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1.
Gastrointest Endosc ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492271

RESUMO

BACKGROUND AND AIMS: Endoscopic differential diagnoses of gastric mucosal lesions (benign gastric ulcer, early gastric cancer [EGC], and advanced gastric cancer) remain challenging. We aimed to develop and validate convolutional neural network-based artificial intelligence (AI) models: lesion detection (AI-LD), differential diagnosis (AI-DDx), and invasion-depth (AI-ID, pT1a vs. pT1b among EGC) models. METHODS: This study included 1,366 consecutive patients with gastric mucosal lesions from 2 referral centers in Korea. One representative endoscopic image from each patient was used. Histological diagnoses were set as the criterion standard. The performances of the AI-DDx (training/internal/external validation set, n=1009/112/245) and AI-ID (training/internal/external validation set, n=620/68/155) were compared with visual diagnoses by independent endoscopists (stratified by novice [<1 year of experience], intermediate [2-3 years of experience], and expert [>5 years of experience]) and endoscopic ultrasonography (EUS) results, respectively. RESULTS: The AI-DDx showed good diagnostic performance for both internal (area under of the receiver operating characteristic curve [AUROC]=0.86) and external validation (AUROC=0.86). The performance of the AI-DDx was better than that of the novice (AUROC=0.82, P=0.01) and intermediate endoscopists (AUROC=0.84, P=0.02), but was comparable to the experts (AUROC=0.89, P=0.12) in the external validation set. The AI-ID showed fair performances in both internal (AUROC=0.78) and external validation sets (AUROC=0.73), which were significantly better than EUS results performed by experts (internal validation: AUROC=0.62, external validation: AUROC=0.56; both P <0.001). CONCLUSION: The AI-DDx was comparable with experts and outperformed novice and intermediate endoscopists for the differential diagnosis of gastric mucosal lesion. The AI-ID performed better than EUS for the invasion-depth evaluation (https://aiscopeseoul.com/).

2.
Radiology ; : 210578, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463551

RESUMO

Background A computer-aided detection (CAD) system may help surveillance for pulmonary metastasis at chest radiography in situations where there is limited access to CT. Purpose To evaluate whether a deep learning (DL)-based CAD system can improve diagnostic yield for newly visible lung metastasis on chest radiographs in patients with cancer. Materials and Methods A regulatory-approved CAD system for lung nodules was implemented to interpret chest radiographs from patients referred by the medical oncology department in clinical practice. In this retrospective diagnostic cohort study, chest radiographs interpreted with assistance from a CAD system after the implementation (January to April 2019, CAD-assisted interpretation group) and those interpreted before the implementation (September to December 2018, conventional interpretation group) of the CAD system were consecutively included. The diagnostic yield (frequency of true-positive detections) and false-referral rate (frequency of false-positive detections) of formal reports of chest radiographs for newly visible lung metastasis were compared between the two groups using generalized estimating equations. Propensity score matching was performed between the two groups for age, sex, and primary cancer. Results A total of 2916 chest radiographs from 1521 patients (1546 men, 1370 women; mean age, 62 years) and 5681 chest radiographs from 3456 patients (2941 men, 2740 women; mean age, 62 years) were analyzed in the CAD-assisted interpretation and conventional interpretation groups, respectively. The diagnostic yield for newly visible metastasis was higher in the CAD-assisted interpretation group (0.86%, 25 of 2916 [95% CI: 0.58, 1.3] vs 0.32%, 18 of 568 [95% CI: 0.20, 0.50%]; P = .004). The false-referral rate in the CAD-assisted interpretation group (0.34%, 10 of 2916 [95% CI: 0.19, 0.64]) was not inferior to that in the conventional interpretation group (0.25%, 14 of 5681 [95% CI: 0.15, 0.42]) at the noninferiority margin of 0.5% (95% CI of difference: -0.15, 0.35). Conclusion A deep learning-based computer-aided detection system improved the diagnostic yield for newly visible metastasis on chest radiographs in patients with cancer with a similar false-referral rate. © RSNA, 2021 Online supplemental material is available for this article.

