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AbstractQuantifying changes that occur during brain maturation may help in diagnosing diseases that affect pediatric patients. By obtaining normative curves that define brain maturation, pathological changes may be easier to recognize. We assessed diffusion changes which are inherently related to the brain structure during maturation and obtained normative curves. MR scans were obtained for 26 pediatric subjects (ages 0 to 11 years) and four adults. The MR images were all normal. Maps of the average diffusion constant (Dav) were calculated for each subject. Changes in Dav were determined with distribution analysis for the entire brain and compared with regions of interest measurements from the periventricular white matter and thalamus. The mean diffusion constant of the whole brain changes quite rapidly as the brain matures. The data suggest that at least two distinct processes are responsible for the change. Quantitative diffusion tensor imaging may provide means of quantifying overall human brain maturation that may be useful in diagnosing pathology.

Understanding genetic and environmental effects on white matter development in the first years of life is of great interest, as it provides insights into the etiology of neurodevelopmental disorders. In this study, the genetic and environmental effects on white matter were estimated using data from 173 neonatal twin subjects. Diffusion tensor imaging scans were acquired around 40 days after birth and were non-rigidly registered to a group-specific atlas and parcellated into 98 ROIs. A model of additive genetic, and common and specific environmental variance components was used to estimate overall and regional genetic and environmental contributions to diffusion parameters of fractional anisotropy, radial diffusivity, and axial diffusivity. Correlations between the regional heritability values and diffusion parameters were also examined. Results indicate that individual differences in overall white matter microstructure, represented by the average diffusion parameters over the whole brain, are heritable, and estimates are higher than found in studies in adults. Estimates of genetic and environmental variance components vary considerably across different white matter regions. Significant positive correlations between radial diffusivity heritability and radial diffusivity values are consistent with regional genetic variation being modulated by maturation status in the neonatal brain: the more mature the region is, the less genetic variation it shows. Common environmental effects are present in a few regions that tend to be characterized by low radial diffusivity. Results from the joint diffusion parameter analysis suggest that multivariate modeling approaches might be promising to better estimate maturation status and its relationship with genetic and environmental effects.

AbstractIn this study, the development of white matter was studied using an optimized diffusion tensor imaging (DTI) protocol in 20 normal subjects (10–40 years old). The normal development of white matter tracts was addressed by comparing the diffusion anisotropy results between two sub‐groups: eight adults (26–38 years old) and eight adolescents (13–15 years old). The difference in myelination extent between these two groups as indexed by the fractional anisotropy was identified by conducting a studentt‐test of the measured diffusion anisotropy maps. Significant differences (p< 0.01) were detected in the gyrus frontalis medialis (GFM), gyrus temporalis medialis (GTM) and gyrus cinguli (GC), in addition to the developmental changes in corpus callosum. A brief overview of previous published DTI studies in developmental science and current progress in DTI techniques is also given at the end of this paper. It may be useful for readers interested in using DTI to study developmental problems but who are not familiar with the various technical aspects.

Abstract
Background and Study Aims/Objective Despite its invasiveness, computed tomography myelography (CTM) is still considered an important supplement to conventional magnetic resonance imaging (MRI) for preoperative evaluation of multilevel cervical spondylotic myelopathy (CSM). We analyzed if diffusion tensor imaging (DTI) could be a less invasive alternative for this purpose.
Material and Methods In 20 patients with CSM and an indication for decompression of at least one level, CTM was performed preoperatively to determine the extent of spinal canal/cerebrospinal fluid (CSF) space and cord compression (Naganawa score) for a decision on the number of levels to be decompressed. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were correlated with these parameters and with MRI-based increased signal intensity (ISI). Receiver operating characteristic analysis was performed to determine the sensitivity to discriminate levels requiring decompression surgery. European Myelopathy Score (EMS) and neck/radicular visual analog scale (VAS-N/R) were used for clinical evaluation.
Results According to preoperative CTM, 20 levels of maximum and 16 levels of relevant additional stenosis were defined and decompressed. Preoperative FA and particularly ADC showed a significant correlation with the CTM Naganawa score but also with the ISI grade. Furthermore, both FA and ADC facilitated a good discrimination between stenotic and nonstenotic levels with cutoff values < 0.49 for FA and > 1.15 × 10−9 m2/s for ADC. FA and especially ADC revealed a considerably higher sensitivity (79% and 82%, respectively) in discriminating levels requiring decompression surgery compared with ISI (55%). EMS and VAS-N/R were significantly improved at 14 months compared with preoperative values.
Conclusion DTI parameters are highly sensitive at distinguishing surgical from nonsurgical levels in CSM patients and might therefore represent a less invasive alternative to CTM for surgical planning.

