Association of Plaque Features with Infarct Patterns in Patients with Acutely Symptomatic Middle Cerebral Artery Atherosclerotic Disease.

BACKGROUND AND PURPOSE: Understanding the stroke mechanism of middle cerebral artery (MCA) atherosclerosis is important for stroke triage and future trial design. The aim of this study was to characterize intrinsic MCA plaque and acute cerebral infarct in vivo by using high-resolution black-blood (BB) and diffusion-weighted magnetic resonance (MR) imaging and to investigate the relationship between plaque features and infarct patterns. METHODS: A single-center retrospective study was conducted at a tertiary referral center between March 2017 and August 2019. Patients consecutively admitted for acute ischemic stroke with MCA stenosis underwent diffusion-weighted and BB MR imaging. Plaque features and infarct patterns were assessed. The association between plaque features and infarct patterns (binary variable: single/multiple) was evaluated using a multivariate logistic regression model. RESULTS: Of 49 patients with MCA atherosclerotic stenosis, diffusion-weighted MR imaging showed that 28 patients (57%) had multiple acute cerebral infarcts and 21 patients had single acute cerebral infarcts. In contrast to single infarct, multiple infarcts were associated with greater plaque burden (81.9±7.24 versus 71.3±13.7; P=0.012). A multivariate logistic regression model adjusted for 7 potential confounders confirmed a statistically significant positive association between plaque burden and multiple acute infarcts (adjusted R2 =0.432, P< 0.001). The rate of plaque surface irregularity was significantly greater in patients with multiple infarcts than those with single infarct (71% versus 43%, P=0.044). For single acute penetrating artery infarct, patients with infarct size > 2cm had greater plaque burden compared with patients with infarct size < 2cm (75.3±13.4 versus 63.4±10.9; P = 0.016). CONCLUSIONS: Increased plaque burden, plaque surface irregularity in patients with MCA stenosis is associated with its likelihood to have caused an artery-to-artery embolism that produces multiple cerebral infarcts, especially along the border zone region, and increased plaque burden may promote subcortical single infarct size by occluding penetrating arteries. Our results provide important insight into stroke mechanism of MCA atherosclerosis.

Fluoxetine induces vascular endothelial growth factor/Netrin over-expression via the mediation of hypoxia-inducible factor 1-alpha in SH-SY5Y cells.

Fluoxetine has become one of the most promising drugs for improving clinical outcome in patients with cerebral infarction. Although the clinical efficacy of fluoxetine has been preliminarily demonstrated, its mechanism remains unclear. Hypoxia-inducible factor 1-alpha (HIF-1α) is upstream to Netrin and vascular endothelial growth factor (VEGF), and under hypoxia conditions it may induce expression of Netrin-1 and VEGF in vascular endothelial cells. We sought to explore whether it can regulate their expression in hypoxia and mediate the effect of fluoxetine in hypoxia. In this study, the effect of hypoxia on the expression of VEGF and Netrin was observed in vitro by real-time PCR and western blotting in SH-SY5Y cells; the binding sites of HIF-1α in VEGF and Netrin gene promoters were identified by luciferase reporter; the effect of fluoxetine on binding of HIF-1α with Netrin and VEGF promoters in hypoxia was observed by Chromatin Immunoprecipitation (ChIP) Assay. We prove that HIF-1α regulates transcription of both VEGF and Netrin, and that in hypoxia fluoxetine up-regulates VEGF and Netrin expression via mediation of HIF-1α that binds to hypoxia-response element sites of VEGF and Netrin promoters. Our study indicates that HIF-1α may play an important role in the treatment of cerebral infarction through mediating the recovery of neurological function induced by fluoxetine, which provides theoretical basis for the development of gene therapeutic drugs targeting HIF-1α. We show that hypoxia-inducible factor 1-alpha (HIF-1α) regulates transcription of both vascular endothelial growth factor (VEGF) and Netrin. Furthermore, we also show that in hypoxia fluoxetine up-regulates VEGF and Netrin expression via mediation of HIF-1α that binds to hypoxia-response element (HRE) sites of VEGF and Netrin promoters. Our study indicates that HIF-1α may play an important role in the treatment of cerebral infarction through mediating the recovery of neurological function induced by fluoxetine. These findings provide a theoretical basis for development of gene therapeutic drugs targeting HIF-1α.

