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Pancreatic neuroendocrine tumors (PNETs) represent one-third of gastroenteropancreatic neuroendocrine tumors and are the second malignancy of the pancreas. The 5-year survival rate of metastatic PNETs is only about 15%. We have recently demonstrated that receptor for hyaluronic acid-mediated motility isoform B (RHAMMB) is upregulated in PNETs and promotes metastasis of PNETs. We have also reported that Bcl-xL accelerates the formation of PNETs with invasive properties. Here, we propose a RHAMM-targeted combination therapy (RCT), as a novel treatment for PNETs. RCT is designed to accomplish a synergistic apoptotic/anticancer effect, by aiming RHAMMB, a receptor for hyaluronic acid (HA), and codelivering Bcl-xL siRNA with mitochondria-fusing peptide to kill PNET cells. Yet, it is a substantial challenge to codeliver multiple drugs to RHAMM-expressing tumors. To simultaneously transport these unconventional therapeutics for a synergistic effect, a siRNA for Bcl-xL and a mitochondria-fusing peptide are layered onto a nanocore by charge-charge interaction, followed by a layer of HA for targeting RHAMMB. We showed that the prepared RCT is efficiently internalized by RHAMMB-positive cells, but not by RHAMMB-negative cells. We have found that the encapsulated Bcl-xL siRNA and the mitochondria-fusing peptide are released inside cells to silence Bcl-xL gene expression and induce apoptosis by fusing the mitochondrial membrane. A synergistic cell killing effect was achieved in vitro (> 83% cell death). In a preclinical mouse model, we demonstrated that systemically-injected RCT significantly reduced tumor burden (> 65% reduction) and sustained the blood glucose levels of mice bearing RHAMMB-positive PNETs. Together, the developed RCT can serve as a promising drug delivery system for RHAMMB-overexpressed cancer treatments. Citation Format: Seung Koo Lee, Xiang Chen, Yi-Chieh Nancy Du, Ching-Hsuan Tung. Nanotherapy targeting metastatic factor RHAMMB-positive pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-230.

To analyze the altered brain regions and intrinsic brain activity patterns in trauma-exposed firefighters without posttraumatic stress disorder (PTSD).Resting-state functional MRI (rsfMRI) was performed for all subjects. Thirty-one firefighters over 40 years of age without PTSD (31 men; mean age, 49.8 ± 4.7 years) were included. Twenty-six non-traumatized healthy controls (HCs) (26 men; mean age, 65.3 ± 7.84 years) were also included. Voxel-based morphometry was performed to investigate focal differences in the brain anatomy. Seed-based functional connectivity analysis was performed to investigate differences in spontaneous brain characteristics.The mean z-scores of the Seoul Verbal Learning Test for immediate and delayed recall, Controlled Oral Word Association Test (COWAT) score for animals, and COWAT phonemic fluency were significantly lower in the firefighter group than in the HCs, indicating decreased neurocognitive function. Compared to HCs, firefighters showed reduced gray matter volume in the left superior parietal gyrus and left inferior temporal gyrus. Further, in contrast to HCs, firefighters showed alterations in rsfMRI values in multiple regions, including the fusiform gyrus and cerebellum.Structural and resting-state functional abnormalities in the brain may be useful imaging biomarkers for identifying alterations in trauma-exposed firefighters without PTSD.외상 후 스트레스 장애(posttraumatic stress disorder; 이하 PTSD)가 없는 외상에 노출된 소방관들에서 뇌 구조의 변화와 휴식기 뇌기능 변화를 연구하고자 한다.모든 피험자는 휴식기 기능 뇌자기공명영상(resting-state functional MRI; 이하 rsfMRI) 검사를 시행하였다. PTSD가 없는 40세 이상의 31명의 소방관(31명, 평균 연령, 49.8 ± 4.7세)이 포함되었다. 26명의 외상을 받지 않은 건강한 대조군(26명, 평균 연령, 65.3 ± 7.84세)도 포함되었다. Voxel-based morphometry 분석을 시행하여 뇌 해부학상의 국소적 차이를 조사하였으며, 휴식기 뇌기능의 차이를 조사하기 위해 seed-based functional connectivity analysis 분석을 시행하였다.서울언어학습결과(Seoul Verbal Learning Test)의 평균 z 값을 비교했을때 소방관은 건강한 대조군에 비해 즉각회상(immediate recall), 지연 회상(delayed recall), 통제단어연상검사(Controlled Oral Word Association Test; 이하 COWAT)의 동물(animal)과 음소(phonemic) 항목에서 점수가 유의하게 낮았으며, 신경인지 기능이 감소한 것으로 나타났다. 소방관은 좌위마루이랑(left superior parietal gyrus)과 좌하관자이랑(left inferior temporal gyrus)의 회색질 부피가 건강한 대조군에 비해 감소되어 있었다. 소방관은 방추향이랑(fusiform gyrus)과 소뇌(cerebellum) 등을 포함한 여러 부위에서 rsfMRI 값의 변화를 보였다.구조적 뇌 및 휴식 상태 기능 이상은 외상에 노출된 소방관의 변화를 확인하는 데 유용한 이미징 바이오 마커일 수 있다.

Objective To evaluate radiomics analysis in studies on mild cognitive impairment (MCI) and Alzheimer's disease (AD) using a radiomics quality score (RQS) system to establish a roadmap for further improvement in clinical use. Materials and Methods PubMed MEDLINE and EMBASE were searched using the terms ‘cognitive impairment’ or ‘Alzheimer’ or ‘dementia’ and ‘radiomic’ or ‘texture’ or ‘radiogenomic’ for articles published until March 2020. From 258 articles, 26 relevant original research articles were selected. Two neuroradiologists assessed the quality of the methodology according to the RQS. Adherence rates for the following six key domains were evaluated: image protocol and reproducibility, feature reduction and validation, biologic/clinical utility, performance index, high level of evidence, and open science. Results The hippocampus was the most frequently analyzed (46.2%) anatomical structure. Of the 26 studies, 16 (61.5%) used an open source database (14 from Alzheimer's Disease Neuroimaging Initiative and 2 from Open Access Series of Imaging Studies). The mean RQS was 3.6 out of 36 (9.9%), and the basic adherence rate was 27.6%. Only one study (3.8%) performed external validation. The adherence rate was relatively high for reporting the imaging protocol (96.2%), multiple segmentation (76.9%), discrimination statistics (69.2%), and open science and data (65.4%) but low for conducting test-retest analysis (7.7%) and biologic correlation (3.8%). None of the studies stated potential clinical utility, conducted a phantom study, performed cut-off analysis or calibration statistics, was a prospective study, or conducted cost-effectiveness analysis, resulting in a low level of evidence. Conclusion The quality of radiomics reporting in MCI and AD studies is suboptimal. Validation is necessary using external dataset, and improvements need to be made to feature reproducibility, feature selection, clinical utility, model performance index, and pursuits of a higher level of evidence.

