Catriona D. Good

A voxel-based morphometric study of ageing in 465 normal adult human brains.

Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans.

A voxel-based morphometric study of ageing in 465 normal adult human brains

Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans.

Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains.

We used voxel-based morphometry (VBM) to examine human brain asymmetry and the effects of sex and handedness on brain structure in 465 normal adults. We observed significant asymmetry of cerebral grey and white matter in the occipital, frontal, and temporal lobes (petalia), including Heschls gyrus, planum temporale (PT) and the hippocampal formation. Males demonstrated increased leftward asymmetry within Heschls gyrus and PT compared to females. There was no significant interaction between asymmetry and handedness and no main effect of handedness. There was a significant main effect of sex on brain morphology, even after accounting for the larger global volumes of grey and white matter in males. Females had increased grey matter volume adjacent to the depths of both central sulci and the left superior temporal sulcus, in right Heschls gyrus and PT, in right inferior frontal and frontomarginal gyri and in the cingulate gyrus. Females had significantly increased grey matter concentration extensively and relatively symmetrically in the cortical mantle, parahippocampal gyri, and in the banks of the cingulate and calcarine sulci. Males had increased grey matter volume bilaterally in the mesial temporal lobes, entorhinal and perirhinal cortex, and in the anterior lobes of the cerebellum, but no regions of increased grey matter concentration.

Automatic differentiation of anatomical patterns in the human brain: Validation with studies of degenerative dementias

We compared voxel-based morphometry (VBM) with independent accurate region-of-interest (ROI) measurements of temporal lobe structures in order to validate the usefulness of this fully automated and unbiased technique in Alzheimers disease (AD) and semantic dementia (SD). In AD, ROI analyses appear more sensitive to volume loss in the amygdalae, whereas VBM analyses appear more sensitive to right middle temporal gyrus and regional hippocampal volume loss. In SD, ROI analyses appear more sensitive to left middle and inferior temporal gyrus volume loss, whereas VBM appears more sensitive to regional hippocampal volume loss. In addition the significance of volume reductions was generally less in VBM owing to more stringent corrections for multiple comparisons. In conclusion, the automated technique detects a general trend of atrophy similar to that of expertly labeled ROI measurements in AD and SD, although there are discrepancies in the ranking of severity and in the significance of volume reductions that are more marked in AD.

Accuracy of dementia diagnosis—a direct comparison between radiologists and a computerized method

There has been recent interest in the application of machine learning techniques to neuroimaging-based diagnosis. These methods promise fully automated, standard PC-based clinical decisions, unbiased by variable radiological expertise. We recently used support vector machines (SVMs) to separate sporadic Alzheimers disease from normal ageing and from fronto-temporal lobar degeneration (FTLD). In this study, we compare the results to those obtained by radiologists. A binary diagnostic classification was made by six radiologists with different levels of experience on the same scans and information that had been previously analysed with SVM. SVMs correctly classified 95% (sensitivity/specificity: 95/95) of sporadic Alzheimers disease and controls into their respective groups. Radiologists correctly classified 65–95% (median 89%; sensitivity/specificity: 88/90) of scans. SVM correctly classified another set of sporadic Alzheimers disease in 93% (sensitivity/specificity: 100/86) of cases, whereas radiologists ranged between 80% and 90% (median 83%; sensitivity/specificity: 80/85). SVMs were better at separating patients with sporadic Alzheimers disease from those with FTLD (SVM 89%; sensitivity/specificity: 83/95; compared to radiological range from 63% to 83%; median 71%; sensitivity/specificity: 64/76). Radiologists were always accurate when they reported a high degree of diagnostic confidence. The results show that well-trained neuroradiologists classify typical Alzheimers disease-associated scans comparable to SVMs. However, SVMs require no expert knowledge and trained SVMs can readily be exchanged between centres for use in diagnostic classification. These results are encouraging and indicate a role for computerized diagnostic methods in clinical practice.

