Enhancing Badminton Game Analysis: An Approach to Shot Refinement via a Fusion of Shuttlecock Tracking and Hit Detection from Monocular Camera.

Extracting the flight trajectory of the shuttlecock in a single turn in badminton games is important for automated sports analytics. This study proposes a novel method to extract shots in badminton games from a monocular camera. First, TrackNet, a deep neural network designed for tracking small objects, is used to extract the flight trajectory of the shuttlecock. Second, the YOLOv7 model is used to identify whether the player is swinging. As both TrackNet and YOLOv7 may have detection misses and false detections, this study proposes a shot refinement algorithm to obtain the correct hitting moment. By doing so, we can extract shots in rallies and classify the type of shots. Our proposed method achieves an accuracy of 89.7%, a recall rate of 91.3%, and an F1 rate of 90.5% in 69 matches, with 1582 rallies of the Badminton World Federation (BWF) match videos. This is a significant improvement compared to the use of TrackNet alone, which yields 58.8% accuracy, 93.6% recall, and 72.3% F1 score. Furthermore, the accuracy of shot type classification at three different thresholds is 72.1%, 65.4%, and 54.1%. These results are superior to those of TrackNet, demonstrating that our method effectively recognizes different shot types. The experimental results demonstrate the feasibility and validity of the proposed method.

Potential of stem cell therapy in intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a common disease associated with high mortality and morbidity. The treatment of patients with ICH includes medical and surgical interventions. New areas of surgical intervention have been focused on the evacuation of hematoma through minimally invasive neurosurgery. In contrast, there have been no significant advances in the development of medical interventions for functional recovery after ICH. Stem cells exert multiple therapeutic functions and have emerged as a promising treatment strategy. Herein, we summarized the pathophysiology of ICH and its treatment targets, and we introduced the therapeutic mechanisms of stem cells (e.g. neutrotrophy and neuroregeneration). Moreover, we reviewed and summarized the experimental designs of the preclinical studies, including the types of cells and the timing and routes of stem cell administration. We further listed and reviewed the completed/published and ongoing clinical trials supporting the safety and efficacy of stem cell therapy in ICH. The limitations of translating preclinical studies into clinical trials and the objectives of future studies were discussed. In conclusion, current literatures showed that stem cell therapy is a promising treatment in ICH and further translation research on judiciously selected group of patients is warranted before it can be extensively applied in clinical practice.

Aberrant astrocytes impair vascular reactivity in Huntington disease.

OBJECTIVE: Huntington disease (HD) is an inherited neurodegenerative disease caused by the mutant huntingtin gene (mHTT), which harbors expanded CAG repeats. We previously reported that the brain vessel density is higher in mice and patients with HD than in controls. The present study determines whether vascular function is altered in HD and characterizes the underlying mechanism. METHODS: The brain vessel density and vascular reactivity (VR) to carbogen challenge of HD mice were monitored by 3D ΔR2 -mMRA and blood oxygenation level-dependent (BOLD)/flow-sensitive alternating inversion recovery (FAIR) magnetic resonance imaging (MRI), respectively. The amount of vascular endothelial growth factor (VEGF)-A and the pericyte coverage were determined by immunohistochemistry and enzyme-linked immunosorbent assay in human and mouse brain sections, primary mouse astrocytes and pericytes, and human astrocytes derived from induced pluripotent stem cells. RESULTS: Expression of mHTT in astrocytes and neurons is sufficient to increase the brain vessel density in HD mice. BOLD and FAIR MRI revealed gradually impaired VR to carbogen in HD mice. Astrocytes from HD mice and patients contained more VEGF-A, which triggers proliferation of endothelial cells and may be responsible for the augmented neurovascular changes. Moreover, an astrocytic inflammatory response, which reduces the survival of pericytes through an IκB kinase-dependent pathway, mediates the low pericyte coverage of blood vessels in HD brains. INTERPRETATION: Our findings suggest that the inflammation-prone HD astrocytes provide less pericyte coverage by promoting angiogenesis and reducing the number of pericytes and that these changes can explain the inferior VR in HD mice. The resultant impaired VR might hinder cerebral hemodynamics and increase brain atrophy during HD progression.

Negative cerebral blood volume fMRI response coupled with Ca²âº-dependent brain activity in a dopaminergic road map of nociception.