3.
Sci Rep ; 11(1): 15828, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349156

RESUMO

Precise remote evaluation of both suicide risk and psychiatric disorders is critical for suicide prevention as well as for psychiatric well-being. Using questionnaires is an alternative to labor-intensive diagnostic interviews in a large general population, but previous models for predicting suicide attempts suffered from low sensitivity. We developed and validated a deep graph neural network model that increased the prediction sensitivity of suicide risk in young adults (n = 17,482 for training; n = 14,238 for testing) using multi-dimensional questionnaires and suicidal ideation within 2 weeks as the prediction target. The best model achieved a sensitivity of 76.3%, specificity of 83.4%, and an area under curve of 0.878 (95% confidence interval, 0.855-0.899). We demonstrated that multi-dimensional deep features covering depression, anxiety, resilience, self-esteem, and clinico-demographic information contribute to the prediction of suicidal ideation. Our model might be useful for the remote evaluation of suicide risk in the general population of young adults for specific situations such as the COVID-19 pandemic.


Assuntos
Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Redes Neurais de Computação , Ideação Suicida , Tentativa de Suicídio/psicologia , Adolescente , Adulto , Ansiedade/psicologia , Área Sob a Curva , Depressão/psicologia , Feminino , Humanos , Masculino , Transtornos Mentais/prevenção & controle , Prognóstico , Escalas de Graduação Psiquiátrica , República da Coreia , Resiliência Psicológica , Fatores de Risco , Autoimagem , Sensibilidade e Especificidade , Tentativa de Suicídio/prevenção & controle , Inquéritos e Questionários , Adulto Jovem
4.
Korean J Radiol ; 22(9): 1514-1524, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34269536

RESUMO

OBJECTIVE: To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma. MATERIALS AND METHODS: One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.5 ± 13.5 years) with glioblastoma who underwent preoperative MRI were enrolled in the study. Six hundred and forty-two radiomic features were extracted from volume transfer constant (Ktrans), fractional volume of vascular plasma space (Vp), and fractional volume of extravascular extracellular space (Ve) maps of DCE MRI, wherein the regions of interest were based on both T1-weighted contrast-enhancing areas and non-enhancing T2 hyperintense areas. Using feature selection algorithms, salient radiomic features were selected from the 642 features. Next, a radiomics risk score was developed using a weighted combination of the selected features in the discovery set (n = 105); the risk score was validated in the validation set (n = 45) by investigating the difference in prognosis between the "radiomics risk score" groups. Finally, multivariable Cox regression analysis for progression-free survival was performed using the radiomics risk score and clinical variables as covariates. RESULTS: 16 radiomic features obtained from non-enhancing T2 hyperintense areas were selected among the 642 features identified. The radiomics risk score was used to stratify high- and low-risk groups in both the discovery and validation sets (both p < 0.001 by the log-rank test). The radiomics risk score and presence of isocitrate dehydrogenase (IDH) mutation showed independent associations with progression-free survival in opposite directions (hazard ratio, 3.56; p = 0.004 and hazard ratio, 0.34; p = 0.022, respectively). CONCLUSION: We developed and validated the "radiomics risk score" from the features of DCE MRI based on non-enhancing T2 hyperintense areas for risk stratification of patients with glioblastoma. It was associated with progression-free survival independently of IDH mutation status.

5.
Sci Rep ; 11(1): 9974, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976264

RESUMO

Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903-1.000) for local recurrence; 0.864 (0.726-0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or "radiomic risk score", increased risk of recurrence/progression (hazard ratio, 1.61; p = 0.03) in multivariate Cox regression on progression-free survival.

6.
Cancer Immunol Immunother ; 70(7): 1995-2008, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33416947

RESUMO

PURPOSE: To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures. METHODS: The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications. RESULTS: The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (p = 0.019), and T8 dominant group than T4 dominant group (p = 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps. CONCLUSIONS: Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.


Assuntos
Neoplasias Encefálicas/imunologia , Glioma/imunologia , Processamento de Imagem Assistida por Computador/métodos , Macrófagos/imunologia , Imageamento por Ressonância Magnética/métodos , Microambiente Tumoral/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , Humanos , Isocitrato Desidrogenase/genética , Mutação , Fenótipo , Prognóstico , Taxa de Sobrevida
7.
Radiology ; 297(1): 178-188, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32749203

