Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context - Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. Objective - To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design - Cross-sectional, case-control, whole-brain DTI using TBSS. Setting - University research institute. Participants - Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures - Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results - Subjects with BD vs controls had significantly greater FA (t > 3.0, P = .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P = .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions - To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.

The intra-firm diffusion of complementary innovations: Evidence from the adoption of management practices by British establishments

This paper presents a simple profitability-based decision model to show how synergistic gains generated by the joint adoption of complementary innovations may influence the firm's adoption decision. For this purpose a weighted index of intra-firm diffusion is built to investigate empirically the drivers of the intensity of joint use of a set of complementary innovations. The findings indicate that establishment size, ownership structure and product market concentration are important determinants of the intensity of use. Interestingly, the factors that affect the extent of use of technological innovations do also affect that of clusters of management practices. However, they can explain only part of the heterogeneity of the benefits from joint use.

Three-dimensional modeling of the human eye based on magnetic resonance imaging

PURPOSE. A methodology for noninvasively characterizing the three-dimensional (3-D) shape of the complete human eye is not currently available for research into ocular diseases that have a structural substrate, such as myopia. A novel application of a magnetic resonance imaging (MRI) acquisition and analysis technique is presented that, for the first time, allows the 3-D shape of the eye to be investigated fully. METHODS. The technique involves the acquisition of a T2-weighted MRI, which is optimized to reveal the fluid-filled chambers of the eye. Automatic segmentation and meshing algorithms generate a 3-D surface model, which can be shaded with morphologic parameters such as distance from the posterior corneal pole and deviation from sphericity. Full details of the method are illustrated with data from 14 eyes of seven individuals. The spatial accuracy of the calculated models is demonstrated by comparing the MRI-derived axial lengths with values measured in the same eyes using interferometry. RESULTS. The color-coded eye models showed substantial variation in the absolute size of the 14 eyes. Variations in the sphericity of the eyes were also evident, with some appearing approximately spherical whereas others were clearly oblate and one was slightly prolate. Nasal-temporal asymmetries were noted in some subjects. CONCLUSIONS. The MRI acquisition and analysis technique allows a novel way of examining 3-D ocular shape. The ability to stratify and analyze eye shape, ocular volume, and sphericity will further extend the understanding of which specific biometric parameters predispose emmetropic children subsequently to develop myopia. Copyright © Association for Research in Vision and Ophthalmology.

Drusen detection in retro-mode imaging by a scanning laser ophthalmoscope

Purpose: The Nidek F-10 is a scanning laser ophthalmoscope that is capable of a novel fundus imaging technique, so-called ‘retro-mode’ imaging. The standard method of imaging drusen in age-related macular degeneration (AMD) is by fundus photography. The aim of the study was to assess drusen quantification using retro-mode imaging. Methods: Stereoscopic fundus photographs and retro-mode images were captured in 31 eyes of 20 patients with varying stages of AMD. Two experienced masked retinal graders independently assessed images for the number and size of drusen, using purpose-designed software. Drusen were further assessed in a subset of eight patients using optical coherence tomography (OCT) imaging. Results: Drusen observed by fundus photography (mean 33.5) were significantly fewer in number than subretinal deposits seen in retro-mode (mean 81.6; p < 0.001). The predominant deposit diameter was on average 5 µm smaller in retro-mode imaging than in fundus photography (p = 0.004). Agreement between graders for both types of imaging was substantial for number of deposits (weighted ? = 0.69) and moderate for size of deposits (weighted ? = 0.42). Retro-mode deposits corresponded to drusen on OCT imaging in all eight patients. Conclusion: The subretinal deposits detected by retro-mode imaging were consistent with the appearance of drusen on OCT imaging; however, a larger longitudinal study would be required to confirm this finding. Retro-mode imaging detected significantly more deposits than conventional colour fundus photography. Retro-mode imaging provides a rapid non-invasive technique, useful in monitoring subtle changes and progression of AMD, which may be useful in monitoring the response of drusen to future therapeutic interventions.

Source localization of reaction-diffusion models for brain tumors

We propose a mathematically well-founded approach for locating the source (initial state) of density functions evolved within a nonlinear reaction-diffusion model. The reconstruction of the initial source is an ill-posed inverse problem since the solution is highly unstable with respect to measurement noise. To address this instability problem, we introduce a regularization procedure based on the nonlinear Landweber method for the stable determination of the source location. This amounts to solving a sequence of well-posed forward reaction-diffusion problems. The developed framework is general, and as a special instance we consider the problem of source localization of brain tumors. We show numerically that the source of the initial densities of tumor cells are reconstructed well on both imaging data consisting of simple and complex geometric structures.