Cortical Spreading Depression (CSD), a depolarization wave originat- ing in the visual cortex and traveling towards the frontal lobe, is com- monly accepted as a correlate of migraine visual aura. As of today, little is known about the mechanisms that can trigger or stop such phenomenon. However, the complex and highly individual characteristics of the brain cortex suggest that the geometry might have a significant impact in sup- porting or contrasting the propagation of CSD. Accurate patient-specific computational models are fundamental to cope with the high variability in cortical geometries among individuals, but also with the conduction anisotropy induced in a given cortex by the complex neuronal organisa- tion in the grey matter. In this paper we integrate a distributed model for extracellular potassium concentration with patient-specific diffusivity tensors derived locally from Diffusion Tensor Imaging data. ; This work was supported by the Bizkaia Talent and European Commission through COFUND under the grant BRAhMS - Brain Aura Mathematical Sim- ulation (AYD-000-285), by the Basque Government through the BERC 2014- 2017 program, and by the Spanish Ministry of Economics and Competitiveness MINECO through the BCAM Severo Ochoa excellence accreditation SEV-2013- 0323 and the Spanish "Plan Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad" under Grant BELEMET - Brain ELEctro- METabolic modeling and numerical approximation (MTM2015-69992-R). JMC acknowledges financial support from Ikerbasque: The Basque Foundation for Science and Euskampus at UPV/EHU.

Low back pain (LBP) is a common musculoskeletal complaint, and is a particularly large problem in the military. Heavy load carriage and unusual postures military members operate under in training and in combat have been implicated as primary causes of LBP. The muscles of the lumbar spine (LS) are crucial for providing stability and maintaining posture; lumbar instability is associated with chronic LBP and can result in injury. With injury and age, degenerative structural changes in muscle tissue are observed in concert with gross alterations in posture, however the relationship between muscle microstructure and posture isn't well understood. The purpose of these studies was to investigate the predictive capacity of muscle structure on LS posture in active-duty Marines under operationally relevant conditions. Fractional anisotropy, a measure of muscle microstructure made with diffusion tensor imaging (DTI), was found to be a key predictor of LS posture. Trying to translate these findings to physiologic measures of muscle, it became evident that DTI is nonspecific to individual features of muscle microstructure. To address this gap in our understanding of skeletal muscle DTI's capacity to non-invasively quantify muscle microstructure, we sought to establish an accurate and precise, DTI based tool to measure individual components of muscle microstructure. To achieve this goal we used in silico-based simulation to create a theoretical framework between DTI and key features of muscle microstructure. A precision engineered, nano-fabricated diffusion phantom was developed and tested to validate this framework in real world experiments. The main findings from these studies were the DT is most sensitive to fiber size under 60μm diameter. Using this framework to interpret the relationship between muscle microstructure and posture, Marines with smaller muscle fibers in the erector spinae muscle group have decreased lumbar lordosis, decreased lumbar extension and decreased sacral slope. Clinically and operationally, these findings are significant because they provide the framework for a non-invasive tool that can be used to measure and predict maladaptive posture in operational conditions from musculoskeletal health, which could allow clinicians to tailor rehabilitation protocols to prevent injury, and potentially be used to predict an individual's risk for LS injury.

The incidence of traumatic brain injury (TBI) among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak reflected overpressures of either 100 or 450 kPa (39 and 110 kPa incident pressure, respectively) and subsequently underwent a battery of behavioral tests. Diffusion tensor imaging (DTI), a promising method to detect blast injury in humans, was performed on fixed brains to detect and visualize the spatial dependence of blast injury. Blast TBI caused significant deficits in memory function as evidenced by the Morris Water Maze, but limited emotional deficits as evidenced by the Open Field Test and Elevated Plus Maze. Fractional anisotropy, a metric derived from DTI, revealed significant brain abnormalities in blast-exposed animals. A significant relationship between memory deficits and brain microstructure was evident in the hippocampus, consistent with its role in memory function. The results provide fundamental insight into the neurological consequences of blast TBI, including the evolution of injury during the sub-acute phase and the spatially dependent pattern of injury. The relationship between memory dysfunction and microstructural brain abnormalities may provide insight into the persistent cognitive difficulties experienced by soldiers exposed to blast neurotrauma and may be important to guide therapeutic and rehabilitative efforts.