RESUMO

Background Pharmacokinetic (PK) parameters obtained from dynamic contrast agent-enhanced (DCE) MRI evaluates the microcirculation permeability of astrocytomas, but the unreliability from arterial input function (AIF) remains a challenge. Purpose To develop a deep learning model that improves the reliability of AIF for DCE MRI and to validate the reliability and diagnostic performance of PK parameters by using improved AIF in grading astrocytomas. Materials and Methods This retrospective study included 386 patients (mean age, 52 years ± 16 [standard deviation]; 226 men) with astrocytomas diagnosed with histopathologic analysis who underwent dynamic susceptibility contrast (DSC)-enhanced and DCE MRI preoperatively from April 2010 to January 2018. The AIF was obtained from each sequence: AIF obtained from DSC-enhanced MRI (AIFDSC) and AIF measured at DCE MRI (AIFDCE). The model was trained to translate AIFDCE into AIFDSC, and after training, outputted neural-network-generated AIF (AIFgenerated DSC) with input AIFDCE. By using the three different AIFs, volume transfer constant (Ktrans), fractional volume of extravascular extracellular space (Ve), and vascular plasma space (Vp) were averaged from the tumor areas in the DCE MRI. To validate the model, intraclass correlation coefficients and areas under the receiver operating characteristic curve (AUCs) of the PK parameters in grading astrocytomas were compared by using different AIFs. Results The AIF-generated, DSC-derived PK parameters showed higher AUCs in grading astrocytomas than those derived from AIFDCE (mean Ktrans, 0.88 [95% confidence interval {CI}: 0.81, 0.93] vs 0.72 [95% CI: 0.63, 0.79], P = .04; mean Ve, 0.87 [95% CI: 0.79, 0.92] vs 0.70 [95% CI: 0.61, 0.77], P = .049, respectively). Ktrans and Ve showed higher intraclass correlation coefficients for AIFgenerated DSC than for AIFDCE (0.91 vs 0.38, P < .001; and 0.86 vs 0.60, P < .001, respectively). In AIF analysis, baseline signal intensity (SI), maximal SI, and wash-in slope showed higher intraclass correlation coefficients with AIFgenerated DSC than AIFDCE (0.77 vs 0.29, P < .001; 0.68 vs 0.42, P = .003; and 0.66 vs 0.45, P = .01, respectively. Conclusion A deep learning algorithm improved both reliability and diagnostic performance of MRI pharmacokinetic parameters for differentiating astrocytoma grades. © RSNA, 2020 Online supplemental material is available for this article.


Assuntos
Astrocitoma/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/farmacocinética , Aprendizado Profundo , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
8.
Acta Radiol Open ; 9(4): 2058460120922147, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32426164

RESUMO

Background: The coronary artery calcium scoring (CCS) has been widely used for cardiac risk stratification for asymptomatic patients. Purpose: To assess the reproducibility of CCS performed on four different computed tomography (CT) scanners, and compare the variability between two reconstruction algorithms, filtered back projection (FBP), and iterative reconstruction (IR). Material and Methods: A CCS phantom was made from agar and contained 23 pieces of chicken bones. The phantom was repeatedly scanned using four different CT scanners: Toshiba; GE; Philips; and Siemens. Images were reconstructed using FBP and IR. Agatston and volume scores of total bone fragments were calculated and the overall differences between the instruments were evaluated using the Friedman test. Comparison of the Agatston and volume scores between the two reconstruction algorithms, for each instrument, was evaluated using the Wilcoxon signed rank test. Results: The difference in the Agatston scores was significantly different between the four machines (P = 0.001). The Toshiba scanner yielded the highest score followed by Philips, GE, and Siemens scanners. There was no difference in the CCS evaluated using the two reconstruction algorithms, except in case of the Siemens scanner (P = 0.032). Conclusion: CCS performed on different scanners varied significantly. In the Toshiba, Philips, and GE scanners, there was no significant difference in the CCS determined using either an IR or the FBP algorithm. In the Siemens scanner, applying the IR algorithm resulted in a slightly different scores, which might not be clinically significant.

