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Find video protocols related to scientific articles indexed in Pubmed.
From cartoon to real time MRI: in vivo monitoring of phagocyte migration in mouse brain.
Sci Rep
PUBLISHED: 07-07-2014
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Recent studies have demonstrated that immune cells play an important role in the pathogenesis of many neurological conditions. Immune cells constantly survey the brain microvasculature for irregularities in levels of factors that signal homeostasis. Immune responses are initiated when necessary, resulting in mobilisation of the microglial cells resident in the central nervous system (CNS) and/or of infiltrating peripheral cells. However, little is known about the kinetics of immune cells in healthy and diseased CNS, because it is difficult to perform long-term visualisation of cell motility in live tissue with minimal invasion. Here, we describe highly sensitive in vivo MRI techniques for sequential monitoring of cell migration in the CNS at the single-cell level. We show that MRI combined with intravenous administration of super-paramagnetic particles of iron oxide (SPIO) can be used to monitor the transmigration of peripheral phagocytes into healthy or LPS-treated mouse brains. We also demonstrate dynamic cell migration in live animal brains with time-lapse MRI videos. Time-lapse MRI was used to visualise and track cells with low motility in a control mouse brain. High-sensitivity MRI cell tracking using SPIO offers new insights into immune cell kinetics in the brain and the mechanisms of CNS homeostasis.
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In vivo magnetic resonance imaging at 11.7 Tesla visualized the effects of neonatal transection of infraorbital nerve upon primary and secondary trigeminal pathways in rats.
Brain Res.
PUBLISHED: 06-20-2014
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Using 11.7T ultra high-field T2-weighted MRI, the present study aimed to investigate pathological changes of primary and secondary trigeminal pathways following neonatal transection of infraorbital nerve in rats. The trigeminal pathways consist of spinal trigeminal tract, trigeminal sensory nuclear complex, medial lemniscus, ventromedial portion of external medullary lamina and ventral posterior nucleus of thalamus. By selecting optimum parameters of MRI such as repetition time, echo time, and slice orientation, this study visualized the trigeminal pathways in rats without any contrast agents. Pathological changes due to the nerve transection were found at 8 weeks of age as a marked reduction of the areas of the trigeminal pathways connecting from the injured nerve. In addition, T2-weighted MR images of the trigeminal nerve trunk and the spinal trigeminal tract suggest a communication of CSF through the trigeminal nerve between the inside and outside of the brain stem. These results support the utility of ultra high-field MRI system for noninvasive assessment of effects of trigeminal nerve injury upon the trigeminal pathways.
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Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria.
Cell Host Microbe
PUBLISHED: 03-05-2014
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Cerebral malaria is a complication of Plasmodium falciparum infection characterized by sudden coma, death, or neurodisability. Studies using a mouse model of experimental cerebral malaria (ECM) have indicated that blood-brain barrier disruption and CD8 T cell recruitment contribute to disease, but the spatiotemporal mechanisms are poorly understood. We show by ultra-high-field MRI and multiphoton microscopy that the olfactory bulb is physically and functionally damaged (loss of smell) by Plasmodium parasites during ECM. The trabecular small capillaries comprising the olfactory bulb show parasite accumulation and cell occlusion followed by microbleeding, events associated with high fever and cytokine storm. Specifically, the olfactory upregulates chemokine CCL21, and loss or functional blockade of its receptors CCR7 and CXCR3 results in decreased CD8 T cell activation and recruitment, respectively, as well as prolonged survival. Thus, early detection of olfaction loss and blockade of pathological cell recruitment may offer potential therapeutic strategies for ECM.
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Ratiometric MRI sensors based on core-shell nanoparticles for quantitative pH imaging.
Adv. Mater. Weinheim
PUBLISHED: 01-22-2014
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Ratiometric MRI sensors consist of paramagnetic cores and pH-sensitive polymer shells. The core-shell nanostructure enables the coexistence of two incompatible NMR relaxation properties in one particle. The sensors show pH sensitivity in transverse relaxivity (r2 ), but not in longitudinal relaxivity (r1 ). Quantitative pH imaging is achieved by measuring the r2 /r1 value with a clinical 3 T MRI scanner.
