Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases and a major contributor to dementia. Although the cause of this condition has been identified long ago as aberrant aggregations of amyloid and tau proteins, effective therapies for it remain elusive. The complexities of drug development for AD treatment are often compounded by the impermeable blood-brain barrier and low-yield brain delivery. In addition, the use of high drug concentrations to overcome this challenge may entail side effects. To address these challenges and enhance the precision of delivery into brain regions affected by amyloid aggregation, we proposed a transferrin-conjugated nanoparticle-based drug delivery system. The transferrin-conjugated melittin-loaded L-arginine-coated iron oxide nanoparticles (Tf-MeLioNs) developed in this study successfully mitigated melittin-induced cytotoxicity and hemolysis in the cell culture system. In the 5XFAD mouse brain, Tf-MeLioNs remarkably reduced amyloid plaque accumulation, particularly in the hippocampus. This study suggested Tf-LioNs as a potential drug delivery platform and Tf-MeLioNs as a candidate for therapeutic drug targeting of amyloid plaques in AD. These findings provide a foundation for further exploration and advancement in AD therapeutics.

Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging.

Serine protease is linked to a wide range of diseases, prompting the development of robust, selective, and sensitive protease assays and sensing methods. However, the clinical needs for serine protease activity imaging have not yet been met, and the efficient in vivo detection and imaging of serine protease remain challenging. Here, we report the development of the gadolinium-cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-click-Sulfonyl Fluoride (Gd-DOTA-click-SF) MRI contrast agent targeting serine protease. The HR-FAB mass spectrum confirmed the successful formation of our designed chelate. The molar longitudinal relaxivity (r1) of the Gd-DOTA-click-SF probe (r1 = 6.82 mM-1 s-1) was significantly higher than that of Dotarem (r1 = 4.63 mM-1 s-1), in the range of 0.01-0.64 mM at 9.4 T. The in vitro cellular study and the transmetallation kinetics study showed that the safety and stability of this probe are comparable to those of conventional Dotarem. Ex vivo abdominal aortic aneurysm (AAA) MRI revealed that this probe has a contrast-agent-to-noise ratio (CNR) that is approximately 51 ± 23 times greater than that of Dotarem. This study of superior visualization of AAA suggests that it has the potential to detect elastase in vivo and supports the feasibility of probing serine protease activity in T1-weighted MRI.

From 2D to 4D Phase-Contrast MRI in the Neurovascular System: Will It Be a Quantum Jump or a Fancy Decoration?

Considering the crosstalk between the flow and vessel wall, hemodynamic assessment of the neurovascular system may offer a well-integrated solution for both diagnosis and management by adding prognostic significance to the standard CT/MR angiography. 4D flow MRI or time-resolved 3D velocity-encoded phase-contrast MRI has long been promising for the hemodynamic evaluation of the great vessels, but challenged in clinical studies for assessing intracranial vessels with small diameter due to long scan times and low spatiotemporal resolution. Current accelerated MRI techniques, including parallel imaging with compressed sensing and radial k-space undersampling acquisitions, have decreased scan times dramatically while preserving spatial resolution. 4D flow MRI visualized and measured 3D complex flow of neurovascular diseases such as aneurysm, arteriovenous shunts, and atherosclerotic stenosis using parameters including flow volume, velocity vector, pressure gradients, and wall shear stress. In addition to the noninvasiveness of the phase contrast technique and retrospective flow measurement through the wanted windows of the analysis plane, 4D flow MRI has shown several advantages over Doppler ultrasound or computational fluid dynamics. The evaluation of the flow status and vessel wall can be performed simultaneously in the same imaging modality. This article is an overview of the recent advances in neurovascular 4D flow MRI techniques and their potential clinical applications in neurovascular disease. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Time-saving synthetic magnetic resonance imaging protocols for pediatric neuroimaging: impact of echo train length and bandwidth on image quality.

