Prenatal Irradiation-Induced Hippocampal Abnormalities in Rats Evaluated Using Manganese-Enhanced MRI

The aim of this study was to characterize hippocampal abnormalities in rats after prenatal x-ray irradiation using manganese-enhanced MRI (MEMRI). All radiation-exposed rat brains showed a reduced volume with prominent dilatation of lateral ventricles. Moreover, MEMRI-enhanced areas within the hippocampus were reduced in volumes by approximately 25% of controls, although the entire volume of hippocampus was decreased by approximately 50% of controls. MEMRI signals were enhanced strongly in the hilus and granular layer of the dentate gyrus (DG) and the pyramidal layer and infrapyramidal region of the CA3 region, and moderately along the CA1/2 pyramidal cell layer in the control rats. In radiation-exposed rats, MEMRI signals in the CA1/2 regions disappeared due to disrupting their laminar organization, although strong MEMRI signals were sustained in the DG and CA3 regions. Histopathological examinations in radiation-exposed rats revealed disorganizations of the DG granule cell layer and the CA3 pyramidal cell layer with reducing the cell density. The CA1/2 pyramidal cell layer was disrupted by invading ectopic cell mass. Neural cell adhesion molecule (NCAM)-positive fiber bundles were sustained in radiation-exposed rats, although they distributed aberrantly in the suprapyramidal CA3 region with a slight reduction of NCAM staining. Furthermore, glial components consisted largely by astrocytes and minor by microglia were densely distributed in the DG rather than in other hippocampal regions, and their density radiation-exposed rats. In conclusion, MEMRI signal enhancements could delineate different neuronal and/or glial components among hippocampal regions. We characterized microstructures of the deformed hippocampus as well as its macrostructures in a prenatally radiation-exposed rat model using in vivo MEMRI. The present findings provide advantageous information for detecting nondestructively hippocampal deformations in neurodevelopmental disorders

Cavity flow over a wall-mounted fence

Ventilated cavity flow over a wall mounted fence is experimentally investigated in a cavitation tunnel. The flow over a 2-D fence, attached to the tunnel test section ceiling, is examined for a range of free-stream conditions. The dependence of cavity topology, cavitation number, upstream wall pressure distribution and drag on several parameters, including ventilation rate, fence height based Froude number (Fr), vapour pressure based cavitation number (σv ) and degree of fence immersion in the oncoming wall boundary layer, is investigated. Three different flow regimes are identified throughout the range of cavitation numbers for a particular set of free-stream conditions: shear layer cavitation, fully developed cavity and ‘blocked’ flow. The cavity exhibits a typical re-entrant jet closure and the re-entrant jet intensity is found to be a function of Fr. The high intensity re-entrant jet, present at high Fr, leads to an increase in drag. Drag decreases significantly with an increase in fence immersion in the oncoming boundary layer. Complementary measurements for a naturally cavitating flow are obtained for comparison. A more detailed examination of the topology and unsteady behaviour of ventilated and natural cavity flows over a 2-D wall-mounted fence was undertaken for fixed length cavities with varying free-stream velocity using high-speed and still imaging, X-ray densitometry and dynamic surface pressure measurements in two experimental facilities. Two main unsteady features are observed, the irregular small-scale shedding of structures at the cavity closure and a larger-scale re-entrant jet oscillation. Small-scale cavity break-up was associated with a high-frequency broad-band peak in the wall pressure spectra, found to be governed by the overlying turbulent boundary layer characteristics, similar to observations from single-phase flow over a forward-facing step. A low-frequency peak reflecting the oscillations in size of re-entrant jet, analogous to the ‘flapping’ motion in single-phase flow, was found to be modulated by gravity effects (i.e. a Froude number dependency). Likewise, a significant change in cavity behaviour was observed as the flow underwent transition analogous to the transition from sub- to super- critical regime in open-channel flow. A companion numerical study is undertaken to provide additional insight into particular flow features such as the separated flow region upstream of the fence and to assess the influence of blockage. An implicit unsteady compressible solver is used with a RANS k − ω SST turbulence model and VOF approach to capture the cavity interface. The numerical results are found to compare reasonably with the experimental data, additionally showing a significant influence of blockage on the studied flow. Along with the 2-D fence, a 3-D wall mounted fence, spanning nominally a quarter of the tunnel test section, is investigated. The impact that 3-D effects have on the cavity topology and the relations between the parameters characterizing the flow is observed. The most notable effect of 3-D flow is a change in the closure mechanism observed for low Fr. Following a decrease in Fr the closure topology transforms from a well defined single re-entrant jet regime, through a phase of gradual re-entrant jet widening to a completely split re-entrant jet separated into two branches. Generally, the 2-D and 3-D flows exhibited similar trends with any significant difference attributable to differing levels of flow confinement due to lesser width of 3-D fence

