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1.
PLoS One ; 18(4): e0279323, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37058505

RESUMO

BACKGROUND: The differentiation of minimal-fat-or low-fat-angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples. MATERIALS AND METHODS: Laboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner. RESULTS: We have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a qualitative and quantitative difference between mfAML samples (58±4 HUp) and oncocytomas (44±10 HUp, p = 0.057) and RCCs (ccRCCs: 40±12 HUp, p = 0.012; pRCCs: 43±9 HUp, p = 0.017; chrRCCs: 40±7 HUp, p = 0.057) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI, although not all differences were statistically significant. Due to the heterogeneity and lower signal of oncocytomas, quantitative differentiation of the samples based on HUp or in combination with HUs was not possible. CONCLUSIONS: GBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI.


Assuntos
Adenoma Oxífilo , Angiomiolipoma , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/patologia , Raios X , Tomografia Computadorizada por Raios X/métodos , Adenoma Oxífilo/diagnóstico por imagem , Diagnóstico Diferencial , Estudos Retrospectivos
3.
Eur Radiol ; 30(1): 1-10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31278580

RESUMO

OBJECTIVES: Various imaging methods have been evaluated regarding non-invasive differentiation of renal cell carcinoma (RCC) subtypes. Dual-energy computed tomography (DECT) allows iodine concentration (IC) analysis as a correlate of tissue perfusion. Microvascular density (MVD) in histopathology specimens is evaluated to determine intratumoral vascularization. The objective of this study was to assess the potential of IC and MVD regarding the differentiation between papillary and clear cell RCC and between well- and dedifferentiated tumors. Further, we aimed to investigate a possible correlation between these parameters. METHODS: DECT imaging series of 53 patients with clear cell RCC (ccRCC) and 15 with papillary RCC (pRCC) were analyzed regarding IC. Histology samples were stained using CD31/CD34 monoclonal antibodies; MVD was evaluated digitally. Statistical analysis included performance of Mann-Whitney U test, ROC analysis, and Spearman rank correlation. RESULTS: Analysis of IC demonstrated significant differences between ccRCC and pRCC (p < 0.001). A cutoff value of ≤ 3.1 mg/ml at IC analysis allowed identification of pRCC with an accuracy of 86.8%. Within the ccRCC subgroup, G1/G2 tumors could significantly be differentiated from G3/G4 carcinomas (p = 0.045). A significant positive correlation between IC and MVD could be determined for the entire RCC cohort and the ccRCC subgroup. Limitations include the small percentage of pRCCs. CONCLUSIONS: IC analysis is a useful method to differentiate pRCC from ccRCC. The significant positive correlation between IC and MVD indicates valid representation of tumor perfusion by DECT. KEY POINTS: • Analysis of iodine concentration using DECT imaging could reliably distinguish papillary from clear cell subtypes of renal cell cancer (RCC). • A cutoff value of 3.1 mg/ml allowed a distinction between papillary and clear cell RCCs with an accuracy of 86.8%. • The positive correlation with microvascular density in tumor specimens indicates correct display of perfusion by iodine concentration analysis.


Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/irrigação sanguínea , Carcinoma Papilar/diagnóstico por imagem , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/diagnóstico por imagem , Transformação Celular Neoplásica/patologia , Meios de Contraste/farmacocinética , Feminino , Humanos , Iodo/farmacocinética , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/diagnóstico por imagem , Masculino , Microvasos/diagnóstico por imagem , Microvasos/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Tomografia Computadorizada por Raios X/métodos , Carga Tumoral
4.
Radiol Med ; 124(9): 926-933, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31175536

RESUMO

PURPOSE: To evaluate the rate and types of complications after minimally invasive radiological central vein port implantation without ultrasound guidance. MATERIALS AND METHODS: We retrospectively evaluated 8654 patients who underwent port implantations in the subclavian vein without ultrasound guidance in our institution from 1998 to 2014 with regard to types and rates of peri-, early and late post-interventional complications according to the common classification for complications published by the Society of Interventional Radiology (SIR). Additionally, the impact of the training level of the operators on the rate of complications was analyzed. RESULTS: Successful port implantations were performed in 99.8% (8636/8654 procedures). From 1998 to 2014, a total of 565 (6.52%) complications were recorded. The overall percentage of the peri-, early and late post-interventional complications according to the SIR criteria was 1.69, 0.15 and 4.68, respectively. Significant differences due to the training level of the performing physician could be seen for the rates of pneumothorax, arterial puncture and hematoma. CONCLUSION: Minimally invasive radiological interventional port implantation is a safe treatment option with a low rate of complications even without ultrasound guidance.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Cateteres de Demora , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Radiologia Intervencionista , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos , Veia Subclávia , Ultrassonografia de Intervenção , Adulto Jovem
5.
PLoS One ; 14(1): e0210291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30625220

