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BACKGROUND: Application of machine learning (ML) algorithms has shown promising results in estimating ischemic core volumes using non-contrast CT (NCCT). OBJECTIVE: To assess the performance of the e-Stroke Suite software (Brainomix) in assessing ischemic core volumes on NCCT compared with CT perfusion (CTP) in patients with acute ischemic stroke. METHODS: In this retrospective multicenter study, patients with anterior circulation large vessel occlusions who underwent pretreatment NCCT and CTP, successful reperfusion (modified Thrombolysis in Cerbral Infarction ≥2b), and post-treatment MRI, were included from three stroke centers. Automated calculation of ischemic core volumes was obtained on NCCT scans using ML algorithm deployed by e-Stroke Suite and from CTP using Olea software (Olea Medical). Comparative analysis was performed between estimated core volumes on NCCT and CTP and against MRI calculated final infarct volume (FIV). RESULTS: A total of 111 patients were included. Estimated ischemic core volumes (mean±SD, mL) were 20.4±19.0 on NCCT and 19.9±18.6 on CTP, not significantly different (P=0.82). There was moderate (r=0.40) and significant (P<0.001) correlation between estimated core on NCCT and CTP. The mean difference between FIV and estimated core volume on NCCT and CTP was 29.9±34.6 mL and 29.6±35.0 mL, respectively (P=0.94). Correlations between FIV and estimated core volume were similar for NCCT (r=0.30, P=0.001) and CTP (r=0.36, P<0.001). CONCLUSIONS: Results show that ML-based estimated ischemic core volumes on NCCT are comparable to those obtained from concurrent CTP in magnitude and in degree of correlation with MR-assessed FIV.
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Breast cancer recurrence after autologous flap reconstruction is rare and typically occurs at the contact zone between the flap and the native tissue. When a new lesion is found in a reconstructed breast without the characteristic appearance of benign entities such as fat necrosis, definitive tissue diagnosis is often warranted to rule out recurrence or metastasis. Angiolipomas are rare, benign lipomatous tumors that have nonspecific imaging appearances and are thus frequently biopsied or excised for definitive diagnosis. Here, we report a case of a new breast mass found at the contact zone of a reconstructed breast in a patient with a history of ductal carcinoma in situ (DCIS), which was ultimately excised and proven to be an angiolipoma.
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Lung adenocarcinoma with lepidic growth pattern (LPA) is characterized by tumor cell proliferation along intact alveolar walls, and further classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive lepidic predominant adenocarcinoma (iLPA). Accurate diagnosis of lepidic lesions is critical for appropriate prognostication and management as five-year survival in patients with iLPA is lower than in those with AIS and MIA. We aimed to evaluate the accuracy of CT-guided core needle lung biopsy classifying LPA lesions and identify clinical and radiologic predictors of invasive disease in biopsied lesions. Thirty-four cases of adenocarcinoma with non-invasive lepidic growth pattern on core biopsy pathology that subsequently were resected between 2011 and 2018 were identified. Invasive LPA vs. non-invasive LPA (AIS or MIA) was defined based on explant pathology. Histopathology of core biopsy and resected tumor specimens was compared for concordance, and clinical, radiologic and pathologic variables were analyzed to assess for correlation with invasive disease. The majority of explanted tumors (70.6%) revealed invasive disease. Asian race (p = 0.03), history of extrathoracic malignancy (p = 0.02) and absence of smoking history (p = 0.03) were associated with invasive disease. CT-measured tumor size was not associated with invasiveness (p = 0.15). CT appearance of density (p = 0.61), shape (p = 0.78), and margin (p = 0.24) did not demonstrate a significant difference between the two subgroups. Invasiveness of tumors with lepidic growth patterns can be underestimated on transthoracic core needle biopsies. Asian race, absence of smoking, and history of extrathoracic malignancy were associated with invasive disease.
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Adenocarcinoma in Situ , Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma in Situ/patología , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Invasividad Neoplásica/patología , Estadificación de NeoplasiasRESUMEN
Deep venous thrombosis is a hitherto under-recognized complication occurring in patients with polysplenia syndrome, despite the high prevalence of venous anomalies such as interrupted inferior vena cava (IVC) with azygos/hemiazygos continuation. Here we report the first case of concurrent polysplenia (as evidenced by interrupted IVC with azygos/hemiazygos continuation, multiple left-sided spleens, bowel malrotation with inverted mesenteric veins, preduodenal portal vein, and pancreatic hypoplasia/partial agenesis of the dorsal pancreas) and sickle cell trait, complicated by extensive deep venous thrombosis refractory to medical and interventional radiologic management.