Decreased cerebral blood volume/flow (CBV/CBF) contributes to negative blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signals. But it is still strongly debated whether these negative BOLD or CBV/CBF signals are indicative of decreased or increased neuronal activity. The fidelity of Ca(2+) signals in reflecting neuronal excitation is well documented. However, the roles of Ca(2+) signals and Ca(2+)-dependent activity in negative fMRI signals have never been explored; an understanding of this is essential to unraveling the underlying mechanisms and correctly interpreting the hemodynamic response of interest. The present study utilized a nociception-induced negative CBV fMRI response as a model. Ca(2+) signals were investigated in vivo using Mn(2+)-enhanced MRI (MEMRI), and the downstream Ca(2+)-dependent signaling was investigated using phosphorylated cAMP response-element-binding (pCREB) immunohistology. The results showed that nociceptive stimulation led to (1) striatal CBV decreases, (2) Ca(2+) increases via the nigrostriatal pathway, and (3) substantial expression of pCREB in substantia nigra dopaminergic neurons and striatal neurons. Interestingly, the striatal negative fMRI response was abolished by blocking substantia nigra activity but was not affected by blocking the striatal activity. This suggests the importance of input activity other than output in triggering the negative CBV signals. These findings indicate that the striatal negative CBV fMRI signals are associated with Ca(2+) increases and Ca(2+)-dependent signaling along the nigrostriatal pathway. The obtained data reveal a new brain road map in response to nociceptive stimulation of hemodynamic changes in association with Ca(2+) signals within the dopaminergic system.

Visualization of rodent brain tumor angiogenesis and effects of antiangiogenic treatment using 3D ΔR2-µMRA.

Understanding of structural and functional characteristics of the vascular microenvironment in gliomas and the impact of antiangiogenic treatments is essential for developing better therapeutic strategies. Although a number of methods exist in which this process can be studied experimentally, no single noninvasive test has the capacity to provide information concerning both microvascular function and morphology. The purpose of present study is to demonstrate the feasibility of using a novel three-dimensional ΔR2-based microscopic magnetic resonance angiography (3D ΔR2-µMRA) technique for longitudinal imaging of tumor angiogenesis and monitoring the effects of antiangiogenic treatment in rodent brain tumor models. Using 3D ΔR2-µMRA, a generally consistent early pattern of vascular development in gliomas was revealed, in which a single feeding vessel was visualized first (arteriogenesis), followed by sprouting angiogenesis. Considerable variability of the tumor-associated vasculature was then noted at later stages of tumor evolution. ΔR2-µMRA revealed that anti-vascular endothelial growth factor treatment induced a rapid and significant alteration of the intratumoral angiogenic phenotype. In summary, 3D ΔR2-µMRA enables high-resolution visualization of tumor-associated vessels while simultaneously providing functional information on the tumor microvasculature. It can serve as a useful tool for monitoring both the temporal evolution of tumor angiogenesis and the impact of antiangiogenic therapies.

Gelatin-Based Hydrogel for Three-Dimensional Neuron Culture Application.

Gelatin is a biocompatible biomaterial composed of a variety of amino acids that provides a possibility to regulate the interaction between cationic amino acids and neural cells. Based on our first finding that the neuron viability was improved as the lysine on the gelatin was converted into a guanidine structure, a three-dimensional (3D) gelatin hydrogel composed of gelatin and poly(allylguanidine) (PAG) was prepared to investigate neural cell behaviors. As expected, improved neuron viability, neurite outgrowth, synaptogenesis, and inhibited glial cell growth were simultaneously observed in the gelatin cross-linked with the PAG hydrogel (G-PAG) but not in the gelatin hydrogel cross-linked with poly-d-lysine (PDL) or polyethylenimine (PEI). In addition, in vivo tests also illustrated that G-PAG could provide an environment for neural culture, with improving neuron viability and neurite outgrowth. Several hydrogel characteristics-including the swelling ratio, mechanical strength, and electric property-that theoretically can influence neural cell response showed no significant difference among them. Therefore, the guanidine structure of PAG was proposed to determine the behaviors of neural cells within the gelatin-polycation hydrogels, and we proposed that the neural cell behavior is regulated by a specific gelatin-neuron relationship. The information found in this study provides a concept to design and modify gelatin-based hydrogels for neural tissue engineering applications.

Brain-derived neurotrophic factor contributes to neurogenesis after intracerebral hemorrhage: a rodent model and human study.