BACKGROUND: Synthetic MRI is a time-efficient imaging technique that provides both quantitative MRI and contrast-weighted images simultaneously. However, a rather long single scan time can be challenging for children. OBJECTIVE: To evaluate the clinical feasibility of time-saving synthetic MRI protocols adjusted for echo train length and receiver bandwidth in pediatric neuroimaging based on image quality assessment and quantitative data analysis. MATERIALS AND METHODS: In total, we included 33 children ages 1.6-17.4 years who underwent synthetic MRI using three sets of echo train length and receiver bandwidth combinations (echo train length [E]12-bandwidth [B in KHz]22, E16-B22 and E16-B83) at 3 T. The image quality and lesion conspicuity of synthetic contrast-weighted images were compared between the suggested protocol (E12-B22) and adjusted protocols (E16-B22 and E16-B83). We also compared tissue values (T1, T2, proton-density values) and brain volumetry. RESULTS: For the E16-B83 combination, image quality was sufficient except for 15.2% of T1-W and 3% of T2-W fluid-attenuated inversion recovery (FLAIR) images, with remarkable scan time reduction (up to 35%). The E16-B22 combination demonstrated a comparable image quality to E12-B22 (P>0.05) with a scan time reduction of up to 8%. There were no significant differences in lesion conspicuity among the three protocols (P>0.05). Tissue value measurements and brain tissue volumes obtained with the E12-B22 protocol and adjusted protocols showed excellent agreement and strong correlations except for gray matter volume and non-white matter/gray matter/cerebrospinal fluid volume in E12-B22 vs. E16-B83. CONCLUSION: The adjusted synthetic protocols produced image quality sufficient or comparable to that of the suggested protocol while maintaining lesion conspicuity with reduced scan time. The quantitative values were generally consistent with the suggested MRI-protocol-derived values, which supports the clinical application of adjusted protocols in pediatric neuroimaging.

Beneficial Effects of SREBP Decoy Oligodeoxynucleotide in an Animal Model of Hyperlipidemia.

Hyperlipidemia is a chronic disorder that plays an important role in the development of cardiovascular diseases, type II diabetes, atherosclerosis, hypertension, and non-alcoholic fatty liver disease. Hyperlipidemias have created a worldwide health crisis and impose a substantial burden not only on personal health but also on societies and economies. Transcription factors in the sterol regulatory element binding protein (SREBP) family are key regulators of the lipogenic genes in the liver. SREBPs regulate lipid homeostasis by controlling the expression of a range of enzymes required for the synthesis of endogenous cholesterol, fatty acids, triacylglycerol, and phospholipids. Thereby, SREBPs have been considered as targets for the treatment of metabolic diseases. The aim of this study was to investigate the beneficial functions and the possible underlying molecular mechanisms of SREBP decoy ODN, which is a novel inhibitor of SREBPs, in high-fat diet (HFD)-fed hyperlipidemic mice. Our studies using HFD-induced hyperlipidemia animal model revealed that SREBB decoy ODN inhibited the increased expression of fatty acid synthetic pathway, such as SREBP-1c, FAS, SCD-1, ACC1, and HMGCR. In addition, SREBP decoy ODN decreased pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-8, and IL-6 expression. These results suggest that SREBP decoy ODN exerts its anti-hyperlipidemia effects in HFD-induced hyperlipidemia mice by regulating their lipid metabolism and inhibiting lipogenesis through inactivation of the SREPB pathway.

Safety of gadobutrol in over 23,000 patients: the GARDIAN study, a global multicentre, prospective, non-interventional study.

OBJECTIVES: To investigate the safety and tolerability of gadobutrol at the recommended dose in patients requiring contrast-enhanced magnetic resonance imaging/angiography (MRI/MRA) in the routine setting. METHODS: GARDIAN prospectively enrolled 23,708 patients undergoing routine gadobutrol-enhanced MRI/MRA for approved indications at 272 study centres in Europe, Asia, North America, and Africa and monitored for adverse events. RESULTS: Median gadobutrol dose was 0.11 mmol/kg body weight. The overall incidence of adverse drug reactions (ADRs) was 0.7 % (n = 170 patients), with similar incidences in patients with renal impairment or cardiac disease, from different geographic regions and in different gadobutrol dose groups. Patients at risk for contrast media reaction had an ADR incidence of 2.5 %. Five patients (0.02 %) experienced serious adverse events, four were drug-related. One patient experienced a fatal anaphylactoid shock, assessed to be related to injection of gadobutrol. The contrast quality of gadobutrol-enhanced images was rated by treating physicians as good or excellent in 97 % cases, with similar ratings in all patient subgroups and indications. CONCLUSIONS: The GARDIAN study shows that gadobutrol at the recommended dose is well tolerated across a large, diverse patient population. KEY POINTS: • Gadobutrol at recommended dose shows low rates of adverse drug reactions • Gadobutrol demonstrates a uniform safety profile across diverse patient groups • Gadobutrol provides excellent contrast quality in routine practice.