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Multifunctional core–shell silica nanoparticles for highly sensitive (19)F magnetic resonance imaging.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-22-2014
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19F magnetic resonance imaging (19F MRI) is useful for monitoring particular signals from biological samples, cells, and target tissues, because background signals are missing in animal bodies. Therefore, highly sensitive 19F MRI contrast agents are in great demand for their practical applications. However, we have faced the following challenges: 1) increasing the number of fluorine atoms decreases the solubility of the molecular probes, and 2) the restriction of the molecular mobility attenuates the 19F MRI signals. Herein, we developed novel multifunctional core–shell nanoparticles to solve these issues. They are composed of a core micelle filled with liquid perfluorocarbon and a robust silica shell. These core–shell nanoparticles have superior properties such as high sensitivity, modifiability of the surface, biocompatibility, and sufficient in vivo stability. By the adequate surface modifications, gene expression in living cells and tumor tissue in living mice were successfully detected by 19F MRI.
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A new mouse allele of glutamate receptor delta 2 with cerebellar atrophy and progressive ataxia.
PLoS ONE
PUBLISHED: 01-01-2014
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Spinocerebellar degenerations (SCDs) are a large class of sporadic or hereditary neurodegenerative disorders characterized by progressive motion defects and degenerative changes in the cerebellum and other parts of the CNS. Here we report the identification and establishment from a C57BL/6J mouse colony of a novel mouse line developing spontaneous progressive ataxia, which we refer to as ts3. Frequency of the phenotypic expression was consistent with an autosomal recessive Mendelian trait of inheritance, suggesting that a single gene mutation is responsible for the ataxic phenotype of this line. The onset of ataxia was observed at about three weeks of age, which slowly progressed until the hind limbs became entirely paralyzed in many cases. Micro-MRI study revealed significant cerebellar atrophy in all the ataxic mice, although individual variations were observed. Detailed histological analyses demonstrated significant atrophy of the anterior folia with reduced granule cells (GC) and abnormal morphology of cerebellar Purkinje cells (PC). Study by ultra-high voltage electron microscopy (UHVEM) further indicated aberrant morphology of PC dendrites and their spines, suggesting both morphological and functional abnormalities of the PC in the mutants. Immunohistochemical studies also revealed defects in parallel fiber (PF)-PC synapse formation and abnormal distal extension of climbing fibers (CF). Based on the phenotypic similarities of the ts3 mutant with other known ataxic mutants, we performed immunohistological analyses and found that expression levels of two genes and their products, glutamate receptor delta2 (grid2) and its ligand, cerebellin1 (Cbln1), are significantly reduced or undetectable. Finally, we sequenced the candidate genes and detected a large deletion in the coding region of the grid2 gene. Our present study suggests that ts3 is a new allele of the grid2 gene, which causes similar but different phenotypes as compared to other grid2 mutants.
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Diffusion tensor imaging of brain abnormalities induced by prenatal exposure to radiation in rodents.
PLoS ONE
PUBLISHED: 01-01-2014
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We assessed brain abnormalities in rats exposed prenatally to radiation (X-rays) using magnetic resonance imaging (MRI) and histological experiments. Pregnant rats were divided into 4 groups: the control group (n?=?3) and 3 groups that were exposed to different radiation doses (0.5, 1.0, or 1.5 Gy; n?=?3 each). Brain abnormalities were assessed in 32 neonatal male rats (8 per group). Ex vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed using 11.7-T MRI. The expression of markers of myelin production (Kluver-Barrera staining, KB), nonpyramidal cells (calbindin-D28k staining, CaBP), and pyramidal cells (staining of the nonphosphorylated heavy-chain neurofilament SMI-32) were histologically evaluated. Decreased brain volume, increased ventricle volume, and thinner cortices were observed by MRI in irradiated rats. However, no abnormalities in the cortical 6-layered structure were observed via KB staining in radiation-exposed rats. The DTI color-coded map revealed a dose-dependent reduction in the anisotropic signal (vertical direction), which did not represent reduced numbers of pyramidal cells; rather, it indicated a signal reduction relative to the vertical direction because of low nerve cell density in the entire cortex. We conclude that DTI and histological experiments are useful tools for assessing cortical and hippocampal abnormalities after prenatal exposure to radiation in rats.
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An adhesive (19)F MRI chemical probe allows signal off-to-on-type molecular sensing in a biological environment.
Chem. Commun. (Camb.)
PUBLISHED: 10-31-2013
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We report a new strategy for designing a signal off-to-on-type (19)F MRI chemical probe that operates in biological environments. The present strategy is based on the control of adherence of a (19)F MRI chemical probe to certain blood proteins, accompanied by a change in transverse relaxation time of (19)F nuclei.
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Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model.
Int. Immunol.
