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1.
J Nucl Med ; 57(2): 180-5, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26609177

RESUMEN

UNLABELLED: This prospective study compared a 1-d SPECT/CT protocol with the commonly used 3-d protocol for somatostatin receptor scintigraphy in patients with gastroenteropancreatic neuroendocrine neoplasms. Additionally, the influence of SPECT/CT on patient management was evaluated. METHODS: From October 2011 to October 2012, all gastroenteropancreatic neuroendocrine neoplasm patients undergoing restaging with somatostatin receptor scintigraphy on a modern SPECT/CT device were enrolled in this study. The protocol consisted of planar imaging at 4, 24, and 48 h; low-dose SPECT/CT at 24 and 48 h; diagnostic CT at 24 h using a triple-phase delay after administration of contrast; and diagnostic SPECT/CT at 24 h. All components of the imaging data were reassessed by 3 masked interpreters. The results were compared with a reference standard based on all clinical, imaging, and histopathology follow-up data available (follow-up range, 24-36 mo; mean, 29.9 mo). The reference standard was defined by a study-specific interdisciplinary tumor board that also reassessed treatment decisions. RESULTS: Thirty-one patients were eligible for analysis (18 men and 13 women; mean age, 60.4 y). Ten had no imaging signs of disease and remained disease-free during follow-up. Twenty-one had persistent or recurrent disease (82 lesions: 24 in the liver, 21 in the lymph nodes, 16 in bone, 12 in the pancreas, and 9 in other locations). The respective lesion detection rates for interpreters 1, 2, and 3 were 51.9%, 49.4%, and 71.6% for low-dose SPECT/CT at 24 h; 51.9%, 55.6%, and 67.9% for low-dose SPECT/CT at 48 h; 63.0%, 70.4%, and 85.2% for diagnostic CT; and 77.8%, 84.0%, and 88.9% for diagnostic SPECT/CT. Interobserver agreement was moderate for diagnostic SPECT/CT (κ = 0.44), diagnostic CT (κ = 0.43), low-dose SPECT/CT at 48 h (κ = 0.61), and low-dose SPECT/CT at 24 h (κ = 0.55). For planar imaging, interobserver agreement was fair after 48 h (κ = 0.36) and 24 h (κ = 0.38) and moderate after 4 h (κ = 0.42). Every lesion detectable on planar imaging or low-dose SPECT/CT was also detectable on diagnostic SPECT/CT. The CT and SPECT components of diagnostic SPECT/CT strongly complemented each other, as 34 of 82 lesions (41.4%) were detected on only the CT component or only the SPECT component. Therapeutic management was influenced by the diagnostic SPECT/CT interpretation in 8 of 31 patients (25.8%). CONCLUSION: The highest detection rates were achieved by diagnostic SPECT/CT. Thus, a more patient-friendly 1-d protocol is feasible. Furthermore, multiphase SPECT/CT affected management in about a quarter of patients.


Asunto(s)
Neoplasias Gastrointestinales/diagnóstico por imagen , Tumores Neuroendocrinos/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Receptores de Somatostatina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Variaciones Dependientes del Observador , Estudios Prospectivos , Radiofármacos , Estándares de Referencia , Tomografía Computarizada de Emisión de Fotón Único/métodos , Imagen de Cuerpo Entero
2.
Eur Radiol ; 25(9): 2608-16, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25735513

RESUMEN

OBJECTIVES: Transarterial chemoembolization (TACE) is established as bridging therapy of HCC listed for transplantation (LT). CT-guided brachytherapy (CTB) has not been evaluated as a bridging concept. We compared CTB and TACE for bridging before LT in HCC patients. METHODS: Twelve patients with HCC received LT after CTB (minimal tumour dose, 15-20 Gy). Patients were matched (CTB:TACE, 1:2) by sex, age, number and size of lesions, and underlying liver disease with patients who received TACE before transplantation. Study endpoints were extent of necrosis at histopathology and recurrence rate after OLT. RESULTS: There were no significant differences between the CTB and TACE groups regarding Child-Pugh category (p = 0.732), AFP (0.765), time on waiting list (p = 0.659), number (p = 0.698) and size (p = 0.853) of HCC lesions, fulfilment of Milan-criteria (p = 0.638), or previous liver-specific treatments. CTB achieved higher tumour necrosis rates than TACE (p = 0.018). The 1- and 3-year recurrence rate in the CTB group was 10 and 10 % vs. TACE, 14 and 30 % (p = 0.292). CONCLUSIONS: Our data show comparable or even better response and post-LT recurrence rates of CTB compared to TACE for treating HCC in patients prior to LT. CTB should be further evaluated as an alternative bridging modality, especially for patients not suited for TACE. KEY POINTS: • CT-guided interstitial brachytherapy (CTB) is a promising alternative to transarterial chemoembolization (TACE). • CTB instead of TACE is possible for bridging to liver transplantation in HCC patients. • HCC recurrence was not associated with CTB despite potential tumour seeding.