Objective Compressed sensing (CS) has gained wide interest since it accelerates MRI acquisition. We aimed to compare the 3D post-contrast T1-weighted volumetric isotropic turbo spin echo acquisition (VISTA) with CS (VISTA-CS) and without CS (VISTA-nonCS) in intracranial vessel wall MRIs (VW-MRI). Materials and methods From April 2017 to July 2018, 72 patients who underwent VW-MRI, including both VISTA-CS and VISTA-nonCS, were retrospectively enrolled. Wall and lumen volumes, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured from normal and lesion sites. Two neuroradiologists independently evaluated overall image quality and degree of normal and lesion wall delineation with a four-point scale (scores ≥ 3 defined as acceptable). Results Scan coverage was increased in VISTA-CS to cover both anterior and posterior circulations with a slightly shorter scan time compared to VISTA-nonCS (approximately 7 minutes vs. 8 minutes). Wall and lumen volumes were not significantly different with VISTA-CS or VISTA-nonCS (interclass correlation coefficient = 0.964-0.997). SNR was or trended towards significantly higher values in VISTA-CS than in VISTA-nonCS. At normal sites, CNR was not significantly different between two sequences (p = 0.907), whereas VISTA-CS provided lower CNR in lesion sites compared with VISTA-nonCS (p = 0.003). Subjective wall delineation was superior with VISTA-nonCS than with VISTA-CS (p = 0.019), although overall image quality did not differ (p = 0.297). The proportions of images with acceptable quality were not significantly different between VISTA-CS (83.3-97.8%) and VISTA-nonCS (75-100%). Conclusion CS may be useful for intracranial VW-MRI as it allows for larger scan coverage with slightly shorter scan time without compromising image quality.

Firefighters have a high risk of developing cardiovascular and mental disorders due to their physical and chemical environments. However, in Korea, few studies have been conducted on environmental risk of firefighters. The Firefighter Research on the Enhancement of Safety and Health (FRESH) study aimed to discover the risk factors for cardiovascular disease and mental disorders among firefighters. Former and current firefighters were recruited from three university hospitals. A total of 1022 participants completed baseline health examinations from 2016 to 2017. All participants were scheduled for follow-ups every 2 years. Baseline health survey, laboratory testing of blood and urine samples, blood heavy metal concentration, urine polycyclic aromatic hydrocarbons (PAHs) metabolites, stress-related hormone test, natural killer cell activity, as well as physical and mental health examinations that focused on cardiovascular and mental disorders, were conducted. In addition, 3 Tesla (3T) brain magnetic resonance imaging (MRI) and neuropsychological tests were also performed to investigate structural and functional changes in the brains of 352 firefighters aged >40 years or new hires with less than 1 year of service.

To assess the utility of amide proton transfer (APT) imaging as an imaging biomarker to predict prognosis and molecular marker status in high-grade glioma (HGG, WHO grade III/IV). We included 71 patients with pathologically diagnosed HGG who underwent preoperative MRI with APT imaging. Overall survival (OS) and progression-free survival (PFS) according to APT signal, clinical factors, MGMT methylation status, and IDH mutation status were analyzed. Multivariate Cox regression models with and without APT signal data were constructed. Model performance was compared using the integrated AUC (iAUC). Associations between APT signals and molecular markers were assessed using the Mann-Whitney test. High APT signal was a significant predictor for poor OS (HR = 3.21, 95% CI = 1.62–6.34) and PFS (HR = 2.22, 95% CI = 1.33–3.72) on univariate analysis. On multivariate analysis, high APT signals were an independent predictor of poor OS and PFS when clinical factors alone (OS: HR = 2.89; PFS: HR = 2.13), or in combination with molecular markers (OS: HR = 2.85; PFS: HR = 2.00), were included as covariates. The incremental prognostic value of APT signals was significant for OS and PFS. IDH-wild type was significantly associated with high APT signals (p = 0.001) when compared to IDH-mutant; however, there was no difference based on MGMT methylation status (p = 0.208). High APT signal was a significant predictor of poor prognosis in HGG. APT data showed significant incremental prognostic value over clinical prognostic factors and molecular markers and may also predict IDH mutation status. • Amide proton transfer (APT) imaging is a promising prognostic marker of high-grade glioma. • APT signals were significantly higher in IDH-wild type compared to IDH-mutant high-grade glioma. • APT imaging may be valuable for preoperative screening and treatment guidance.

BACKGROUND: IDH-wild type lower grade gliomas are known to be similar to glioblastoma in terms of genetic alterations and prognostically heterogeneous. The purpose of this study was to investigate the prognostic value of imaging phenotypes using machine learning in IDH-wild type lower grade gliomas. METHODS: Preoperative MRIs of 112 patients with histopathologically confirmed IDH-wild type grade II or III gliomas were retrospectively analyzed according to the Visually Accessible Rembrandt Images (VASARI) features set. A radiologic risk score (RRS) for overall survival (OS) and progression free survival (PFS) was produced by selected features and their regression coefficients from LASSO and Elastic net regression model with 100 times of repeated cross validation. Multivariable Cox analysis was performed including age, Karnofsky Performance score (KPS), grade, extent of resection and RRS. The added predictive value of RRS was calculated by comparing C-indices after bootstrapping between multivariable Cox models with and without RRS. RESULTS: For OS and PFS prediction, a Cox regression model comprising clinical features showed C-index of 0.741 and 0.737, respectively. When RRS derived from LASSO (RRS_L) was added to the model, C-index increased to 0.783 and 0.782 for OS and PFS prediction, respectively, without statistical significance. RRS_L was a strong predictor for both OS (HR 3.31) and PFS (HR 3.24). When RRS derived from Elastic net (RRS_E) was added to the model, the model achieved superior performance with C-index being 0.793 and 0.783 for OS and PFS prediction, respectively, with statistical significance (p < 0.05). RRS_E was an independent predictor for both OS (HR 2.62) and PFS (HR 2.80). CONCLUSION: RRS derived from MRI features using machine learning was independent predictors for survival in patients with IDH-wild type lower grade gliomas. Radiological phenotypes may have added prognostic value in patients with IDH-wild type lower grade gliomas.