PUBLISHED: 10-22-2013
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Magnetic resonance imaging (MRI) is widely employed for the diagnosis of multiple sclerosis (MS). However, sometimes, the lesions found by MRI do not correlate with the neurological impairments observed in MS patients. We recently showed autoreactive T cells accumulate in the fifth lumbar cord (L5) to pass the blood-brain barrier and cause inflammation in the central nervous system of experimental autoimmune encephalomyelitis (EAE) mice, an MS model. We here investigated this early event using ultrahigh-field MRI. T2-weighted image signals, which conform to the water content, increased in L4 and L5 during the development of EAE. At the same time, the sizes of L4 and L5 changed. Moreover, angiographic images of MRI showed branch positions of the blood vessels in the lower lumbar cords were significantly altered. Interestingly, EAE mice showed occluded and thickened vessels, particularly during the peak phase, followed by reperfusion in the remission phase. Additionally, demyelination regions of some MS patients had increased lactic acid content, suggesting the presence of ischemic events. These results suggest that inflammation-mediated alterations in the lower lumbar cord change the homeostasis of the spinal cord and demonstrate that ultrahigh-field MRI enables the detection of previously invisible pathological alterations in EAE.
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Activation of efferents from the basolateral amygdala during the retrieval of conditioned taste aversion.
Neurobiol Learn Mem
PUBLISHED: 05-24-2013
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The basolateral amygdala (BLA) is critical in the retrieval of conditioned taste aversion (CTA). Although BLA neurons have axonal connections with several brain regions, it is unclear which efferent pathways are functional in CTA. The present study investigated the involvement of efferents from BLA in CTA retrieval with manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI). Rats receiving intraoral saccharin infusion paired with intraperitoneal administration of lithium chloride (LiCl) were presented with saccharin (C-S and BC-S groups) or water (C-W group) on the test day. The BC-S group was administered with LiCl 15min before saccharin presentation on the conditioning day (backward conditioning, BC). Another two groups were injected with saline (S-S and S-W groups) instead of LiCl. On the test day, 50 nL of 40-mM manganese chloride (MnCl2) was injected into BLA before the intraoral fluid infusion. Using MRI, we analyzed Mn(2+) movements, which indicated the activation of efferent neurons. The C-S group showed the highest activities in several efferents from BLA. Of them, the activities of the efferents to the nucleus accumbens core (NAcC), the anterior part of the bed nucleus of the stria terminalis (aBNST), and the central amygdala (CeA) were larger in the C-S group than in the Q group, which was presented with a normally aversive quinine solution. Although rats equivalently rejected conditioned aversive saccharin and quinine, the aversive responses in the C-S group, and not the Q group, were due to CTA retrieval. Therefore, our results indicated that BLA efferents to NAcC, aBNST, and CeA were specifically activated during CTA retrieval, suggesting that these efferents are key components in the neural mechanisms of CTA.
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A nanospherical polymer as an MRI sensor without paramagnetic or superparamagnetic species.
Dalton Trans
PUBLISHED: 04-22-2013
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We report here a nanospherical polymer consisting of methacrylic acid and N,N-methylenebisacrylamide, which works as a metal-free magnetic resonance imaging (MRI) sensor for pH. The nanospherical polymer gave a lower signal T2-weighted MRI image with decreasing pH. In contrast, it had little effect on the T1-weighted MRI image.
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Dose-related cerebellar abnormality in rats with prenatal exposure to X-irradiation by magnetic resonance imaging volumetric analysis.
Congenit Anom (Kyoto)
PUBLISHED: 01-28-2013
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Cerebellar abnormalities in 4-week-old rats with a single whole body X-irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 were examined by magnetic resonance imaging (MRI) volumetry. A 3D T2 W-MRI anatomical sequence with high-spatial resolution at 11.7-tesla was acquired from the fixed rat heads. By MRI volumetry, whole cerebellar volumes decreased dose-dependently. Multiple linear regression analysis revealed that the cortical volume (standardized ?=0.901; P<0.001) was a major explanatory variable for the whole cerebellar volume, whereas both volumes of the white matter and deep cerebellar nuclei also decreased depending on the X-irradiation dose. The present MRI volumetric analysis revealed a dose-related cerebellar cortical hypoplasia by prenatal exposure to X-irradiation on E15.
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Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages.