Asunto(s)
Braquiterapia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Trasplante de Hígado , Radiografía Intervencional , Tomografía Computarizada por Rayos X , Carcinoma Hepatocelular/diagnóstico por imagen , Femenino , Humanos , Hígado/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos
3.
Eur Radiol ; 25(5): 1329-38, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25433414

RESUMEN

OBJECTIVES: Evaluation of computed tomography (CT) and magnetic resonance imaging (MRI) for differentiation of pancreatic intraductal papillary mucinous neoplasm (IPMN) subtypes based on objective imaging criteria. METHODS: Fifty-eight patients with 60 histologically confirmed IPMNs were included in this retrospective study. Eighty-three imaging studies (CT,n = 42; MRI,n = 41) were analysed by three independent blinded observers (O1-O3), using established imaging criteria to assess likelihood of malignancy (-5, very likely benign; 5, very likely malignant) and histological subtype (i.e., low-grade (LGD), moderate-grade (MGD), high-grade dysplasia (HGD), early invasive carcinoma (IPMC), solid carcinoma (CA) arising from IPMN). RESULTS: Forty-one benign (LGD IPMN,n = 20; MGD IPMN,n = 21) and 19 malignant (HGD IPMN,n = 3; IPMC,n = 6; solid CA,n = 10) IPMNs located in the main duct (n = 6), branch duct (n = 37), or both (n = 17) were evaluated. Overall accuracy of differentiation between benign and malignant IPMNs was 86/92 % (CT/MRI). Exclusion of overtly malignant cases (solid CA) resulted in overall accuracy of 83/90 % (CT/MRI). The presence of mural nodules and ductal lesion size ≥30 mm were significant indicators of malignancy (p = 0.02 and p < 0.001, respectively). CONCLUSIONS: Invasive IPMN can be identified with high confidence and sensitivity using CT and MRI. The diagnostic problem that remains is the accurate radiological differentiation of premalignant and non-invasive subtypes. KEY POINTS: • CT and MRI can differentiate benign from malignant forms of IPMN. • Identifying (pre)malignant histological IPMN subtypes by CT and MRI is difficult. • Overall, diagnostic performance with MRI was slightly (not significantly) superior to CT.


Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Papilar/diagnóstico , Imagen por Resonancia Magnética , Neoplasias Pancreáticas/diagnóstico , Tomografía Computarizada por Rayos X , Diagnóstico Diferencial , Diagnóstico por Imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conductos Pancreáticos/diagnóstico por imagen , Conductos Pancreáticos/patología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
4.
Acta Radiol ; 56(12): 1419-27, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25406435

RESUMEN

BACKGROUND: Despite novel software solutions, liver volume segmentation is still a time-consuming procedure and often requires further manual optimization. With the high signal intensity of the liver parenchyma in Gd-EOB enhanced magnetic resonance imaging (MRI), liver volume segmentation may be improved. PURPOSE: To evaluate the practicability of threshold-based segmentation of the liver volume using Gd-EOB-enhanced MRI including a customized three-dimensional (3D) sequence. MATERIAL AND METHODS: A total of 20 patients examined with Gd-EOB MRI (hepatobiliary phase T1-weighted (T1W) 3D sequence [VIBE]; flip angle [FA], 10° and 30°) were enrolled in this retrospective study. The datasets were independently processed by two blinded observers (O1 and O2) in two ways: manual (man) and threshold-based (thresh; study method) segmentation of the liver each followed by an optimization step (man+opt and thresh+opt; man+opt [FA10°] served as reference method). Resulting liver volumes and segmentation times were compared. A liver conversion factor was calculated in percent, describing the non-hepatocellular fraction of the total liver volume, i.e. bile ducts and vessels. RESULTS: Thresh+opt (FA10°) was significantly faster compared to the reference method leading to a median volume overestimation of 4%/8% (P < 0.001). Using thresh+opt (FA30°), segmentation was even faster (P < 0.001) and even reduced median volume deviation of 0%/2% (O1/O2; both P > 0.2). The liver conversion factor was found to be 10%. CONCLUSION: Threshold-based liver segmentation employing Gd-EOB-enhanced hepatobiliary phase standard T1W 3D sequence is accurate and time-saving. The performance of this approach can be further improved by increasing the FA.