Background and purpose: Intracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF). Methods: A rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA). Results: In the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume. Conclusion: BDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH.

Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse.

BACKGROUND: The blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). However, this barrier prevents the safe transmission of beneficial drugs from the blood to the CSF and thus the spinal cord and brain, limiting their effectiveness in treating a variety of CNS diseases. METHODS: This study demonstrates a method on SD rats for reversible and site-specific opening of the BCSFB via a noninvasive, low-energy focused shockwave (FSW) pulse (energy flux density 0.03 mJ/mm2) with SonoVue microbubbles (2 × 106 MBs/kg), posing a low risk of injury. RESULTS: By opening the BCSFB, the concentrations of certain CNS-impermeable indicators (70 kDa Evans blue and 500 kDa FITC-dextran) and drugs (penicillin G, doxorubicin, and bevacizumab) could be significantly elevated in the CSF around both the brain and the spinal cord. Moreover, glioblastoma model rats treated by doxorubicin with this FSW-induced BCSFB (FSW-BCSFB) opening technique also survived significantly longer than untreated controls. CONCLUSION: This is the first study to demonstrate and validate a method for noninvasively and selectively opening the BCSFB to enhance drug delivery into CSF circulation. Potential applications may include treatments for neurodegenerative diseases, CNS infections, brain tumors, and leptomeningeal carcinomatosis.

Longitudinal study of tumor-associated macrophages during tumor expansion using MRI.

MRI is being used increasingly for the noninvasive longitudinal monitoring of cellular processes in various pathophysiological conditions. Macrophages are the main stromal cells in neoplasms and have been suggested to be the major cell type ingesting superparamagnetic iron oxide (SPIO) nanoparticles. However, no MRI study has described longitudinally the presence of tumor-associated macrophages (TAMs) during tumorigenesis with histological confirmation. To address this, we injected SPIO nanoparticles into the circulation of tumor-bearing mice and used MRI and post-mortem histology to monitor TAMs at different time points. The MRI results demonstrated that TAMs, as hypointense signals, appeared continually with the expansion of the tumor. The histological findings also revealed that SPIO-labeled TAMs tended to deposit closer to the vessel lumen with time prior to rapid tumor growth. The present study demonstrates the potential of using MRI to assess longitudinally TAM accumulation during tumorigenesis, and provides the first in vivo insight into the topographical arrangement of TAMs in relation to the progression of tumors. In vivo monitoring of the presence of TAMs could be useful for the development of tumor treatments that target TAM functions.

An anti-inflammatory gelatin hemostatic agent with biodegradable polyurethane nanoparticles for vulnerable brain tissue.

Hemostasis plays a fundamental and critical role in all surgical procedures. However, the currently used topical hemostatic agents may at times undesirably induce inflammation, infection, and foreign body reaction and hamper the healing process. This may be serious in the central nervous system (CNS), especially for some neurosurgical diseases which have ongoing inflammation causing secondary brain injury. This study was aimed to develop a hemostatic agent with anti-inflammatory property by incorporating carboxyl-functionalized biodegradable polyurethane nanoparticles (PU NPs) and to evaluate its functionality using a rat neurosurgical model. PU NPs are specially-designed anti-inflammatory nanoparticles and absorbed by a commercially available hemostatic gelatin powder (Spongostan™). Then, the gelatin was implanted to the injured rat cortex and released anti-inflammatory PU NPs. The time to hemostasis, the cerebral edema formation, and the brain's immune responses were examined. The outcomes showed that PU NP-contained gelatin attenuated the brain edema, suppressed the gene expression levels of pro-inflammatory M1 biomarkers (e.g., IL-1ß level to be about 25%), elevated the gene expression levels of anti-inflammatory M2 biomarkers (e.g., IL-10 level to be about 220%), and reduced the activation of inflammatory cells in the implanted site, compared with the conventional gelatin. Moreover, PU NP-contained gelatin increased the gene expression level of neurotrophic factor BDNF by nearly 3-folds. We concluded that the PU NP-contained hemostatic agents are anti-inflammatory with neuroprotective potential in vivo. This new hemostatic agent will be useful for surgery involving vulnerable tissue or organ (e.g., CNS) and also for diseases such as stroke, traumatic brain injury, and neurodegenerative diseases.

Poly(allylguanidine)-Coated Surfaces Regulate TGF-ß in Glioblastoma Cells to Induce Apoptosis via NF-κB Pathway Activation.

