Deterministic diffusion fiber tracking improved by quantitative anisotropy

Diffusion MRI tractography has emerged as a useful and popular tool for mapping connections between brain regions. In this study, we examined the performance of quantitative anisotropy (QA) in facilitating deterministic fiber tracking. Two phantom studies were conducted. The first phantom study examined the susceptibility of fractional anisotropy (FA), generalized factional anisotropy (GFA), and QA to various partial volume effects. The second phantom study examined the spatial resolution of the FA-aided, GFA-aided, and QA-aided tractographies. An in vivo study was conducted to track the arcuate fasciculus, and two neurosurgeons blind to the acquisition and analysis settings were invited to identify false tracks. The performance of QA in assisting fiber tracking was compared with FA, GFA, and anatomical information from T 1-weighted images. Our first phantom study showed that QA is less sensitive to the partial volume effects of crossing fibers and free water, suggesting that it is a robust index. The second phantom study showed that the QA-aided tractography has better resolution than the FA-aided and GFA-aided tractography. Our in vivo study further showed that the QA-aided tractography outperforms the FA-aided, GFA-aided, and anatomy-aided tractographies. In the shell scheme (HARDI), the FA-aided, GFA-aided, and anatomy-aided tractographies have 30.7%, 32.6%, and 24.45% of the false tracks, respectively, while the QA-aided tractography has 16.2%. In the grid scheme (DSI), the FA-aided, GFA-aided, and anatomy-aided tractographies have 12.3%, 9.0%, and 10.93% of the false tracks, respectively, while the QA-aided tractography has 4.43%. The QA-aided deterministic fiber tracking may assist fiber tracking studies and facilitate the advancement of human connectomics. © 2013 Yeh et al

Neural correlates of impaired vision in adolescents born extremely preterm and/or extremely low birthweight

BACKGROUND: Adolescents born extremely preterm (EP; <28 weeks' gestation) and/or extremely low birthweight (ELBW; <1000 g) experience high rates of visual impairments, however the potential neural correlates of visual impairments in EP/ELBW adolescents require further investigation. This study aimed to: 1) compare optic radiation and primary visual cortical structure between EP/ELBW adolescents and normal birthweight controls; 2) investigate associations between perinatal factors and optic radiation and primary visual cortical structure in EP/ELBW adolescents; 3) investigate associations between optic radiation and primary visual cortical structure in EP/ELBW adolescents and the odds of impaired vision. METHODS: 196 EP/ELBW adolescents and 143 controls underwent magnetic resonance imaging at a mean age of 18 years. Optic radiations were delineated using constrained spherical deconvolution based probabilistic tractography. Primary visual cortices were segmented using FreeSurfer software. Diffusion tensor variables and tract volume of the optic radiations, as well as volume, surface area and thickness of the primary visual cortices, were estimated. RESULTS: Axial, radial and mean diffusivities within the optic radiations, and primary visual cortical thickness, were higher in the EP/ELBW adolescents than controls. Within EP/ELBW adolescents, postnatal corticosteroid exposure was associated with altered optic radiation diffusion values and lower tract volume, while decreasing gestational age at birth was associated with increased primary visual cortical volume, area and thickness. Furthermore, decreasing optic radiation fractional anisotropy and tract volume, and increasing optic radiation diffusivity in EP/ELBW adolescents were associated with increased odds of impaired vision, whereas primary visual cortical measures were not associated with the odds of impaired vision. CONCLUSIONS: Optic radiation and primary visual cortical structure are altered in EP/ELBW adolescents compared with controls, with the greatest alterations seen in those exposed to postnatal corticosteroids and those born earliest. Structural alterations to the optic radiations may increase the risk of impaired vision in EP/ELBW adolescents.Claire E. Kelly, Jeanie L. Y. Cheong, Carly Molloy, Peter J. Anderson, Katherine J. Lee, Alice C. Burnet

Observed infant-parent attachment and brain morphology in middle childhood

Poor quality of the early infant-parent bond predicts later child problems. Infant-parent attachment has been suggested to influence brain development, but this association has hardly been examined. In adults, larger amygdala volumes have been described in relation to early attachment disorganization; neuroimaging studies of attachment in children, however, are lacking. We examined the association between infant-parent attachment and brain morphology in 551 children from a population-based cohort in the Netherlands. Infant-parent attachment was observed with the Strange-Situation Procedure at age 14 months and different brain measures were collected with magnetic resonance imaging at mean age 10 years. Children with disorganized infant attachment had larger hippocampal volumes than those with organized attachment patterns. This finding was robust to the adjustment for confounders and consistent across hemispheres. The association was not explained by cognitive or emotional and behavioral problems. Disorganized attachment did not predict any other difference in brain morphology. Moreover, children with insecure organized infant attachment patterns did not differ from those who were securely attached in any brain outcome. Causality cannot be inferred, but our findings in this large population-based study provide novel evidence for a long-term association between the quality of infant-parent attachment and specific brain differences in childhood

Effects of Orientation and Anisometry of Magnetic Resonance Imaging Acquisitions on Diffusion Tensor Imaging and Structural Connectomes