Asunto(s)
Gadolinio DTPA , Aumento de la Imagen , Imagenología Tridimensional , Neoplasias Hepáticas/patología , Hígado/patología , Imagen por Resonancia Magnética , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
5.
Eur J Radiol ; 83(10): 1723-7, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25022980

RESUMEN

OBJECTIVES: To estimate the additional value of an increased flip angle of 35° in late phase Gd-EOB-DTPA-enhanced magnetic resonance cholangiography, as compared to T2w-MRCP. METHODS: 40 adult patients underwent Gd-EOB-DTPA enhanced MRI of the liver including a T2-weighted 3D TSE MRCP (T2w-MRCP) as well as a late phase T1-weighted THRIVE sequences applying a flip angle of 35° (fa35). Two experienced observers evaluated the images regarding the delineation of the different biliary regions using a three-point grading system. A five-point scale was applied to determine the readers' confidence in identifying anatomical variations of the biliary tree. ROI analysis was performed to compare the signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. RESULTS: The quality for visualizing the biliary tree differed between T2w-MRCP and fa35 (p=<0.001). Late phase EOB-MRC was rated as good for delineating the entire biliary system, whereas T2w-MRCP received an overall poor rating. Especially the depiction of the intrahepatic bile ducts was estimated as problematic in T2w-MRCP. T2w-MRCP and fa35 revealed a discordant assessment of anatomical variations in 12.5% of the cases, comprising a generally higher confidence level for fa35 (4.0 ± 1.1 vs. 2.2 ± 1.2, p=<0.001). SNR proofed to be significantly higher in fa35 (p=<0.001), whereas T2w-MRCP revealed a significantly higher CNR (<0.001). CONCLUSIONS: Gd-EOB-DTPA enhanced magnetic resonance cholangiography acquired with a flip angle of 35° revealed a better diagnostic performance compared to T2w-MRCP and might be a valuable adjunct in assessing functional bile duct abnormalities.


Asunto(s)
Enfermedades de las Vías Biliares/diagnóstico , Pancreatocolangiografía por Resonancia Magnética/métodos , Medios de Contraste , Gadolinio DTPA , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Relación Señal-Ruido
6.
Acta Radiol ; 55(2): 149-54, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23908244

RESUMEN

BACKGROUND: The optimal sequence for Gd-EOB-DTPA uptake measurement in the liver with the purpose of liver function measurement is still not defined. PURPOSE: To prospectively evaluate the effect of an increased flip angle (FA) of a T1-weighted fat-saturated 3D sequence for the measurement of hepatocyte uptake of Gd-EOB-DTPA magnetic resonance imaging (MRI) after right portal vein embolization (PVE). MATERIAL AND METHODS: Ten patients who received a PVE prior to an extended hemihepatectomy were examined 14 days after PVE using Gd-EOB-DTPA enhanced MRI of the liver using the standard FA of 10° and the increased FA of 30°. RESULTS: Relative enhancement of the right liver lobe (RLL) was 0.52 ± 0.12 for 10° and 1.41 ± 0.39 for 30°. Relative enhancement of the left liver lobe (LLL) was 0.58 ± 0.11 for 10° and 2.05 ± 0.61 for 30°. Relative enhancement of the RLL was significantly higher for 30° than for 10° (P = 0.009) and significantly higher in the 30° than in the 10° sequences (P = 0.005) for the LLL. CONCLUSION: A flip angle of 30° increases the contrast between liver partitions with and without portal venous embolization. Thereby, the sensitivity for differences in uptake intensity is increased. This could be of value for a more exact determination of differences in regional liver function and, consequently, the estimation of the future remnant liver function.


Asunto(s)
Colangiocarcinoma/diagnóstico , Medios de Contraste/farmacocinética , Embolización Terapéutica , Gadolinio DTPA/farmacocinética , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética , Adulto , Anciano , Colangiocarcinoma/terapia , Femenino , Hepatectomía , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Vena Porta , Estudios Prospectivos , Sensibilidad y Especificidad
7.
J Comput Assist Tomogr ; 37(4): 602-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23863539

RESUMEN

OBJECTIVE: The objective of this study was to evaluate computed tomography (CT) findings in patients with sepsis with unknown inflammatory focus and acute respiratory distress syndrome. METHODS: Acute respiratory distress syndrome findings on CT of 36 patients with sepsis were graded on a 6-point scale, and the percentage of affected lung was estimated. Resulting CT scores were correlated to intensive care scores and survival. RESULTS: Forty-four percent of the patients died, revealing a significantly higher CT score than survivors (P = 0.01). Survivors showed larger areas of unaffected lung (P < 0.001), whereas patients with fatal outcome had more ground-glass opacities (P = 0.002; sensitivity, 73%; specificity, 57%) and traction bronchiectasis (P = 0.009; sensitivity, 54%; specificity, 68%). Pulmonary findings on CT did not allow discriminating between a pulmonary and extrapulmonary focus. No significant coherence between CT score and intensive care scores could be revealed. CONCLUSIONS: A CT scoring system based on pulmonary findings in patients with sepsis with acute respiratory distress syndrome comprises prognostic implications in terms of the patients' survival.