Forprófun á íslenskri útgáfu Sjálfsmatskvarða Becks fyrir börn og unglinga

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenGerð var forprófun á Sjálfsmatskvörðum Becks fyrir börn á aldrinum 7-14 ára til þess að athuga próffræðilega eiginleika íslenskrar útgáfu af kvörðunum. Þátttakendur voru 293 úr 12 grunnskólum í Reykjavík. Próffræðilegir eiginleikar reyndust sambærilegir við erlendar rannsóknir. Innri áreiðanleiki var hár og fylgni atriða við heildarskor hvers kvarða viðunandi. Samleitni kvarða var athugað með þáttagreiningu og niðurstöður sýndu að þunglyndi, kvíði og hegðunarvandi voru einsleitir kvarðar en atriði sjálfsmyndar og reiði mynduðu tvo þætti. Gerð var þáttagreining á öllum 100 atriðum kvarðanna. Niðurstöður sýndu þrjá þætti sem skýrðu 38,6% dreifingar. Fyrsti þáttur samanstóð af þunglyndi, reiði og kvíða. Á annan þátt lögðust þrjú atriði reiði og 18 atriði hegðunarvanda og á þriðja þátt lögðust 18 atriði sjálfsmyndar. Há fylgni reyndist vera milli kvíða, þunglyndis og reiði en það er sambærilegt niðurstöðum erlendra rannsókna. Réttmæti kvarðanna var athugað með þremur spurningum um líðan í skóla og stríðni. Spurning um líðan í frímínútum hafði hæstu fylgni við þunglyndi sem bendir til þess að nemendur sem sýna þunglyndiseinkenni líður frekar illa í frímínútum. Spurning um líðan í kennslustundum hafði hæstu fylgni við hegðunarvanda og reiði og loks var hæst fylgni milli hegðunarvanda og stríðni. Enginn kynja- eða aldursmunur kom fram á kvörðum fyrir þunglyndi, reiði og kvíða. Hins vegar var meðaltal eldri hóps og drengja hærra á kvarða fyrir hegðunarvanda en hjá yngri hóp og stúlkum. Meðaltal á sjálfsmyndarkvarða var lægra í hópi eldri þáttakenda og meiri munur var á milli yngri og eldri stúlkna sem bendir til að sjálfsmynd verði neikvæðari á unglingsárum og sérstaklega hjá stúlkum. Próffræðilegir eiginleikar reyndust í megindráttum góðir en safna þarf meiri gögnum um áreiðanleika og réttmæti kvarðanna áður en hægt er að mæla með almennri notkun þeirra hér á landi.A pilot study of the Beck Youth Inventories (BYI) for children 7-14 years was undertaken to evaluate the psychometric properties of the Icelandic version. Participants were 293 from 12 elementary schools in Reykjavík. Psychometric properties revealed similar findings as other studies abroad have revealed. The internal consistency reliability was high and item total correlation acceptable. A principal axis factor analysis was conducted to evaluate the homogeneity of the BYI. Depression, anxiety and disruptive behavior were unidimensional but self-concept and anger revealed two factors. Additionally a principal axis factor analysis of all items of the inventories indicated three factors explaining 38,6% of variance. Items of depression, anxiety and anger loaded on the first factor. Disruptive behavior and 3 items of anger loaded on the second factor. Items of self-concept loaded on the third factor. Depression, anxiety and anger correlated highly, consistent with studies abroad and the factor analysis results. The scales´ validity was evaluated by three items assesing emotional well being in school and teasing other pupils. The highest correlation was between emotional well being in school breaks and depression, emotional well being in classrooms and disruptive behavior and anger, and between teasing other pupils and disruptive behavior. No significant age and gender differences were found on depression, anxiety and anger. Mean score for boys was higher than for girls on disruptive behavior and older students scored higher than younger students. Older students´ mean score was lower than younger students´ mean on self-concept and this difference was greater for girls than boys. Psychometric properties were good, but additonal studies need to be undertaken on the scales´ reliability and validity before we can recommend general use of the scales for clinical purposes in Iceland

Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics

Rumiana Bakalova1, Zhivko Zhelev1, Daisuke Kokuryo1, Lubomir Spasov2, Ichio Aoki1, Tsuneo Saga11Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; 2Medical Faculty, Sofia University, Sofia, BulgariaBackground: One of the most attractive properties of quantum dots is their potential to extend the opportunities for fluorescent and multimodal imaging in vivo. The aim of the present study was to clarify whether the composition and structure of organic coating of nanoparticles are crucial for their application in vivo.Methods: We compared quantum dots coated with non-crosslinked amino-functionalized polyamidoamine (PAMAM) dendrimers, quantum dots encapsulated in crosslinked carboxyl-functionalized PAMAM dendrimers, and silica-shelled amino-functionalized quantum dots. A multimodal fluorescent and paramagnetic quantum dot probe was also developed and analyzed. The probes were applied intravenously in anesthetized animals for visualization of brain vasculature using two-photon excited fluorescent microscopy and visualization of tumors using fluorescent IVIS® imaging (Caliper Life Sciences, Hopkinton, MA) and magnetic resonance imaging.Results: Quantum dots coated with non-crosslinked dendrimers were cytotoxic. They induced side effects in vivo, including vasodilatation with a decrease in mean arterial blood pressure and heart rate. The quantum dots penetrated the vessels, which caused the quality of fluorescent imaging to deteriorate. Quantum dots encapsulated in crosslinked dendrimers had low cytotoxicity and were biocompatible. In concentrations <0.3 nmol quantum dots/kg bodyweight, these nanoparticles did not affect blood pressure and heart rate, and did not induce vasodilatation or vasoconstriction. PEGylation (PEG [polyethylene glycol]) was an indispensable step in development of a quantum dot probe for in vivo imaging, based on silica-shelled quantum dots. The non-PEGylated silica-shelled quantum dots possessed low colloidal stability in high-salt physiological fluids, accompanied by rapid aggregation in vivo. The conjugation of silica-shelled quantum dots with PEG1100 increased their stability and half-life in the circulation without significant enhancement of their size. In concentrations <2.5 nmol/kg bodyweight, these quantum dots did not affect the main physiological variables. It was possible to visualize capillaries, which makes this quantum dot probe appropriate for investigation of mediators of vasoconstriction, vasodilatation, and brain circulation in intact animals in vivo. The multimodal silica-shelled quantum dots allowed visualization of tumor tissue in an early stage of its development, using magnetic resonance imaging.Conclusion: The present study shows that the type and structure of organic/bioorganic shells of quantum dots determine their biocompatibility and are crucial for their application in imaging in vivo, due to the effects of the shell on the following properties: colloidal stability, solubility in physiological fluids, influence of the basic physiological parameters, and cytotoxicity.Keywords: quantum dot, organic shell, biocompatibility, in vivo imaging, two-photon excited fluorescent microscopy, magnetic resonance imagin

Trial of Brain Redox Imaging and Estimation of Radiation-Induced Redox Change in Mouse Brain