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Síndrome de Heterotaxia , Rasgo Drepanocítico , Trombofilia , Trombosis de la Vena , Humanos , Vena Cava Inferior/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiologíaRESUMEN
BACKGROUND: Gadofosveset is a gadolinium-based blood pool contrast agent that was approved by the United States Food and Drug Administration in 2008. Its unanticipated withdrawal from production in 2016 created a void in the blood pool agent inventory and highlighted the need for an alternative agent with comparable imaging properties. OBJECTIVE: The purpose of our study is to compare the diagnostic image quality, vascular contrast-to-noise ratio (CNR) and temporal signal characteristics of gadofosveset trisodium and ferumoxytol at similar molar doses for high-resolution, three-dimensional (3-D) magnetic resonance (MR) venography in children. MATERIALS AND METHODS: The medical records and imaging data sets of patients who underwent high-resolution 3-D gadofosveset-enhanced MR venography (GE-MRV) or ferumoxytol-enhanced MR venography (FE-MRV) were retrospectively reviewed. Two groups of 20 pediatric patients (age- and weight-matched with one patient common to both groups; age range: 2 days-15 years) who underwent high-resolution 3-D GE-MRV or FE-MRV at similar molar doses were identified and analyzed. Qualitative analysis of image quality and vessel definition was performed by two blinded pediatric radiologists. Interobserver agreement was assessed with the AC1 (first-order agreement coefficient) statistic. Signal-to-noise ratio (SNR) and CNR of the inferior vena cava and aorta were measured in the steady-state venous phase. Medical records were retrospectively reviewed for any adverse reactions associated with either contrast agent. RESULTS: Measured SNR and CNR of the inferior vena cava were higher for FE-MRV than GE-MRV (P = 0.034 and P < 0.001, respectively). The overall image quality score and individual vessel scores of FE-MRV were equal to or greater than GE-MRV (P = 0.084), with good interobserver agreement (AC1 = 0.657). The venous signal on FE-MRV was stable over the longest interval measured (1 h, 13 min and 46 s), whereas venous signal on GE-MRV showed more variability and earlier loss of signal. No adverse reactions were noted in any patient with either contrast agent. CONCLUSION: Ferumoxytol produces more uniform and stable enhancement throughout the entire venous circulation in children than gadofosveset, offering a wider time window for optimal image acquisition. FE-MRV offers a near-ideal approach to high-resolution venography in children at all levels of anatomical complexity.
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Gadolinio , Compuestos Organometálicos , Niño , Preescolar , Medios de Contraste , Óxido Ferrosoférrico , Humanos , Angiografía por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Flebografía/métodos , Estudios RetrospectivosRESUMEN
INTRODUCTION: The off-label use of ferumoxytol as a vascular MR imaging agent is growing rapidly. However, the properties of ferumoxytol suggest that it may play an important role in the detection and characterization of abdominal mass lesions. METHODS: Thirty-six patients with benign abdominal mass lesions who underwent MR angiography with ferumoxytol also had T2-weighted HASTE imaging and fat-suppressed 3D T1-weighted imaging. The T1 and T2 enhancement characteristics of the lesions were analyzed and correlated with other imaging modalities and/or surgical findings and/or clinical follow-up. RESULTS: In all patients with benign masses in the liver (n = 22 patients), spleen (n = 6 patients), kidneys (n = 33 patients), adrenal (n = 2 patients) and pancreas (n = 4 patients), based on the enhancement characteristics with ferumoxytol, readers were confident of the benign nature of the lesions and their conclusions were consistent with correlative imaging, tissue sampling and follow-up. One patient with a suspicious enhancing 2F Bosniak renal cyst had renal cell carcinoma confirmed on biopsy. CONCLUSION: Ferumoxytol-enhanced MRI can increase diagnostic confidence for benign abdominal masses and can increase the conspicuity of mass lesions, relative to unenhanced MRI.