Small-nucleic-acid-based therapeutic strategy targeting the transcription factors regulating the vascular inflammation, remodeling and fibrosis in atherosclerosis.

Atherosclerosis arises when injury to the arterial wall induces an inflammatory cascade that is sustained by a complex network of cytokines, together with accumulation of lipids and fibrous material. Inflammatory cascades involve leukocyte adherence and chemotaxis, which are coordinated by the local secretion of adhesion molecules, chemotactic factors, and cytokines. Transcription factors are critical to the integration of the various steps of the cascade response to mediators of vascular injury, and are induced in a stimulus-dependent and cell-type-specific manner. Several small-nucleic-acid-based therapeutic strategies have recently been developed to target transcription factors: antisense oligodeoxynucleotides, RNA interference, microRNA, and decoy oligodeoxynucleotides. The aim of this review was to provide an overview of these particular targeted therapeutic strategies, toward regulation of the vascular inflammation, remodeling and fibrosis associated with atherosclerosis.

Propagation-based phase-contrast X-ray microtomography of a cerebral protection device retrieved after carotid artery stenting.

Phase-contrast synchrotron X-ray microtomography (pcSyncX) based on the highly coherent X-ray beam has previously been used to visualize the microstructures of biologic specimens, but it has never been used to evaluate embolic debris adherent on a cerebral protection device (CPD). The purpose of this study was to demonstrate the feasibility of pcSyncX for evaluating embolic debris during carotid artery stenting (CAS). Five patients (four males, age range 67-77 years) with severe carotid artery stenosis underwent CAS. The retrieved CPD was exposed to synchrotron radiation and 1000 pcSyncX projection images were obtained by rotating the CPD through 180°. An X-ray shadow of a CPD was converted into a visual image by the scintillator. After microtomographic reconstruction, the three-dimensionally reconstructed images were further segmented into the embolic debris and CPD. The total volume of emboli was calculated by summing the volume at each scanning level. The number of membrane pores covered by emboli as seen from the outer surface was counted and the percentage of covered area was calculated. Embolic debris was clearly demonstrated not only on the inner surface and within pores but also on the outer surface of the CPD. The mean total volume of embolic debris was 0.538 × 10(-6) mm(3) (range 0.225-0.965 × 10(-6) mm(3)). Most (61.5%) of the debris was located at the apical one-third of the CPD and 20.8% of the pore area was covered by debris.

Microcurrent wave alleviates mouse intracranial arterial dolichoectasia development.

Intracranial arterial dolichoectasia (IADE) is associated with the interaction of hypertension and inflammation, and microcurrent can be effective in hypertension. Therefore, this study aimed to investigate the therapeutic effect of microcurrent electrical stimulation in a mouse IADE model. This study randomly categorized 20 mice into five groups: group 1-C (healthy control), group 2-D (IADE model), group 3-M + D (microcurrent administration before nephrectomy and until brain surgery), group 4-D + M (microcurrent administration for 4 weeks following brain surgery), and group 5-M (microcurrent administration for 4 weeks). Cerebral artery diameter and thickness and cerebral arterial wall extracellular matrix components were assessed. Among the five groups, group 2-D showed significantly higher cerebral arterial wall diameter (117.79 ± 17.05 µm) and proportion of collagen (42.46 ± 14.12%) and significantly lower arterial wall thickness (9.31 ± 2.26 µm) and proportion of smooth muscle cell (SMC) and elastin in the cerebral arterial wall (SMC: 38.05 ± 10.32%, elastin: 11.11 ± 6.97%). Additionally, group 4-D + M exhibited a non-significantly lower diameter (100.28 ± 25.99 µm) and higher thickness (12.82 ± 5.17 µm). Group 5-M demonstrated no evidence of toxicity in the liver and brain. The pilot study revealed that microcurrent is effective in preventing IADE development, although these beneficial effects warrant further investigation.