Polycationic biomaterials are currently widely applied in neuronal cell cultures to promote cell adhesion and viability. However, polycations generally have cytotoxic properties that limit their application in the field of biomaterials. In this study, we examined the use of a novel polycation poly(allylguanidine) (PAG), which contains a guanidine group in the side chain and a structure similar to poly(allylamine hydrochloride) (PAH), an example of another commonly used polycation. Our findings showed that exposure to PAG induced apoptosis in glioblastoma (GBM) cells, while exposure to PAH induced necrosis. Compared to control groups, the PAG coating significantly limited the proliferation of GBM8901 in vitro and in vivo. Furthermore, GBM8901 cells exposed to the PAG coating exhibited increased levels of phospho-p65 and phosphor-IκB, implying that GBM8901 cells underwent apoptotic cell death via the NF-κB pathway by the regulation of TGF-ß. This result was further confirmed to be consistent with the experimental results from western blot protein analysis and apoptosis/necrosis assays. These findings indicate that the polycation PAG has the potential to not only suppress the proliferation of GBM8901 cancer cells but also improve the neural viability and promote the differentiation of neural stem/precursor cells into mature neurons. In conclusion, biomaterials such as PAG act as extremely potent options for applications in the treatment of pathological conditions such as brain cancer.

Semi-Interpenetrating Polymer Network of Hyaluronan and Chitosan Self-Healing Hydrogels for Central Nervous System Repair.

The repair of the central nervous system (CNS) is a major challenge because of the difficulty for neurons or axons to regenerate after damages. Injectable hydrogels have been developed to deliver drugs or cells for neural repair, but these hydrogels usually require conditional stimuli or additional catalysts to control the gelling process. Self-healing hydrogels, which can be injected locally to fill tissue defects after stable gelation, are attractive candidates for CNS treatment. In the current study, the self-healing hydrogel with a semi-interpenetrating polymer network (SIPN) was prepared by incorporation of hyaluronan (HA) into the chitosan-based self-healing hydrogel. The addition of HA allowed the hydrogel to pass through a narrow needle much more easily. As the HA content increased, the hydrogel showed a more packed nanostructure and a more porous microstructure verified by coherent small-angle X-ray scattering and scanning electron microscopy. The unique structure of SIPN hydrogel enhanced the spreading, migration, proliferation, and differentiation of encapsulated neural stem cells in vitro. Compared to the pristine chitosan-based self-healing hydrogel, the SIPN hydrogel showed better biocompatibility, CNS injury repair, and functional recovery evaluated by the traumatic brain injury zebrafish model and intracerebral hemorrhage rat model. We proposed that the SIPN of HA and chitosan self-healing hydrogel allowed an adaptable environment for cell spreading and migration and had the potential as an injectable defect support for CNS repair.

All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan.

BACKGROUND: Both end-stage renal disease and chronic kidney disease are increasing worldwide; however, the full effect of chronic kidney disease is unknown because mortality risks for all five stages are unavailable. We assessed prevalence and mortality risks for all stages of chronic kidney disease and quantified its attributable mortality in Taiwan. METHODS: The cohort consisted of 462 293 individuals aged older than 20 years who participated in a standard medical screening programme since 1994. As of Dec 31, 2006, we identified 14 436 deaths. Chronic kidney disease was determined by glomerular filtration rate and urinary protein. We estimated national prevalence in Taiwan from the cohort by adjusting age and educational levels. Hazard ratios (HRs) were calculated with Cox proportionate hazards model. We calculated mortality attributable to chronic kidney disease for national population and for low socioeconomic status. FINDINGS: The national prevalence of chronic kidney disease was 11.93% (95% CI 11.66-12.28), but only 3.54% (3.37-3.68) of participants in the cohort were aware of their disorder. Prevalence was substantially higher in the group with low socioeconomic status than in the high status group (19.87% [19.84-19.91] vs 7.33% [7.31-7.35]). 56 977 (12%) of cohort participants had chronic kidney disease; those with disease had 83% higher mortality for all cause (HR 1.83 [1.73-1.93]) and 100% higher for cardiovascular diseases (2.00 [1.78-2.25]), in a cohort that was observed for 13 years with median follow-up of 7.5 years (IQR 4.0-10.1). 10.3% (95% CI 9.57-11.03) of deaths in the entire population were attributable to chronic kidney disease, but 17.5% (16.27-18.67) of deaths in the low socioeconomic status population. 2350 (39%) deaths occurred before 65 years of age in those with chronic kidney disease. Regular users of Chinese herbal medicines had a 20% (odds ratio 1.20 [1.16-1.24]) increased risk of developing chronic kidney disease. INTERPRETATION: The high prevalence of chronic kidney disease and its associated all-cause mortality, especially in people with low socioeconomic status, make reduction of this disorder a public-health priority. Promotion of its recognition through the general public knowing their glomerular filtration rate and testing their urine is crucial to reduce premature deaths from all causes and to attenuate this global epidemic.