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Medios de Contraste , Óxido Ferrosoférrico , Humanos , Imagen por Resonancia Magnética/métodosAsunto(s)
COVID-19 , Fibrosis Pulmonar , Humanos , Pulmón/diagnóstico por imagen , Pulmón/cirugía , SARS-CoV-2RESUMEN
OBJECTIVES: To evaluate the safety of irreversible electroporation (IRE) on swine pancreatic tissue including its effects on peripancreatic vessels, bile ducts, and bowel. METHODS: Eighteen Yorkshire pigs underwent IRE ablation of the pancreas successfully and without clinical complications. Contrast-enhanced computed tomography angiography and laboratory studies before the IRE ablation with follow-up computed tomography angiography, laboratory testing, and pathological examination up to 4 weeks postablation were performed. RESULTS: In a subset of cases, anatomic peripancreatic vessel narrowing was seen by 1 week postablation, persisting at 4 weeks postablation, without apparent functional impairment of blood flow. Laboratory studies revealed elevated amylase and lipase at 24 hours post-IRE, suggestive of acute pancreatitis, which normalized by 4 weeks post-IRE. There was extensive pancreatic tissue damage 24 hours after IRE with infiltration of immune cells, which was gradually replaced by fibrotic tissue. Ductal regeneration without loss of pancreatic acinar tissue and glandular function was observed at 1 and 4 weeks postablation. CONCLUSIONS: In our study, we demonstrated and confirmed the safety and minimal complications of IRE ablation in the pancreas and its surrounding vital structures. These results show the potential of IRE as an alternative treatment modality in patients with pancreatic cancer, especially those with locally advanced disease.
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Electroporación/métodos , Modelos Animales , Páncreas/patología , Neoplasias Pancreáticas/terapia , Amilasas/metabolismo , Animales , Angiografía por Tomografía Computarizada , Femenino , Humanos , Lipasa/metabolismo , Páncreas/irrigación sanguínea , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Reproducibilidad de los Resultados , Porcinos , Factores de Tiempo , Tomografía Computarizada por Rayos XAsunto(s)
Adenocarcinoma/terapia , Electroporación/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patología , Humanos , Evaluación de Resultado en la Atención de Salud/métodos , Neoplasias Pancreáticas/patología , Análisis de SupervivenciaRESUMEN
INTRODUCTION: To assess the technical feasibility and safety of repeated percutaneous computed tomography (CT)-guided transthoracic biopsies and intratumoral injections of gene-modified dendritic cells in metastatic NSCLC. METHODS: A total of 15 patients with 15 NSCLC lesions measuring greater than 1.0 cm underwent two cycles of intratumoral biopsies and CCL21 dendritic cell injections separated by 7 days. All needle placements and injections were done under CT guidance. Clinical and imaging follow-up was done approximately 4 weeks after the first procedure. Safety and feasibility were determined as: (1) safety and feasibility similar to that of single-needle biopsy, and (2) an absence of serious adverse events defined as grade greater than or equal to three according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 30 percutaneous, transthoracic intratumoral biopsies and injections into the lung cancer were performed, two cycles (at d 0 and 7) received by each patient (311 biopsies and 96 intratumoral injections). All percutaneous cases achieved technical success with respect to needle placement for both biopsy and injection of CCL21 dendritic cells. Only minor complications were observed (grade <3), including pneumothorax (n = 10, 33%) and small postbiopsy hemorrhage (n = 2, 7%). Pneumothorax was moderate (n = 1) or trace (n = 9), with resolution of the moderate pneumothorax after manual aspiration without chest tube placement. No patient required chest tube placement. No other complications or serious adverse effects related to the biopsy or dendritic cell injection were noted. All patients were in stable condition after up to 4 hours in the recovery unit and were discharged home on the same day. No procedure-related complications were observed on imaging or clinical follow-up at 4 weeks. CONCLUSIONS: Repeated percutaneous, transthoracic CT-guided biopsies and intratumoral gene-modified cell-based immunotherapy injections into lung cancers are technically feasible, safe, and reproducible. There were no procedure-related serious (defined as grade ≥3) adverse events.