Susceptibility Vessel Sign in Isolated Brainstem Infarction with Large Artery Occlusion.

BACKGROUND/AIMS: It is crucial to detect the composition of the thrombus in isolated brainstem infarction with large artery occlusion. The aim of this study was to explore the susceptibility vessel sign (SVS) whose composition is mainly deoxidized red cells in patients with isolated brainstem infarction and posterior circulation large artery occlusion. METHODS: This was a single-center retrospective study. All patients with posterior circulation large artery occlusion from January 2003 to September 2013 were included. We identified 213 patients who had posterior circulation large artery occlusion, and 81 patients met the imaging eligibility criteria. Among the 81 patients, 21 had isolated brainstem infarction. RESULTS: Among the 21 patients, 7 (33%) had SVS and 2 (10%) had pseudo-SVS (calcified vessels without thrombosis). In the 7 patients with SVS, we found atrial fibrillation in 2 patients, dissection in 3 patients and large artery atherosclerotic disease (LAAD) in 2 patients. There were SVS in 100% (2/2) of patients with atrial fibrillation, 50% (3/6) of patients with dissection, and 20% (2/10) of patients with LAAD. CONCLUSIONS: SVS reflects pathology of deoxidized red cells composition in patients with isolated brainstem infarction. This finding may be useful to explore the different stroke mechanisms and therapy strategies.

Enhanced heterogeneous interface to construct intelligent conductive hydrogel gas sensor for individualized treatment of infected wounds.

In this study, we developed an enhanced heterogeneous interface intelligent conductive hydrogel NH3 sensor for individualized treatment of infected wounds. The sensor achieved monitoring, self-diagnosis, and adaptive gear adjustment functions. The PPY@PDA/PANI(3/6) sensor had a minimum NH3 detection concentration of 50 ppb and a response value of 2.94 %. It also had a theoretical detection limit of 49 ppt for infected wound gas. The sensor exhibited a fast response time of 23.2 s and a recovery time of 42.9 s. Tobramycin (TOB) was encapsulated in a self-healing QCS/OD hydrogel formed by quaternized chitosan (QCS) and oxidized dextran (OD), followed by the addition of polydopamine-coated polypyrrole nanowires (PPY@PDA) and polyaniline (PANI) to prepare electrically conductive drug-loaded PPY@PDA/PANI hydrogels. The drug-loaded PPY@PDA/PANI hydrogel was combined with a PANI/PVDF membrane to form an enhanced heterogeneous interfacial PPY@PDA/PANI/PVDF-based sensor, which could adaptively learn the individual wound ammonia response and adjust the speed of drug release from the PPY@PDA/PANI hydrogel with electrical stimulation. Drug release and animal studies demonstrated the efficacy of the PPY@PDA/PANI hydrogel in inhibiting infection and accelerating wound healing. In conclusion, the gas-sensitive conductive hydrogel sensing system is expected to enable intelligent drug delivery and provide personalized treatment for complex wound management.

Targeted tumor computed tomography imaging using low-generation dendrimer-stabilized gold nanoparticles.

We report a facile approach to fabricating low-generation poly(amidoamine) (PAMAM) dendrimer-stabilized gold nanoparticles (Au DSNPs) functionalized with folic acid (FA) for in vitro and in vivo targeted computed tomography (CT) imaging of cancer cells. In this study, amine-terminated generation 2 PAMAM dendrimers were employed as stabilizers to form Au DSNPs without additional reducing agents. The formed Au DSNPs with an Au core size of 5.5 nm were covalently modified with the targeting ligand FA, followed by acetylation of the remaining dendrimer terminal amines to endow the particles with targeting specificity and improved biocompatibility. Our characterization data show that the formed FA-modified Au DSNPs are stable at different pH values (5-8) and temperatures (4-50 °C), as well as in different aqueous media. MTT assay data along with cell morphology observations reveal that the FA-modified Au DSNPs are noncytotoxic in the particle concentration range of 0-3000 nM. X-ray attenuation coefficient measurements show that the CT value of FA-modified Au DSNPs is much higher than that of Omnipaque (a clinically used CT contrast agent) at the same concentration of the radiodense elements (Au or iodine). Importantly, the FA-modified Au DSNPs are able to specifically target a model cancer cell line (KB cells, a human epithelial carcinoma cell line) over-expressing FA receptors and they enable targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo after intravenous administration of the particles. With the simple synthesis approach, easy modification, good cytocompatibility, and high X-ray attenuation coefficient, the FA-modified low-generation Au DSNPs could be used as promising contrast agents for targeted CT imaging of different tumors over-expressing FA receptors.