Nature
PUBLISHED: 01-22-2013
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Macrophages consist of at least two subgroups, M1 and M2 (refs 1-3). Whereas M1 macrophages are proinflammatory and have a central role in host defence against bacterial and viral infections, M2 macrophages are associated with responses to anti-inflammatory reactions, helminth infection, tissue remodelling, fibrosis and tumour progression. Trib1 is an adaptor protein involved in protein degradation by interacting with COP1 ubiquitin ligase. Genome-wide association studies in humans have implicated TRIB1 in lipid metabolism. Here we show that Trib1 is critical for the differentiation of F4/80(+)MR(+) tissue-resident macrophages--that share characteristics with M2 macrophages (which we term M2-like macrophages)--and eosinophils but not for the differentiation of M1 myeloid cells. Trib1 deficiency results in a severe reduction of M2-like macrophages in various organs, including bone marrow, spleen, lung and adipose tissues. Aberrant expression of C/EBP? in Trib1-deficient bone marrow cells is responsible for the defects in macrophage differentiation. Unexpectedly, mice lacking Trib1 in haematopoietic cells show diminished adipose tissue mass accompanied by evidence of increased lipolysis, even when fed a normal diet. Supplementation of M2-like macrophages rescues the pathophysiology, indicating that a lack of these macrophages is the cause of lipolysis. In response to a high-fat diet, mice lacking Trib1 in haematopoietic cells develop hypertriglyceridaemia and insulin resistance, together with increased proinflammatory cytokine gene induction. Collectively, these results demonstrate that Trib1 is critical for adipose tissue maintenance and suppression of metabolic disorders by controlling the differentiation of tissue-resident M2-like macrophages.
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MR contrast in mouse lymph nodes with subcutaneous administration of iron oxide particles: size dependency.
Magn Reson Med Sci
PUBLISHED: 05-27-2011
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We investigated the spatiotemporal changes in signal in draining lymph nodes of mice to ascertain the size-dependent effects of variously sized particles of iron oxide used to enhance magnetic resonance (MR) lymphography.
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Carnosic acid prevents obesity and hepatic steatosis in ob/ob mice.
Hepatol. Res.
PUBLISHED: 01-05-2011
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Aim:? Carnosic acid (CA) inhibits adipogenesis in vitro. The present study evaluated the therapeutic effects of CA in ob/ob mice. Methods:? The experimental animals were given a standard chow diet with or without CA for 5?weeks. Bodyweight gain and food intake were measured during this period. Magnetic resonance imaging analysis, histological examination, serum chemistry analysis and intraperitoneal glucose tolerance test (IPGTT) were all performed. Results:? The mice fed CA experienced significant weight loss and reduced visceral adiposity, in addition to significantly reduced serum triglyceride (TG) and cholesterol levels. Importantly, CA had a dramatic effect on the liver by reducing the hepatic TG content, thus decreasing serum alanine aminotransferase levels. In addition, IPGTT revealed that CA significantly improved glucose tolerance. Conclusion:? These data suggest that CA is a novel therapeutic agent for obesity-related non-alcoholic fatty liver disease.
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Brain temperature measured by using proton MR spectroscopy predicts cerebral hyperperfusion after carotid endarterectomy.
Radiology
PUBLISHED: 08-20-2010
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To determine whether brain temperature measured by using preoperative proton magnetic resonance (MR) spectroscopy could help identify patients at risk for cerebral hyperperfusion after carotid endarterectomy (CEA).
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MR molecular imaging of HER-2 in a murine tumor xenograft by SPIO labeling of anti-HER-2 affibody.
Contrast Media Mol Imaging
PUBLISHED: 02-09-2010
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In vivo molecular imaging is a rapidly growing research area both for basic and clinical science. Non-invasive imaging of in vivo conditions at the molecular level increases understanding of the biological characteristics of normal and diseased tissues without the need for invasive surgical procedures. Among the various imaging modalities, magnetic resonance imaging (MRI) has garnered interest as a molecular imaging modality due to its high spatial resolution. Here, we have demonstrated that the combined use of HER-2 targeting affibody, a small 7 kDa molecule that behaves similarly to antibodies, and superparamagnetic iron oxide (SPIO) can non-invasively image HER-2 expressing cells or tissues both in vitro and in vivo by MRI. This preliminary study demonstrates that affibody-SPIO is a feasible, target-specific contrast agent for in vivo MR molecular imaging.
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Brain temperature measured using proton MR spectroscopy detects cerebral hemodynamic impairment in patients with unilateral chronic major cerebral artery steno-occlusive disease: comparison with positron emission tomography.
Stroke
PUBLISHED: 07-09-2009
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Brain temperature is determined by the balance between heat produced by cerebral energy turnover and heat removed by cerebral blood flow. The purpose of the present study was to investigate whether brain temperature measured noninvasively using proton MR spectroscopy can detect cerebral hemodynamic impairment in patients with unilateral chronic internal carotid or middle cerebral artery occlusive disease when compared with positron emission tomography.
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Impact of surface coating and particle size on the uptake of small and ultrasmall superparamagnetic iron oxide nanoparticles by macrophages.