Asunto(s)
Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/mortalidad , Sepsis/diagnóstico por imagen , Sepsis/mortalidad , Tasa de Supervivencia , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Estadística como Asunto , Análisis de Supervivencia
8.
Mol Imaging Biol ; 15(6): 768-75, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23722880

RESUMEN

PURPOSE: This study aims to develop a molecular imaging strategy for response assessment of arginine deiminase (ADI) treatment in melanoma xenografts using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]-FLT) positron emission tomography (PET). PROCEDURES: F-FLT response to ADI therapy was studied in preclinical models of melanoma in vitro and in vivo. The molecular mechanism of response to ADI therapy was investigated, with a particular emphasis on biological pathways known to regulate (18)F-FLT metabolism. RESULTS: Proliferation of SK-MEL-28 melanoma tumors was potently inhibited by ADI treatment. However, no metabolic response was observed in FLT PET, presumably based on the known ADI-induced degradation of PTEN, followed by instability of the tumor suppressor p53 and a relative overexpression of thymidine kinase 1, the enzyme mainly responsible for intracellular FLT processing. CONCLUSION: The specific pharmacological properties of ADI preclude using (18)F-FLT to evaluate clinical response in melanoma and argue for further studies to explore the use of other clinically applicable PET tracers in ADI treatment.


Asunto(s)
Antineoplásicos/uso terapéutico , Didesoxinucleósidos/farmacocinética , Hidrolasas/uso terapéutico , Melanoma/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Didesoxinucleósidos/química , Hidrolasas/farmacología , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Melanoma/patología , Ratones , Transducción de Señal/efectos de los fármacos , Timidina Quinasa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Invest Radiol ; 48(6): 471-6, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23442776

RESUMEN

OBJECTIVES: The objective of this study was to evaluate the accuracy, safety, and efficacy of magnetic resonance (MR)-guided periradicular nerve root injection therapy using an open 1.0-T magnetic resonance imaging (MRI) system with fast dynamic imaging. MATERIALS AND METHODS: Between April 2008 and November 2011, a total of 249 MR-guided periradicular nerve root injections were performed in 141 patients experiencing lumbosacral radicular pain. All interventions were performed in an open 1.0-T MRI system. An interactive proton-density-weighted fast spin-echo sequence was used for real-time guidance. An in-room monitor, a wireless MR mouse for operator-controlled multiplanar imaging, a flexible surface coil, and an MR-compatible 20-G needle were used. Informed consent was obtained from all patients. Clinical outcome was evaluated through clinical follow-up and a questionnaire before injection therapy (baseline) and 6 months after using a numeric visual analog scale. RESULTS: All procedures were technically successful. No major complications occurred. At 6 months, of the 103 patients (197 injections; 57 men, 46 women; mean age, 49.5 years; range, 20-80) who enrolled in the outcome analysis, 14.6% reported complete remission of radicular pain; 53.4%, significant relief of pain; 22.3%, mild relief; and 9.7%, no relief of pain. We found a significant decrease of the visual analog scale score from the preintervention compared with the follow-up after 6 months (P < 0.001). No significant difference in the outcome was observed between the patients with degenerative foraminal stenoses and the patients with herniated disks. CONCLUSIONS: Magnetic resonance fluoroscopy-guided periradicular injection therapy for the lumbosacral spine under open 1.0-T MRI guidance is accurate, safe, and efficient in the symptomatic treatment of radicular pain. This technique may be a promising alternative to fluoroscopy- or computed tomography-guided spinal injections in the lumbosacral region, especially for young patients and patients undergoing serial therapeutic regimens.


Asunto(s)
Bupivacaína/administración & dosificación , Dolor de la Región Lumbar/prevención & control , Imagen por Resonancia Magnética Intervencional/métodos , Radiculopatía/tratamiento farmacológico , Radiculopatía/patología , Triamcinolona Acetonida/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Anestésicos Locales/administración & dosificación , Antiinflamatorios/administración & dosificación , Sistemas de Computación , Quimioterapia Combinada/métodos , Femenino , Humanos , Dolor de la Región Lumbar/etiología , Región Lumbosacra/patología , Masculino , Persona de Mediana Edad , Radiculopatía/complicaciones , Resultado del Tratamiento , Adulto Joven
10.
Cell Transplant ; 22(11): 1959-70, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23294541