Haemodynamic alterations in cerebral blood vessels after carotid artery revascularisation: quantitative analysis using 2D phase-contrast MRI.

OBJECTIVES: This study was conducted to evaluate the effect of revascularisation, whether revascularisation improves total cerebral blood flow volume (FVTCBF), and how cerebral veins would respond to altered FVTCBF. METHODS: The 39 carotid artery stenoses in 37 patients who underwent revascularisation including 32 stentings and 7 endarterectomies were included in this prospective study. From the two-dimensional phase-contrast (2D-PC) MRI acquired before and after revascularisation, the flow volumes (FVs) of the arteries and veins were compared using paired t-test. The relationships between these parameters were correlated using Pearson's correlation coefficient. RESULTS: The mean FV in the treated carotid artery (proportion of treated artery among total FV) increased from 162.06 ml/min (25.80 %) to 267.71 ml/min (37.21 %; P < 0.001). Revascularisation increased the FVTCBF of patients from 638.66 ml/min to 716.72 ml/min (P < 0.001). The FV of the internal jugular veins, superior sagittal and straight sinuses (FVSS + SSS), and transverse sinuses increased after revascularisation (P < 0.05). Positive relationships were shown between the FVTCBF and the FVSS + SSS (r = 0.584-0.741, P < 0.001). CONCLUSIONS: Revascularisation improves the FVTCBF by increasing the FV in the treated carotid artery. The venous drainages are closely linked to FVTCBF. 2D-PC-MRI is a feasible method for evaluating comprehensively the haemodynamic improvement after revascularisation. KEY POINTS: • Revascularisation may be beneficial in ischaemic strokes due to carotid artery stenosis. • Revascularisation of the affected artery increases total cerebral blood flow volume ( FV TCBF). • Cerebral venous drainage, closely linked to FV TCBF, is also improved. • Two-dimensional phase-contrast MRI can comprehensively assess these haemodynamic improvements after carotid revascularisation.

Piecing Arterial Branching Pattern Together from Non-Contrast and Angiographic Brain Computed Tomography before Endovascular Thrombectomy for Acute Ischemic Stroke.

Predicting the unseen arterial course and branching pattern distal to vessel occlusion is crucial for endovascular thrombectomy in acute stroke patients. We investigated whether a comprehensive interpretation of NCT and CTA would enhance arterial course prediction more than either NCT or CTA interpretation alone. Among 150 patients who achieved post-thrombectomy TICI grades ≥ IIb for anterior circulation occlusions, we assessed visualization grade on both NCT and CTA by five scales at the thrombosed and the distal-to-thrombus segment, using DSA as the reference standard. The visualization grades were compared and related to various subgroups. The mean visualization grade of the distal-to-thrombus segment on NCT was significantly larger than that of CTA (mean ± SD, 3.62 ± 0.87 versus 3.31 ± 1.20; p < 0.05). On CTA, visualization grade of distal-to-thrombus segment in the good collateral flow subgroup was higher than that in the poor collateral flow subgroup (mean ± SD, 4.01 ± 0.93 versus 2.56 ± 0.99; p < 0.001). After the comprehensive interpretation of NCT and CTA, seventeen cases (11%) showed visualization grade of distal-to-thrombus segment upgrading. Tracing arterial course and piecing branching patterns together in distal-to-occlusion of stroke patients was feasible on the routine pre-interventional NCT and CTA, which may provide timely guidance during thrombectomy.

Surface patterning of glass via electrostatic imprinting using a platinum mold.

Electrostatic imprinting is a highly suitable process for patterning large area and high efficiency glasses because it enables glass patterning at low temperatures with low pressures. Because high DC voltage bias is applied to the mold and glass during the thermal imprinting, the mold materials should have electrical conductivity, appropriate glass adhesion properties, and excellent thermal and electrochemical stability. In this study, thin Pt/Ni molds were fabricated via Si micromachining and electroforming techniques and were then used in the electrostatic imprint process in order to evaluate their feasibility as molds. Under the investigated process conditions, the pattern transfer to glass was accomplished without noticeable degradation of the mold. Furthermore, the process parameter effects on replication fidelity and potential defects were investigated.

Delayed Rupture of an Anterior Communicating Artery Pseudoaneurysm Caused by Distal Occlusion Thrombectomy Using a Stent Retriever: A Case Report and Mechanism of Injury.