9.
Acta Radiol ; 61(10): 1406-1413, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31979979

RESUMO

BACKGROUND: The image quality of abdominal magnetic resonance imaging (MRI) in children who cannot hold their breath has been severely impaired by motion artifacts. PURPOSE: To evaluate the usefulness of T1-weighted (T1W) BLADE MRI for axial abdominal imaging in children who cannot hold their breath. MATERIAL AND METHODS: Two different BLADE sequences, with and without an inversion recovery (IR-BLADE), were compared to conventional turbo-spin echo (TSE) with a high number of excitations in 18 consecutive patients who cannot hold their breath. Overall image quality, motion artifact, radial artifact, hepatic vessel sharpness, renal corticomedullary differentiation, and lesion conspicuity were retrospectively assessed by two radiologists, using 4- or 5-point scoring systems. Signal variations of each sequence were measured for a quantitative comparison. The acquisition times of the three sequences were compared. RESULTS: IR-BLADE and BLADE showed significantly improved overall image quality and reduced motion artifact compared with TSE. IR-BLADE showed significantly better hepatic vessel sharpness and corticomedullary differentiation compared to both BLADE and TSE. Radial artifacts were only observed on IR-BLADE and BLADE. In nine patients with lesions, there were no significant differences in lesion conspicuity among three sequences. Compared to TSE, both IR-BLADE and BLADE showed decreased signal variations in the liver and muscle, and an increased signal variation through air. The mean acquisition times for IR-BLADE, BLADE, and TSE were comparable. CONCLUSION: Compared to the TSE sequence, T1W IR-BLADE for pediatric abdominal MRI resulted in improved image quality, tissue contrast with a diminished respiratory motion artifact, and a comparable acquisition time.


Assuntos
Abdome/diagnóstico por imagem , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Artefatos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Movimento (Física) , República da Coreia , Estudos Retrospectivos
10.
Int J Mol Sci ; 20(23)2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31771288

RESUMO

Glucose is a basic nutrient in most of the creatures; its transport through biological membranes is an absolute requirement of life. This role is fulfilled by glucose transporters, mediating the transport of glucose by facilitated diffusion or by secondary active transport. GLUT (glucose transporter) or SLC2A (Solute carrier 2A) families represent the main glucose transporters in mammalian cells, originally described as plasma membrane transporters. Glucose transport through intracellular membranes has not been elucidated yet; however, glucose is formed in the lumen of various organelles. The glucose-6-phosphatase system catalyzing the last common step of gluconeogenesis and glycogenolysis generates glucose within the lumen of the endoplasmic reticulum. Posttranslational processing of the oligosaccharide moiety of glycoproteins also results in intraluminal glucose formation in the endoplasmic reticulum (ER) and Golgi. Autophagic degradation of polysaccharides, glycoproteins, and glycolipids leads to glucose accumulation in lysosomes. Despite the obvious necessity, the mechanism of glucose transport and the molecular nature of mediating proteins in the endomembranes have been hardly elucidated for the last few years. However, recent studies revealed the intracellular localization and functional features of some glucose transporters; the aim of the present paper was to summarize the collected knowledge.


Assuntos
Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Glucose/metabolismo , Proteínas de Transporte de Sódio-Glucose/metabolismo , Animais , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Glucose-6-Fosfatase/metabolismo , Complexo de Golgi/metabolismo , Humanos
11.
Neuro Oncol ; 21(9): 1197-1209, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31127834

RESUMO

BACKGROUND: The aim of this study was to predict isocitrate dehydrogenase (IDH) genotypes of gliomas using an interpretable deep learning application for dynamic susceptibility contrast (DSC) perfusion MRI. METHODS: Four hundred sixty-three patients with gliomas who underwent preoperative MRI were enrolled in the study. All the patients had immunohistopathologic diagnoses of either IDH-wildtype or IDH-mutant gliomas. Tumor subregions were segmented using a convolutional neural network followed by manual correction. DSC perfusion MRI was performed to obtain T2* susceptibility signal intensity-time curves from each subregion of the tumors: enhancing tumor, non-enhancing tumor, peritumoral edema, and whole tumor. These, with arterial input functions, were fed into a neural network as multidimensional inputs. A convolutional long short-term memory model with an attention mechanism was developed to predict IDH genotypes. Receiver operating characteristics analysis was performed to evaluate the model. RESULTS: The IDH genotype predictions had an accuracy, sensitivity, and specificity of 92.8%, 92.6%, and 93.1%, respectively, in the validation set (area under the curve [AUC], 0.98; 95% confidence interval [CI], 0.969-0.991) and 91.7%, 92.1%, and 91.5%, respectively, in the test set (AUC, 0.95; 95% CI, 0.898-0.982). In temporal feature analysis, T2* susceptibility signal intensity-time curves obtained from DSC perfusion MRI with attention weights demonstrated high attention on the combination of the end of the pre-contrast baseline, up/downslopes of signal drops, and/or post-bolus plateaus for the curves used to predict IDH genotype. CONCLUSIONS: We developed an explainable recurrent neural network model based on DSC perfusion MRI to predict IDH genotypes in gliomas.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Isocitrato Desidrogenase/genética , Angiografia por Ressonância Magnética/métodos , Redes Neurais de Computação , Adulto , Idoso , Área Sob a Curva , Neoplasias Encefálicas/genética , Meios de Contraste , Aprendizado Profundo , Feminino , Genótipo , Glioma/genética , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mutação , Curva ROC
12.
Gene ; 635: 48-60, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-28887159