RESUMEN

Cellular therapies require methods for noninvasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate a strong contrast in magnetic resonance imaging (MRI) and are therefore ideally suited as an intracellular contrast agent to image cells under clinical conditions. However, MPIOs were previously not applicable for clinical use. Here, we present the development and evaluation of silica-based micron-sized iron oxide particles (sMPIOs) with a functionalizable particle surface. Particles with magnetite content of >40% were composed using the sol-gel process. The particle surfaces were covered with COOH groups. Fluorescein, poly-L-lysine (PLL), and streptavidin (SA) were covalently attached. Monodisperse sMPIOs had an average size of 1.18 µm and an iron content of about 1.0 pg Fe/particle. Particle uptake, toxicity, and imaging studies were performed using HuH7 cells and human and rat hepatocytes. sMPIOs enabled rapid cellular labeling within 4 h of incubation; PLL-modified particles had the highest uptake. In T2*-weighted 3.0 T MRI, the detection threshold in agarose was 1,000 labeled cells, whereas in T1-weighted LAVA sequences, at least 10,000 cells were necessary to induce sufficient contrast. Labeling was stable and had no adverse effects on labeled cells. Silica is a biocompatible material that has been approved for clinical use. sMPIOs could therefore be suitable for future clinical applications in cellular MRI, especially in settings that require strong cellular contrast. Moreover, the particle surface provides the opportunity to create multifunctional particles for targeted delivery and diagnostics.


Asunto(s)
Medios de Contraste/química , Compuestos Férricos/química , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Dióxido de Silicio/química , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Medios de Contraste/metabolismo , Medios de Contraste/toxicidad , Fluoresceína/química , Fluoresceína/metabolismo , Hepatocitos/citología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Nanopartículas de Magnetita/toxicidad , Masculino , Microscopía Electrónica , Tamaño de la Partícula , Polilisina/química , Ratas , Ratas Endogámicas Lew , Estreptavidina/química , Estreptavidina/metabolismo
11.
Mol Imaging ; 12(1): 67-73, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23348793

RESUMEN

Based on their inability to express argininosuccinate synthetase (ASS), some cancer entities feature the characteristic of L-arginine (Arg) auxotrophy. This inability to intrinsically generate Arg makes them applicable for arginine deiminase (ADI) treatment, an Arg-depleting drug. Arg is also used for the synthesis of endothelial nitric oxide (NO), which mainly confers vasodilatation but is also considered to have a major influence on tumor vascularization. The purpose of this study was to define changes in tumor vasculature in an ADI-treated melanoma xenograft mouse model using the blood pool agent AngioSense 750 and fluorescence molecular tomography (FMT). We used an ASS-negative melanoma xenograft mouse model and subjected it to weekly ADI treatment. Changes in tumor size were measured, and alterations in tumor vasculature were depicted by FMT and CD31 immunohistochemistry (IHC). On ADI treatment and effective antitumor therapy, we observed a drop in NO plasma levels and visualized changes in tumor vascularization with FMT and IHC. ADI treatment in melanoma xenografts has a tumor-reducing effect, which can be noninvasively imaged by quantifying tumor vascularization with FMT and IHC.


Asunto(s)
Hidrolasas/farmacología , Melanoma/irrigación sanguínea , Melanoma/tratamiento farmacológico , Imagen Óptica/métodos , Tomografía/métodos , Animales , Argininosuccinato Sintasa/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Inmunohistoquímica , Ratones , Ratones SCID , Imagen Molecular/métodos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Óxido Nítrico/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Mol Imaging Biol ; 15(2): 166-74, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22847302

RESUMEN

PURPOSE: Sindbis virus (SINV) infect tumor cells specifically and systemically throughout the body. Sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. The ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option. PROCEDURES: The tumor specificity of SINV is mediated by the 67-kDa laminin receptor (LR). We probed different cancer cell lines for their LR expression and, to determine the specific role of LR-expression in the infection cycle, used different molecular imaging strategies, such as bioluminescence, fluorescence molecular tomography, and positron emission tomography, to evaluate SINV-mediated infection in vitro and in vivo. RESULTS: All cancer cell lines showed a marked expression of LR. The infection rates of the SINV particles, however, differed significantly among the cell lines. CONCLUSION: We used novel molecular imaging techniques to visualize vector delivery to different neoplatic cells. SINV infection rates proofed to be not solely dependent on cellular LR expression. Further studies need to evaluate the herein discussed ways of cellular infection and viral replication.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Imagen Molecular/métodos , Imagen Óptica/métodos , Tomografía de Emisión de Positrones/métodos , Virus Sindbis/genética , Animales , Línea Celular , Femenino , Colorantes Fluorescentes , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Humanos , Ratones , Ratones SCID , Receptores de Laminina/genética , Receptores de Laminina/metabolismo , Transfección
13.
Eur J Radiol ; 81(11): e991-5, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22884706

RESUMEN

OBJECTIVES: To assess the improvement of bile duct visualization in Gd-EOB-DTPA enhanced MR-cholangiography (EOB-MRC) by using an increased flip angle. METHODS: 35 patients underwent Gd-EOB-DTPA enhanced MRI of the liver including T2-weighted MRCP and hepatobiliary phase EOB-MRC using a flip angle of 10° (FA10) and of 35° (FA35), respectively. Images were evaluated regarding the delineation of biliary ducts, the order of branching and anatomic visualization of the biliary tree. ROI analysis was performed to estimate the signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. RESULTS: Applying the FA35 resulted in a significantly better SNR and CNR as compared to FA10. The overall image quality was rated as good for both, FA10 and FA35. The overall rating for regional delineation of the biliary system was rated significantly better for FA35 than for FA10 (p=0.02). Classification of bile duct anatomy variations, however, was equivalent in both techniques. CONCLUSIONS: Increasing the flip angle of a T1-weighted 3D-sequence from 10° to 35° during the hepatobiliary phase of Gd-EOB enhanced MRI visually and quantitatively improved the visualization of the biliary ducts.