RESUMO

BACKGROUND: The extent of intraductal carcinoma in situ (DCIS) is commonly underestimated due to the discontinuous growth and lack of microcalcifications. Specimen radiography has been established to reduce the rate of re-excision. However, the predictive value for margin assessment with conventional specimen radiography for DCIS is low. In this study we assessed the potential of grating-based phase-contrast computed tomography (GBPC-CT) at conventional X-ray sources for specimen tomography of DCIS containing samples. MATERIALS AND METHODS: GBPC-CT was performed on four ex-vivo breast specimens containing DCIS and invasive carcinoma of non-specific type. Phase-contrast and absorption-based datasets were manually matched with corresponding histological slices as the standard of reference. RESULTS: Matching of CT images and histology was successful. GBPC-CT showed an improved soft tissue contrast compared to absorption-based images revealing more histological details in the same sections. Non-calcifying DCIS exceeding the invasive tumor could be correlated to areas of dilated bright ducts around the tumor. CONCLUSIONS: GBPC-CT imaging at conventional X-ray sources offers improved depiction quality for the imaging of breast tissue samples compared to absorption-based imaging, allows the identification of diagnostically relevant tissue details, and provides full three-dimensional assessment of sample margins.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Calcinose/diagnóstico por imagem , Calcinose/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Técnicas In Vitro , Mamografia/métodos , Microscopia de Contraste de Fase/métodos , Estudos Prospectivos
6.
Eur Radiol ; 29(3): 1094-1103, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30151643

RESUMO

OBJECTIVES: Diverticular disease represents an increasing pathology and healthcare burden worldwide. Our aim was to study the prevalence, extent and distribution of asymptomatic diverticular disease assessed by magnetic resonance imaging (MRI) in a sample of a Western population. METHODS: Subjects from a population-based cohort study who underwent 3-T MRI were analyzed for the prevalence and extent of diverticula of the colon using an isotropic VIBE-Dixon gradient-echo sequence. The extent of diverticular disease was categorized according to the number of diverticula in each colonic segment. Univariate and adjusted analyses were performed to assess associated characteristics and risk factors. RESULTS: Among 393 subjects included in the analysis (56.4 ± 9.2 years, 57.5% males), 164 (42%) had diverticular disease, with the highest prevalence in the left-sided colonic segments (93% diverticular disease in the descending and sigmoid segment). Subjects with advanced diverticular disease were older (62.1 vs. 54.4 years) and had a higher body mass index (BMI), LDL cholesterol levels and systolic blood pressure (30.2 ± 5.1 vs. 27.8 ± 4.9 kg/m2, 149.8 ± 29.3 vs. 135.2 ± 32.9 mg/dl and 128.2 ± 14.1 vs. 118.4 ± 16.1 mmHg, respectively; all p > 0.003) compared with subjects without diverticular disease. In contrast, no significant correlation could be found for gender, physical activity, smoking status and alcohol consumption (all p > 0.31). Intra-rater reliability was excellent for all colonic segments (intra-class correlation [ICC] = 0.99-1.00), and inter-rater reliability was excellent for left- and right-sided colonic segments (ICC = 0.84-0.97). CONCLUSIONS: These findings provide insights into the disease mechanism of asymptomatic diverticular disease and may help to improve prevention of diverticulosis and its associated complications. KEY POINTS: • Overall prevalence of asymptomatic diverticular disease assessed by MRI was 42%, affecting predominantly the left-sided colon. • Asymptomatic diverticular disease was associated with age and cardiometabolic risk factors. • Magnetic resonance imaging reveals insights into the pathophysiologic mechanism of asymptomatic diverticular disease.