Facile formation of folic acid-modified dendrimer-stabilized gold-silver alloy nanoparticles for potential cellular computed tomography imaging applications.

We report a facile approach to fabricating dendrimer-stabilized gold-silver alloy nanoparticles (Au-Ag alloy DSNPs) for targeted in vitro computed tomography (CT) imaging of cancer cells. In this study, folic acid (FA)-modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5·NH2-FA) were used as stabilizers to prepare Au-Ag alloy DSNPs by simultaneously reducing both gold and silver salts, followed by acetylation of the dendrimer terminal amines. The formed Au-Ag alloy DSNPs were characterized via different techniques. We show that the formed Au-Ag alloy DSNPs are spherical in shape with a relatively narrow size distribution, have good water solubility and colloidal stability, and display higher X-ray attenuation intensity than the iodine-based contrast agent of Omnipaque at the same molar concentration of the active element (i.e., Au plus Ag, or iodine). Cytotoxicity assay results show that the Au-Ag alloy DSNPs are cytocompatible in a given concentration range. Importantly, the formed Au-Ag alloy DSNPs are able to be specifically taken up by cancer cells overexpressing FA receptors and enable targeted CT imaging of the cancer cells. Given the unique structural characteristics of dendrimers and the facile synthesis of DSNPs, the developed Au-Ag alloy DSNPs may be used for various biomedical applications in sensing, diagnosis, and therapeutics.

ARE-PROTACs Enable Co-degradation of an Nrf2-MafG Heterodimer.

Proteolysis-targeting chimera (PROTAC) technology has emerged as a potential strategy to degrade "undruggable" proteins in recent years. Nrf2, an aberrantly activated transcription factor in cancer, is generally considered undruggable as lacking active sites or allosteric pockets. Here, we constructed the chimeric molecule C2, which consists of an Nrf2-binding element and a CRBN ligand, as a first-in-class Nrf2 degrader. Surprisingly, C2 was found to selectively degrade an Nrf2-MafG heterodimer simultaneously via the ubiquitin-proteasome system. C2 impeded Nrf2-ARE transcriptional activity significantly and improved the sensitivity of NSCLC cells to ferroptosis and therapeutic drugs. The degradation character of ARE-PROTACs suggests that the PROTAC hijacking the transcription element of TFs could achieve co-degradation of the transcription complex.

[Retracted] MicroRNA­337 inhibits colorectal cancer progression by directly targeting KRAS and suppressing the AKT and ERK pathways.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing data from flow cytometric experiments in Figs. 2D and 5D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere when it was submitted to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 3187­3196, 2017; DOI: 10.3892/or.2017.5997].

Association of Plaque Morphology With Stroke Mechanism in Patients With Symptomatic Posterior Circulation ICAD.

OBJECTIVE: Although the main mechanisms of stroke in patients with intracranial atherosclerotic disease (ICAD) - perforating artery occlusion (PAO) and artery-to-artery embolism (AAE) - have been identified and described, relatively little is known about the morphology of the symptomatic plaques and how they differ between these two mechanisms. METHODS: We prospectively recruited patients with acute ischemic stroke in the posterior circulation that was attributable to ICAD. 51 eligible patients were enrolled and underwent magnetic resonance imaging before being assigned to the PAO or AAE group according to probable stroke mechanism. Plaque morphological properties including plaque length, lumen area, outer wall area, plaque burden, plaque surface irregularity, vessel wall remodeling, and plaque enhancement, were assessed using high-resolution magnetic resonance imaging (HRMRI). Plaque morphological parameters of both PAO and AAE groups were compared using non-parametric tests. A binary logistic regression model was used to identify independent predictors while a receiver operating characteristic curve tested the sensitivity and specificity of the model. RESULTS: Among patients who met the imaging eligibility criteria, 38 (74.5%) had PAO and 13 (25.5%) had AAE. Plaque length was shorter (6.39 [interquartile range (IQR), 5.18-7.71] mm vs 10.90 [IQR, 8.18-11.85] mm, p<0.01) in PAO patients. Plaque burden was lower in PAO group (78.00 [IQR, 71.94-86.35] % vs 86.37 [IQR, 82.24-93.04] %, p=0.04). The proportion of patients with plaque surface irregularity was higher in AAE patients than in PAO patients (19/38, 50.00% vs 12/13, 92.30%, p=0.008). Plaque length was significantly associated with the PAO mechanism (adjusted OR 0.57, 95% CI, 0.41-0.79). CONCLUSION: Intracranial atherosclerotic plaque morphology differs between patients with PAO and those with AAE. Plaque with shorter length, lower plaque burden and regular surface is more likely to cause perforating artery occlusion.