Asunto(s)
Algoritmos , Neoplasias de los Conductos Biliares/patología , Conductos Biliares/patología , Gadolinio DTPA , Aumento de la Imagen/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
14.
J Nucl Med ; 53(2): 281-6, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22228793

RESUMEN

UNLABELLED: Because of deficiencies in l-arginine biosynthesis, some cancers are susceptible to therapeutic intervention with arginine deiminase (ADI), an enzyme responsible for consuming the dietary supply of l-arginine to deprive the disease of an essential nutrient. ADI is currently being evaluated in several clinical trials, and fully realizing the drug's potential will depend on invoking the appropriate metrics to judge clinical response. Without a clear biologic mandate, PET/CT with (18)F-FDG is currently used to monitor patients treated with ADI. However, it is unclear if it can be expected that (18)F-FDG responses will indicate (or predict) clinical benefit. METHODS: (18)F-FDG responses to ADI therapy were studied in preclinical models of melanoma in vitro and in vivo. The molecular mechanism of response to ADI therapy was also studied, with a particular emphasis on biologic pathways known to regulate (18)F-FDG avidity. RESULTS: Although proliferation of SK-MEL 28 was potently inhibited by ADI treatment in vitro and in vivo, no clear declines in (18)F-FDG uptake were observed. Further investigation showed that ADI treatment induces the posttranslational degradation of phosphatase and tensin homolog and the activation of the PI3K signaling pathway, an event known to enhance glycolysis and (18)F-FDG avidity. A more thorough mechanistic study showed that ADI triggered a complex mechanism of cell death, involving apoptosis via poly (ADP-ribose) polymerase cleavage-independent of caspase 3. CONCLUSION: These findings suggest that some unexpected pharmacologic properties of ADI preclude using (18)F-FDG to evaluate clinical response in melanoma and, more generally, argue for further studies to explore the use of PET tracers that target apoptotic pathway activation or cell death.


Asunto(s)
Fluorodesoxiglucosa F18 , Hidrolasas/farmacología , Melanoma/tratamiento farmacológico , Animales , Línea Celular Tumoral , Femenino , Humanos , Hidrolasas/uso terapéutico , Melanoma/diagnóstico por imagen , Melanoma/metabolismo , Melanoma/patología , Ratones , Tomografía de Emisión de Positrones , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Ann Transplant ; 17(4): 108-12, 2012 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-23274330

RESUMEN

BACKGROUND: The objective was to evaluate contrast enhanced ultrasound (CEUS) based cholangiography compared to conventional radiography as a reference method in patients after liver transplantation. MATERIAL/METHODS: Contrast agents were administered through T-tubes, which were placed during the operation. Twelve patients with side-to-side choledocho-choledochostomy and standardized intraoperative T-tube placement were investigated on the 5th postoperative day (POD 5) with both techniques. All images were digitally acquired and assessed in consensus by two investigators regarding complete anatomic visualization, depiction of pathology (e.g. delayed contrast outflow, stenosis and leakage) and general image quality. RESULTS: CEUS cholangiography showed comparable results in the detection of biliary pathology and overall image quality. Regarding the visualization of the extrahepatic bile duct CEUS produced limited results in 6 patients. CONCLUSIONS: In conclusion, CEUS cholangiography via T-tube represents a potential bedside test for visualization of intrahepatic bile ducts of transplanted livers; its diagnostic value remains to be determined in further studies.


Asunto(s)
Enfermedades de los Conductos Biliares/diagnóstico por imagen , Conductos Biliares Extrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Medios de Contraste , Trasplante de Hígado , Fosfolípidos , Complicaciones Posoperatorias/diagnóstico por imagen , Hexafluoruro de Azufre , Adulto , Anciano , Algoritmos , Enfermedades de los Conductos Biliares/etiología , Colangiografía , Técnicas de Apoyo para la Decisión , Drenaje/instrumentación , Drenaje/métodos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Microburbujas , Persona de Mediana Edad , Cuidados Posoperatorios/instrumentación , Cuidados Posoperatorios/métodos , Ultrasonografía
16.
J Vasc Interv Radiol ; 22(9): 1254-62, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21624837