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OBJECTIVES: To assess the feasibility of a rapid, focused ferumoxytol-enhanced MR angiography (f-FEMRA) protocol in patients with claustrophobia. METHODS: In this retrospective study, 13 patients with claustrophobia expressed reluctance to undergo conventional MR angiography, but agreed to a trial of up to 10 min in the scanner bore and underwent f-FEMRA. Thirteen matched control patients who underwent gadolinium-enhanced MR angiography (GEMRA) were identified for comparison of diagnostic image quality. For f-FEMRA, the time from localizer image acquisition to completion of the angiographic acquisition was measured. Two radiologists independently scored images on both f-FEMRA and GEMRA for arterial and venous image quality, motion artefact and diagnostic confidence using a 5-point scale, five being best. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the aorta and IVC were measured. The Wilcoxon rank-sum test, one-way ANOVA with Tukey correction and two-tailed t tests were utilized for statistical analyses. RESULTS: All scans were diagnostic and assessed with high confidence (scores ≥ 4). Average scan time for f-FEMRA was 6.27 min (range 3.56 to 10.12 min), with no significant difference between f-FEMRA and GEMRA in diagnostic confidence (4.86 ± 0.24 vs 4.69 ± 0.25, p = 0.13), arterial image quality (4.62 ± 0.57 vs 4.65 ± 0.49, p = 0.78) and motion artefact score (4.58 ± 0.49 vs 4.58 ± 0.28, p > 0.99). f-FEMRA scored significantly better for venous image quality than GEMRA (4.62 ± 0.42 vs 4.19 ± 0.56, p = 0.04). CNR in the IVC was significantly higher for steady-state f-FEMRA than GEMRA regardless of the enhancement phase (p < 0.05). CONCLUSIONS: Comprehensive vascular MR imaging of the thorax, abdomen and pelvis can be completed in as little as 5 min within the magnet bore using f-FEMRA, facilitating acceptance by patients with claustrophobia and streamlining workflow. ADVANCES IN KNOWLEDGE: A focused approach to vascular imaging with ferumoxytol can be performed in patients with claustrophobia, limiting time in the magnet bore to 10 min or less, while acquiring fully diagnostic images of the thorax, abdomen and pelvis.
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Medios de Contraste , Óxido Ferrosoférrico , Aumento de la Imagen/métodos , Angiografía por Resonancia Magnética/métodos , Angiografía por Resonancia Magnética/psicología , Trastornos Fóbicos/psicología , Estudios de Cohortes , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , TiempoRESUMEN
Purpose Bronchopleural fistula is a rare but serious complication of lung ablation, as it is difficult to treat and is associated with a high mortality rate. Standard therapy often relies on surgical pleurodesis, which can be particularly problematic in patients with poor baseline lung function. A minimally invasive treatment option for bronchopleural fistula may offer an alternative to surgery for appropriate patients. This case series describes the technique, safety and efficacy of percutaneously administered synthetic hydrogel surgical sealant in the treatment of post-ablation bronchopleural fistula in five patients. Materials and methods Retrospective chart review was carried out in five consecutive patients identified to have had BPF after lung ablation between 2009 and 2017 who were treated with percutaneous administration of synthetic hydrogel surgical sealant using CT guidance. Results The procedure was successfully carried out in all patients without immediate complications, and complete resolution of air leak was achieved in four of five patients (80%). Up to the most recent follow-up, no evidence of delayed complications or recurrent air leak was present (follow-up range 1 week-8 years). Conclusion The authors' initial experience shows that targeted surgical sealant is a potentially safe and effective alternative treatment of post-ablation persistent air leak.