Regulation of Nrf2 by phosphorylation: Consequences for biological function and therapeutic implications.

The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttranslational regulation of NRF2. For instance, PKC, casein kinase 2, and AMP-activated kinase positively, while GSK-3 negatively regulates NRF2 activity through phosphorylation of different sites. Here, we provide an overview of the phosphorylation regulation pattern of NRF2 and discuss the therapeutic potential of interventions targeting NRF2 phosphorylation.

Discovery of 3,5-Dimethyl-4-Sulfonyl-1H-Pyrrole-Based Myeloid Cell Leukemia 1 Inhibitors with High Affinity, Selectivity, and Oral Bioavailability.

Myeloid cell leukemia 1 (Mcl-1) protein is a key negative regulator of apoptosis, and developing Mcl-1 inhibitors has been an attractive strategy for cancer therapy. Herein, we describe the rational design, synthesis, and structure-activity relationship study of 3,5-dimethyl-4-sulfonyl-1H-pyrrole-based compounds as Mcl-1 inhibitors. Stepwise optimizations of hit compound 11 with primary Mcl-1 inhibition (52%@30 µM) led to the discovery of the most potent compound 40 with high affinity (Kd = 0.23 nM) and superior selectivity over other Bcl-2 family proteins (>40,000 folds). Mechanistic studies revealed that 40 could activate the apoptosis signal pathway in an Mcl-1-dependent manner. 40 exhibited favorable physicochemical properties and pharmacokinetic profiles (F% = 41.3%). Furthermore, oral administration of 40 was well tolerated to effectively inhibit tumor growth (T/C = 37.3%) in MV4-11 xenograft models. Collectively, these findings implicate that compound 40 is a promising antitumor agent that deserves further preclinical evaluations.

[MRI monitoring of cerebral spinal fluid metastasis in rabbit model].

OBJECTIVE: To establish a rabbit model of cerebral spinal flow metastasis, to analyze the growth rate of tumor, and to investigate the value of MRI in monitoring the biology of tumor compared with pathology. METHODS: Twenty-four New Zealand white rabbits were inoculated with suspension of VX(2) tumor cells in the subarachnoid space via the foramen magnum (experimental group), and 6 rabbits were inoculated with normal saline (control group). MRI examination, including non-enhanced T(1)WI, T(2)WI, and FLAIR sequences and then T(1)WI, FLAIR after dynamic contrast enhanced with Gd-DTPA were done 7 approximately 22 days after inoculation with a 3-day interval. The rabbits were killed after the last MRI scan with their spinal cords, spinal meninges, and tumor taken out to undergo microscopy. RESULTS: (1) MRI plain scan showed that in the experimental group 2 nodi in the medulla and 1 nodes in the cervical spinal cord were found with low signal on T(1)WI and high signal on T(2)WI; and FLAIR imaging showed local lesions with medial signal in 6 rabbits (25%). And no abnormal signs were seen in the control group. (2) MRI enhancement showed that in the experimental group the images of 15 rabbit models were enhanced markedly with irregular thickening of meninges or nodules at the subarachnoid space on T(1)WI, positive signs were confirmed on FLAIR sequence in 16 of the 24 rabbits, and positive signs were noted on DCE-MRI scanning in 18 of the 24 rabbits (75%). In the control group 5 of the 6 rabbits were negative in images. Microscopy showed thickened of meninges and spinal meninges in 20 of the 24 rabbits of the experimental group and spinal cord metastasis in 22 rabbits. No pathological changes were seen in the control group. Statistics showed a CSF metastasis rate of 91.67%. There were significant difference between the plain scan and T(1)WI with enhancement (P < 0.01) and between FLAIR scan and FLAIR enhancement scans. There was a significant difference between T(1)WI and FLAIR enhancement and pathological findings (P < 0.05). There was no significant difference between DCE-MRI method and pathological results (P > 0.05). CONCLUSION: Gd-DTPA enhanced MRI scan sequences has a high sensitivity and specificity and can be used in monitoring the growth of CSF metastasis. There is a disparity between the MRI signs and pathological findings. It is a key that to improve the spatial resolution of machine and to investigate the best method for detecting early metastasis.