We report a case of delayed rupture of an anterior communicating artery (Acom) pseudoaneurysm following mechanical thrombectomy (MT) of a distal artery occlusion using a stent retriever. An elderly patient with right hemiparesis showed left proximal internal cerebral artery and middle cerebral artery occlusions. During MT, a fragmented thrombus moved to the anterior cerebral artery (ACA). A stent retriever was deployed to the occluded ACA, and the Acom and proximal ACA segment were significantly straightened. Additionally, we attempted a blind exchange mini-pinning (BEMP) technique, but a subarachnoid hemorrhage (SAH) occurred. Bleeding was almost entirely absorbed 9 days after the procedure, but the SAH recurred at 20 days, and computed tomography angiography revealed a new pseudoaneurysm formation in the Acom. We suggest that the proposed mechanism of pseudoaneurysm formation was likely due to the dislocation and avulsion of the Acom perforators when the ipsilateral ACA was pushed and pulled during MT.

Myelin Content in Mild Traumatic Brain Injury Patients with Post-Concussion Syndrome: Quantitative Assessment with a Multidynamic Multiecho Sequence.

OBJECTIVE: This study aimed to explore the myelin volume change in patients with mild traumatic brain injury (mTBI) with post-concussion syndrome (PCS) using a multidynamic multiecho (MDME) sequence and automatic whole-brain segmentation. MATERIALS AND METHODS: Forty-one consecutive mTBI patients with PCS and 29 controls, who had undergone MRI including the MDME sequence between October 2016 and April 2018, were included. Myelin volume fraction (MVF) maps were derived from the MDME sequence. After three dimensional T1-based brain segmentation, the average MVF was analyzed at the bilateral cerebral white matter (WM), bilateral cerebral gray matter (GM), corpus callosum, and brainstem. The Mann-Whitney U-test was performed to compare MVF and myelin volume between patients with mTBI and controls. Myelin volume was correlated with neuropsychological test scores using the Spearman rank correlation test. RESULTS: The average MVF at the bilateral cerebral WM was lower in mTBI patients with PCS (median [interquartile range], 25.2% [22.6%-26.4%]) than that in controls (26.8% [25.6%-27.8%]) (p = 0.004). The region-of-interest myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (1.87 cm3 [1.70-2.05 cm3] vs. 2.21 cm3 [1.86-3.46 cm3]; p = 0.003) and brainstem (9.98 cm3 [9.45-11.00 cm3] vs. 11.05 cm3 [10.10-11.53 cm3]; p = 0.015). The total myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (0.45 cm3 [0.39-0.48 cm3] vs. 0.48 cm3 [0.45-0.54 cm3]; p = 0.004) and brainstem (1.45 cm3 [1.28-1.59 cm3] vs. 1.54 cm3 [1.42-1.67 cm3]; p = 0.042). No significant correlation was observed between myelin volume parameters and neuropsychological test scores, except for the total myelin volume at the bilateral cerebral WM and verbal learning test (delayed recall) (r = 0.425; p = 0.048). CONCLUSION: MVF quantified from the MDME sequence was decreased at the bilateral cerebral WM in mTBI patients with PCS. The total myelin volumes at the corpus callosum and brainstem were decreased in mTBI patients with PCS due to atrophic changes.

Technical strategy in endovascular treatment of proximal anterior cerebral artery aneurysms.

PURPOSE: There have been few reports on the endovascular treatment of aneurysms arising from A1 due to their rarity. We report the angiographic results, clinical outcomes, and technical aspects of endovascular treatment for 13 A1 aneurysms in 12 patients. METHODS: From January 2002 to November 2007, 12 patients (9 females and 3 males) with 13 A1 aneurysms underwent endovascular treatment. Three of these patients presented with subarachnoid hemorrhage, and 10 unruptured aneurysms were detected in 9 patients. All of the aneurysms were successfully treated with coil embolization. Most of the aneurysms projected posteriorly (61.5%) and were located in the proximal A1 segment (69.2%). Procedural, clinical, and radiological follow-up data were reviewed. RESULTS: Procedure-related complications occurred in 3 patients (25%) and included 1 non-leaking aneurysmal perforation and 2 thromboembolic events; none of them were clinically significant. No bleeding or rebleeding occurred during the follow-up period in this cohort of patients. CONCLUSIONS: Endovascular coil embolization is an effective treatment modality for A1 aneurysms. Tailored microcatheter shaping according to aneurysm projection and location is necessary. Long-term follow-up studies involving a larger number of patients and further comparisons with surgical data are needed.