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Técnicas de Ablación/efectos adversos , Fístula Bronquial/terapia , Hidrogeles/uso terapéutico , Enfermedades Pleurales/terapia , Complicaciones Posoperatorias/terapia , Anciano , Anciano de 80 o más Años , Fístula Bronquial/diagnóstico por imagen , Fístula Bronquial/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Pleurales/diagnóstico por imagen , Enfermedades Pleurales/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Radiografía Intervencional/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: The purpose of this study was to establish the feasibility of fusing complementary, high-contrast features from unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for preprocedural vascular mapping in patients with renal impairment. METHODS: In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, 15 consecutive patients underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multifeature image. Source images from CT and MRA were segmented and registered. To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on three-dimensional (3D) models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment. We then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points). Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal). The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets. The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent nonconcordance between the source FE-MRA and fused images. The offsets were compared using concordance correlation coefficients. Interobserver agreement was assessed using intraclass correlation coefficients and Bland-Altman analyses. RESULTS: Thirteen patients (aged 76 ± 12 years; seven female) with aortic valve stenosis and chronic kidney disease and two patients with thoracoabdominal vascular aneurysms and chronic kidney disease underwent FE-MRA for preprocedural vascular assessment, and unenhanced CT examinations were available in all patients. No ferumoxytol-related adverse events occurred. There were 247 matched POIs evaluated on the source FE-MRA and fused images. In patients with implantable medical devices, the mean offsets in spatial position were 0.31 ± 0.51 mm (ρ = 0.99; Cb = 1; 95% confidence interval [CI], 0.99-0.99) for Δx, 0.27 ± 0.69 mm (ρ = 0.99; Cb = 0.99; 95% CI, 0.99-0.99) for Δy, and 0.20 ± 0.59 mm (ρ = 1; Cb = 1; 95% CI, 0.99-1.00) for Δz. Interobserver agreement was excellent (intraclass correlation coefficient, >0.99). The mean difference in offset between readers was 1.5 mm. CONCLUSIONS: Accurate 3D feature fusion is feasible, combining luminal information from FE-MRA with vessel wall information on unenhanced CT. This framework holds promise for combining the complementary strengths of magnetic resonance imaging and CT to generate information-rich, multifeature composite vascular images while avoiding the respective risks and limitations of both modalities.
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Óxido Ferrosoférrico/administración & dosificación , Angiografía por Resonancia Magnética/métodos , Insuficiencia Renal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Enfermedades Vasculares/diagnóstico por imagen , Anciano , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Prótesis e ImplantesRESUMEN
IMPORTANCE: Varices are one of the main clinical manifestations of cirrhosis and portal hypertension. Gastric varices are less common than esophageal varices but are often associated with poorer prognosis, mainly because of their higher propensity to bleed. OBSERVATIONS: Currently, treatments used to control and manage gastric variceal bleeding include ß-blockers, endoscopic injection sclerotherapy, endoscopic variceal ligation, endoscopic variceal obturation, shunt surgery, transjugular intrahepatic portosystemic shunts, balloon-occluded retrograde transvenous obliteration (BRTO), and modified BRTO. In the past few decades, Western (United States and Europe) interventional radiologists have preferred transjugular intrahepatic portosystemic shunts that aim to decompress the liver and reduce portal pressure. Conversely, Eastern radiologists (Japan and South Korea) have preferred BRTO that directly targets the gastric varices. Over the past 20 years, BRTO has evolved and procedure-related risks have decreased. Owing to its safety and efficiency in treating gastric varices, BRTO is now starting to gain popularity among Western interventional radiologists. In this review, we present a comprehensive literature review of current and emerging management options, including BRTO and modified BRTO, for the treatment of gastric varices in the setting of cirrhosis and portal hypertension. CONCLUSIONS AND RELEVANCE: Balloon-occluded retrograde transvenous obliteration has emerged as a safe and effective alternative treatment option for gastric variceal hemorrhage. A proper training, evidence-based consensus and guideline, thorough preprocedural and postprocedural evaluation, and a multidisciplinary team approach with BRTO and modified BRTO are strongly recommended to ensure best patient care.