Blast-induced traumatic brain injury (bTBI) is one of the most common combat-related injuries seen in U.S. military personnel, yet relatively little is known about the underlying mechanisms of injury. In particular, the effects of the primary blast pressure wave are poorly understood. Animal models have proven invaluable for the study of primary bTBI, because it rarely occurs in isolation in human subjects. Even less is known about the effects of repeated primary blast wave exposure, but existing data suggest cumulative increases in brain damage with a second blast. MRI and, in particular, diffusion tensor imaging (DTI), have become important tools for assessing bTBI in both clinical and preclinical settings. Computational statistical methods such as voxelwise analysis have shown promise in localizing and quantifying bTBI throughout the brain. In this study, we use voxelwise analysis of DTI to quantify white matter injury in a rat model of repetitive primary blast exposure. Our results show a significant increase in microstructural damage with a second blast exposure, suggesting that primary bTBI may sensitize the brain to subsequent injury.

Publisher's version (útgefin grein) ; Background: The 15q11.2 BP1-BP2 cytogenetic region has been associated with learning and motor delays, autism, and schizophrenia. This region includes a gene that codes for the cytoplasmic FMR1 interacting protein 1 (CYFIP1). The CYFIP1 protein is involved in actin cytoskeletal dynamics and interacts with the fragile X mental retardation protein. Absence of fragile X mental retardation protein causes fragile X syndrome. Because abnormal white matter microstructure has been reported in both fragile X syndrome and psychiatric disorders, we looked at the impact of 15q11.2 BP1-BP2 dosage on white matter microstructure. Methods: Combining a brain-wide voxel-based approach and a regional-based analysis, we analyzed diffusion tensor imaging data from healthy individuals with the deletion (n = 30), healthy individuals with the reciprocal duplication (n = 27), and IQ-matched control subjects with no large copy number variants (n = 19), recruited from a large genotyped population sample. Results: We found global mirror effects (deletion > control > duplication) on fractional anisotropy. The deletion group showed widespread increased fractional anisotropy when compared with duplication. Regional analyses revealed a greater effect size in the posterior limb of the internal capsule and a tendency for decreased fractional anisotropy in duplication. Conclusions: These results show a reciprocal effect of 15q11.2 BP1-BP2 on white matter microstructure, suggesting that reciprocal chromosomal imbalances may lead to opposite changes in brain structure. Findings in the deletion overlap with previous white matter differences reported in fragile X syndrome patients, suggesting common pathogenic mechanisms derived from disruptions of cytoplasmic CYFIP1-fragile X mental retardation protein complexes. Our data begin to identify specific components of the 15q11.2 BP1-BP2 phenotype and neurobiological mechanisms of potential relevance to the increased risk for disorder. ; This work was supported by Innovative Medicines Initiative Joint Undertaking Grant Nos. 115008 (NEWMEDS [to KS]) and 115300 (EUAIMS [to KS]), of which resources were composed of European Federation of Pharmaceutical Industries and Associations in-kind contribution and financial contribution from European Union Seventh Framework Programme (EU-FP7/2007-2013) Grant No. 602450 (IMAGEMEND) and FP7-People-2011-IAPP Grant No. 286213 (PsychDPC); Wellcome Trust Strategic Award "DEFINE" Grant No. 100202/Z/12/Z (to JH); and core support from the Neuroscience and Mental Health Research Institute , Cardiff University (PhD grant to AS). Approval for this study was obtained from the National Bioethics Committee of Iceland and the Icelandic Data Protection Authority. ; Peer Reviewed

Background: Mild traumatic brain injuries (mTBIs) are a significant social, sport, and military health issue. In spite of advances in the clinical management of these injuries, the underlying pathophysiology is not well-understood. There is a critical need to advance objective biomarkers, allowing the identification and tracking of the long-term evolution of changes resulting from mTBI. Diffusion-weighted imaging (DWI) allows for the assessment of white-matter properties in the brain and shows promise as a suitable biomarker of mTBI pathophysiology.