Phantom assessment of three-dimensional geometric distortion of a dedicated wide-bore MR-simulator for radiotherapy.

This study evaluated the machine-dependent three-dimensional geometric distortion images acquired from a 1.5T 700 mm-wide bore MR-simulator based on a large geometric accuracy phantom. With the consideration of radiation therapy (RT) application requirements, every sequence was examined in various combinations of acquisition-orientations and receiver-bandwidths with console-integrated distortion correction enabled. Distortion was repeatedly measured over a six-month period. The distortion measured from the images acquired at the beginning of this period was employed to retrospectively correct the distortion in the subsequent acquisitions. Geometric distortion was analyzed within the largest field-of-view allowed. Six sequences were examined for comprehensive distortion analysis-VIBE, SPACE, TSE, FLASH, BLADE and PETRA. Based on optimal acquisition parameters, their diameter-sphere-volumes (DSVs) of CT-comparable geometric fidelity (where 1 mm distortion was allowed) were 333.6 mm, 315.1 mm, 316.0 mm, 318.9 mm, 306.2 mm and 314.5 mm respectively. This was a significant increase from 254.0 mm, 245.5 mm, 228.9 mm, 256.6 mm, 230.8 mm and 254.2 mm DSVs respectively, when images were acquired using un-optimized parameters. The longitudinal stability of geometric distortion and the efficacy of retrospective correction of console-corrected images, based on prior distortion measurements, were inspected using VIBE and SPACE. The retrospectively corrected images achieved over 500 mm DSVs with 1 mm distortion allowed. The median distortion was below 1 mm after retrospective correction, proving that obtaining prior distortion map for subsequent retrospective distortion correction is beneficial. The systematic evaluation of distortion using various combinations of sequence-type, acquisition-orientation and receiver-bandwidth in a six-month time span would be a valuable guideline for optimizing sequence for various RT applications.

Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice.

Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits.

MR diffusion tensor imaging detects rapid microstructural changes in amygdala and hippocampus following fear conditioning in mice.

BACKGROUND: Following fear conditioning (FC), ex vivo evidence suggests that early dynamics of cellular and molecular plasticity in amygdala and hippocampal circuits mediate responses to fear. Such altered dynamics in fear circuits are thought to be etiologically related to anxiety disorders including posttraumatic stress disorder (PTSD). Consistent with this, neuroimaging studies of individuals with established PTSD in the months after trauma have revealed changes in brain regions responsible for processing fear. However, whether early changes in fear circuits can be captured in vivo is not known. METHODS: We hypothesized that in vivo magnetic resonance diffusion tensor imaging (DTI) would be sensitive to rapid microstructural changes elicited by FC in an experimental mouse PTSD model. We employed a repeated measures paired design to compare in vivo DTI measurements before, one hour after, and one day after FC-exposed mice (n=18). RESULTS: Using voxel-wise repeated measures analysis, fractional anisotropy (FA) significantly increased then decreased in amygdala, decreased then increased in hippocampus, and was increasing in cingulum and adjacent gray matter one hour and one day post-FC respectively. These findings demonstrate that DTI is sensitive to early changes in brain microstructure following FC, and that FC elicits distinct, rapid in vivo responses in amygdala and hippocampus. CONCLUSIONS: Our results indicate that DTI can detect rapid microstructural changes in brain regions known to mediate fear conditioning in vivo. DTI indices could be explored as a translational tool to capture potential early biological changes in individuals at risk for developing PTSD.

Bilateral substantia nigra and pyramidal tract changes following experimental intracerebral hemorrhage: an MR diffusion tensor imaging study.

The amelioration of secondary neurological damage is among the most important therapeutic goals for patients with intracerebral hemorrhage (ICH). Secondary injury of the ipsilateral substantia nigra (SN) and pyramidal tract (PY) is common after cerebral stroke. Such injury has been characterized previously by anatomical or diffusion MRI, but not in a comprehensive manner, and the knowledge regarding the contralateral changes is relatively poor. This study examined longitudinally both contralateral and ipsilateral SN and PY changes following experimental ICH with diffusion tensor imaging (DTI) and histology. ICH was induced in 14 Sprague-Dawley rats by the infusion of collagenase into the right striatum. Four-shot, spin-echo, echo-planar DTI was performed at 7 T with a b value of 1000 s/mm(2) and 30 diffusion gradient directions at 3.5 h and days 1, 3, 7, 14, 42 and 120 after ICH. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ// ) and radial diffusivity (λ┴ ) were measured in SN and PY accordingly. Two to three rats were sacrificed at days 3, 7, 42 and 120 for histology. The contralateral SN showed an increase in λ// with perivascular enlargement during the first 3 days after ICH. The ipsilateral SN showed increases in FA, λ// , λ┴ and MD at day 1, dramatic decreases at day 3 with neuronal degeneration and neuropil vacuolation, and subsequent gradual normalization. The contralateral PY showed diffusivity decreases at day 1. The ipsilateral PY showed early decreases and then late increases in MD and λ┴, and continuously decreasing FA and λ// with progressive axonal loss and demyelination. In summary, DTI revealed early bilateral changes in SN and PY following ICH. The evolution of the ipsilateral parameters correlated with the histological findings. In the ipsilateral PY, λ// and λ┴ changes indicated evolving and complex pathological processes underlying the monotonic FA decrease. These results support the use of quantitative multiparametric DTI for the evaluation of SN and PY injuries in clinical and preclinical investigations of ICH.