Objectives The purpose of this study was to evaluate the associations between vertebral artery hypoplasia (VAH) and the morphologic types of spontaneous vertebral artery dissection (sVAD) and to assess the chronological changes of VAH after sVAD. Methods and materials In this retrospective study, we included 208 patients with 216 sVADs which were diagnosed between January 2003 and June 2017 at two tertiary hospitals. Morphologic types of sVAD were classified into aneurysmal dilatation without stenosis, pearl-and-string appearance, and steno-occlusion without aneurysmal dilatation. Baseline clinical characteristics and sVAD types were compared according to the presence of VAH on initial imaging. For 143 sVAD patients with follow-up imaging available, chronological changes of VAH and their associations with sVAD types were also evaluated. Result VAH was detected in 29 (13.9%) subjects: 18 (8.7%) with ipsilateral VAH and 11 (5.3%) with contralateral VAH to the sVAD site. Primary lesion shape was statistically associated with the presence of VAH (P = 0.001); steno-occlusion without dilatation was more frequently observed in the ipsilateral VAH group (44.4%) than the no-VAH group (20.9%) or contralateral VAH group (0%). Of a total 143 sVAD patients with follow-up imaging available, VAH-like diffuse VA narrowing was newly observed in seven patients and four patients who were initially classified into the VAH group showed their VAH-like appearances resolved. Conclusions The presence of VAH may be associated with the morphologic subtype of sVAD and the VA diameter can dynamically change, making it possible for the VAH-like appearance to be induced after a sVAD event.

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Triple-negative breast cancer (TNBC) patients exhibit the worst clinical outcome due to its aggressive clinical course, higher rate of recurrence, and a conspicuous lack of FDA-approved targeted therapies. Here, we show that multilayered nanoparticles (NPs) carrying the metastasis suppressor microRNA miR-708 (miR708-NP) localize to orthotopic primary TNBC, and efficiently deliver the miR-708 cargo to reduce lung metastasis. Using a SOX2/OCT4 promoter reporter, we identified a population of miR-708low cancer cells with tumor-initiating properties, enhanced metastatic potential, and marked sensitivity to miR-708 treatment. In vivo, miR708-NP directly targeted the SOX2/OCT4-mCherry+ miR-708low tumor cells to impair metastasis. Together, our preclinical findings provide a mechanism-based antimetastatic therapeutic approach for TNBC, with a marked potential to generate miR-708 replacement therapy for high-risk TNBC patients in the clinic. To our knowledge, this gold nanoparticle-based delivery of microRNA mimetic is the first oligonucleotide-based targeted therapy for TNBC.

Purpose Spinal cord gliomas are rare, and there is no consensus on the optimal radiotherapy (RT) regimen. Herein, we investigated therapeutic outcomes in spinal cord gliomas to obtain clues for the optimal RT regimen. Methods We assessed 45 patients who received RT for primary spinal cord non-ependymoma gliomas between 2005 and 2017: 37 (82%) received postoperative RT, 6 (13%) underwent definitive RT without surgery, and 2 (5%) received salvage RT for recurrent tumors. Craniospinal irradiation (CSI; median, 40 Gy) was administered in 4 patients with seeding at diagnosis; all other patients received local RT only (median, 50.4 Gy). Results In all 23 failures occurred (20 in patients without initial seeding +3 in patients with initial seeding and CSI; median follow-up, 33 months). The 2‑year overall survival and progression-free survival rates were 74 and 54%, respectively. Overall, 13 (32%) new seeding events outside the local RT field developed either first or subsequently. Tumor grade was significantly associated with survival endpoints (p = 0.009, 0.028) and overall seeding rates (p = 0.042). In grade II tumors, seeding developed in 23%, with a dismal prognosis (median, 10 months after RT). In grade III tumors, seeding developed in 45% with diverse prognosis. In grade IV tumors, seeding developed in 45%. The survival of patients with newly developed seeding was significantly worse than the others (2-year 50%, p Conclusion To encompass a considerable rate of progressive disease seeding, aggressive treatment such as pre-emptive application of CSI needs to be considered for high-grade spinal cord gliomas with adverse features. Prophylactic CSI could be an option for survival prolongation and requires prospective validation.

Chemical kinetic simulations are usually based on the law of mass action that applies to behavior of particles in solution. Molecular interactions in a crowded medium as in a cell, however, are not easily described by such conventional mathematical treatment. Fractal kinetics is emerging as a novel method for simulating kinetic reactions in such an environment. To date, there has not been a fast, efficient, and, more importantly, parallel algorithm for such computations. Here, we present an algorithm with several novel features for simulating large (with respect to size and time scale) fractal kinetic models. We applied the fractal kinetic technique and our algorithm to a canonical substrate-enzyme model with explicit phase-separation in the product, and achieved a speed-up of up to 8 times over previous results with reasonably tight bounds on the accuracy of the simulation. We anticipate that this technique and algorithm will have important applications to simulation of intra-cell biochemical reactions with complex dynamic behavior.