Assuntos
Colo/patologia , Doenças Diverticulares/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , Índice de Massa Corporal , Estudos de Coortes , Doenças Diverticulares/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco
7.
PLoS One ; 13(10): e0204930, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30281669

RESUMO

PURPOSE: To investigate αvß3-integrin-targeted optoacoustic imaging and MRI for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma. MATERIALS AND METHODS: Human BRAF V600E-positive melanoma xenograft (A375)-bearing Balb/c nude mice (n = 10) were imaged before (day 0) and after (day 7) a BRAF/MEK inhibitor combination therapy (encorafenib, 1.3 mg/kg/d; binimetinib, 0.6 mg/kg/d, n = 5) or placebo (n = 5), respectively. Optoacoustic imaging was performed on a preclinical system unenhanced and 5 h after i. v. injection of an αvß3-integrin-targeted fluorescent probe. The αvß3-integrin-specific tumor signal was derived by spectral unmixing. For morphology-based tumor response assessments, T2w MRI data sets were acquired on a clinical 3 Tesla scanner. The imaging results were validated by multiparametric immunohistochemistry (ß3 -integrin expression, CD31 -microvascular density, Ki-67 -proliferation). RESULTS: The αvß3-integrin-specific tumor signal was significantly reduced under therapy, showing a unidirectional decline in all animals (from 7.98±2.22 to 1.67±1.30; p = 0.043). No significant signal change was observed in the control group (from 6.60±6.51 to 3.67±1.93; p = 0.500). Immunohistochemistry revealed a significantly lower integrin expression (ß3: 0.20±0.02 vs. 0.39±0.05; p = 0.008) and microvascular density (CD31: 119±15 vs. 292±49; p = 0.008) in the therapy group. Tumor volumes increased with no significant intergroup difference (therapy: +107±42 mm3; control +112±44mm3, p = 0.841). In vivo blocking studies with αvß3-integrin antagonist cilengitide confirmed the target specificity of the fluorescent probe. CONCLUSIONS: αvß3-integrin-targeted optoacoustic imaging allowed for the early non-invasive monitoring of a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma, adding molecular information on tumor receptor status to morphology-based tumor response criteria.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzimidazóis/administração & dosagem , Carbamatos/administração & dosagem , Integrina alfaVbeta3/metabolismo , Melanoma/tratamento farmacológico , Técnicas Fotoacústicas/métodos , Sulfonamidas/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Imageamento por Ressonância Magnética , Melanoma/diagnóstico por imagem , Melanoma/genética , Melanoma/metabolismo , Camundongos , Camundongos Nus , Imagem Molecular , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Sci Rep ; 8(1): 15700, 2018 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30356116

RESUMO

With the introduction of screening mammography, the mortality rate of breast cancer has been reduced throughout the last decades. However, many women undergo unnecessary subsequent examinations due to inconclusive diagnoses from mammography. Two pathways appear especially promising to reduce the number of false-positive diagnoses. In a clinical study, mammography using synchrotron radiation was able to clarify the diagnosis in the majority of inconclusive cases. The second highly valued approach focuses on the application of phase-sensitive techniques such as grating-based phase-contrast and dark-field imaging. Feasibility studies have demonstrated a promising enhancement of diagnostic content, but suffer from dose concerns. Here we present dose-compatible grating-based phase-contrast and dark-field images as well as conventional absorption images acquired with monochromatic x-rays from a compact synchrotron source based on inverse Compton scattering. Images of freshly dissected mastectomy specimens show improved diagnostic content over ex-vivo clinical mammography images at lower or equal dose. We demonstrate increased contrast-to-noise ratio for monochromatic over clinical images for a well-defined phantom. Compact synchrotron sources could potentially serve as a clinical second level examination.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia/instrumentação , Mamografia/métodos , Mastectomia , Síncrotrons , Neoplasias da Mama/cirurgia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Imagens de Fantasmas , Doses de Radiação , Tolerância a Radiação , Raios X
9.
J Glob Oncol ; 4: 1-10, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30241164

RESUMO

Imaging plays many essential roles in nearly all aspects of high-quality cancer care. However, challenges to the delivery of optimal cancer imaging in both developing and advanced countries are manifold. Developing countries typically face dramatic shortages of both imaging equipment and general radiologists, and efforts to improve cancer imaging in these countries are often complicated by poor infrastructure, cultural barriers, and other obstacles. In advanced countries, on the other hand, although imaging equipment and general radiologists are typically accessible, the complexity of oncologic imaging and the need for subspecialists in the field are largely unrecognized; as a result, training opportunities are lacking, and there is a shortage of radiologists with the necessary subspecialty expertise to provide optimal cancer care and participate in advanced clinical research. This article is intended to raise awareness of these challenges and catalyze further efforts to address them. Some promising strategies and ongoing efforts are reviewed, and some specific actions are proposed.


Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/epidemiologia , Radioterapia (Especialidade) , Atenção à Saúde , Países Desenvolvidos , Países em Desenvolvimento , Saúde Global , Custos de Cuidados de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Competência Profissional , Radioterapia (Especialidade)/métodos , Radioterapia (Especialidade)/normas
10.
Int J Radiat Oncol Biol Phys ; 101(4): 965-984, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29976510

RESUMO

PURPOSE: Experimental neuroimaging provides a wide range of methods for the visualization of brain anatomic morphology down to subcellular detail. Still, each technique-specific detection mechanism presents compromises among the achievable field-of-view size, spatial resolution, and nervous tissue sensitivity, leading to partial sample coverage, unresolved morphologic structures, or sparse labeling of neuronal populations and often also to obligatory sample dissection or other sample invasive manipulations. X-ray phase-contrast imaging computed tomography (PCI-CT) is an experimental imaging method that simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity, and ex vivo full organ rodent brain coverage without any need for sample dissection, staining or labeling, or contrast agent injection. In the present study, we explored the benefits and limitations of PCI-CT use for in vitro imaging of normal and cancerous brain neuromorphology after in vivo treatment with synchrotron-generated x-ray microbeam radiation therapy (MRT), a spatially fractionated experimental high-dose radiosurgery. The goals were visualization of the MRT effects on nervous tissue and a qualitative comparison of the results to the histologic and high-field magnetic resonance imaging findings. METHODS AND MATERIALS: MRT was administered in vivo to the brain of both healthy and cancer-bearing rats. At 45 days after treatment, the brain was dissected out and imaged ex vivo using propagation-based PCI-CT. RESULTS: PCI-CT visualizes the brain anatomy and microvasculature in 3 dimensions and distinguishes cancerous tissue morphology, necrosis, and intratumor accumulation of iron and calcium deposits. Moreover, PCI-CT detects the effects of MRT throughout the treatment target areas (eg, the formation of micrometer-thick radiation-induced tissue ablation). The observed neurostructures were confirmed by histologic and immunohistochemistry examination and related to the micro-magnetic resonance imaging data. CONCLUSIONS: PCI-CT enabled a unique 3D neuroimaging approach for ex vivo studies on small animal models in that it concurrently delivers high-resolution insight of local brain tissue morphology in both normal and cancerous micro-milieu, localizes radiosurgical damage, and highlights the deep microvasculature. This method could assist experimental small animal neurology studies in the postmortem evaluation of neuropathology or treatment effects.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Glioblastoma/diagnóstico por imagem , Glioblastoma/radioterapia , Neurorradiografia/métodos , Microtomografia por Raio-X/métodos , Animais , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Imageamento por Ressonância Magnética , Masculino , Microvasos/diagnóstico por imagem , Ratos , Ratos Endogâmicos F344
11.
Eur Radiol ; 28(12): 5284-5292, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29882070

RESUMO

OBJECTIVES: To assess the prognostic value of pre-therapeutic computed tomography (CT) attenuation of liver metastases for overall survival (OS) in metastatic colorectal cancer (mCRC). METHODS: In the open-label, randomised, prospective phase-III FIRE-3 trial, patients with histologically confirmed mCRC received fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) with either cetuximab or bevacizumab. Participating patients gave written informed consent prior to study entry. In CT at baseline (portal venous phase, slice thickness ≤5 mm), mean attenuation [Hounsfield units (HU)] of liver metastases was retrospectively assessed by semi-automated volumetry. Its prognostic influence on OS was analysed in Kaplan-Meier-analysis and Cox proportional hazard regression and an optimal threshold was determined. RESULTS: In FIRE-3, 592 patients were enrolled between 2007 and 2012. Among the 347 patients eligible for liver volumetry, median baseline CT attenuation of liver metastases was 59.67 HU [interquartile range (IQR), 49.13, 68.85]. Increased attenuation was associated with longer OS {per 10 HU: hazard ratio (HR), 0.85 [95% confidence interval (CI), 0.78, 0.93], p < 0.001}. The optimised threshold (≥61.62 HU) was a strong predictor for increased OS [median, 21.3 vs 30.6 months; HR, 0.61 (95% CI, 0.47, 0.80), p < 0.001]. Multivariate regression controlling for correlated and further prognostic factors confirmed this [HR, 0.60 (95% CI, 0.45, 0.81), p = 0.001]. Furthermore, mean attenuation ≥61.62 HU was significantly associated with increased early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012). CONCLUSIONS: Increased mean baseline CT attenuation of liver metastases may identify mCRC patients with prolonged OS and better tumour response. KEY POINTS: • In colorectal cancer, increased attenuation of liver metastases in baseline computed tomography is a prognostic factor for prolonged OS (p < 0.001). • A threshold of ≥61.62 HU was determined as optimal cut-off to identify patients with prolonged OS (p < 0.001), early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012).