RESUMO

Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells. We identified 61 downregulated genes with hypermethylation, including CD74, VAV1, TLR8, and NCF4, as well as 21 upregulated genes with hypomethylation, including ECSCR, MCAM, PGF, and ARHGEF15. Interestingly, gene ontology analysis showed that downregulated genes with hypermethylation were enriched in immune-related functions, and upregulated genes with hypomethylation were enriched in the developmental process and angiogenesis, indicating the important roles of DNA methylation in regulating differentiation. We performed polymerase chain reaction analyses and bisulfite sequencing of representative genes (CD74, VAV1, ECSCR, and MCAM) to verify the negative correlation between DNA methylation and gene expression. Further, inhibition of DNA methyltransferase and demethylase activities using 5'-aza-dc and shRNAs, specific for TET1 and TET2 mRNAs, respectively, revealed that DNA methylation was the main regulator of the reversible expression of functionally important genes. Collectively, our findings implicate DNA methylation as a critical regulator of gene expression during umbilical cord blood derived mononuclear cells to endothelial cell differentiation.


Assuntos
Diferenciação Celular/genética , Metilação de DNA/genética , Células Endoteliais/metabolismo , Leucócitos Mononucleares/metabolismo , Ilhas de CpG , Células Endoteliais/citologia , Epigênese Genética , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Genoma Humano , Humanos , Leucócitos Mononucleares/citologia , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese
13.
J Neuroinflammation ; 14(1): 122, 2017 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-28645333

RESUMO

BACKGROUND: Blood-brain barrier (BBB) breakdown and inflammation are critical events in ischemic stroke, contributing to aggravated brain damage. The BBB mainly consists of microvascular endothelial cells sealed by tight junctions to protect the brain from blood-borne substances. Thus, the maintenance of BBB integrity may be a potential target for neuroprotection. Sac-1004, a pseudo-sugar derivative of cholesterol, enhances the endothelial barrier by the stabilization of the cortical actin ring. RESULTS: Here, we report on the protective effects of Sac-1004 on cerebral ischemia-reperfusion (I/R) injury. Treatment with Sac-1004 significantly blocked the interleukin-1ß-induced monolayer hyperpermeability of human brain microvascular endothelial cells (HBMECs), loss of tight junctions, and formation of actin stress fiber. Sac-1004 suppressed the expression of adhesion molecules, adhesion of U937 cells, and activation of nuclear factor-κB in HBMECs. Using a rat model of transient focal cerebral ischemia, it was shown that Sac-1004 effectively ameliorated neurological deficits and ischemic damage. In addition, Sac-1004 decreased BBB leakage and rescued tight junction-related proteins. Moreover, the staining of CD11b and glial fibrillary acidic protein showed that Sac-1004 inhibited glial activation. CONCLUSIONS: Taken together, these results demonstrate that Sac-1004 has neuroprotective activities through maintaining BBB integrity, suggesting that it is a great therapeutic candidate for stroke.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Saponinas/uso terapêutico , Animais , Barreira Hematoencefálica/metabolismo , Isquemia Encefálica/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/fisiologia , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Humanos , Inflamação/diagnóstico por imagem , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Saponinas/farmacologia
14.
Invest Radiol ; 52(2): 128-133, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27977466