This study aimed to investigate the long-term motor outcome according to early diffusion tensor tractography findings for the affected corticospinal tract (CST) in poststroke hemiplegic patients. A total of 48 supratentorial subacute patients after stroke were enrolled, who had a brain MRI scan within 6 weeks from onset, and no stroke recurrence reported within the 2-year follow-up period. Diffusion tensor images were obtained and CSTs were reconstructed. The participants were classified into three groups: type A, the CST originating from the primary motor cortex was preserved around the lesion area; type B, the CST was similar to type A, except that the fiber originated from the area adjacent to the primary motor cortex; and type C, the CST was interrupted or not shown. Motor functions using Fugl-Meyer Motor Assessment (FMA), the Box and Block Test (BBT), and Functional Ambulation Category, and cognitive function using Mini-Mental Status Examination (MMSE) were measured at baseline and at 2 years from stroke onset. Changes in FMA and BBT were significantly different according to diffusion tensor tractography type at follow-up (P

BACKGROUND AND PURPOSE: Differentiation of tumorous intracerebral hemorrhage from benign etiology is critical in initial treatment plan and prognosis. Our aim was to investigate the diagnostic value of CT densitometry to discriminate tumorous and nontumorous causes of acute intracerebral hemorrhage. MATERIALS AND METHODS: This retrospective study included 110 patients with acute intracerebral hemorrhage classified into 5 groups: primary intracerebral hemorrhage without (group 1) or with antithrombotics (group 2) and secondary intracerebral hemorrhage with vascular malformation (group 3), brain metastases (group 4), or primary brain tumors (group 5). The 5 groups were dichotomized into tumorous (groups 4 and 5) and nontumorous intracerebral hemorrhage (groups 1–3). Histogram parameters of hematoma attenuation on nonenhanced CT were compared among the groups and between tumorous and nontumorous intracerebral hemorrhages. With receiver operating characteristic analysis, optimal cutoffs and area under the curve were calculated for discriminating tumorous and nontumorous intracerebral hemorrhages. RESULTS: Histogram analysis of acute intracerebral hemorrhage attenuation showed that group 1 had higher mean, 5th, 25th, 50th, and 75th percentile values than groups 4 and 5 and higher minimum and 5th percentile values than group 2. Group 3 had higher 5th percentile values than groups 4 and 5. After dichotomization, all histogram parameters except maximum and kurtosis were different between tumorous and nontumorous intracerebral hemorrhages, with tumors having lower cumulative histogram parameters and positive skewness. In receiver operating characteristic analysis, 5th and 25th percentile values showed the highest diagnostic performance for discriminating tumorous and nontumorous intracerebral hemorrhages, with 0.81 area under the curve, cutoffs of 34 HU and 44 HU, sensitivities of 65.6% and 70.0%, and specificities of 85.0% and 80.0%, respectively. CONCLUSIONS: CT densitometry of intracerebral hemorrhage on nonenhanced CT might be useful for discriminating tumorous and nontumorous causes of acute intracerebral hemorrhage.

The durability of a fuel cell electrode was improved by using a boron-doped diamond (BDD) electrode support. BDD nanoparticles were synthesized by a size-controllable electrostatic self-assembly method (ESA). Moreover, the morphological changes as a function of operating time were investigated to prove the durability enhancement. First, diamond seeds were formed by an ESA method. The BDDs were then synthesized around these seeds by a conventional hot-filament chemical vapor deposition process. A Pt catalyst was then deposited by the polyol method, and it was characterized by scanning electron microscopy and transmission electron microscopy. The supporting BDD particles were 100–200 nm in size, whereas the Pt catalyst particles were 2–4 nm. Multiwalled carbon nanotubes (MWCNTs) and a conventional supporting material (Vulcan XC-72) were also studied for comparison. The electrochemical characteristics were examined by cyclic voltammetry and unit cell tests. The BDD support showed a larger surface area and better performance than the MWCNT and Vulcan XC-72 supports. According to the accelerated long-term stability tests, the BDD support material was more stable than the MWCNT and Vulcan XC-72 supports. These results show that BDD supports improve the durability of the fuel cell electrode.

Numerous studies have suggested that postpartum women show a decline in cognitive abilities. However, to date, no study has investigated the presence of qualitative alterations in recognition memory processes in postpartum women that may lead to a decline in cognitive ability. To address this issue, we employed the Remember/Know procedure and functional magnetic resonance imaging (fMRI). Behavioral results demonstrated that compared with the matched control (CTRL) group, the postpartum (PP) group endorsed “Remember” less and “Know” more to old items. A univariate analysis of fMRI data indicated lower neural activity of the subjective recollection network in the PP group than in the CTRL group. We also performed a large-scale functional connectivity multivariate pattern analysis (fcMVPA) using task-dependent time-series to detect differences in functional connectivity patterns and neural interactivity between the PP and CTRL groups. The fcMVPA results revealed that the PP group exhibited altered functional connectivity patterns from which machine learning algorithms could discriminate group membership with 94% accuracy. Collectively, these findings demonstrated that altered subjective recollection processes in the PP group during episodic memory decisions are associated with diminished neural activity and abnormal interactivity across the subjective recollection network. We believe that this is one of the first studies demonstrating qualitative alterations in recognition memory processes in postpartum women.

Degeneration of the substantia innominata (SI) is significantly correlated with cognitive performance in Parkinson’s disease (PD). We examined functional and structural patterns of SI degeneration in drug-naïve PD patients according to the duration of parkinsonism before mild cognitive impairment (MCI) diagnosis. Twenty PD patients with a shorter duration (PD-MCI-SD

Identification of loss of SMARCB1/INI1 expression in poorly differentiated (PD) chordoma in pediatric patients suggests that PD chordoma is an entity molecularly distinct from conventional chordoma or atypical teratoid/rhabdoid tumor, which is also characterized by loss of SMARCB1/INI1 expression by inactivating mutation of the SMARCB1/INI gene. So far, around 20 cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression have been reported. Here, we report two cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression, which is very rare among the pediatric chordoma types. Both patients presented clival masses on preoperative MRI. Histologically, both tumors had nonclassic histologic features for conventional chordoma: sheets of large epithelioid to spindle cells with vesicular nuclei and prominent nucleoli. Both cases revealed nuclear expression of brachyury, loss of SMARCB1/INI1 expression and lack of embryonal, neuroectodermal, or epithelial component. One case showed heterozygous loss of EWSR1 gene by break-apart fluorescence in situ hybridization that reflected loss of SMARCB1/INI1 gene. Based on the clival location and histologic findings along with the loss of SMARCB1/INI1 expression and positivity for nuclear brachyury staining, the final pathologic diagnosis for both cases was PD chordoma.