PEGylation of black kidney bean (Phaseolus vulgaris L.) protein isolate with potential functironal properties.

In this work, we investigated PEGylated black kidney bean protein isolates (BKBPI) by PEG succinimidyl carbonate (PEG-SC), PEG succinimidyl succinate (PEG-SS) and PEG succinimidyl propionate (PEG-SPA) conjugation. The functional properties, thermodynamic stability, in vitro digestion stability, and hemagglutination activity of the modified products were evaluated. The degree of PEGylation was measured, and FTIR analysis revealed that protein-PEG conjugations were formed, and that no obvious changes in water- and fat-holding capacities were observed. The solubility, emulsifying property, and foaming property were all improved through the modification, while, higher thermodynamic stability was achieved with the increase in Td values and reduction of ΔH. The PEGylated proteins were found to be more resistant to in vitro digestion, and the hemagglutination activity was significantly (P < 0.05) decreased, indicating the higher safety of the protein isolate. The results showed that the functional properties, thermodynamic stability, and biological safety of BKBPI were improved by PEGylation, which could serve to increase the applications for this protein.

Rational Design of Conjugated Photosensitizers with Controllable Photoconversion for Dually Cooperative Phototherapy.

High-performance photosensitizers are highly desired for achieving selective tumor photoablation in the field of precise cancer therapy. However, photosensitizers frequently suffer from limited tumor suppression or unavoidable tumor regrowth due to the presence of residual tumor cells surviving in phototherapy. A major challenge still remains in exploring an efficient approach to promote dramatic photoconversions of photosensitizers for maximizing the anticancer efficiency. Here, a rational design of boron dipyrromethene (BDP)-based conjugated photosensitizers (CPs) that can induce dually cooperative phototherapy upon light exposure is demonstrated. The conjugated coupling of BDP monomers into dimeric BDP (di-BDP) or trimeric BDP (tri-BDP) induces photoconversions from fluorescence to singlet-to-triplet or nonradiative transitions, together with distinctly redshifted absorption into the near-infrared region. In particular, tri-BDP within nanoparticles shows preferable conversions into both primary thermal effect and minor singlet oxygen upon near-infrared light exposure, dramatically achieving tumor photoablation without any regrowth through their cooperative anticancer efficiency caused by their dominant late apoptosis and moderate early apoptosis. This rational design of CPs can serve as a valuable paradigm for cooperative cancer phototherapy in precision medicine.

[MRI monitoring ultra-small superparamagnetic iron oxide (USPIO) particle labeling C6 rat glioma cells].

OBJECTIVE: To monitor the effects of labeling C6 rat glioma cells with different concentrations of USPIO in vivo and in vitro. METHODS: C6 rat glioma cells of 1 x 10(6), 2 x 10(6) and 1 x 10(7) were labeled with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO, The signal intensity of cells were evaluated by MRI with T(1)WI, T(2)WI and GRE/30 degrees sequences in vitro. 1 x 10(6) of C6 glioma cells were labeled with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO and inoculated into the right frontal lobe of 2 rats under stereotaxis apparatus respectively (total 6 rats), Same MRI parameters were used just as above. Iron particle density and cells was measured by HE and Prussian blue stain under microscopy. RESULTS: Different cell population was cultured with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO about 12 hours. The MR signal intensity of labeling cells were inversely correlated with the different concentration of USPIO groups in T(2)W and GRE/30 degrees imaging (t = 4.19, 3.38, P < 0.05) in vitro. There was an inversely correlation between the labeling cell population and the signal intensity at the same concentration of USPIO (t = 5.16, 2.35, 4.41; P < 0.05). Dyeing degree of labeling cells stained by Prussian blue gradually deepened from 25 microg/ml to 50 microg/ml by microscopy. In vivo MRI can clearly show the cells labeled with 25 microg/ml USPIO. CONCLUSIONS: Iron particle density in the rat glioma cells were gradually increased with the concentration of USPIO. The MR signal intensity was inversely correlated with the cell population at the same condition. 25 microg/ml USPIO labeling rat glioma cells were enough for in vivo monitoring by MRI.