RESUMEN

PURPOSE: To assess the efficacy and safety of portal vein (PV) embolization versus hepatic artery embolization (HAE) for induction of hepatic hypertrophy before extended right hemihepatectomy in patients with hilar cholangiocarcinoma. MATERIALS AND METHODS: Fifty patients (female, n = 15; male, n = 35; age range, 37-80 y) with hilar cholangiocarcinomas who were planned to undergo extended right hemihepatectomy were prospectively included in 2003-2006. In addition to biliary decompression of the left liver, patients were randomized to undergo embolization of the right hepatic artery (with transfemoral access and polyvinyl alcohol [PVA] particles plus coils) or right PV branches (with computed tomography [CT]-guided transhepatic access and PVA particles). CT was performed before and approximately 3 weeks after embolization for volumetric assessment of the liver. RESULTS: In the HAE group, median growth of the left lateral segments was 40 mL (P < .01), with a median reduction of the whole liver of 10 mL (P = .41); adverse events were observed in two of 25 patients (8%), who each developed an abscess in the right liver lobe. In the PV embolization group, median growth of the left lateral segments was 110 mL (P < .01), with a median growth of the whole liver of 10 mL (P = .92); a subcapsular seroma occurred in one of 25 patients (4%). The median growth of the left lateral segments after PV embolization was significantly greater than after HAE (P = .004). CONCLUSIONS: Compared with HAE, PV embolization was significantly superior regarding induction of hepatic hypertrophy of the left lateral segments.


Asunto(s)
Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/terapia , Embolización Terapéutica/métodos , Hepatectomía , Arteria Hepática , Vena Porta , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Distribución de Chi-Cuadrado , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/cirugía , Descompresión , Embolización Terapéutica/efectos adversos , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Portografía , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
17.
Acta Radiol ; 51(10): 1067-77, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20929294

RESUMEN

BACKGROUND: preoperative assessment of pancreatic masses is still challenging as regards the characterization and assessment of irresectability. The opportunities of modern multidetector computed tomography (MDCT) with image postprocessing can be expected to enhance the diagnostic performance if accurate criteria are elaborated. PURPOSE: to estimate the accuracy of MDCT and multiplanar image reconstructions with the use of standardized imaging criteria for preoperative evaluation of pancreatic masses with respect to irresectability. MATERIAL AND METHODS: a total of 105 consecutive patients who underwent exploratory laparoscopy or pancreatic resection and had preoperative 3-phase MDCT (4-64 rows) were enrolled retrospectively. First, transverse sections and secondly additional 3Ds were reviewed by two independent blinded observers (O1/O2). Preoperative imaging findings were correlated with intraoperative and histopathologic results. RESULTS: among all 105 patients, 70 malignant pancreatic tumors and 35 benign pancreatic diseases were found (accuracy of 93% for O1 and 91% for O2). For arterial tumor invasion, receiver operator characteristic (ROC) analysis (values averaged from the results of O1 and O2) revealed an area under the curve (AUC) of 0.931 for transverse sections and 0.986 for 3Ds. Regarding irresectability, positive predictive values were 97% (with 3Ds, 97%) for O1/O2; negative predictive values were 84% (with 3Ds, 89%) for O1 and 86% (with 3Ds, 91%) for O2. CONCLUSION: MDCT with 3Ds was highly accurate for evaluation and assessment of irresectability criteria in patients with pancreatic masses. However, due to the limited specificity regarding arterial tumor infiltration, the indication for surgical exploration should be made generously in case of inconclusive findings.


Asunto(s)
Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Cuidados Preoperatorios/métodos , Tomografía Computarizada por Rayos X/métodos , Área Bajo la Curva , Medios de Contraste , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Yohexol/análogos & derivados , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Enfermedades Pancreáticas/diagnóstico por imagen , Enfermedades Pancreáticas/cirugía , Valor Predictivo de las Pruebas , Curva ROC , Intensificación de Imagen Radiográfica/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
18.
Neuroendocrinology ; 91(1): 101-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-19996582