Objective Human immunodeficiency virus (HIV) infection has been known to damage the microstructural integrity of white matter (WM). However, only a few studies have assessed the brain regions in HIV-associated neurocognitive disorders (HAND) with diffusion tensor imaging (DTI). Therefore, we sought to compare the DTI data between HIV patients with and without HAND using tract-based spatial statistics (TBSS). Materials and Methods Twenty-two HIV-infected patients (10 with HAND and 12 without HAND) and 11 healthy controls (HC) were enrolled in this study. A whole-brain analysis of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was performed with TBSS and a subsequent 20 tract-specific region-of-interest (ROI)-based analysis to localize and compare altered WM integrity in all group contrasts. Results Compared with HC, patients with HAND showed decreased FA in the right frontoparietal WM including the upper corticospinal tract (CST) and increased MD and RD in the bilateral frontoparietal WM, corpus callosum, bilateral CSTs and bilateral cerebellar peduncles. The DTI values did not significantly differ between HIV patients with and without HAND or between HIV patients without HAND and HC. In the ROI-based analysis, decreased FA was observed in the right superior longitudinal fasciculus and was significantly correlated with decreased information processing speed, memory, executive function, and fine motor function in HIV patients. Conclusion These results suggest that altered integrity of the frontoparietal WM contributes to cognitive dysfunction in HIV patients.

In this article the recent progress in the elements of EUV lithography is presented. Source power around 205W was demonstrated and further scaling up is going on, which is expected to be implemented in the field within 2017. Source availability keeps improving especially due to the introduction of new droplet generator but collector lifetime needs to be verified at each power level. Mask blank defect satisfied the HVM goal. Resist meets the requirements of development purposes and dose needs to be reduced further to satisfy the productivity demand. Pellicle, where both the high transmittance and long lifetime are demanded, needs improvements especially in pellicle membrane. Potential issues in high-NA EUV are discussed including resist, small DOF, stitching, mask infrastructure, whose solutions need to be prepared timely in addition to high-NA exposure tool to enable this technology.

Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals, Inc.

The present study analyzed outcomes of surgery followed by concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) at a single institution. Outcomes were retrospectively reviewed in 252 consecutive patients with newly diagnosed GBM who underwent surgery followed by CCRT with TMZ at the authors' institution between 2005 and 2013. At initial operation, 126 (50.0%), 55 (21.8%), 45 (17.9%), and 26 (10.3%) patients underwent gross total resection (GTR), subtotal resection, partial resection (PR), and biopsy, respectively. Their median overall survival (OS) was 20.8 months (95% confidence interval [CI] 17.7-23.9 months) and their median progression-free survival was 12.7 months (95% CI 11.2-14.2 months). The O-6-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 78 (34.1%) of the 229 patients assayed, and an isocitrate dehydrogenase 1 mutation was detected in 7 (6.6%) of the 106 patients analyzed. Univariate analyses showed that patient age, involvement of eloquent areas, involvement of the subventricular zone, presence of leptomeningeal seeding, Karnofsky Performance Status, extent of resection (EOR), MGMT promoter methylation, and presence of an oligodendroglioma component were prognostic of OS. Multivariate analysis showed that age, involvement of eloquent areas, presence of leptomeningeal seeding, EOR, and MGMT promoter methylation were significantly predictive of survival. OS in patients with GBM who undergo surgery followed by CCRT with TMZ is enhanced by complete resection. Other factors significantly prognostic of OS include that age, involvement of eloquent areas, presence of leptomeningeal seeding, and MGMT promoter methylation. Abbreviations: CCRT = concomitant chemoradiotherapy, EOR = extent of resection, GBM = glioblastoma, GTR = gross total resection, IDH = isocitrate dehydrogenase, KPS = Karnofsky performance status, MGMT = O-6-methylguanine-DNA methyltransferase, MRI = magnetic res

This study examined dark tourism motivation and brand equity of two different destinations. Using a qualitative researched on related field, this study traces visitors of Nanjing Massacre Memorial Hall(China) and Lee SeungBok Memorial Hall(South Korea). Steeped in commemorate the murder of Chines by Japanese and Korean Lee SeungBok by North Kroean Army are Memorial Halls still being remembered and having its own cultural importance as a dark tourism destination throughout Korea and China. Through study that involved visitors observation from November 30, 2016 to December 30, 2016. Among the 700 distributed questionnaires, 650 copies were collected and 609 copies were used for the actual analysis. The content analysis education, friendly, cultural, place factors were found to be key motivation aspects of these dark tourism related to death. Additionally, it was found, that there were significant differences existed mainly between visiting motivation, tourism satisfaction and behavioral intention of visitors of two destinations. Finally, discussed about the important aspects of the dark tourism phenomenon related to Korea?s abandoned dark tourism destination and suggested that, activation of abandoned destination will bring massive the regional development.

Purpose: To investigate horizontal image disparity in three-dimensional (3-D) perception using 3-D animations in normal control patients and patients with intermittent exotropia, anisometropic amblyopia, and partially accommodative esotropia. Materials and Methods: A total of 133 subjects were included. Stereopsis was measured using the Titmus Stereo test (Stereo Optical Inc., Chicago, IL, USA) and a 3-D stereopsis test with a 15 inch 3-D display laptop, adjusting 3-D parameters of 0 mm horizontal disparity to 15 mm horizontal disparity. Results: When compared with normal controls, the average threshold of the 3-D stereopsis test was significantly reduced for esotropia patients ( p

Objective To assess whether radiomics features derived from multiparametric MRI can predict the tumor grade of lower-grade gliomas (LGGs; World Health Organization grade II and grade III) and the nonenhancing LGG subgroup. Materials and methods Two-hundred four patients with LGGs from our institutional cohort were allocated to training (n = 136) and test (n = 68) sets. Postcontrast T1-weighted images, T2-weighted images, and fluid-attenuated inversion recovery images were analyzed to extract 250 radiomics features. Various machine learning classifiers were trained using the radiomics features to predict the glioma grade. The trained classifiers were internally validated on the institutional test set and externally validated on a separate cohort (n = 99) from The Cancer Genome Atlas (TCGA). Classifier performance was assessed by determining the area under the curve (AUC) from receiver operating characteristic curve analysis. An identical process was performed in the nonenhancing LGG subgroup (institutional training set, n = 73; institutional test set, n = 37; and TCGA cohort, n = 37) to predict the glioma grade. Results The performance of the best classifier was good in the internal validation set (AUC, 0.85) and fair in the external validation set (AUC, 0.72) to predict the LGG grade. For the nonenhancing LGG subgroup, the performance of the best classifier was good in the internal validation set (AUC, 0.82), but poor in the external validation set (AUC, 0.68). Conclusion Radiomics feature-based classifiers may be useful to predict LGG grades. However, radiomics classifiers may have a limited value when applied to the nonenhancing LGG subgroup in a TCGA cohort.

