Faculty Bibliography

Analyses were performed on brain MRI scans from individuals who were frequent cannabis users (N = 10; 9 males, 1 female, mean age 21.1 +/- 2.9, range: 18-27) in adolescence and similar age and sex matched young adults who never used cannabis (N = 10; 9 males, 1 female, mean age of 23.0 +/- 4.4, range: 17-30). Cerebral atrophy and white matter integrity were determined using diffusion tensor imaging (DTI) to quantify the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA). Whole brain volumes, lateral ventricular volumes, and gray matter volumes of the amygdala-hippocampal complex, superior temporal gyrus, and entire temporal lobes (excluding the amygdala-hippocampal complex) were also measured. While differences existed between groups, no pattern consistent with evidence of cerebral atrophy or loss of white matter integrity was detected. It is concluded that frequent cannabis use is unlikely to be neurotoxic to the normal developing adolescent brain

A novel magnetic resonance imaging method was used to determine whether it is feasible to detect early signs of cortical atrophy among individuals who are at high risk for developing schizophrenia. Fifteen individuals at high-risk for schizophrenia and 15 of their first degree relatives diagnosed with schizophrenia were compared with controls (n=25) who did not have a family history of psychiatric illness or psychiatric hospitalizations. On the basis of a voxelwise analysis of apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance imaging, these individuals showed evidence of deficits in four separate regions of the brain, all on the left side only: parahippocampal gyrus, lingual gyrus, superior frontal gyrus, and middle frontal gyrus. However, conventional volumetric quantification of ventricular space to detect atrophy failed to reveal differences between high-risk subjects and controls. It is concluded that ADC may be a more sensitive measure than ventricular volume assessments for use in future studies of early prediction of schizophrenia

Mutual information (MI) has proven to be a useful similarity measure for spatial registration between related pairs of images in various medical imaging applications. Image registration algorithms that utilize the MI assume that the best alignment between a pair of images is reached when their MI is at its maximum. However, this assumption is not always valid because the MI is not only sensitive to dissimilarity between images, but also to the image interpolation operations performed during the optimization process in image registration algorithms. When the images that are being registered are close to their optimum spatial alignment, MI's sensitivity to interpolation may become dominant over its sensitivity to image misalignment, hence limiting the accuracy of the image registration method. In this paper, we present an entropy-based cost function, closely related to MI, that can be made relatively insensitive to interpolation effects, and can be generalized to registration of multispectral images

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with schizophrenia

The objective of inter-subject registration of three-dimensional volumetric brain scans is to reduce the anatomical variability between the images scanned from different individuals. This is a necessary step in many different applications such as voxelwise group analysis of imaging data obtained from different individuals. In this paper, the ability of three different image registration algorithms in reducing inter-subject anatomical variability is quantitatively compared using a set of common high-resolution volumetric magnetic resonance imaging scans from 17 subjects. The algorithms are from the automatic image registration (AIR; version 5), the statistical parametric mapping (SPM99), and the automatic registration toolbox (ART) packages. The latter includes the implementation of a non-linear image registration algorithm, details of which are presented in this paper. The accuracy of registration is quantified in terms of two independent measures: (1) post-registration spatial dispersion of sets of homologous landmarks manually identified on images before or after registration; and (2) voxelwise image standard deviation maps computed within the set of images registered by each algorithm. Both measures showed that the ART algorithm is clearly superior to both AIR and SPM99 in reducing inter-subject anatomical variability. The spatial dispersion measure was found to be more sensitive when the landmarks were placed after image registration. The standard deviation measure was found sensitive to intensity normalization or the method of image interpolation