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Hepáticas/secundário , Terapia de Alvo Molecular/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Feminino , Alemanha/epidemiologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências
12.
Eur J Radiol ; 100: 124-129, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29496069

RESUMO

PURPOSE: To determine the prognostic impact of radiologically enlarged lymph nodes ≥ 10 mm on the survival of patients with metastatic colorectal cancer. MATERIALS AND METHODS: The prospective, randomized, open-label FIRE-3/AIO KRK0306 trial evaluated the first-line therapy of patients with KRAS exon 2 wild-type metastatic colorectal cancer with fluorouracil, folinic acid and irinotecan plus either cetuximab or bevacizumab. In the RAS wild-type population (n = 400), adequately evaluable baseline computed tomographies (n = 339) were reviewed for enlarged regional and distant lymph nodes. Their prognostic relevance was retrospectively analyzed in uni- and multivariable Cox proportional hazard regressions. RESULTS: Median overall survival was 21.7 months in patients with enlarged lymph nodes and 33.2 months in patients without (hazard rate ratio [HR] = 1.61, 95% confidence interval [CI], 1.23-2.09; P < 0.001). This was confirmed in multivariable analysis (HR = 1.37, 95% CI, 1.02-1.83; P = 0.036). Progression-free survival of patients with enlarged lymph nodes showed a consistent but insignificant trend (9.9 vs. 11.1 months; HR = 1.23, 95% CI, 0.98-1.54; P = 0.072). Enlarged lymph nodes were also associated with BRAF-mutations (P = 0.004). CONCLUSION: The presence of radiologically enlarged lymph nodes in baseline staging has a negative prognostic value beyond established and potential prognostic parameters.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Tomografia Computadorizada por Raios X/métodos , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Cetuximab/uso terapêutico , Colo/diagnóstico por imagem , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Cancer Imaging ; 18(1): 2, 2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29347968

RESUMO

BACKGROUND: The purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by 18F-FDG-PET/CT and diffusion-weighted MRI (DW-MRI). METHODS: Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by 18F-FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were scanned on a small animal PET after intravenous administration of 20 MBq 18F-FDG. Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced CT data sets were subsequently acquired for anatomic coregistration. Tumor diffusivity was assessed by DW-MRI using the apparent diffusion coefficient (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry for validation purposes (microvascular density - CD31; tumor cell proliferation - Ki-67). RESULTS: Tumor glucose uptake was significantly suppressed under therapy (∆TTLTherapy - 1.00 ± 0.53 vs. ∆TTLControl 0.85 ± 1.21; p < 0.001). In addition, tumor diffusivity was significantly elevated following the BRAF and CDK 4/6 inhibitor combination therapy (∆ADCTherapy 0.12 ± 0.14 × 10-3 mm2/s; ∆ADCControl - 0.12 ± 0.06 × 10-3 mm2/s; p < 0.001). Immunohistochemistry revealed a significant suppression of microvascular density (CD31, 147 ± 48 vs. 287 ± 92; p = 0.001) and proliferation (Ki-67, 3718 ± 998 vs. 5389 ± 1332; p = 0.007) in the therapy compared to the control group. CONCLUSION: A novel BRAF and CDK 4/6 inhibitor combination therapy exhibited significant anti-angiogenic and anti-proliferative effects in experimental human melanomas, monitored by 18F-FDG-PET/CT and DW-MRI.