The aim of this study was to investigate spinal cord injury (SCI) on the basis of diffusion tensor imaging (DTI) in patients with high-voltage electrical injury. We recruited eight high-voltage electrical injury patients and eight healthy subjects matched for age and sex. DTI and central motor conduction time were acquired in both the patient and control groups. We obtained DTI indices according to the spinal cord levels (from C2 to C7) and cross-section locations (anterior, lateral, and posterior). Fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between the two groups; additionally, they were compared in relation to spinal cord level and cross-section location. In the patient group relative to the control group, the FA value decreased and the MD and RD values increased in all of the regions of interest (ROI) with statistical significance (p

This study describes the effect of surfactant concentration on the chemical mechanical polishing process of Ge1Sb6Te3 film using nanodiamond-based slurry. Aggregated diamond nanoparticles were dispersed in a slurry solution containing anionic poly(sodium 4-styrene sulfonate) using milling system. The zeta-potential, particle size and transmission electron microscopy image of the dispersed nanodiamond particles were analyzed for slurries having varying surfactant concentrations to identify the effect of the surfactant concentration on the milling process. The cationic nanodiamond particles were covered with the anionic poly(sodium 4-styrene sulfonate) polymer, and the polymer acted as a dispersion agent on account of the electrostatic repulsion. By increasing the surfactant concentration in the milling process, the average particle size of the nanodiamond particle decreased until the concentration reached 0.9 wt%. In addition, the surface roughness and material removal rate of the Ge1Sb6Te3 film in the polishing process strongly-depended on the surfactant concentration. Both surface roughness and material removal rate decreased with an increase in the surfactant concentration. Excess poly(sodium 4-styrene sulfonate) acted as a passivation layer, resulting in a decrease in the surface roughness and material removal rate of the Ge1Sb6Te3 film.

Enzymatic biosensor reactions follow the Michaelis–Menten kinetics, coupled with diffusion. The diffusion reaction processes for amperometric enzyme biosensors have been simulated to explore the geometrical effects of nanowire array electrodes (NWAEs) and nanowire array stack electrodes (NWASEs) from the viewpoint of enhanced mass transport and increased reaction surface area in two limiting cases. For practical analysis considering sensor fabrication, most samples are assumed to have the same unit square (1 cm × 1 cm) footprint. In the reaction-controlled case, the surface area increment improves the sensitivity regardless of electrode geometry. However, in the diffusion-controlled case, well-controlled NWAE or NWASE geometries as well as the increased surface area improve the sensitivity when the peak current at an early stage of the reaction is measured. Peak current engineering by adjusting the geometric parameters of NWAEs and NWASEs will result in a highly sensitive amperometric enzyme biosensor in the diffusion-controlled case. In contrast to previous micro- and nanoelectrode array studies, we investigated NWASEs representing entangled nanowire network electrodes, and report significant improvements in both limiting cases.

Persistent gene silencing is crucially required for the successful therapeutics of short interfering RNA (siRNA). Here, we describe a nanoparticle based delivery system which assembled by layering siRNAs between protease degradable polypeptides to extend the therapeutic window. These tightly packed nanoparticles are efficiently taken up by cells by endocytosis, and the fabricated siRNAs are gradually released following intracellular degradation of the polypeptide layers. During cell division, the particles are distributed to the daughter cells. Due to the slow degradation through the multiple layers, the particles continuously release siRNA in all cells. Using this controlled release construct, the in vivo gene silencing effect of siRNA is consistent for an ultra-long period of time (>3 weeks) with only a single treatment.

To identify brain cortical regions relevant to HIV-associated neurocognitive disorder (HAND) in HIV patients. HIV patients with HAND (n = 10), those with intact cognition (HIV-IC; n = 12), and age-matched, seronegative controls (n = 11) were recruited. All participants were male and underwent 3-dimensional T1-weighted imaging. Both vertex-wise and region of interest (ROI) analyses were performed to analyse cortical thickness. Compared to controls, both HIV-IC and HAND showed decreased cortical thickness mainly in the bilateral primary sensorimotor areas, extending to the prefrontal and parietal cortices. When directly comparing HIV-IC and HAND, HAND showed cortical thinning in the left retrosplenial cortex, left dorsolateral prefrontal cortex, left inferior parietal lobule, bilateral superior medial prefrontal cortices, right temporoparietal junction and left hippocampus, and cortical thickening in the left middle occipital cortex. Left retrosplenial cortical thinning showed significant correlation with slower information processing, declined verbal memory and executive function, and impaired fine motor skills. This study supports previous research suggesting the selective vulnerability of the primary sensorimotor cortices and associations between cortical thinning in the prefrontal and parietal cortices and cognitive impairment in HIV-infected patients. Furthermore, for the first time, we propose retrosplenial cortical thinning as a possible major contributor to HIV-associated cognitive impairment. • Primary sensorimotor and supplementary motor cortices were selectively vulnerable to HIV infection • Prefrontal and parietal cortical thinning was associated with HIV-associated cognitive impairment • Retrosplenial cortical thinning might be a major contributor to HIV-associated cognitive impairment