Magnetic resonance spectroscopy reveals N-acetylaspartate reduction in hippocampus and cingulate cortex after fear conditioning.

The fear conditioning in rodents provides a valuable translational tool to investigate the neural basis of learning and memory and potentially the neurobiology of post-traumatic stress disorder (PTSD). Neurobiological changes induced by fear conditioning have largely been examined ex vivo while progressive 'real-time' changes in vivo remain under-explored. Single voxel proton magnetic resonance spectroscopy (1H MRS) of the hippocampus, cingulate cortex and thalamus of adult male C57BL/6N mice (N=12) was performed at 1 day before, 1 day and 1 week after, fear conditioning training using a 7T scanner. N-acetylaspartate (NAA), a marker for neuronal integrity and viability, significantly decreased in the hippocampus at 1 day and 1 week post-conditioning. Significant NAA reduction was also observed in the cingulate cortex at 1 day post-conditioning. These findings of hippocampal NAA decrease indicate reduced neuronal dysfunction and/or neuronal integrity, contributing to the trauma-related PTSD-like symptoms. The neurochemical changes characterized by 1H MRS can shed light on the biochemical mechanisms of learning and memory. Moreover, such information can potentially facilitate prompt intervention for patients with psychiatric disorders.

Effect of cerebrovascular changes on brain DTI quantitation: a hypercapnia study.

Quantitative diffusion tensor imaging (DTI) offers a valuable tool to probe the microstructural changes in neural tissues in vivo, where absolute quantitation accuracy and reproducibility are essential. It has been long recognized that measurement of apparent diffusion coefficient (ADC) using DTI could be influenced by the presence of water molecules in cerebrovasculature. However, little is known about to what extent such blood signal affects DTI quantitation. In this study, we quantitatively examined the effect of cerebral hemodynamic change on DTI indices by using a standard multislice echo planar imaging (EPI) spin echo (SE) DTI acquisition protocol and a rat model of hypercapnia. In response to 5% CO(2) challenge, mean, radial and axial diffusivities measured with diffusion factor (b-value) of b=1.0 ms/µm(2) were found to increase in whole brain (1.52%±0.22%, 1.66%±0.16% and 1.35%±0.37%, respectively), gray matter (1.56%±0.23%, 1.63%±0.14% and 1.47%±0.45%, respectively) and white matter regions (1.45%±0.28%, 1.88%±0.33% and 1.10%±0.26%, respectively). Fractional anisotropy (FA) was found to decrease by 1.67%±0.38%, 1.91%±0.59% and 1.46%±0.30% in whole brain, gray matter and white matter regions, respectively. In addition, these diffusivity increases and FA decreases became more pronounced at a lower b-value (b=0.3 ms/µm(2)). The results indicated that in vivo DTI quantitation in brain can be contaminated by vascular factors on the order of few percentages. Consequently, alterations in cerebrovasculature and hemodynamics can affect the DTI quantitation and its efficacy in characterizing the neural tissue microstructures in normal and diseased states. Caution should be taken in designing and interpreting quantitative DTI studies as all DTI indices can be potentially confounded by physiologic conditions and by cerebrovascular and hemodynamic characteristics.

The effects of hypercapnia on DTI quantification in anesthetized rat brain.

Diffusion Tensor Imaging (DTI) offers a valuable in vivo tool to characterize water diffusion behavior in biological tissues, particularly brain tissues. The accuracy of DTI derived parameters can directly affect the interpretation of underlying microstructures, physiology or pathologies. It is anticipated that measurement of apparent diffusion coefficient (ADC) using DTI could be influenced and complicated by the presence of water molecules in brain vasculature. However, little is known about to what degree does blood signal from vasculature affect the diffusion quantitation. In this study, we examined the effects of hypercapnia on DTI quantification in rat brains using inhalation of 5% carbon dioxide (CO2). It was found that statistically significant changes occurred in parametric DTI maps in response to cerebrovascular challenges, indicating that vascular factors could interfere with in vivo DTI characterization of neural tissues. Consequently, hemodynamic alterations can potentially affect the DTI quantitation and detection of tissue microstructures and pathological alterations. Therefore, cautions must be taken when interpreting DTI parameters in vivo.

In vivo diffusion tensor imaging of chronic spinal cord compression in rat model.

Chronic spinal cord compression induced cervical myelopathy is a comon cause of spinal cord dysfunction. The exact mechanisms of underlying progressive cell death remain to be elucidated. In this study, in vivo diffusion tensor imaging (DTI) has been applied to investigate the microstructural changes of white matter (WM) in this neurodegenerative disease. Compared with conventional MRI techniques, DTI is believed to be more specific to pathological changes. Radial diffusivity (lambda upper left and right quadrants) is higher in the ipilesional region, suggesting demyelination or axonal degradation may occur after prolonged compression. Near the epicenter of lesion, axial diffusivity (lambda(//)) is lower. Also, caudal-rostral asymmetry has been observed in lambda(//). Feasibility of using DTI to detect microstructural changes in chronic disease has been demonstrated.