Assuntos
Antineoplásicos/uso terapêutico , Imagem de Difusão por Ressonância Magnética/métodos , Fluordesoxiglucose F18/farmacocinética , Melanoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Compostos Radiofarmacêuticos/farmacocinética , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Feminino , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Masculino , Melanoma/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oximas/administração & dosagem , Oximas/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Purinas/administração & dosagem , Purinas/uso terapêutico
14.
Invest Radiol ; 53(1): 26-34, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28846552

RESUMO

OBJECTIVES: Grating-based phase-contrast computed tomography (gb-PCCT) relies on x-ray refraction instead of absorption to generate high-contrast images in biological soft tissue. The aim of this study was to evaluate the potential of gb-PCCT for the depiction of structural changes in heart disease. MATERIALS AND METHODS: Four human heart specimens from patients with hypertensive disease, ischemic disease, dilated heart disease, and cardiac lipomatosis were examined. The gb-PCCT setup consisted of an x-ray tube (40 kV, 70 mA), grating-interferometer, and detector, and allowed simultaneous acquisition of phase- and absorption-contrast data. With histopathology as the standard of reference, myocardium (MC), fibrotic scar (FS), interstitial fibrosis (IF), and fatty tissue (FT) were visually and quantitatively evaluated. Systematic differences in absorption- and phase-contrast Hounsfield units (HUabs and HUp) were assessed. RESULTS: Thirteen corresponding cross-sections were included, and MC, FS, IF, and FT were found in 13 (100%), 4 (30.8%), 7 (53.8%), and 13 (100%) cross-sections, respectively. Mean HUp/HUabs were 52.5/54.1, 86.6/69.7, 62.4/62.3, and -38.6/-258.9 for MC, FS, IF, and FT, respectively. An overlap in HUabs was observed for MC and IF (P = 0.84) but not for HUp (P < 0.01). Contrast-to-noise ratios were significantly higher in phase- than in absorption-contrast for MC/FT (35.4 vs 7.8; P < 0.01) and for MC/FS (12.3 vs 0.2; P < 0.01). CONCLUSIONS: Given its superior soft tissue contrast, gb-PCCT is able to depict structural changes in different cardiomyopathies, which can currently not be obtained by x-ray absorption-based imaging methods. If current technical limitations can be overcome, gb-PCCT may evolve as a powerful tool for the anatomical assessment of cardiomyopathy.


Assuntos
Meios de Contraste , Cardiopatias/diagnóstico por imagem , Coração/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Estudos de Avaliação como Assunto , Humanos , Reprodutibilidade dos Testes
15.
Cardiovasc Intervent Radiol ; 40(11): 1740-1747, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28584948

RESUMO

BACKGROUND: Radioembolization (RE) with 90yttrium (90Y) resin microspheres generally employs a sandwich technique with separate sequential administration of contrast medium (CM), followed by vehicle (e.g., glucose 5% [G5] solution), then 90Y resin microspheres (in G5), then G5, and then CM again to avoid contact of CM and microspheres under fluoroscopic guidance. This study evaluates the visualization quality and safety of a modified sandwich technique with a 50/50-mixture of CM (Imeron 300) and G5 for administration of 90Y resin microspheres. MATERIALS AND METHODS: A retrospective analysis of 81 RE procedures in patients with primary or secondary liver tumors was performed. The quality of angiographic visualization of the hepatic vessels was assessed before the first injection and immediately before the whole dose has been injected. Visualization and flow rate were graded on a 5-point scale: 1 = very good to 5 = not visible/no antegrade flow. Univariate logistic regression models and multiple linear regression models were used to evaluate the prognostic variables associated with visualization and flow scores. RESULTS: Visualization quality was inversely related to flow rate, the lower the flow rate the better the grade of the visualization. Visualization quality was also inversely related to body-mass-index (BMI). Performing RE with the 50/50-CM/G5 mixture resulted in a mean injection time for 1 GBq of 15 min. No clinically significant adverse events, including radiation-induced liver disease were reported. CONCLUSION: RE with a 50/50-mixture of CM and G5 for administration of 90Y resin microspheres in a modified sandwich technique is a safe administration alternative and provides good visualization of hepatic vessels, which is inversely dependent on flow rate and BMI. Injection time was reduced compared with our experience with the standard sandwich technique.