Faster Region-Based Convolutional Neural Network in the Classification of Different Parkinsonism Patterns of the Striatum on Maximum Intensity Projection Images of [18F]FP-CIT Positron Emission Tomography.

The aim of this study was to compare the performance of a deep-learning convolutional neural network (Faster R-CNN) model to detect imaging findings suggestive of idiopathic Parkinson's disease (PD) based on [18F]FP-CIT PET maximum intensity projection (MIP) images versus that of nuclear medicine (NM) physicians. The anteroposterior MIP images of the [18F]FP-CIT PET scan of 527 patients were classified as having PD (139 images) or non-PD (388 images) patterns according to the final diagnosis. Non-PD patterns were classified as overall-normal (ONL, 365 images) and vascular parkinsonism with definite defects or prominently decreased dopamine transporter binding (dVP, 23 images) patterns. Faster R-CNN was trained on 120 PD, 320 ONL, and 16 dVP pattern images and tested on the 19 PD, 45 ONL, and seven dVP patterns images. The performance of the Faster R-CNN and three NM physicians was assessed using receiver operating characteristics curve analysis. The difference in performance was assessed using Cochran's Q test, and the inter-rater reliability was calculated. Faster R-CNN showed high accuracy in differentiating PD from non-PD patterns and also from dVP patterns, with results comparable to those of NM physicians. There were no significant differences in the area under the curve and performance. The inter-rater reliability among Faster R-CNN and NM physicians showed substantial to almost perfect agreement. The deep-learning model accurately differentiated PD from non-PD patterns on MIP images of [18F]FP-CIT PET, and its performance was comparable to that of NM physicians.

Melittin-loaded Iron Oxide Nanoparticles Prevent Intracranial Arterial Dolichoectasia Development through Inhibition of Macrophage-mediated Inflammation.

Rationale: In intracranial arterial dolichoectasia (IADE) development, the feedback loop between inflammatory cytokines and macrophages involves TNF-α and NF-κB signaling pathways and leads to subsequent MMP-9 activation and extracellular matrix (ECM) degeneration. In this proof-of-concept study, melittin-loaded L-arginine-coated iron oxide nanoparticle (MeLioN) was proposed as the protective measure of IADE formation for this macrophage-mediated inflammation and ECM degeneration. Methods: IADE was created in 8-week-old C57BL/6J male mice by inducing hypertension and elastase injection into a basal cistern. Melittin was loaded on the surface of ION as a core-shell structure (hydrodynamic size, 202.4 nm; polydispersity index, 0.158). Treatment of MeLioN (2.5 mg/kg, five doses) started after the IADE induction, and the brain was harvested in the third week. In the healthy control, disease control, and MeLioN-treated group, the morphologic changes of the cerebral arterial wall were measured by diameter, thickness, and ECM composition. The expression level of MMP-9, CD68, MCP-1, TNF-α, and NF-κB was assessed from immunohistochemistry, polymerase chain reaction, and Western blot assay. Results: MeLioN prevented morphologic changes of cerebral arterial wall related to IADE formation by restoring ECM alterations and suppressing MMP-9 expression. MeLioN inhibited MCP-1 expression and reduced CD68-positive macrophage recruitments into cerebral arterial walls. MeLioN blocked TNF-α activation and NF-κB signaling pathway. In the Sylvian cistern, co-localization was found between the CD68-positive macrophage infiltrations and the MeLioN distributions detected on Prussian Blue and T2* gradient-echo MRI, suggesting the role of macrophage harboring MeLioN. Conclusions: The macrophage infiltration into the arterial wall plays a critical role in the MMP-9 secretion. MeLioN, designed for ION-mediated melittin delivery, effectively prevents IADE formation by suppressing macrophage-mediated inflammations and MMP activity. MeLioN can be a promising strategy preventing IADE development in high-risk populations.

Persistent dysarthria after cefazolin-induced status epilepticus.