MicroRNA­337 inhibits colorectal cancer progression by directly targeting KRAS and suppressing the AKT and ERK pathways.

Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Tumour progression and development in CRC is a multi-step process involving a large number of genetic and epigenetic alterations. Previous studies indicated that abnormally expressed microRNAs play critical roles in CRC through regulation of oncogenic and tumour-suppressor genes. Hence, determination of the function of microRNAs may provide novel therapeutic targets for CRC diagnosis and treatments. MicroRNA­337 (miR­337) has been reported to be downregulated in several cancer types. However, the expression, function and underlying mechanisms of miR­337 in CRC have not been clearly elucidated. In this study, miR­337 was significantly decreased in CRC tissues and cell lines. Low miR­337 expression level was correlated with lymph node metastasis, distant metastasis and TNM stage of CRC patients. In addition, upregulation of miR­337 suppressed cell proliferation and invasion and promoted apoptosis in CRC. Based on bioinformatics analysis, we assumed that Kirsten rat sarcoma viral oncogene homolog (KRAS) was directly modulated by miR­337 in CRC. Luciferase reporter assay demonstrated the direct interaction between miR­337 and 3'­UTR of KRAS mRNA. Furthermore, reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that miR­337 could negatively regulate endogenous KRAS expression in CRC cells at both mRNA and protein levels. Moreover, KRAS was highly expressed in CRC tissues and inversely correlated with miR­337 expression in CRC tissues. KRAS knockdown recapitulates effects similar to those induced by miR­337 overexpression in CRC cells, whereas KRAS overexpression partially restored the tumour suppressive effects of miR­337. Besides, ectopic expression of miR­337 inactivates the AKT and ERK signalling pathways in CRC. These results suggested that miR­337 may act as a tumour suppressor during the process of CRC malignant transformation by interacting with KRAS.

Intracranial Posterior Circulation Large Artery Thrombi Visualized Using Susceptibility-Weighted MRI.

PURPOSE: To identify thrombi in patients with posterior circulation large artery occlusion using susceptibility-weighted magnetic resonance imaging (MRI). METHODS: All patients hospitalized with intracranial posterior circulation occlusion from January 2003 to September 2013 were included. MRI and computed tomography angiography were reviewed to determine the presence of arterial occlusion and identify thrombi. Eighty-one patients were analyzed to investigate susceptibility vessel sign (SVS) that was identified as blooming artifact (BA) on T2*-weighted gradient echo imaging. RESULTS: We identified 21 of 63 (33.3%) patients with BA in symptomatic patients, and 1 of 18 (5.6%) in the asymptomatic group with significant difference (P = .019). BAs were found in 6 of 10 (60.0%) patients with cardioembolism, 5 of 13 (38.5%) with dissection, 9 of 34 (26.5%) with large artery atherosclerotic disease, and 1 of 6 (16.7%) with undetermined cause. CONCLUSION: Identifying SVS may be useful in exploring the fresh thrombi and the mechanism of posterior circulation stroke.

Computed Tomography Perfusion Alberta Stroke Program Early Computed Tomography Score Is Associated with Hemorrhagic Transformation after Acute Cardioembolic Stroke.