The purpose of this study is to evaluate direct in vivo visualization of nigrosome-1 in substantia nigra (SN) with 3D FLAIR imaging and its diagnostic value in predicting the intactness of presynaptic dopaminergic function of the nigrostriatal pathway.Forty-five patients showing parkinsonism who underwent both 3D FLAIR and dopamine transporter (DAT) imaging were recruited. In total, 90 SNs were reviewed on axial 3D FLAIR images. We regarded oval or linear hyperintensities on the posterolateral side of SN as intact nigrosome-1. Two neuroradiologists independently evaluated the appearance of nigrosome-1, and disagreements were settled by consensus. Kappa values for interrater agreement were calculated. Diagnostic performances of the appearance of nigrosome-1 for predicting presynaptic dopaminergic function on DAT imaging and Parkinson disease (PD) were calculated.The diagnostic performances of a loss of nigrosome-1 on 3D FLAIR images were sensitivity of 85.7%, specificity of 85.4%, positive predictive value (PPV) of 83.7%, and negative predictive value (NPV) of 87.2% for predicting impaired presynaptic dopaminergic function on DAT imaging, and sensitivity of 94.7%, specificity of 76.9%, PPV of 85.7%, and NPV of 90.9% for predicting PD. When only oval hyperintensity was considered as intact nigrosome-1, its sensitivity and NPV were increased up to 95.2% and 91.7%, respectively, for predicting impaired presynaptic dopaminergic function on DAT imaging, and both increased to 100% for predicting PD. Interobserver agreement for the appearance of nigrosome-1 on 3D FLAIR images was substantial (κ = 0.625).Nigrosome-1 could be visualized on 3D FLAIR images, and its loss can be used to predict presynaptic dopaminergic function and to diagnose PD with high accuracy.

OBJECTIVE Young patients with moyamoya disease can exhibit infarction after revascularization surgery. This analysis of the characteristics of infarction after encephaloduroarteriosynangiosis (EDAS) in young patients with moyamoya disease was undertaken in an effort to elucidate the infarction mechanism. METHODS The authors retrospectively collected clinical information and reviewed pre- and postoperative MRI studies from cases involving patients younger than 18 years who underwent EDAS for the treatment of moyamoya disease between January 2012 and February 2015. Infarction patterns were categorized into watershed, territorial, or mixed pattern. The Wilcoxon rank sum test, chi-square test, and Fisher exact test were used to compare the clinical and imaging variables between patient groups. The characteristics of patients with and without postoperative infarction were compared using univariate and multivariate analysis. The cumulative proportion of patients without postoperative infarction according to operation stage was calculated using the Kaplan-Meier method and the resulting curves were compared using the log-rank test. RESULTS In 100 patients, 171 EDAS procedures had been performed. There were 38 cases of preoperative infarction in 35 patients and 20 cases of postoperative infarction in 13 patients. Territorial infarction was more frequent in the postoperative infarction group than in the preoperative infarction group (55.0% vs 37.8%, p = 0.037). Infarction was more common on the bilateral or contralateral side of the operation after first-stage EDAS (9 [75.0%] of 12 infarctions) than in the second-stage operation (2 [25.0%] of 8 infarctions), but the difference was not statistically significant (p = 0.068). The frequency of postoperative infarction was not significantly different depending on the stage of the operation (p = 0.694). CONCLUSIONS An acute infarction pattern after EDAS was more frequently territorial, suggesting an underlying occlusive mechanism. Operation stage did not affect the rate of postoperative infarction occurrence.

To investigate the quality of images reconstructed with adaptive statistical iterative reconstruction V (ASIR-V), using pediatric head CT protocols. A phantom was scanned at decreasing 20% mA intervals using our standard pediatric head CT protocols. Each study was then reconstructed at 10% ASIR-V intervals. After the phantom study, we reduced mA by 10% in the protocol for

Purpose The study was conducted to assess the long-term outcome of antiepileptic drug (AED) treatment in drug-naive patients with cavernous malformation (CM) related epilepsy (CRE). Method This is a retrospective, single-center, long-term observational study of 34 patients with previously untreated seizures related to CM. All patients were followed-up for at least two years. Drug resistant epilepsy (DRE) was defined as two or more seizures per year after trial of two appropriate AEDs. Patients who had only one seizure during the previous one year were assigned as "epilepsy with rare seizures (ERSs)". Results Terminal 1-year seizure remission (1-YTR) was achieved in 22 (64.7%) patients, nine (26.5%) patients were diagnosed as DRE, and three (8.8%) patients were as ERSs. 1-YTR was achieved in 18 (52.9%) patients by the first drug regimen and in additional four (11.8%) patients by the second drug regimen. None of nine patients who failed to first two drug regimens did achieve 1-YTR. The location of CM in the temporal lobe was the only prognostic factor predicting a poor seizure outcome (p=0.012). Conclusion The outcome of AEDs therapy in patients who were presented with new onset of CRE was quite comparable with that of patients with newly diagnosed epilepsy. Failure to achieve seizure-free after adequate trials of two AEDs seems appropriate as the criteria for their referral to surgical treatment. For patients with temporal lobe CRE, earlier presurgical evaluation may be considered justifiable once they failed to an adequate trial of the first drug.

To evaluate the added value of amide proton transfer (APT) imaging to the apparent diffusion coefficient (ADC) from diffusion tensor imaging (DTI) and the relative cerebral blood volume (rCBV) from perfusion magnetic resonance imaging (MRI) for discriminating between high- and low-grade gliomas.Forty-six consecutive adult patients with diffuse gliomas who underwent preoperative APT imaging, DTI and perfusion MRI were enrolled. APT signals were compared according to the World Health Organization grade. The diagnostic ability and added value of the APT signal to the ADC and rCBV for discriminating between low- and high-grade gliomas were evaluated using receiver operating characteristic (ROC) analyses and integrated discrimination improvement.The APT signal increased as the glioma grade increased. The discrimination abilities of the APT, ADC and rCBV values were not significantly different. Using both the APT signal and ADC significantly improved discrimination vs. the ADC alone (area under the ROC curve [AUC], 0.888 vs. 0.910; P = 0.007), whereas using both the APT signal and rCBV did not improve discrimination vs. the rCBV alone (AUC, 0.927 vs. 0.923; P = 0.222).APT imaging may be a useful imaging biomarker that adds value to the ADC for discriminating between low- and high-grade gliomas.• Higher APT values were correlated with higher glioma grades. • Adding the APT signal to the ADC improved glioma grading. • Adding the APT signal to rCBV did not improve glioma grading. • APT is a useful adjunct to the ADC for glioma grading.