fMRI indicates cortical activation through TRPV1 modulation during acute gouty attacks.

Gout is one of the most painful disease conditions. The central mechanism of pain processing in this condition remains elusive. Cerebral blood volume (CBV) responses are faithful correlates of brain activity changes; the application of CBV-weighted functional magnetic resonance imaging (fMRI) may shed light on the issue of interest. Transient receptor potential vanilloid 1 (TRPV1) is a critical ion channel expressed both peripherally in nociceptors and centrally in the brain. Whether TRPV1 plays a critical role in gout pain was also explored. Results showed that, in rats with gouty arthritis, noxious stimulation induced CBV increases in the primary somatosensory cortex and thalamus. These increases were correlated with up-regulated TRPV1 protein expression and pain behavior. Selective blockage of central TRPV1 channel activity by intrathecal administration of AMG9810 reversed the induced pain, and abolished the induced CBV increase in thalamocortical regions. The findings support that TRPV1 activation in the central pain pathway is crucial to the augmentation of pain in gouty conditions. This new information supports the development of TRPV1-based drugs for treating gout pain, while fMRI can be useful for repeated evaluation of brain activity changes induced by gout.

Cavitation-induced traumatic cerebral contusion and intracerebral hemorrhage in the rat brain by using an off-the-shelf clinical shockwave device.

Traumatic cerebral contusion and intracerebral hemorrhages (ICH) commonly result from traumatic brain injury and are associated with high morbidity and mortality rates. Current animal models require craniotomy and provide less control over injury severity. This study proposes a highly reproducible and controllable traumatic contusion and ICH model using non-invasive extracorporeal shockwaves (ESWs). Rat heads were exposed to ESWs generated by an off-the-shelf clinical device plus intravenous injection of microbubbles to enhance the cavitation effect for non-invasive induction of injury. Results indicate that injury severity can be effectively adjusted by using different ESW parameters. Moreover, the location or depth of injury can be purposefully determined by changing the focus of the concave ESW probe. Traumatic contusion and ICH were confirmed by H&E staining. Interestingly, the numbers of TUNEL-positive cells (apoptotic cell death) peaked one day after ESW exposure, while Iba1-positive cells (reactive microglia) and GFAP-positive cells (astrogliosis) respectively peaked seven and fourteen days after exposure. Cytokine assay showed significantly increased expressions of IL-1ß, IL-6, and TNF-α. The extent of brain edema was characterized with magnetic resonance imaging. Conclusively, the proposed non-invasive and highly reproducible preclinical model effectively simulates the mechanism of closed head injury and provides focused traumatic contusion and ICH.

Neuronal dysfunction of a long projecting multisynaptic pathway in response to methamphetamine using manganese-enhanced MRI.

RATIONALE: Manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) is an emerging in vivo MR approach for pharmacological research. One new application of MEMRI in this area is to characterize functional changes of a specific neural circuit that is essential to the central effects of a drug challenge. OBJECTIVES: To develop and validate such use of MEMRI in neuropharmacology, the current study applied MEMRI to visualize functional changes within a multisynaptic pathway originating from fasciculus retroflexus (FR) that is central to a commonly abused psychostimulant, methamphetamine (MA). METHODS: Twelve rats were injected intraperitoneally with MA (10 mg/kg) or saline every 2 h for a total of four injections. After 6 days, Mn2+ was injected into the habenular nucleus (FR origin) of all animals, and MEMRI was repeatedly performed at certain points in time over 48 h. The evolution of Mn2+-induced signal enhancement was assessed across the FR tract, the ventral tegmental area (VTA), the striatum, the nucleus accumbens, and the prefrontal cortex (PFC), in both MA-injected animals and controls. RESULTS: MA treatment was found to affect the complexity and efficiency of Mn2+ uptake in the VTA, via the FR tract, with significantly increased Mn2+ accumulation in the VTA, the dorsomedial part of the striatum, and the PFC. CONCLUSIONS: MEMRI successfully visualizes disruptions in the multisynaptic pathway as the consequences of repeated MA exposure. MEMRI is potentially an important method in the future to investigate functional changes within a specific pathway under the influences of pharmacological agents, given its excellent functional, in vivo, spatial, and temporal properties.