RESUMEN

AIM: Retrospective evaluation of the impact of integrated positron emission tomography/computed tomography (PET/CT) using (68)Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide ((68)Ga-DOTATOC) on the therapeutic management of patients with neuroendocrine tumors (NET). METHODS: The (68)Ga-DOTATOC-PET/CT data of 66 patients (31 male, 35 female; age: 29-79, mean age: 56 years) with known or suspected NET were included. Imaging data (PET and triple-phase contrast-enhanced CT) were evaluated in consensus by two readers for the visualization of NET manifestations. Combined PET/CT, clinical and imaging follow-up as well as histopathology (if available) served as the reference standard. In order to assess the impact of the respective submodalities on the therapeutic strategy chosen, the results were compared to the treatment decision made by the interdisciplinary NET tumor board of our institution. RESULTS: Two of the initial 66 patients included did not suffer from NET according to further immunohistopathological examination. In 50 of the remaining 64 (78%) NET patients, a total of 181 NET manifestations were detected by PET/CT. 59/181 (32.6%) were detected by one submodality only (CT 17.1%, PET 15.5%, p for comparison of both = 0.459). Combined PET/CT reading had an impact on the therapeutic management in 24 of 64 (38%) NET patients: primary resection (n = 5), curative lymph node resection (n = 1), initiation/switch of chemotherapy (CTx) due to progressive disease (n = 10), no surgery due to systemic disease (n = 2), radiopeptide receptor therapy instead of CTx (n = 1), additional bisphosphonate therapy (n = 4), and hepatic brachytherapy (n = 1). In 12 of 24 (50%) of these patients, relevant findings were detected by a single submodality only: CT (n = 5), PET (n = 7); p for comparison = 0.774). CONCLUSION: (68)Ga-DOTATOC-PET/CT influences therapeutic management in about one third of patients examined. CT and PET are comparably sensitive, deliver complementary information and equally contribute to therapeutic decision-making. Thus, despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended.


Asunto(s)
Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Octreótido/análogos & derivados , Compuestos Organometálicos , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad
19.
Eur Radiol ; 20(1): 108-17, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19662418

RESUMEN

The purpose of this study was to evaluate the accuracy of MDCT for preoperative assessment of hepatic vascular anatomy and the identification of liver-transplantation (OLT) patients at risk of developing subsequent splenic artery steal syndrome (SASS). A total of 145 patients with liver cirrhosis who had undergone OLT and had pre-operative three-phase MDCT (4- to 64-rows) within 100 days before OLT were enrolled retrospectively. MDCT and 3Ds were reviewed by two independent blinded observers (O1/O2). Pre-operative imaging findings were correlated with intra-operative results; findings indicative for SASS were correlated with clinical data and DSA. Among all 145 patients, 16 patients (11%) showed accessory hepatic arteries (accuracy O1/O2, 97%; with 3Ds, 100%); 32 (22%) patients had replaced hepatic arteries (accuracy O1, 97%; O2, 95%; with 3Ds, 100%; kappa = 0.87 and 0.89, P < 0.001). Among 119 patients, 12 patients developed SASS after OLT. The logistic regression model revealed the spleen volume (P = 0.0105) as a predictive factor of SASS. With spleen volumes >or=829 ml, an accuracy of 75% for prediction of SASS was obtained. MDCT with three-dimensional post-processing (3Ds) was highly accurate for pre-operative hepatic vessel evaluation in patients before OLT. In addition, spleen volume was a predictive factor for developing SASS after OLT.


Asunto(s)
Arteria Hepática/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Cirrosis Hepática/cirugía , Trasplante de Hígado/diagnóstico por imagen , Trasplante de Hígado/estadística & datos numéricos , Arteria Esplénica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/estadística & datos numéricos , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Factores de Riesgo , Sensibilidad y Especificidad , Método Simple Ciego
20.
Mol Imaging Biol ; 12(1): 25-34, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-19582510

RESUMEN

PURPOSE: The aim of our study was to modify an aminosilane-coated superparamagnetic nanoparticle for cell labeling and subsequent multimodal imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescent imaging in vivo. PROCEDURES: We covalently bound the transfection agent HIV-1 tat, the fluorescent dye fluorescein isothiocyanate, and the positron-emitting radionuclide gallium-68 to the particle and injected them intravenously into Wistar rats, followed by animal PET and MRI at 3.0 T. As a proof of principle hepatogenic HuH7 cells were labeled with the particles and observed for cell toxicity as well as detectability by MRI and biodistribution in vivo. RESULTS: PET imaging and MRI revealed increasing hepatic and splenic accumulation of the particles over 24 h. Adjacent in vitro studies in hepatogenic HuH7 cells showed a rapid intracellular accumulation of the particles with high labeling efficiency and without any signs of toxicity. In vivo dissemination of the labeled cells could be followed by dynamic biodistribution studies. CONCLUSIONS: We conclude that our modified superparamagnetic nanoparticles are stable under in vitro and in vivo conditions and are therefore applicable for efficient cell labeling and subsequent multimodal molecular imaging. Moreover, their multiple free amino groups suggest the possibility for further modifications and might provide interesting opportunities for various research fields.


Asunto(s)
Imagen por Resonancia Magnética , Magnetismo , Imagen Molecular/métodos , Nanopartículas , Tomografía de Emisión de Positrones , Silanos/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Estudios de Factibilidad , Fluorescencia , Humanos , Espacio Intracelular/metabolismo , Hígado/citología , Ratas , Ratas Wistar , Bazo/citología , Coloración y Etiquetado , Distribución Tisular
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