The in vivo T1-weighted contrasting abilities and signal decay behaviors of several nitroxyl contrast agents, which have been used as redox responsive contrast agents in several magnetic resonance-based imaging modalities, in mouse brain were compared. In addition, daily variations of redox behavior in mouse brain after irradiation of X-ray or carbon-ion beams (C-beam) were tried to estimate based on the in vivo reduction rate of amphiphilic nitroxyl contrast agents.Injection solutions of five types of five-membered-ring nitroxyl contrast agents, i.e. 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP), 3-methoxy-carbonyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (MCP), acetoxymethyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-carboxylate (CxP-AM), and 4-(N-methylpiperidine)-2,2,5,5-tetramethylpyrroline-N-oxyl (23c), and a six-membered-ring nitroxyl contrast agent, i.e. 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), were prepared. The nitroxyl contrast agent was i.v. injected to a mouse through tail vein. Then, the distributions and pharmacokinetics of nitroxyl contrast agents were compared based on the time course of T1-weighted MRI. The MRI experiments using CMP or TEMPOL were repeated for mice irradiated by X-ray or C-beam to their head on several deferent timings, i.e. 1, 2, 4, 8 day(s) after irradiation. C-beam was irradiated at Heavy-Ion Medical Accelerator in Chiba (HIMAC, National Institute of Radiological Sciences/ National Institutes for Quantum and Radiological Science and Technology).The blood-brain-barrier (BBB)-impermeable CxP could not be distributed in the brain. The slightly lipophilic CmP showed slight distribution only in the ventricle, but not in the medulla and cortex. The amphiphilic MCP and TEMPOL had good initial uniform distribution in the brain and showed typical 2-phase signal decay profiles. A brain-seeking nitroxyl probe, CxP-AM, showed an accumulating phase, and then its accumulation was maintained in the medulla and ventricle regions, but not in the cortex. The lipophilic 23c was well distributed in the cortex and medulla, but slightly in the ventricle, and showed relatively rapid linear signal decay.Decay rates of MCP in mouse brain after irradiation of 8 Gy X-ray, 8 Gy C-beam or 16 Gy C-beams did not show marked clear changes, however relatively little decreasing were observed at day 1 and day 2 after irradiation. Decay rates of TEMPOL was increased 1 after irradiation then gradually recovered to the control level. MCP and TEMPOL showed opposite responses but the timing of redox change may be 1 or 2 days after irradiation.Nitroxyl contrast agents equipped with a suitable lipophilic substitution group could be BBB-permeable functional contrast agents. MR redox imaging, which can estimate not only the redox characteristics but also the detailed distribution of the contrast agents, is a good candidate for a theranostic tool. Irradiation of ionized radiation to head could cause alternation of redox status in the brain. Detail of redox mechanisms were still in progress.第7回国際放射線神経生物学会大

Nitroxyl Radical as a Theranostic Contrast Agent in Magnetic Resonance Redox Imaging

Significance: In vivo assessment of paramagnetic and diamagnetic conversions of nitroxyl radicals based on cyclic redox mechanism can be an index of tissue redox status. The redox mechanism of nitroxyl radicals, which enables their use as a normal tissue-selective radioprotector, is seen as being attractive on planning radiation therapy. Recent Advances: In vivo redox imaging using nitroxyl radicals as redox-sensitive contrast agents has been developed to assess tissue redox status. Chemical and biological behaviors depending on chemical structures of nitroxyl radical compounds have been understood in detail. Polymer types of nitroxyl radical contrast agents and/or nitroxyl radical-labeled drugs were designed for approaching theranostics. Critical Issues: Nitroxyl radicals as magnetic resonance imaging (MRI) contrast agents have several advantages compared with those used in electron paramagnetic resonance (EPR) imaging, while support by EPR spectroscopy is important to understand information from MRI. Redox-sensitive paramagnetic contrast agents having a medicinal benefit, that is, nitroxyl-labeled drug, have been developed and proposed. Future Directions: A development of suitable nitroxyl contrast agent for translational theranostic applications with high reaction specificity and low normal tissue toxicity is under progress. Nitroxyl radicals as redox-sensitive magnetic resonance contrast agents can be a useful tool to detect an abnormal tissue redox status such as disordered oxidative stress

Chemogenetic sensory fMRI reveals behaviorally relevant bidirectional changes in primate somatosensory network

手と足の感覚は、実は脳の中でつながっていた --脳障害による活動変化の広がりを見ることで常識を覆す発見、脳機能・疾患機序の理解へ前進--. 京都大学プレスリリース. 2021-10-21.Concurrent genetic neuromodulation and functional magnetic resonance imaging (fMRI) in primates has provided a valuable opportunity to assess the modified brain-wide operation in the resting state. However, its application to link the network operation with behavior still remains challenging. Here, we combined chemogenetic silencing of the primary somatosensory cortex (SI) with tactile fMRI and related behaviors in macaques. Focal chemogenetic silencing of functionally identified SI hand region impaired grasping behavior. The same silencing also attenuated hand stimulation-evoked fMRI signal at both the local silencing site and the anatomically and/or functionally connected downstream grasping network, suggesting altered network operation underlying the induced behavioral impairment. Furthermore, the hand region silencing unexpectedly disinhibited foot representation with accompanying behavioral hypersensitization. These results demonstrate that focal chemogenetic silencing with sensory fMRI in macaques unveils bidirectional network changes to generate multifaceted behavioral impairments, thereby opening a pivotal window toward elucidating the causal network operation underpinning higher brain functions in primates

