1‐weighted brain MRIs of 24 male children with ASD (age: 9.5 years ± 3.2 SD) and 26 age‐matched healthy controls (age: 10.3 ± 2.4 SD) were fluidly registered to match a common anatomical template. Autistic children had significantly enlarged frontal lobes (by 3.6% on the left and 5.1% on the right), and all other lobes of the brain were enlarged significantly, or at trend level. By analyzing the applied deformations statistically point‐by‐point, we detected significant gray matter volume deficits in bilateral parietal, left temporal and left occipital lobes (P = 0.038, corrected), trend‐level cerebral white matter volume excesses, and volume deficits in the cerebellar vermis, adjacent to volume excesses in other cerebellar regions. This profile of excesses and deficits in adjacent regions may (1) indicate impaired neuronal connectivity, resulting from aberrant myelination and/or an inflammatory process, and (2) help to understand inconsistent findings of regional brain tissue excesses and deficits in autism. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

CSF sub-compartments in relation to plasma osmolality in healthy controls and in patients with first episode schizophrenia

Preliminary evidence suggests that plasma Na(+) level/osmolality may have effects on brain morphology; thus we investigated the link between plasma osmolality and ventricle size in healthy controls and patients with first episode schizophrenia. A total of 16 patients and 28 healthy controls were examined with magnetic resonance imaging (MRI) and gave blood samples. High-resolution 3D SPGR images were obtained on a 1.5 Tesla scanner. Scalp-edited MRI volumes were used for estimates of intracranial gray, white matter and CSF. Regional changes in CSF concentration and ventricular morphology were measured. The groups did not differ in plasma osmolality, but patients had higher plasma Na(+). There were no differences in ventricle size. Controlling for plasma osmolality did not change the results. A mixed model procedure indicated a significant group effect and a significant osmolality by group interaction in ventricle measures. Healthy control group showed a significant relationship between osmolality and ventricle measures; this relationship was absent in the patients. Significant correlations between osmolality and lateral ventricle surface deformations were observed along the superior horn of the lateral ventricles in the healthy controls. These results suggest that plasma osmolality is related to ventricle size in healthy volunteers and that this physiological link is impaired in patients with first episode schizophrenia.     

Dynamic mapping of hippocampal development in childhood onset schizophrenia

Prior cross-sectional anatomic brain imaging studies of the hippocampus in schizophrenia have generally shown loss in total hippocampal volume although the progressive course of these changes remains unknown. We report the first prospective sub-regional maps of hippocampal development in childhood onset schizophrenia (COS), reconstructed from serial brain MRI scans of 29 children with COS scanned every 2 years (87 scans) and compared to 31 controls matched for age, sex, and scan interval (94 scans). As expected, the COS subjects showed significant bilateral deficits (9–10%) in total hippocampal volume which remained consistent between age 9 and 26. However sub-regional maps showed heterogeneous changes with loss of hippocampal volume in both anterior as well as posterior ends while the body of the hippocampus gained in volume suggesting that hippocampal subunits are differentially affected in schizophrenia.     

Asymmetries of cortical thickness: effects of handedness, sex, and schizophrenia

Sex, handedness, and disease processes in schizophrenia may affect the magnitude and/or direction of structural brain asymmetries. Using MRI data from 67 healthy (30 men, 10 nondextral) and 84 schizophrenia patients (60 men, 16 nondextral), cortical thickness asymmetries were compared at high spatial resolution. Within-group asymmetries were observed in sensorimotor, perisylvian, and parahippocampal cortices (leftward) and in anterior mesial frontal cortices (rightward). Asymmetry patterns were similar across diagnosis and sex, although some regional asymmetry increases were observed in men. Hand preference (dextrality) significantly influenced regional asymmetries in parietal association and dorsomedial frontal cortices (false discovery rate-corrected), where medial-frontal regions showed diagnosis by dextrality effects (uncorrected). Thus, dextrality relates to cortical thickness asymmetries, although schizophrenia may differentially affect asymmetry patterns across handedness.     