Optimization of 3-D MP-RAGE sequences for structural brain imaging

Abstract An optimized MR sequence for structural three-dimensional brain scans is presented, giving good T1 contrast and excellent white matter/gray matter segmentation. Modification of the usual linear phase encoding order to centric phase encoding restores the contrast loss, which usually occurs after magnetization preparation during the acquisition process when large volumes are imaged. The deleterious effects on the point-spread function are compensated by means of an appropriate k-space filter. RF coil inhomogeneities are corrected by means of shaped excitation pulses. High contrast-to-noise images of the entire brain with 1 mm isotropic resolution can be obtained in 12 min. The contrast-to-noise-ratio is about 100% higher than for sequences based on linear phase encoding.

Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry

OBJECTIVE Structural neuroimaging studies have suggested an association between schizophrenia and abnormalities in brain morphology such as ventricular enlargement and differences in gray matter distribution. Less consistently reported are findings of regional abnormalities such as selective differences in thalamic volume. The authors applied an unbiased technique to test for differences in cerebral morphometry between patients with schizophrenia and matched comparison subjects. METHOD T(1)-weighted images from 20 schizophrenic patients and matched comparison subjects were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. RESULTS Global differences in gray matter volume were seen between the schizophrenic and comparison subjects, with selective regional gray matter differences noted in the mediodorsal thalamus and across cortical regions, including the ventral and medial prefrontal cortices. Within the schizophrenic subjects, a relationship was observed between gray matter volume loss in the medial prefrontal cortex and a positive family history of schizophrenia. There was no significant difference between patients and comparison subjects in rates of proportional gray matter reduction with age. CONCLUSIONS These observations confirm an association between thalamocortical morphometric abnormalities and schizophrenia, consistent with theoretical models of primary pathoetiological dysfunction in filtering, integration, and information transfer processes in patients with schizophrenia.

RF inhomogeneity compensation in structural brain imaging.

Three‐dimensional T1‐weighted magnetization‐prepared rapid gradient‐echo (MP‐RAGE) sequences with centric phase encoding (PE) in the inner loop provide structural brain images with a high spatial resolution and high tissue contrast. A disadvantage of this sequence type is the susceptibility to inhomogeneities of the radiofrequency (RF) coil, which may result in poor image contrast in some peripheral regions. A special excitation pulse is presented which compensates for these effects in both the head/foot and anterior/posterior directions. This pulse has a duration of only 1.3 ms and is thus compatible with the short repetition times (TRs) required for MP‐RAGE imaging. It is shown experimentally that images acquired with the compensation pulse may be segmented without using intensity correction algorithms during data postprocessing. Magn Reson Med 47:398–402, 2002.

Changes in cerebral morphology consequent to peripheral autonomic denervation.

Pure autonomic failure (PAF) is characterized by an acquired, selective, peripheral denervation of the autonomic nervous system. Patients with PAF fail to generate bodily states of arousal via the autonomic nervous system in response to physical or cognitive effort. We used voxel-based morphometry to test the hypothesis that changes in the morphology of brain regions involved in autonomic control would arise as a consequence to the longstanding absence of peripheral autonomic responses in PAF patients. Optimized voxel-based morphometry of structural magnetic resonance scans was used to test for regional differences in grey and white matter in 15 PAF patients and matched controls. There were no group differences observed in global measures of grey matter, white matter, or cerebrospinal fluid (CSF). We identified morphometric differences reflecting regional decreases in grey matter volume and concentration in anterior cingulate and insular cortices in PAF patients relative to controls. Morphometric differences in brainstem and subcortical regions did not reach statistical significance. Our findings suggest that peripheral autonomic denervation is associated with grey matter loss in cortical regions encompassing areas that we have previously shown are functionally involved in generation and representation of bodily states of autonomic arousal. The nature of these changes cannot be determined from morphometric analysis alone, but we suggest that they reflect experience-dependent change consequent upon loss of afferent input to brain regions involved in representation of autonomic states.

Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series

BACKGROUND Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. OBJECTIVES The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimers disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. METHOD PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohens kappa. RESULTS Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0-0.25 for PCA to 0.29-0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. CONCLUSION The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practice.