RESUMO

OBJECTIVE: The aim of this study was to evaluate an extremely small pseudoparamagnetic iron oxide nanoparticle (ESPIO), KEG3, as a potential blood pool agent in 3 T coronary magnetic resonance angiography (MRA) in canine models and compare its efficacy to that of a gadolinium-based contrast agent. MATERIALS AND METHODS: Nine mongrel dogs were subjected to whole-heart coronary MRA in 2 separate sessions at 7-day intervals with a 3 T scanner using the FLASH sequence with either gadoterate meglumine (Gd-DOTA) or the ESPIO (KEG3). Coronary MRA was performed twice at each MR examination: the first scan during the administration of the contrast agent and the subsequent second scan at 15 minutes after contrast injection. Objective measurements of the Gd-DOTA and ESPIO images, including the signal-to-noise ratios (SNRs) for the coronary arteries and cardiac veins, contrast-to-noise ratios (CNRs) between the vessels and fat (CNRfat) and the vessels and the myocardium (CNRmyocardium), and subjective image quality scores on a 4-point scale were evaluated and compared. RESULTS: The mean SNRs and CNRs of all vascular regions in the ESPIO images were similar to those of the corresponding regions in the Gd-DOTA images in the first scan (98.1 ± 32.5 vs 79.1 ± 38.4 for SNR of coronary arteries, P = 0.3; 74.2 ± 30.1 vs 61.4 ± 38.5 for CNR, P = 0.7) and more than 2 times higher than the latter in the second scan (95.2 ± 31.3 vs 32.1 ± 8.1 for SNR of coronary arteries, P = 0.008; 76.1 ± 35.8 vs 17.6 ± 19.2 for CNR, P 0.008). Similarly, the mean values of the subjective measurements of the ESPIO images were similar to those of the Gd-DOTA images (3.9 ± 0.3 vs 3.3 ± 0.8 for coronary arteries, P = 0.1) in the first scan and significantly better than the latter in the second scan (3.9 ± 0.2 vs 2.1 ± 0.6 for coronary arteries, P = 0.007). CONCLUSIONS: The experimental blood pool agent KEG3 offers equivalent image quality for whole-heart coronary MRA at 3 T upon contrast administration and persistent better quality in the subsequent scans, compared with a traditional extracellular gadolinium-based contrast agent.


Assuntos
Meios de Contraste , Vasos Coronários/diagnóstico por imagem , Compostos Férricos , Aumento da Imagem/métodos , Angiografia por Ressonância Magnética/métodos , Meglumina , Compostos Organometálicos , Animais , Cães , Injeções Intravenosas , Modelos Animais , Nanopartículas , Razão Sinal-Ruído
15.
Eur J Radiol ; 85(10): 1695-1700, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27666604

RESUMO

PURPOSE: To assess the usefulness of the relative position of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) in diagnosing intestinal malrotation in situs anomaly. MATERIALS AND METHODS: From January 2004 to April 2015, 33 patients with situs anomalies were enrolled in this study who underwent abdominal USG, CT or MRI as well as upper gastrointestinal series (UGIS) or surgery: situs inversus (n=16), left isomerism (n=10), and right isomerism (n=7); age 21.2±23.2years (mean±standard deviation), range 0-72 years. The intestinal malrotation was confirmed with UGIS and/or operation in 16 patients. Relative positions of the SMV to the SMA were classified into four groups by reviewing abdominal USG, CT, or MRI: right sided, left sided, ventral sided, and dorsal sided. The incidence of malrotation was analyzed for each group. RESULTS: In 16 patients with situs inversus, there was reversed SMA-SMV relationship: left sided (n=11) or ventral sided (n=5). One situs inversus patient with ventral sided SMV had intestinal malrotation (6.25%). 17 patients with situs ambiguus showed various SMA-SMV relationships (ventral sided, n=7; left sided, n=5; right sided, n=4; dorsal sided, n=1). Among them, 15 patients (88.2%) had intestinal malrotation. Two patients with normal rotation had either right sided or dorsal sided SMV. CONCLUSION: Situs ambiguus was commonly associated with intestinal malrotation with a variable SMA-SMV relationship. Reversal of the mesenteric vascular relationship was observed in situs inversus with normal rotation, not excluding the possibility of intestinal malrotation.


Assuntos
Anormalidades do Sistema Digestório/diagnóstico por imagem , Volvo Intestinal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Artéria Mesentérica Superior/diagnóstico por imagem , Veias Mesentéricas/diagnóstico por imagem , Radiografia , Situs Inversus/diagnóstico por imagem , Ultrassonografia , Adulto , Idoso , Anormalidades do Sistema Digestório/patologia , Feminino , Humanos , Volvo Intestinal/patologia , Masculino , Artéria Mesentérica Superior/anormalidades , Veias Mesentéricas/anormalidades , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Rotação , Situs Inversus/patologia
16.
Cell Signal ; 28(11): 1642-51, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27498087