Regional cortical thinning in subjects with violent antisocial personality disorder or schizophrenia

Violent behavior is associated with antisocial personality disorder and to a lesser extent with schizophrenia. Neuroimaging studies have suggested that several biological systems are disturbed in schizophrenia, and structural changes in frontal and temporal lobe regions are reported in both antisocial personality disorder and schizophrenia. The neural substrates that underlie violent behavior specifically and their structural analogs, however, remain poorly understood. Nor is it known whether a common biological basis exists for aggressive, impulsive, and violent behavior across these clinical populations. To explore the correlates of violence with brain structure in antisocial personality disorder and schizophrenia, the authors used magnetic resonance imaging data to investigate for the first time, to the authors' knowledge, regional differences in cortical thickness in violent and nonviolent individuals with schizophrenia and/or antisocial personality disorder and in healthy comparison subjects. Subject groups included right-handed men closely matched for demographic variables (total number of subjects=56). Violence was associated with cortical thinning in the medial inferior frontal and lateral sensory motor cortex, particularly in the right hemisphere, and surrounding association areas (Brodmann's areas 10, 11, 12, and 32). Only violent subjects with antisocial personality disorder exhibited cortical thinning in inferior mesial frontal cortices. The biological underpinnings of violent behavior may therefore vary between these two violent subject groups in which the medial frontal cortex is compromised in antisocial personality disorder exclusively, but laminar abnormalities in sensorimotor cortices may relate to violent behavior in both antisocial personality disorder and schizophrenia.     

Frontal and temporal volumes in children with epilepsy

This study examined if children with cryptogenic epilepsy and complex partial seizures (CPS) have smaller total brain, frontal, and temporal lobe volumes than normal children and how this is related to seizure, cognitive, psychiatric, and demographic variables. Forty-four children with CPS and 38 normal children, aged 5-16 years, underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, frontal parcellation, and temporal lobe volumes were computed. Other than significantly larger temporal lobe white matter volumes in the CPS group, there were no significant differences in brain volumes between the CPS and normal groups. Earlier onset, longer duration of illness, younger chronological age, and presence of a psychiatric diagnosis were significantly related to smaller frontotemporal volumes in subjects with CPS. Although these findings suggest that CPS might affect development of the temporal and frontal regions, we are unable to rule out the possibility that smaller frontotemporal volumes might predispose children to CPS. These findings highlight the need to control for seizure, cognitive, psychiatric, and demographic variables in studies of frontotemporal volumes in pediatric CPS.     

Lung carcinoma: diffusion-weighted mr imaging--preliminary evaluation with apparent diffusion coefficient

PURPOSE: To prospectively evaluate diffusion-weighted (DW) magnetic resonance (MR) imaging with a split acquisition of fast spin-echo signals for diffusion imaging (SPLICE) sequence for tissue characterization of lung carcinomas by using apparent diffusion coefficients (ADCs). Materials and METHODS: An institutional review board approved this study; informed consent was obtained from patients. Thirty patients (nine women, 21 men; mean age, 68.0 years) with lung carcinoma underwent DW MR imaging with the SPLICE sequence. ADC of each lung carcinoma was calculated from DW MR images obtained with low and high b values. ADCs of lung carcinomas were statistically compared among histologic types. Nine surgically excised lung carcinomas were evaluated for correlation between ADCs and tumor cellularities. Analysis of variance was used to determine changes in ADCs and histologic lung carcinoma types. Spearman rank correlation was calculated between ADCs and tumor cellularities. RESULTS: ADCs for lung carcinomas were 1.63 x 10(-3) mm(2)/sec +/- 0.5 (mean +/- standard deviation) for squamous cell carcinoma, 2.12 x 10(-3) mm(2)/sec +/- 0.6 for adenocarcinoma, 1.30 x 10(-3) mm(2)/sec +/- 0.4 for large-cell carcinoma, and 2.09 x 10(-3) mm(2)/sec +/- 0.3 for small-cell carcinoma. ADC of adenocarcinoma was significantly higher than that of squamous cell carcinoma and large-cell carcinoma (P < .05). ADCs were 1.59 x 10(-3) mm(2)/sec +/- 0.5 and 1.70 x 10(-3) mm(2)/sec +/- 0.4 for moderately and poorly differentiated squamous cell carcinoma, respectively. ADCs were 2.52 x 10(-3) mm(2)/sec +/- 0.4 and 1.44 x 10(-3) mm(2)/sec +/- 0.3 for well- and poorly differentiated adenocarcinoma, respectively. ADC of well-differentiated adenocarcinoma was significantly higher than that of moderately and poorly differentiated squamous cell carcinoma and poorly differentiated adenocarcinoma (P < .05). With the Spearman rank test, ADCs of lung carcinomas correlated well with tumor cellularities (Spearman coefficient, -0.75; P < .02). CONCLUSION: ADCs of lung carcinomas overlap, but ADCs of well-differentiated adenocarcinoma appear to be higher than those of other histologic lung carcinoma types.