Alberta Stroke Program Early Computed Tomography (CT) score (ASPECTS) has been applied to CT perfusion (CTP) with good interrater agreement to predict early ischemic stroke, and it can be useful in decision making in acute ischemic stroke. The aim of the present study was to assess the predictive value of CTP ASPECTS of hemorrhagic transformation (HT) in acute cardioembolic stroke. This is a single-enter, retrospective study. All patients hospitalized with acute cardioembolic stroke from January 2008 to September 2013 were included. ASPECTS of baseline non-contrast CT, CTP maps of cerebral blood volume (CBV), cerebral blood flow, and mean transit time were collected from 52 consecutive patients with less than 12-h anterior circulation ischemic stroke. MRI scan was performed within 72 h of symptom onset after index stroke including T2*-weighted gradient echo to identify HT. For bleeding risk assessment, CTP and diffusion-weighted imaging ASPECTS were categorized into 0-7 or 8-10. Baseline characteristics, ASPCETS scores and HT were compared. Eighteen (34.6%) patients had HT and four (7.7%) developed symptomatic HT. On univariate analysis, the proportion of patients with CBV-ASPECTS 0-7 was significantly higher in HT patients as compared to patients without HT (44 versus 9%, P = 0.005). CBV ASPECTS 0-7 remained independent prognostic factors for HT after adjustment for clinical baseline variables. CBV ASPECTS could be of value to predict HT risk after acute cardioembolic stroke and may be a quick risk assessment approach before reperfusion therapy.

Differentiation between adrenal adenomas and nonadenomas using dynamic contrast-enhanced computed tomography.

This study was performed to evaluate the findings including the time density curve (TD curve), the relative percentage of enhancement washout (Washr) and the absolute percentage of enhancement washout (Washa) at dynamic contrast-enhanced computed tomography (DCE-CT) in 70 patients with 79 adrenal masses (including 44 adenomas and 35 nonadenomas) confirmed histopathologically and/or clinically. The results demonstrated that the TD curves of adrenal masses were classified into 5 types, and the type distribution of the TD curves was significantly different between adenomas and nonadenomas. Types A and C were characteristic of adenomas, whereas types B, D and E were features of nonadenomas. The sensitivity, specificity and accuracy for the diagnosis of adenoma based on the TD curves were 93%, 80% and 87%, respectively. Furthermore, when myelolipomas were excluded, the specificity and accuracy for adenoma were 90% and 92%, respectively. The Washr and the Washa values for the adenomas were higher than those for the nonadenomas. The diagnostic efficiency for adenoma was highest at 7-min delay time at DCE-CT; Washr was more efficient than Washa. Washr ≥34% and Washa ≥43% were both suggestive of adenomas and, on the contrary, suspicious of nonadenomas. The sensitivity, specificity and accuracy for the diagnosis of adenoma were 84%, 77% and 81%, respectively. When myelolipomas were precluded, the diagnostic specificity and accuracy were 87% and 85%, respectively. Therefore, DCE-CT aids in characterization of adrenal tumors, especially for lipid-poor adenomas which can be correctly categorized on the basis of TD curve combined with the percentage of enhancement washout.

Tumoral angiogenesis in both adrenal adenomas and nonadenomas: a promising computed tomography biomarker for diagnosis.

To explore the correlation between the typical findings of dynamic contrast-enhanced computed tomography (DCE-CT) and tumoral angiogenesis (microvessel density [MVD] and vascular endothelial growth factor [VEGF]) in adenomas and nonadenomas such that the enhancement mechanism of DCE-CT in adrenal masses can be explained more precisely. Forty-two patients with 46 adrenal masses confirmed by surgery and pathology were included in the study; these masses included 23 adenomas, 18 nonadenomas, and 5 hyperplastic nodules. The findings of DCE-CT and angiogenesis in adrenal masses were studied. The features of DCE-CT in adenomas and nonadenomas were evaluated to determine whether the characteristics of DCE-CT in adrenal masses were closely correlated with tumoral angiogenesis. Adrenal adenomas were significantly different from nonadenomas in the time density curve and the mean percentage of enhancement washout at the 7-minute delay time in DCE-CT. The mean MVD and VEGF expression exhibited significant differences between the rapid washout group (types A and C) and the slow washout group (types B, D, and E) and between the relative washout (Washr) ≥34% and the absolute washout (Washa) ≥43% on the 7-minute enhanced CT scans (P=0.000). Adenomas were suggested when adrenal masses presented as types A and C, and/or the Washr ≥34%, and/or the Washa ≥43%, and the opposite was suggested for nonadenomas. These results showed a close correlation between the characteristics of DCE-CT and both MVD and VEGF expression in adrenal masses. There was also a significant difference in MVD and VEGF expression between adenomas and nonadenomas. In conclusion, MVD and VEGF expression are two important pathological factors that play important roles in the characterization of DCE-CT in adrenal masses because they cause different time density curve types, the Washr and the Washa for adrenal adenomas and nonadenomas.