Assuntos
Braquiterapia/métodos , Meios de Contraste/administração & dosagem , Glucose/administração & dosagem , Neoplasias Hepáticas/radioterapia , Radiografia Intervencionista/métodos , Radioisótopos de Ítrio/uso terapêutico , Angiografia/métodos , Feminino , Fluoroscopia , Humanos , Iopamidol/administração & dosagem , Iopamidol/análogos & derivados , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Microesferas , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Radioisótopos de Ítrio/administração & dosagem
16.
J Nucl Med ; 58(10): 1580-1587, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28450556

RESUMO

68Ga-DOTATATE PET/CT enables detection of meningioma tissue based on somatostatin receptor 2 expression. Transosseous extension of intracranial meningiomas is known to be an important risk factor for tumor recurrence and patient mortality. We analyzed the diagnostic performance of 68Ga-DOTATATE PET/CT and contrast-enhanced MRI (CE-MRI) for the detection of osseous infiltration using qualitative and quantitative imaging parameters. Methods: In this institutional review board-approved retrospective study, subjects were selected from 327 consecutive 68Ga-DOTATATE PET/CT examinations for evaluation of confirmed or suspected meningioma. Inclusion criteria were CE-MRI within 30 d and pathology-confirmed meningioma diagnosis with inclusion or exclusion of transosseous extension as the standard of reference. Imaging was analyzed by two readers. Tracer uptake values and meningioma volumes were determined. χ2, Mann-Whitney U, Wilcoxon signed rank, and McNemar tests, as well as receiver-operating-characteristic analyses, were performed to compare variables and diagnostic performance. Results: Eighty-two patients fulfilled the inclusion criteria. Patients with transosseous extension of meningioma (n = 67) showed significantly larger lesions (median, 12.8 vs. 3.3 mL; P < 0.001) and significantly higher tracer uptake values (median SUVmax, 14.2 vs. 7.6; P = 0.011) than patients with extraosseous meningiomas (n = 15). 68Ga-DOTATATE PET/CT in comparison to CE-MRI performed at a higher sensitivity (98.5% vs. 53.7%) while maintaining high specificity (86.7% vs. 93.3%) in the detection of osseous involvement (P < 0.001). In receiver-operating-characteristic analysis, PET/CT assessment performed better than CE-MRI (area under the curve, 0.932 vs. 0.773). PET/CT- and CE-MRI-based volume estimation yielded comparable results for extraosseous meningiomas (P = 0.132) and the extraosseous part of transosseous meningiomas (P = 0.636), whereas the volume of the intraosseous part was assessed as significantly larger by PET/CT (P < 0.001). Conclusion:68Ga-DOTATATE PET/CT enables improved detection of the transosseous extension of intracranial meningiomas compared with CE-MRI.


Assuntos
Meios de Contraste , Imageamento por Ressonância Magnética , Meningioma/diagnóstico por imagem , Compostos Organometálicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Feminino , Humanos , Masculino , Meningioma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Tumoral
17.
Sci Rep ; 7: 45400, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-28361951

RESUMO

Current clinical imaging methods face limitations in the detection and correct characterization of different subtypes of renal cell carcinoma (RCC), while these are important for therapy and prognosis. The present study evaluates the potential of grating-based X-ray phase-contrast computed tomography (gbPC-CT) for visualization and characterization of human RCC subtypes. The imaging results for 23 ex vivo formalin-fixed human kidney specimens obtained with phase-contrast CT were compared to the results of the absorption-based CT (gbCT), clinical CT and a 3T MRI and validated using histology. Regions of interest were placed on each specimen for quantitative evaluation. Qualitative and quantitative gbPC-CT imaging could significantly discriminate between normal kidney cortex (54 ± 4 HUp) and clear cell (42 ± 10), papillary (43 ± 6) and chromophobe RCCs (39 ± 7), p < 0.05 respectively. The sensitivity for detection of tumor areas was 100%, 50% and 40% for gbPC-CT, gbCT and clinical CT, respectively. RCC architecture like fibrous strands, pseudocapsules, necrosis or hyalinization was depicted clearly in gbPC-CT and was not equally well visualized in gbCT, clinical CT and MRI. The results show that gbPC-CT enables improved discrimination of normal kidney parenchyma and tumorous tissues as well as different soft-tissue components of RCCs without the use of contrast media.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Tomografia Computadorizada por Raios X/métodos , Antígenos de Neoplasias , Humanos , Proteínas Quinases Ativadas por Mitógeno , Sensibilidade e Especificidade
18.
Sci Rep ; 7(1): 402, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28341830