To determine the relationship between the number of administrations of various gadolinium-based contrast agents (GBCAs) and increased T1 signal intensity in the globus pallidus (GP) and dentate nucleus (DN). This retrospective study included 122 patients who underwent double-dose GBCA-enhanced magnetic resonance imaging. Two radiologists calculated GP-to-thalamus (TH) signal intensity ratio, DN-to-pons signal intensity ratio and relative change (Rchange) between the baseline and final examinations. Interobserver agreement was evaluated. The relationships between Rchange and several factors, including number of each GBCA administrations, were analysed using a generalized additive model. Six patients (4.9%) received linear GBCAs (mean 20.8 number of administration; range 15–30), 44 patients (36.1%) received macrocyclic GBCAs (mean 26.1; range 14–51) and 72 patients (59.0%) received both types of GBCAs (mean 31.5; range 12–65). Interobserver agreement was almost perfect (0.99; 95% CI: 0.99–0.99). Rchange (DN:pons) was associated with gadodiamide (p = 0.006) and gadopentetate dimeglumine (p

BACKGROUND AND PURPOSE: The higher cortical burden of Lewy body and Alzheimer disease–type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. MATERIALS AND METHODS: Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (

To evaluate the ability of the initial area under the curve (IAUC) derived from dynamic contrast-enhanced MR imaging (DCE-MRI) and apparent diffusion coefficient (ADC) in differentiating between primary central nervous system lymphoma (PCNSL) and atypical glioblastoma (GBM). We retrospectively identified 19 patients with atypical GBM (less than 13 % necrosis of the enhancing tumour), and 23 patients with PCNSL. The histogram parameters of IAUC at 30, 60, 90 s (IAUC30, IAUC60, and IAUC90), and ADC were compared between PCNSL and GBM. The diagnostic performances and added values of the IAUC and ADC for differentiating between PCNSL and GBM were evaluated. Interobserver agreement was assessed via intraclass correlation coefficient (ICC). The IAUC and ADC parameters were higher in GBM than in PCNSL. The 90th percentile (p90) of IAUC30 and 10th percentile (p10) of ADC showed the best diagnostic performance. Adding p90 of IAUC30 to p10 of ADC improved the differentiation between PCNSL and GBM (area under the ROC curve [AUC] = 0.886), compared to IAUC30 or ADC alone (AUC = 0.789 and 0.744; P

OBJECTIVE The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. MATERIALS AND METHODS Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. RESULTS Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min(-1) vs. 0.07 ± 0.02 min(-1), p = 0.661 for K(trans); 0.30 ± 0.05 min(-1) vs. 0.37 ± 0.11 min(-1), p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). CONCLUSION Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.

The aim of this study was to characterize amide proton transfer (APT)-weighted signals in acute and subacute haemorrhage brain lesions of various underlying aetiologies. Twenty-three patients with symptomatic haemorrhage brain lesions including tumorous (n = 16) and non-tumorous lesions (n = 7) were evaluated. APT imaging was performed and analyzed with magnetization transfer ratio asymmetry (MTR asym ). Regions of interest were defined as the enhancing portion (when present), acute or subacute haemorrhage, and normal-appearing white matter based on anatomical MRI. MTR asym values were compared among groups and components using a linear mixed model. MTR asym values were 3.68 % in acute haemorrhage, 1.6 % in subacute haemorrhage, 2.65 % in the enhancing portion, and 0.38 % in normal white matter. According to the linear mixed model, the distribution of MTR asym values among components was not significantly different between tumour and non-tumour groups. MTR asym in acute haemorrhage was significantly higher than those in the other regions regardless of underlying pathology. Acute haemorrhages showed high MTR asym regardless of the underlying pathology, whereas subacute haemorrhages showed lower MTR asym than acute haemorrhages. These results can aid in the interpretation of APT imaging in haemorrhage brain lesions. • Acute haemorrhages show significantly higher MTR asym values than subacute haemorrhages. • MTR asym is higher in acute haemorrhage than in enhancing tumour tissue. • MTR asym in haemorrhage does not differ between tumorous and non-tumorous lesions.

Background An early and reliable diagnosis of intracranial arterial dissection is important to reduce the risk of neurological complication. The purpose of this study was to assess the clinical usefulness of three-dimensional high-resolution MRI (3D-HR-MRI) including pre- and post-contrast T1-weighted volumetric isotropic turbo spin echo acquisition with improved motion-sensitized driven equilibrium preparation (3D-iMSDE-T1) and proton-density weighted image (3D-PD) in detecting dissection and to evaluate the added value of 3D-PD in diagnosing intracranial arterial dissection. Methods We retrospectively recruited patients who underwent 3D-HR-MRI with clinical suspicion of arterial dissection. Among them, we selected patients who were diagnosed with definite dissection according to the Spontaneous Cervicocephalic Arterial Dissections Study criteria. For each patient, the presence of intimal flap, intramural hematoma, and vessel dilatation were evaluated independently by two neuroradiologists on each sequence. Interobserver agreement was assessed. Results Seventeen patients (mean age: 41 ± 10 [SD] years; 13 men) were diagnosed with definite dissection. The intimal flaps were more frequently detected on 3D-PD (88.2%, 15/17) than on 3D-iMSDE-T1 (29.4%, 5/17), and post-contrast 3D-iMSDE-T1 (35.3%, 6/17; P = 0.006 and P = 0.004, respectively). No significant difference was found in the detection rate of intramural hematomas (59–71%) and vascular dilatations (47%) on each sequence. Interobserver agreement for detection of dissection findings showed almost perfect agreement (k = 0.84–1.00), except for detection of intimal flaps on pre-contrast 3D-iMSDE-T1 (k = 0.62). After addition of 3D-PD to pre- and post-contrast 3D-iMSDE-T1, more patients were diagnosed with definite dissection with the initial MRI (88.2% vs. 47.1%; P = 0.039). Conclusions The intimal flap might be better visualized on the 3D-PD sequence than the 3D-iMSDE-T1 sequences, allowing diagnosis of definite dissection without follow-up imaging.

Small interfering RNA (siRNA)-mediated gene silencing has shown prominent therapeutic effects in treating various diseases. However, adequate delivery and persistent gene silencing remain challenging. A nanoparticle-based delivery system which assembled by layering siRNAs between protease degradable polypeptides to show ultra-long gene silencing effect in vivo is developed. Gold nanoparticle is used as a scaffold for its unique properties including uniform size, biocompatibility, ready synthesis, and easy functionalization. A simple layer-by-layer fabrication approach, based on the electrostatic interaction between positively and negatively charged polymers, is applied to package the therapeutic siRNAs.