RESUMO

Cell-to-cell junctions are critical for the formation of endothelial barriers, and its disorganization is required for sprouting angiogenesis. Members of the angiomotin (AMOT) family have emerged as key regulators in the control of endothelial cell (EC) junction stability and permeability. However, the underlying mechanism by which the AMOT family is regulated in ECs remains unclear. Here we report that HECW2, a novel EC ubiquitin E3 ligase, plays a critical role in stabilizing endothelial cell-to-cell junctions by regulating AMOT-like 1 (AMOTL1) stability. HECW2 physically interacts with AMOTL1 and enhances its stability via lysine 63-linked ubiquitination. HECW2 depletion in human ECs decreases AMOTL1 stability, loosening the cell-to-cell junctions and altering subcellular localization of yes-associated protein (YAP) from cytoplasm into the nucleus. Knockdown of HECW2 also results in increased angiogenic sprouting, and this effect is blocked by depletion of ANG-2, a potential target of YAP. These results demonstrate that HECW2 is a novel regulator of angiogenesis and provide new insights into the mechanisms coordinating junction stability and angiogenic activation in ECs.


Assuntos
Células Endoteliais da Veia Umbilical Humana/metabolismo , Junções Intercelulares/metabolismo , Lisina/metabolismo , Proteínas de Membrana/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Angiopoietina-2/metabolismo , Deleção de Genes , Humanos , Neovascularização Fisiológica , Fosfoproteínas/metabolismo , Poliubiquitina/metabolismo , Ligação Proteica , Estabilidade Proteica , Transporte Proteico , Fatores de Transcrição
17.
Radiology ; 281(2): 444-453, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27243549

RESUMO

Purpose To determine the yield of follow-up abdominopelvic computed tomography (CT) in detecting extragastric recurrence after curative endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs) that meet the expanded criteria. Materials and Methods Institutional review board approval was obtained for this retrospective study, and the requirement to obtain informed consent was waived. Patients who underwent curative ESD for EGCs that met the expanded criteria between November 2005 and December 2009 and who underwent post-ESD CT and endoscopy were included. The final cohort comprised 415 EGCs in 404 patients (261 EGCs in 251 patients met the conventional criteria, and 154 EGCs in 153 patients met the expanded criteria). The primary outcome was post-ESD CT discovery of extragastric recurrence (ie, lymph node or distant metastasis) not detected with endoscopy. The mean radiation dose from each CT examination was calculated. The incidence of gastric recurrence detected with endoscopy and/or CT was also analyzed. The cumulative incidence of gastric recurrence during the post-ESD follow-up period was analyzed with the Kaplan-Meier method. Results From a total of 2182 post-ESD CT examinations, extragastric recurrence (lymph node metastasis) was detected in only two patients (one with EGC that met conventional criteria and one with EGC that met expanded criteria). The mean (±standard deviation) volume CT dose index, dose-length product, and size-specific dose estimate per CT examination was 28.95 mGy ± 8.44, 876.80 mGy · cm ± 161.86, and 43.78 mGy ± 11.54, respectively. From a total of 3262 post-ESD endoscopic examinations, 41 gastric recurrences were detected (11 local recurrences and five synchronous and 25 metachronous gastric cancers). Among them, eight gastric recurrences were also detected with CT. The cumulative incidences of gastric recurrence 1, 3, and 5 years after ESD were 1.7% (two of 404 patients), 3.2% (13 of 404 patients), and 7.4% (30 of 404 patients), respectively. Conclusion When EGC meets the expanded criteria, surveillance CT after curative ESD rarely depicts extragastric recurrence during 5-year post-ESD follow-up. © RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Gastroscopia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Ann Surg Treat Res ; 90(3): 117-23, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26942154

RESUMO

PURPOSE: The goal of oncoplastic breast surgery is to restore the appearance of the breast and improve patient satisfaction. Thus, the assessment of cosmetic results and patient-reported outcomes (PROs) using appropriately constructed and validated instruments is essential. The aim of the present study was to assess the long-term objective cosmetic results and corresponding PROs after oncoplastic breast surgery. METHODS: Cosmetic results were assessed by the patients, a medical panel, and a computer program (BCCT.core). PROs were assessed using BREAST-Q, a questionnaire that measures the perception of patients having breast surgery. The cosmetic results and PROs were analyzed in patients who underwent quadrantectomy and partial breast reconstruction utilizing the latissimus dorsi flap. RESULTS: The mean duration of the follow-up period was 91.6 months (range, 33.3-171.0 months), and mean age of the patients was 51 years old (range, 33-72 years). The mean tumor size was 2.1 cm (range, 0.9-5.5 cm). There was fair agreement between the medical panel and BCCT.core score (K = 0.32, P < 0.001), and a statistically significant correlation between the BCCT.core score and medical panel cosmetic results was identified (r = 0.606, P < 0.001). A better BCCT.core result was related to a higher PRO of each BREAST-Q domain-satisfaction with breasts (R(2) = 0.070, P = 0.039), satisfaction with outcome (R(2) = 0.087, P = 0.021), psychosocial well-being (R(2) = 0.085, P = 0.023), sexual well-being (R(2) = 0.082, P = 0.029), and satisfaction with information (R(2) = 0.064, P = 0.049). CONCLUSION: Our long-term results of oncoplastic surgery achieved a high level of patient satisfaction with good cosmetic results. The medical panel and BCCT.core results correlated well with the PROs of the patients using valid, reliable, and procedure-specific measures.