RESUMO

Accounting for about 1.5 million deaths annually, lung cancer is the prevailing cause of cancer deaths worldwide, mostly associated with long-term smoking effects. Numerous small-animal studies are performed currently in order to better understand the pathogenesis of the disease and to develop treatment strategies. Within this letter, we propose to exploit X-ray dark-field imaging as a novel diagnostic tool for the detection of lung cancer on projection radiographs. Here, we demonstrate in living mice bearing lung tumors, that X-ray dark-field radiography provides significantly improved lung tumor detection rates without increasing the number of false-positives, especially in the case of small and superimposed nodules, when compared to conventional absorption-based imaging. While this method still needs to be adapted to larger mammals and finally humans, the technique presented here can already serve as a valuable tool in evaluating novel lung cancer therapies, tested in mice and other small animal models.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Radiografia/métodos , Animais , Modelos Animais de Doenças , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Mutantes , Raios X
19.
NMR Biomed ; 30(3)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26114411

RESUMO

Diffusion-weighted MRI (DWI) of the vertebral bone marrow is a clinically important tool for the characterization of bone-marrow pathologies and, in particular, for the differentiation of benign (osteoporotic) and malignant vertebral compression fractures. DWI of the vertebral bone marrow is, however, complicated by some unique MR and tissue properties of vertebral bone marrow. Due to both the spongy microstructure of the trabecular bone and the proximity of the lungs, soft tissue, or large vessels, substantial magnetic susceptibility variations occur, which severely reduce the magnetic field homogeneity as well as the transverse relaxation time T*2 , and thus complicate MRI in particular with echoplanar imaging (EPI) techniques. Therefore, alternative diffusion-weighting pulse sequence types such as single-shot fast-spin-echo sequences or segmented EPI techniques became important alternatives for quantitative DWI of the vertebral bone marrow. This review first describes pulse sequence types that are particularly important for DWI of the vertebral bone marrow. Then, data from 24 studies that made diffusion measurements of normal vertebral bone marrow are reviewed; summarizing all results, the apparent diffusion coefficient (ADC) of normal vertebral bone marrow is typically found to be between 0.2 and 0.6 × 10-3 mm2 /s. Finally, DWI of vertebral compression fractures is discussed. Numerous studies demonstrate significantly greater ADCs in osteoporotic fractures (typically between 1.2 and 2.0 × 10-3 mm2 /s) than in malignant fractures or lesions (typically 0.7-1.3 × 10-3 mm2 /s). Alternatively, several studies used the (qualitative) image contrast of diffusion-weighted acquisitions for differentiation of lesion etiology: a very good lesion differentiation can be achieved, particularly with diffusion-weighted steady-state free precession sequences, which depict malignant lesions as hyperintense relative to normal-appearing vertebral bone marrow, in contrast to hypointense or isointense osteoporotic lesions. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Doenças da Medula Óssea/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Reconhecimento Automatizado de Padrão/métodos , Doenças da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Animais , Medula Óssea/patologia , Medicina Baseada em Evidências , Humanos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Coluna Vertebral/patologia
20.
Clin Endocrinol (Oxf) ; 86(3): 325-331, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27748964

RESUMO

OBJECTIVE: To evaluate volumetric and densitometric properties of the adrenal glands in patients with unilateral and bilateral disease in comparison with normal controls. DESIGN: A total of 77 patients (56 males and 21 females) diagnosed with primary aldosteronism (PA) with a mean age of 53 ± 10 years were prospectively enrolled. Unenhanced and contrast-enhanced computed tomography scans were analysed for adrenal volumes and mean densities. These values were compared with normal controls and between PA subtypes. RESULTS: Adrenals containing an aldosterone-producing adenoma (APA, n = 56) had on average higher attenuation values as compared to adrenals with bilateral adrenal hyperplasia (n = 21). Mean adrenal gland volume in PA patients was not significantly different between PA subtypes. In comparison with normal adrenal glands, volumes were significantly higher in PA patients (P < 0·0001) including adrenals contralateral to APAs, which were significantly larger in comparison with controls. CONCLUSION: Independent of subtype differentiation, adrenal volumetry reveals higher adrenal volumes in PA patients in comparison with normal controls. These findings provide indirect evidence for a general adrenal growth dysregulation in the context of PA.


Assuntos
Glândulas Suprarrenais/patologia , Hiperaldosteronismo/diagnóstico , Adenoma/metabolismo , Adenoma/patologia , Glândulas Suprarrenais/crescimento & desenvolvimento , Adulto , Idoso , Aldosterona/metabolismo , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Alemanha , Humanos , Hiperplasia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Tomografia Computadorizada por Raios X , Adulto Jovem
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