BACKGROUND: Cefazolin is a well-known antibiotic associated with seizures. However, intrathecal cefazolin-induced status epilepticus (SE) is very rare and resultant persistent dysarthria has not been previously reported. CASE REPORT: A 66-year-old woman underwent epidural adhesiolysis due to lumbar spinal stenosis and 500 mg of cefazolin was infused through the thecal puncture site during the procedure. SE developed abruptly 40 minutes later and it persisted for 3 days. Severe dysarthria, dysphagia and cognitive dysfunction developed after the cessation of SE. Although the patient's other symptoms showed much improvement after rehabilitation, the dysarthria did not improve after intense speech therapy for 8 months. The brain MRI showed no abnormal findings, but the 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG PET) of the brain demonstrated hypometabolic areas in the bilateral inferior frontal gyrus and the primary motor cortex, representing the oromotor area. CONCLUSION: Although the exact mechanism underlying the dysarthria is unknown, the dysfunction of the inferior frontal network for speech production revealed by the brain FDG-PET, including the motor speech area (Broca's area), left insula and bilateral primary and premotor cortex representing the oromotor area, might have been responsible for the persistent dysarthria in this patient.

Analysis of the time-velocity curve in phase-contrast magnetic resonance imaging: a phantom study.

The aim of this study was to analyze the characteristics of time-velocity curve acquired by phase-contrast magnetic resonance imaging (PC-MRI) using an in-vitro flow model as a reference for hemodynamic studies. The time- velocity curves of the PC-MRI were compared with Doppler ultrasonography (US) and also compared with those obtained in the electromagnetic flowmeter. The correlation between techniques was analyzed using an electromagnetic flowmeter as a reference standard; the maximum, minimum, and average velocities, full-width at half-maximum (FWHM), and ascending gradient (AG) were measured from time-velocity curves. The correlations between an electromagnetic flowmeter and the respective measurement technique for the PC-MRI and Doppler US were found to be high (mean R2 > 0.9, p < 0.05). These results indicate that these measurement techniques are useful for measuring blood flow information and reflect actual flow. The PC-MRI was the best fit for the minimum velocity and FWHM, and the maximum velocity and AG were the best fit for Doppler US. The PC-MRI showed lower maximum velocity value and higher minimum velocity value than Doppler US. Therefore, PC-MRI demonstrates more obtuse time-velocity curve than Doppler US. In addition, the time- velocity curve of PC-MRI could be calibrated by introducing formulae that can convert each measurement value to a reference standard value within a 10% error. The PC-MRI can be used to estimate the Doppler US using this formula.

Perfusion CT of the brain using 40-mm-wide detector and toggling table technique for initial imaging of acute stroke.

OBJECTIVE: Limited coverage of the brain in the z-axis has been a drawback of perfusion CT. The purpose of this study was to evaluate the usefulness of perfusion CT with extended coverage in the z-axis for the assessment of acute stroke in an emergent clinical setting. MATERIALS AND METHODS: Fifty-eight patients who underwent 80-mm-coverage perfusion CT within 24 hours after stroke onset were included. Perfusion CT was performed using a 64-MDCT unit equipped with 40-mm-wide detector and the toggling table technique. Lesion detection by perfusion CT was analyzed using follow-up diffusion-weighted imaging and MR angiography as the reference standards. More conventional 20-mm-coverage perfusion CT was simulated by extracting data obtained at the basal ganglia level for comparison with 80-mm-coverage perfusion CT. RESULTS: Fifty-one patients had acute infarctions and seven patients did not. For 80-mm-coverage perfusion CT, perfusion abnormality was detected in 42 of 51 patients (sensitivity, 82.4%; and specificity, 85.7%). When patients with small artery disease (small acute infarctions in the basal ganglia, thalamus, corona radiata, and pons) were excluded, sensitivity increased to 92.3%. As compared with 80-mm-coverage perfusion CT, 20-mm-coverage perfusion CT missed nine acute infarctions located above or below the level of the basal ganglia (p = 0.0039). CONCLUSION: Perfusion CT with 80-mm-coverage was found to be useful as an initial imaging method in acute ischemic stroke, although it had low sensitivity for detecting small acute infarctions. In particular, this technique provided higher lesion detection than 20-mm-coverage perfusion CT.