Int J Nanomedicine
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Magnetic resonance imaging (MRI) using contrast agents like superparamagnetic iron oxide (SPIO) is an extremely versatile technique to diagnose diseases and to monitor treatment. This study tested the relative importance of particle size and surface coating for the optimization of MRI contrast and labeling efficiency of macrophages migrating to remote inflammation sites.
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Multilayered, core/shell nanoprobes based on magnetic ferric oxide particles and quantum dots for multimodality imaging of breast cancer tumors.
Biomaterials
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Multilayered, core/shell nanoprobes (MQQ-probe) based on magnetic nanoparticles (MNPs) and quantum dots (QDs) have been successfully developed for multimodality tumor imaging. This MQQ-probe contains Fe(3)O(4) MNPs, visible-fluorescent QDs (600 nm emission) and near infrared-fluorescent QDs (780 nm emission) in multiple silica layers. The fabrication of the MQQ-probe involves the synthesis of a primer Fe(3)O(4) MNPs/SiO(2) core by a reverse microemulsion method. The MQQ-probe can be used both as a fluorescent probe and a contrast reagent of magnetic resonance imaging. For breast cancer tumor imaging, anti-HER2 (human epidermal growth factor receptor 2) antibody was conjugated to the surface of the MQQ-probe. The specific binding of the antibody conjugated MQQ-probe to the surface of human breast cancer cells (KPL-4) was confirmed by fluorescence microscopy and fluorescence-activated cell sorting analysis in vitro. Due to the high tissue permeability of near-infrared (NIR) light, NIR fluorescence imaging of the tumor mice (KPL-4 cells transplanted) was conducted by using the anti-HER2 antibody conjugated MQQ-probe. In vivo multimodality images of breast tumors were successfully taken by NIR fluorescence and T(2)-weighted magnetic resonance. Antibody conjugated MQQ-probes have great potential to use for multimodality imaging of cancer tumors in vitro and in vivo.
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(19)F MRI monitoring of gene expression in living cells through cell-surface ?-lactamase activity.
Chembiochem
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Magnetic resonance imaging provides important intravital information on deep tissues that cannot be visualized by other methods. Although we had previously developed an off/on switching (19)F MRI probe to monitor reporter enzyme activity on the basis of the paramagnetic relaxation enhancement effect, it was difficult to monitor biological events in living cells because the (19)F MRI probe did not permeate living cell membrane. In this study, we have developed a new (19)F MRI system for monitoring gene expression in living cells by exploiting cell-surface-displayed ?-lactamase and the specifically designed (19)F MRI probe. By using this system, cellular gene expression was successfully detected by (19)F MRI without cell fixation. This imaging strategy shows promise for monitoring in vivo gene expression, and therefore it could lead to useful technologies for the diagnosis and therapy of various diseases.
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Noninvasive measurement of human brain temperature adjacent to arteriovenous malformation using 3.0T magnetic resonance spectroscopy.
Clin Neurol Neurosurg
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The brain temperature at rest is determined by the balance between heat produced by cerebral energy turnover, which is identical to cerebral metabolism, and heat that is removed, primarily by cerebral blood flow. The present study investigated whether brain temperature measured by proton magnetic resonance (MR) spectroscopy can detect cerebral hemodynamic impairment in patients with arteriovenous malformations (AVMs) as shown by single photon emission computed tomography (SPECT).
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High-resolution ex vivo imaging in mouse spinal cord using micro-CT with 11.7T-MRI and myelin staining validation.
Neurosci. Res.
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We investigated the use of micro-CT with contrast agent for the characterization of fixed mouse spinal cord as a means to differentiate between gray and white matter. The spinal cords were soaked in a concentration of nonionic iodinated contrast agent for 14 days. Micro-CT was performed and then compared using 11.7T-MRI images and myelin staining. Soaking the spinal cords in contrast agent resulted in clear differences in signal between the gray and white matter at 3 planes. Micro-CT provides more relevant information on mouse spinal cord GM and WM anatomical structures.
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In vivo diagnostic imaging using micro-CT: sequential and comparative evaluation of rodent models for hepatic/brain ischemia and stroke.
PLoS ONE
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There is an increasing need for animal disease models for pathophysiological research and efficient drug screening. However, one of the technical barriers to the effective use of the models is the difficulty of non-invasive and sequential monitoring of the same animals. Micro-CT is a powerful tool for serial diagnostic imaging of animal models. However, soft tissue contrast resolution, particularly in the brain, is insufficient for detailed analysis, unlike the current applications of CT in the clinical arena. We address the soft tissue contrast resolution issue in this report.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.