19.
AJR Am J Roentgenol ; 205(4): 789-96, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26204113

RESUMO

OBJECTIVE: The purpose of this study is to evaluate whether DWI provides additional value to conventional MRI with MRCP (MRI-MRCP) in the characterization of perihilar biliary strictures and in the evaluation of the longitudinal extent of perihilar cholangiocarcinomas. MATERIALS AND METHODS: One hundred fourteen patients with perihilar strictures (81 malignant and 33 benign) underwent gadobutrol-enhanced MRI-MRCP and DWI using 10 b values (0-1000 s/mm(2)). Two readers independently reviewed a conventional set of MRI-MRCP images and a combined set of MRI-MRCP and DW images and scored the likelihoods of malignancy for perihilar strictures and involvement of the bilateral secondary confluence in malignant cases on a 5-point scale. The diagnostic performance of the two imaging sets was compared using ROC analysis. RESULTS: In the characterization of 114 perihilar strictures, the addition of DWI showed no statistically significant improvement in diagnostic performance (reader 1, area under the ROC curve (Az) = 0.947 vs 0.923; reader 2, Az = 0.930 vs 0.905; all p > 0.05) with an interobserver agreement of κ = 0.763-0.818. In determining bilateral secondary confluence involvement for the 81 surgically confirmed malignant strictures, the conventional and combined sets showed no statistically significant difference in diagnostic performance (reader 1, Az = 0.820 vs 0.868; reader 2, Az = 0.826 vs 0.829; all p > 0.05), with κ = 0.564-0.588. CONCLUSION: The addition of DWI to conventional MRI-MRCP did not improve diagnostic performance in the characterization of perihilar strictures or in determining whether the bilateral secondary biliary confluence was involved in perihilar cholangiocarcinomas.


Assuntos
Colestase/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia por Ressonância Magnética , Constrição Patológica/diagnóstico , Meios de Contraste , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos
20.
Korean J Radiol ; 16(4): 736-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26175572

RESUMO

OBJECTIVE: To evaluate the technical feasibility and clinical outcome of percutaneous aspiration embolectomy for embolic occlusion of the superior mesenteric artery (SMA). MATERIALS AND METHODS: Between January 2010 and December 2013, 9 patients with embolic occlusion of the SMA were treated by percutaneous aspiration embolectomy in 2 academic teaching hospitals. The aspiration embolectomy procedure was performed with the 6-Fr and 7-Fr guiding catheter. Thrombolysis was performed with urokinase using a multiple-sidehole infusion catheter. The clinical outcome was investigated retrospectively. RESULTS: Superior mesenteric artery occlusion was initially diagnosed by computed tomography (CT) in all patients, and all patients had no obvious evidence of bowel infarction on CT scan. Percutaneous aspiration embolectomy was primarily performed in 6 patients, and thrombolysis was initially performed in 3 patients. In 3 patients who received primary thrombolysis, percutaneous aspiration was undertaken because the emboli were resistant to urokinase. Complete angiographic success was achieved in 6 patients and partial angiographic success was accomplished in 3 patients. One patient underwent bowel resection. One patient died of whole bowel necrosis and sepsis, and 8 patients survived without complications. CONCLUSION: Percutaneous aspiration embolectomy is a useful tool in recanalization of embolic occlusion of the SMA in select patients.


Assuntos
Embolectomia/métodos , Embolia/cirurgia , Artéria Mesentérica Superior/cirurgia , Oclusão Vascular Mesentérica/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia/métodos , Embolia/complicações , Embolia/diagnóstico por imagem , Feminino , Humanos , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Oclusão Vascular Mesentérica/diagnóstico por imagem , Oclusão Vascular Mesentérica/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Sucção/instrumentação , Sucção/métodos , Terapia Trombolítica/métodos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Dispositivos de Acesso Vascular
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