Magnetization Transfer Prepared Gradient Echo MRI for CEST Imaging

Chemical exchange saturation transfer (CEST) is an emerging MRI contrast mechanism that is capable of noninvasively imaging dilute CEST agents and local properties such as pH and temperature, augmenting the routine MRI methods. However, the routine CEST MRI includes a long RF saturation pulse followed by fast image readout, which is associated with high specific absorption rate and limited spatial resolution. In addition, echo planar imaging (EPI)-based fast image readout is prone to image distortion, particularly severe at high field. To address these limitations, we evaluated magnetization transfer (MT) prepared gradient echo (GRE) MRI for CEST imaging. We proved the feasibility using numerical simulations and experiments in vitro and in vivo. Then we optimized the sequence by serially evaluating the effects of the number of saturation steps, MT saturation power (B1), GRE readout flip angle (FA), and repetition time (TR) upon the CEST MRI, and further demonstrated the endogenous amide proton CEST imaging in rats brains (n = 5) that underwent permanent middle cerebral artery occlusion. The CEST images can identify ischemic lesions in the first 3 hours after occlusion. In summary, our study demonstrated that the readily available MT-prepared GRE MRI, if optimized, is CEST-sensitive and remains promising for translational CEST imaging

MRマイクロイメージングとガドリニウム-デンドロン修飾ナノリポソーム造影剤を用いた3D微小血管およびナノ粒子分布の腫瘍内評価

The enhanced permeability and retention (EPR) effect is variable depending on nanoparticle properties and tumor/vessel conditions. Thus, intratumoral evaluations of the vasculature and nanoparticle distribution are important for predicting the therapeutic efficacy and the intractability of tumors. We aimed to develop a tumor vasculature evaluation method and high-resolution nanoparticle delivery imaging using magnetic resonance (MR) micro-imaging technology with a gadolinium (Gd)-dendron assembled liposomal contrast agent. Using the Gd-liposome and a cryogenic receiving coil, we achieved 50-μm isotropic MR angiography with clear visualization of tumor micro-vessel structure. The Gd-liposome-enhanced MR micro-imaging revealed differences in the vascular structures between Colon26- and SU-DHL6-grafted mice models. The vessel volumes and diameters measured for both tumors were significantly correlated with histological observations. The MR micro-imaging methods facilitate the evaluation of intratumoral vascularization patterns, the quantitative assessment of vascular-properties that alter tumor malignancy, particle retentivity, and the effects of treatment

Abnormal axon guidance signals and reduced interhemispheric connection via anterior commissure in neonates of marmoset ASD model

In autism spectrum disorder (ASD), disrupted functional and structural connectivity in the social brain has been suggested as the core biological mechanism underlying the social recognition deficits of this neurodevelopmental disorder. In this study, we aimed to identify genetic and neurostructural abnormalities at birth in a non-human primate model of ASD, the common marmoset with maternal exposure to valproic acid (VPA), which has been reported to display social recognition deficit in adulthood. Using a comprehensive gene expression analysis, we found that 20 genes were significantly downregulated in VPA-exposed neonates. Of these, Frizzled3 (FZD3) and PIK3CA were identified in an axon guidance signaling pathway. FZD3 is essential for the normal development of the anterior commissure (AC) and corpus callosum (CC); hence, we performed diffusion tensor magnetic resonance imaging with a 7-Tesla scanner to measure the midsagittal sizes of these structures. We found that the AC size in VPA-exposed neonates was significantly smaller than that in age-matched controls, while the CC size did not differ. These results suggest that downregulation of the genes related to axon guidance and decreased AC size in neonatal primates may be linked to social brain dysfunctions that can happen later in life