Diffusion-weighted imaging (DWI) quantifies water molecule diffusion within tissues and is becoming an increasingly used technique. However, it is very challenging as correct quantification depends on many different factors, ranging from acquisition parameters to a long pipeline of image processing. In this work, we investigated the influence of voxel geometry on diffusion analysis, comparing different acquisition orientations as well as isometric and anisometric voxels. Diffusion-weighted images of one rat brain were acquired with four different voxel geometries (one isometric and three anisometric in different directions) and three different encoding orientations (coronal, axial and sagittal). Diffusion tensor scalar measurements, tractography and the brain structural connectome were analyzed for each of the 12 acquisitions. The acquisition direction with respect to the main magnetic field orientation affected the diffusion results. When the acquisition slice-encoding direction was not aligned with the main magnetic field, there were more artifacts and a lower signal-to-noise ratio that led to less anisotropic tensors (lower fractional anisotropic values), producing poorer quality results. The use of anisometric voxels generated statistically significant differences in the values of diffusion metrics in specific regions. It also elicited differences in tract reconstruction and in different graph metric values describing the brain networks. Our results highlight the importance of taking into account the geometric aspects of acquisitions, especially when comparing diffusion data acquired using different geometries

Nerve diffusion tensor imaging

Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that in vivo visualises random translational movement of water molecules. DTI has inherent difficulties with low signal-to-noise ratio, sensitivity to patient motion, field inhomogeneities and fast T2 relaxation. It has been used in the central nervous system, although it has not been assessed in the peripheral nervous system. The aim of this thesis was to investigate if DTI in peripheral nerves was feasible, and if so, to investigate clinical implications. Study I showed that in healthy volunteers the peripheral nerves, the sciatic nerves, could be visualised in vivo using DTI and fiber tracking. Study II showed that sciatic nerves, including their division into the tibial and common fibular nerves, have a characteristic diffusion pattern with most impaired diffusion perpendicular to the nerve direction. This allowed nerves, excluding other tissues and artifacts, to be visualised using a novel approach called diffusion-direction- dependent imaging and with a simple unidirectional diffusion maximum-intensity projection approach. Study III showed that the olfactory bulbs (OBs) and olfactory tracts could be visualised in vivo using DTI and fiber tracking. In Study IV, Parkinson’s disease (PD) patients with impaired olfaction were evaluated with DTI of the OBs. A novel approach of DTI was used, taking advantage of the technique’s inherent directional information, for region of interest placement and diffusion measurements in the OBs. In the PD patient group diffusion was altered in the OBs, compared to healthy controls. This was hypothesised, since α-synuclein inclusions and Lewy neurites interfering with nerve structure have been detected in the OBs. However, the coefficient of variation between two identical DTI series was high, due to the small size of the OBs and their location in an area susceptible to artifacts, and the difference between the groups was statistically significant only for the first of two series. In Study V, patients of the Swedish ‘Huddinge Spinocerebellar ataxia (SCA) Family’ with peripheral neuropathy, were evaluated with DTI of a peripheral nerve. Diffusion alterations were found in peripheral nerves in SCA patients, compared to healthy controls, which was statistically significant. In conclusion, DTI in peripheral nerves is feasible and can be used to detect diffusion alterations in OBs in PD patients and in peripheral nerves in SCA patients with peripheral neuropathy

Early-Life Adversities and Neurocognitive Outcomes:An Epidemiological Study

This thesis is the compilation of studies that assessed stress and adversity using different approaches, and investigated the relation between adversities and early‑life stress with subsequent neurocognitive outcomes in the general population. This thesis also includes studies that addressed the role of protective factors, and the interplay between adversity and multiple protective factors in relation to brain morphology. Data from the population‑based Generation R Study, and the high‑risk Mannheim Study of Children at Risk were used in the studies presented here

Blast Injury Outcome Study in Armed forces Personnel (BIOSAP) and Blast injury in pigs study (BIIPs)

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Exploring brain structure and blood metabolic profiles using Alzheimer's pathway specific polygenic risk scores

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects older people. It is common, affecting around one in ten people over 65 years old. In addition to the autosomal dominant AD genes and Apolipoprotein E (APOE), genome wide association studies (GWAS) have identified a number of small risk loci. These can be combined into polygenic risk scores (PRS) which can predict AD relatively accurately and are associated with a number of neurodegeneration phenotypes. Pathway analyses of GWAS data have implicated a number of biological processes, including the immune response and lipid metabolism. How AD pathway specific genetic burden manifests in brain structure or serum metabolic profiles is not well understood. In this thesis, volumetric and diffusion MRI and serum lipid and inflammatory markers were used to investigate manifestations of AD polygenic risk in two large population cohorts. Specifically, these analyses sought to determine 1) whether AD polygenic risk scores were associated with neuroimaging and blood marker phenotypes linked to neurodegeneration in younger and older adult cohorts; and 2) whether PRS informed by disease pathways were associated with different patterns of alteration in brain structure, serum lipids or inflammatory markers. The relationships between PRS and phenotypes were explored using linear regression. There were significant associations between pathway specific PRS, grey matter volumes and white matter microstructure. Although some of these attenuated when the APOE region was excluded from the score, some were maintained, in particular cortical thickness in mature adults, which appeared to be independent of APOE. Increased pathway specific polygenic risk for AD was also associated with serum markers such as increased blood lipids, particularly low density lipoprotein (LDL) cholesterol and total cholesterol, and decreased C-Reactive Protein (CRP). However, these effects seemed to be driven by the APOE locus. Further longitudinal studies, combining advanced MRI techniques with cerebrospinal fluid and neuroradiology biomarkers, will be required to confirm these findings and assess their biological significance