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Manejo de la Enfermedad , Várices Esofágicas y Gástricas/complicaciones , Hemorragia Gastrointestinal/terapia , Técnicas Hemostáticas , Oclusión con Balón/métodos , Hemorragia Gastrointestinal/etiología , Humanos , Derivación Portosistémica Intrahepática Transyugular/métodosRESUMEN
BACKGROUND: Although cardiovascular magnetic resonance venography (CMRV) is generally regarded as the technique of choice for imaging the central veins, conventional CMRV is not ideal. Gadolinium-based contrast agents (GBCA) are less suited to steady state venous imaging than to first pass arterial imaging and they may be contraindicated in patients with renal impairment where evaluation of venous anatomy is frequently required. We aim to evaluate the diagnostic performance of 3-dimensional (3D) ferumoxytol-enhanced CMRV (FE-CMRV) for suspected central venous occlusion in patients with renal failure and to assess its clinical impact on patient management. METHODS: In this IRB-approved and HIPAA-compliant study, 52 consecutive adult patients (47 years, IQR 32-61; 29 male) with renal impairment and suspected venous occlusion underwent FE-CMRV, following infusion of ferumoxytol. Breath-held, high resolution, 3D steady state FE-CMRV was performed through the chest, abdomen and pelvis. Two blinded reviewers independently scored twenty-one named venous segments for quality and patency. Correlative catheter venography in 14 patients was used as the reference standard for diagnostic accuracy. Retrospective chart review was conducted to determine clinical impact of FE-CMRV. Interobserver agreement was determined using Gwet's AC1 statistic. RESULTS: All patients underwent technically successful FE-CMRV without any adverse events. 99.5% (1033/1038) of venous segments were of diagnostic quality (score ≥ 2/4) with very good interobserver agreement (AC1 = 0.91). Interobserver agreement for venous occlusion was also very good (AC1 = 0.93). The overall accuracy of FE-CMRV compared to catheter venography was perfect (100.0%). No additional imaging was required prior to a clinical management decision in any of the 52 patients. Twenty-four successful and uncomplicated venous interventions were carried out following pre-procedural vascular mapping with FE-CMRV. CONCLUSIONS: 3D FE-CMRV is a practical, accurate and robust technique for high-resolution mapping of central thoracic, abdominal and pelvic veins and can be used to inform image-guided therapy. It may play a pivotal role in the care of patients in whom conventional contrast agents may be contraindicated or ineffective.
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Medios de Contraste/administración & dosificación , Óxido Ferrosoférrico/administración & dosificación , Imagenología Tridimensional/métodos , Angiografía por Resonancia Magnética/métodos , Flebografía/métodos , Enfermedades Vasculares/diagnóstico por imagen , Venas/diagnóstico por imagen , Adulto , Constricción Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Pronóstico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/terapiaRESUMEN
AIMS: In myocardial ischaemia, vascular endothelial growth factor (VEGF) induces permeability by activating a signalling pathway that includes VEGF receptor 2 (VEGFR2), resulting in increased oedema and inflammation and thereby expanding the area of tissue damage. In this study, we investigated the role of receptor-interacting protein 2 (Rip2) in VEGF signalling and myocardial ischaemia/reperfusion injury. METHODS AND RESULTS: To determine whether Rip2 has a role in VEGF signalling, we used cultured endothelial cells in which Rip2 was or was not inactivated. In Rip2-deficient endothelial cells, stimulation with VEGF resulted in more rapid kinetics of VEGFR2 phosphorylation than in control cells. Rip2 deficiency also enhanced VEGF-induced activation of ERK1/2, suggesting an increased propensity for endothelial permeability. In a mouse model of myocardial ischaemia, Rip2 deficiency resulted in enhanced vascular permeability, increased oedema and expanding area of myocardial damage, and markedly reduced heart function after long-term follow-up. CONCLUSION: Our results show that Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. These findings indicate that Rip2 may be a promising novel therapeutic target to reduce excess vascular permeability in ischaemic heart disease.
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Células Endoteliales/metabolismo , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Animales , Permeabilidad Capilar/fisiología , Células Cultivadas , Enfermedad de la Arteria Coronaria/metabolismo , Humanos , Ratones , Daño por Reperfusión Miocárdica/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The evidence that links classical protein-coding proto-oncogenes and tumor suppressors, such as MYC, RAS, P53, and RB, to carcinogenesis is indisputable. Multiple lines of proof show how random somatic genomic alteration of such genes (e.g., mutation, deletion, or amplification), followed by selection and clonal expansion, forms the main molecular basis of tumor development. Many important cancer genes were discovered using low-throughput approaches in the pre-genomic era, and this knowledge is today solidified and expanded upon by modern genome-scale methodologies. In several recent studies, non-coding RNAs (ncRNAs), such as microRNAs and long ncRNAs (lncRNAs), have been shown to contribute to tumor development. However, in comparison with coding cancer genes, the genomic (DNA-level) evidence is sparse for ncRNAs. The coding proto-oncogenes and tumor suppressors that we know of today are major molecular hubs in both normal and malignant cells. The search for ncRNAs with tumor driver or suppressor roles therefore holds the additional promise of pinpointing important, biologically active, ncRNAs in a vast and largely uncharacterized non-coding transcriptome. Here, we assess the available DNA-level data that links non-coding genes to tumor development. We further consider historical, methodological, and biological aspects, and discuss future prospects of ncRNAs in cancer.