Transgenic mouse models have been essential for understanding the pathogenesis of Alzheimer's disease (AD) including those that model the deposition process of beta-amyloid (Abeta). Several laboratories have focused on research related to the non-invasive detection of early changes in brains of transgenic mouse models of Alzheimer's pathology. Most of this work has been performed using regional image analysis of individual mouse brains and pooling the results for statistical assessment. Here we report the implementation of a non-linear image registration algorithm to register anatomical and transverse relaxation time (T2) maps estimated from MR images of transgenic mice. The algorithm successfully registered mouse brain magnetic resonance imaging (MRI) volumes and T2 maps, allowing reliable estimates of T2 values for different regions of interest from the resultant combined images. This approach significantly reduced the data processing and analysis time, and improved the ability to statistically discriminate between groups. Additionally, 3D visualization of intra-regional distributions of T2 of the resultant registered images provided the ability to detect small changes between groups that otherwise would not be possible to detect

Males with an extra-X chromosome (Klinefelter's syndrome) frequently, although not always, have an increased prevalence of psychiatric disturbances that range from attention deficit disorder in childhood to schizophrenia or severe affective disorders during adulthood. In addition, they frequently have characteristic verbal deficits. Thus, examining brain magnetic resonance imaging (MRI) scans of these individuals may yield clues to the influence of X chromosome genes on brain structural variation corresponding to psychiatric and cognitive disorders. Eleven adult XXY and 11 age matched XY male controls were examined with a structured psychiatric interview, battery of cognitive tests, and an MRI scan. Ten of eleven of the XXY men had some form of psychiatric disturbance, four of whom had auditory hallucinations compared with none of the XY controls. Significantly smaller frontal lobe, temporal lobe, and superior temporal gyrus (STG) cortical volumes were observed bilaterally in the XXY men. In addition, diffusion tensor imaging (DTI) of white matter integrity resulted in four regions of reduced fractional anisotropy (FA) in XXY men compared with controls, three in the left hemisphere, and one on the right. These correspond to the left posterior limb of the internal capsule, bilateral anterior cingulate, and left arcuate bundle. Specific cognitive deficits in executive functioning attributable to frontal lobe integrity and verbal comprehension were noted. Thus, excess expression of one or more X chromosome genes influences both gray and white matter development in frontal and temporal lobes, as well as white matter tracts leading to them, and may in this way contribute to the executive and language deficits observed in these adults. Future prospective studies are needed to determine which gene or genes are involved and whether their expression could be modified with appropriate treatments early in life. Brain expressed genes that are known to escape inactivation on extra-X chromosomes would be prime candidates

Loss of cortical gray matter is accompanied by a commensurate increase in the sulcal and intraventricular cerebrospinal fluid volume. On diffusion-weighted magnetic resonance imaging, this would be reflected as a higher apparent diffusion coefficient in affected brain regions. On the basis of the above premise, we suggest that the apparent diffusion coefficient may be used as a surrogate marker for the assessment of regional brain volume deficits. We demonstrate this approach by voxelwise analysis of registered apparent diffusion coefficient images from a group of 15 patients with schizophrenia and 15 age-matched healthy controls. We found widespread regional apparent diffusion coefficient increases in patients. Affected areas included the bilateral insular cortex, hippocampus, temporal lobe, and occipital areas. These results largely concur with previous findings of cortical volume deficits in schizophrenia

Apolipoprotein E epsilon4 is a major genetic risk factor for Alzheimer's disease, but the neurobiological basis for this risk is unknown. We used diffusion tensor imaging to measure diffusion anisotropy in the parahippocampal gyrus white matter in healthy elderly apolipoprotein E epsilon4 carriers and noncarriers. We also measured volumes of the lateral ventricles and temporal horns as proxies of cerebral atrophy. The epsilon4 carriers (n=14) showed significantly lower fractional anisotropy and higher radial diffusivity in the parahippocampal white matter 15 mm below the anterior commissure-posterior commissure plane than noncarriers (n=15). No group differences in ventricular volumes were found, nor were diffusion tensor imaging measures modulated by ventricular volumes. Diffusion tensor imaging may be sufficiently sensitive to detect preclinical brain changes related to Alzheimer's disease