A distinct phenotypic change in gliomas at the time of magnetic resonance imaging detection.

OBJECT: Although gliomas remain refractory to treatment, it is not clear whether this characteristic is fixed at the time of its origin or develops later. The authors have been using a model of neurocarcinogenesis to determine whether a time exists during a glioma's evolution during which it is detectable but still curable, thus providing a justification for exploring the clinical merits of an early detection and treatment strategy. The authors recently reported the presence of 2 distinct cellular subsets, 1 expressing nestin and the other both glial fibrillary acidic protein (GFAP) and osteopontin (OPN), within all examined gliomas that developed after in utero exposure to ethylnitrosourea. METHODS: In this study, the authors used magnetic resonance (MR) imaging to assess when these 2 subpopulations appeared during glioma evolution. RESULTS: Using T2-weighted and diffusion-weighted MR imaging, the authors observed that gliomas grew exponentially once detected at rates that were location-dependent. Despite large differences in growth rates, however, they determined by correlating histochemistry with imaging in a second series of animals, that all lesions initially detected on T2-weighted images contained both subsets of cells. In contrast, lesions containing only nestin-positive cells, which appeared on average 40 days before detection on MR images, were not detected. CONCLUSIONS: The sequential appearance of first the nestin-positive cells followed several weeks later by those expressing GFAP/OPN suggests that all gliomas arise through common early steps in this model. Furthermore, the authors hypothesize that the expression of OPN, a molecule associated with cancer aggressiveness, at the time of T2-weighted detection signals a time during glioma development when the lesion becomes refractory to treatment.

Multiparametric MRI evaluation of kainic acid-induced neuronal activation in rat hippocampus.

We investigated the pathogenic mechanisms of hippocampal structural changes and neuronal activation in a kainic acid (KA)-treated rat model using non-invasive high-resolution diffusion-weighted imaging, T2-weighted imaging, and manganese-enhanced magnetic resonance imaging (MEMRI). We found that high-resolution MRI can reveal KA-induced subtle lesions in hippocampus. The signal changes were first observed in the CA3 area and then the CA1 area, and were revealed to be focal edema and neuronal death in histopathological studies. MR signal intensity was higher in CA1 area than in CA3 area at 168 h post KA treatment due to the increase of proliferating astrocytes as shown by histopathological studies. MEMRI studies revealed signal hyperintensity in the CA3 pyramidal cell layer after KA treatment, and the MEMRI signal can be attenuated by diltiazem, an L-type calcium channel blocker. Histopathological study revealed attenuation of focal edema and neuronal swelling following diltiazem treatment. It indicated that KA-induced neuronal activation mainly developed in CA3, and calcium channels may play important roles in pathogenesis of KA-induced hippocampal lesions. We conclude that high-resolution MRI is able to identify KA-induced hippocampal damage, and that MEMRI can be used to investigate the role of calcium channels in the pathogenic mechanisms of neurological conditions.

Focused shockwave induced blood-brain barrier opening and transfection.

Despite extensive efforts in recent years, the blood-brain barrier (BBB) remains a significant obstacle for drug delivery. This study proposes using a clinical extracorporeal shockwave instrument to open the BBB, combined with a laser assisted bi-axial locating platform to achieve non-invasive, controllable-focus and reversible BBB opening in the brains of rats. Under shockwave treatment with an intensity level of 5 (P-9.79 MPa, energy flux density (EFD) 0.21 mJ/mm2) and a pulse repetition frequency of 5 Hz, the BBB could be opened after 50 shocks without the use of an ultrasound contrast agent. With the proposed method, the BBB opening can be precisely controlled in terms of depth, size and location. Moreover, a shockwave based gene transfection was demonstrated using a luciferase gene.

Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.

3,4-Methylenedioxymethamphetamine (MDMA), also known as "Ecstasy", is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI). Rats were injected subcutaneously six times with MDMA (5 mg/kg) or saline once daily. Eight days after the last injection, manganese ions (Mn2+) were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB), and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum.