[Diagnostic Value of Contrast-enhanced Ultrasound in Extrathyroidal Extension of Papillary Thyroid Carcinoma].

Objective To evaluate the diagnostic value of contrast-enhanced ultrasound(CEUS)in thyroid extrathyroidal extension(ETE)of papillary thyroid carcinoma(PTC).Methods Totally 172 PTC patients(184 thyroid nodules)were examined by conventional ultrasound(US)and CEUS before operation.Sonographic features of thyroid nodules and the relationship between nodules and thyroid capsule were retrospectively evaluated.The diagnostic efficacy of these two methods for ETE was compared,and the effect of nodule enhancement level on the diagnosis of ETE was analyzed.Results The sensitivity,specificity,and accuracy of CEUS were 78.9%,89.4% and 84.2% in diagnosing ETE,while those of US were 60.0%,86.2%,and 73.4%,respectively.Among them,the sensitivity(P=0.000)and accuracy(P=0.009)of CEUS in diagnosing ETE were significantly higher than those of US,but there was no statistically significant difference in specificity(P=0.375).The area under the receiver operator characteristic curve of CEUS(0.84)was significantly larger than that of US(0.73)(Z=2.24,P=0.01).The diagnostic value of CEUS in ETE was related to the enhancement level of nodules.The sensitivity,specificity,and accuracy of CEUS in the diagnosis of ETE were highest in hypo-enhanced nodules,followed by hyper-enhanced nodules and the iso-enhanced nodules.Conclusion CEUS has higher performance than US in detecting ETC of PTC.

Assessing Microcirculation in Resectable Oesophageal Squamous Cell Carcinoma with Dynamic Contrast-enhanced MRI for Identifying Primary tumour and Lymphatic Metastasis.

This study aimed to determine whether dynamic contrast-enhanced MRI (DCE-MRI) derived parameters can identify oesophageal squamous cell carcinoma (SCC) and lymphatic metastasis. Thirty-nine oesophageal SCC patients underwent DCE-MRI. Quantitative parameters including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume and fractional plasma volume, and semi-quantitative parameters including time to peak (TTP), max concentration, Max Slope and area under concentration-time curve of both oesophageal SCC and normal oesophagus were measured. Mann-Whitney U test revealed that Ktrans and Kep of oesophageal SCC were higher while TTP was shorter when compared to normal oesophagus (all P-values < 0.05); and areas under receiver operating characteristic [ROC] curves displayed that Kep was superior to TTP or Ktrans for identifying oesophageal SCC (0.903 vs. 0.832 or 0.713). Mann-Whitney U test also demonstrated that Kep was higher and TTP was shorter in patients with lymphatic metastasis when compared to non-metastatic cancer patients (both P-values < 0.05), and area under ROC curve also showed that TTP was superior to Kep for predicting lymphatic metastasis (0.696 vs. 0.659). In conclusion, the combination of quantitative and semi-quantitative parameters derived from DCE-MRI can aid in the identification of oesophageal SCC and lymphatic metastasis.

Contrast radiography before diverting stoma closure in rectal cancer is not necessary on a routine basis. / El estudio radiológico con contraste antes del cierre del estoma derivativo en el cáncer de recto no es necesario de forma rutinaria.

INTRODUCTION: Diverting stomata are recommended in patients with low anterior resection and risk factors in order to reduce the severity of anastomotic leaks. Usually, a radiology study is performed prior to the closure of the stoma to detect subclinical leaks. The aim of the present study is to assess the clinical utility of the radiology study. METHODS: A prospective cohort study of patients undergoing anterior rectal resection for rectal cancer and those who underwent stoma closure without contrast enema. This study was carried out after a retrospective review of radiology study results prior to the closure of the stoma in patients operated from 2007 to 2011. RESULTS: Eighty-six patients met the study criteria. Thirteen patients (15.1%) presented pelvic sepsis. Contrast enema before stoma closure was pathological in 8 patients (9.3%). Five out of the 13 patients with pelvic sepsis had a pathological radiological study, compared to only 3 out of the 73 patients without intra-abdominal complications after rectal resection (38.5% vs. 4.1%; P=.001). Based on these results, we conducted a prospective study omitting the contrast enema in patients with no postoperative complications. Thirty-eight patients had their stoma closed without a prior radiology study. None of the patients presented pelvic sepsis. CONCLUSIONS: Radiology studies of the colorectal anastomosis before reconstruction can safely be omitted in patients without pelvic sepsis after the previous rectal resection.

Investigating the Lymphatic System by Dual-Color Elemental Mass Spectrometry Imaging.

Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA) with inductively coupled plasma mass spectrometry imaging (ICP-MSI) is presented. As a possible lymph marker, thulium(III)(1R,4R,7R,10R)-α,α',α'',α'''-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA) is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III)2,2',2''-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Gd-DO3A-butrol). Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors) of the lymph nodes after application of contrast agents in different areas.

Myocardial Viability on Cardiac Magnetic Resonance / Viabilidade Miocárdica pela Ressonância Magnética Cardíaca

Abstract The study of myocardial viability is of great importance in the orientation and management of patients requiring myocardial revascularization or angioplasty. The technique of delayed enhancement (DE) is accurate and has transformed the study of viability into an easy test, not only for the detection of fibrosis but also as a binary test detecting what is viable or not. On DE, fibrosis equal to or greater than 50% of the segmental area is considered as non-viable, whereas that below 50% is considered viable. During the same evaluation, cardiac magnetic resonance (CMR) may also use other techniques for functional and perfusion studies to obtain a global evaluation of ischemic heart disease. This study aims to highlight the current concepts and broadly emphasize the use of CMR as a method that over the last 20 years has become a reference in the detection of infarction and assessment of myocardial viability.

Resumo O estudo de viabilidade miocárdica é de grande importância para a orientação e manejo de pacientes que necessitam de cirurgia de revascularização miocárdica ou angioplastia. A técnica de realce tardio (RT) é precisa e transformou o estudo de viabilidade em um teste fácil, não só para a detecção de fibrose, mas também como um modelo binário para a detecção do que é ou não é viável. Uma fibrose identificada pelo RT é considerada como não viável quando igual ou maior do que 50% da área segmentar e como viável quando menor que 50%. A ressonância magnética cardíaca (RMC) também pode lançar mão de outras técnicas para estudo funcional e de perfusão para uma avaliação global da doença isquêmica do coração no mesmo exame. Este estudo tem como objetivo destacar os conceitos atuais e enfatizar amplamente o uso da RMC como um método que nos últimos 20 anos se tornou referência na detecção de infarto e avaliação de viabilidade miocárdica.

Gd2O3 and GH combined with red blood cells to improve the sensitivity of contrast agents for cancer targeting MR imaging.

Herein, we fabricated efficient MR imaging probes by incorporating gadolinium oxide nanoparticles (Gd2O3) and gadolinium hybrid nanoparticles (GH) within RBCs. The Gd2O3 and GH encapsulated in the RBCs exhibited high relaxation rates and revealed high sensitivity for T1 MR imaging.

CT enterography: Mannitol versus VoLumen.

INTRODUCTION: Several different neutral oral contrast agents have been trialled in magnetic resonance and CT enterography (CTE). In the Auckland region, Mannitol 2.5% and VoLumen are both used in CTE. This study compares the performance of these two neutral oral contrast agents in CTE. METHODS: Computed tomography enterography data were collected from 25 consecutive studies that used either Mannitol or VoLumen in 2014. All images were reviewed by three radiologists blinded to the type of oral contrast. Each quadrant was assessed for maximum distension, proportion of bowel loops distended, presence of inhomogeneous content and bowel wall visibility. Assessment also included whether the contrast agent reached the caecum and an overall subjective quality assessment. Patients were invited to answer a questionnaire regarding tolerability of the preparations. RESULTS: Mannitol achieves better wall visibility in the right upper quadrant, left upper quadrant and left lower quadrant (P < 0.01). Overall differences in study quality favours Mannitol (P < 0.01) with 48% of the Mannitol studies being considered excellent compared with 4% of the VoLumen studies. There was no difference in maximal distension or proportion of loops distended. CONCLUSION: Mannitol in CTE achieves studies of a better quality than and is a viable alternative to VoLumen.

Recall strategies for patients found to have a nodule in cirrhosis: is there still a role for CEUS?

Development of liver tumors and their evolution to hepatocellular carcinoma (HCC) is a multi-step process in which different HCC-etiologies induce continuous rounds of hepatocyte damage and regeneration. Over an extended time, this triggers cirrhosis which is a pathological state of the liver in which lesions can progress to become dysplastic nodules. Later, these nodules may evolve into HCC and occasionally generate metastatic events. To provide optimal care, patients with liver cancer should be managed using a multidisciplinary approach in specialized centers in which all the diagnostic and therapeutic resources are available. Among the different imaging modalities the introduction on contrast agents for ultrasound use has opened new further applications in different clinical settings. In fact, contrast enhanced ultrasound (CEUS) has been applied for more than ten years and plays increasingly important roles in the management of HCC. Since early 2000, international societies including the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific association for the Study of the Liver (APASL), the Japanese society of Hepatology (JSH), the Italian society for the study of the liver (AISF), the World Federation for Ultrasound in Medicine and Biology (WFUMB), and the European Federation of Societies for Ultrasound in Medicine and Biology (EFUSMB) have discussed the important role of CEUS in the diagnosis of HCC. In the present review an update of the literature and a detailed discussion of the present Guidelines regarding the role of CEUS in the evaluation of nodules in cirrhotic patients is offered.

Radiation dose analysis of large and giant internal carotid artery aneurysm treatment with the pipeline embolization device versus traditional coiling techniques.

BACKGROUND: Flow diversion is an effective and increasingly accepted method for endovascular treatment of cerebral aneurysms. Additionally, the public has heightened concerns regarding radiation exposure from medical procedures. This study analyzes radiation dose and fluoroscopy time during treatment of large and giant proximal internal carotid artery (ICA) aneurysms with the pipeline embolization device (PED) versus traditional coiling techniques. METHODS: Radiation dose, fluoroscopy time, and contrast dye administration were retrospectively analyzed in 55 patients undergoing endovascular treatment of aneurysms ≥ 10 mm from petrous to superior hypophyseal ICA segments. Patients were treated by either PED (37 patients) or traditional coiling techniques (18 patients). Aortic arch type and proximal ICA tortuosity were also assessed as markers of access difficulty. RESULTS: Average radiation dose with PED treatment was 2840 ± 213 mGy and 4010 ± 708 mGy with traditional coiling techniques (p=0.048; 29% decrease with PED). Mean fluoroscopy time for PED was 56.1 ± 5.0 min and 85.9 ± 11.9 min for coiling cases (p=0.0087; 35% decrease with PED). These benefits existed despite more difficult arch anatomy and a trend towards greater proximal vessel tortuosity in PED cases. Contrast dye amounts were also reduced by 37.5% in PED cases (75 ± 6 mL) versus coiling cases (120 ± 13 mL, p=0.0008). CONCLUSIONS: Treatment of large and giant proximal ICA aneurysms using PED requires less radiation, less fluoroscopy time, and less contrast administration than standard coiling techniques. This further demonstrates the benefits of flow diversion for treatment of these aneurysms.

Search for novel contrast materials in dual-energy x-ray breast imaging using theoretical modeling of contrast-to-noise ratio.

Contrast-enhanced (CE) dual-energy (DE) x-ray breast imaging uses a low- and high-energy x-ray spectral pair to eliminate soft-tissue signal variation and thereby increase the detectability of exogenous imaging agents. Currently, CEDE breast imaging is performed with iodinated contrast agents. These compounds are limited by several deficiencies, including rapid clearance and poor tumor targeting ability. The purpose of this work is to identify novel contrast materials whose contrast-to-noise ratio (CNR) is comparable or superior to that of iodine in the mammographic energy range. A monoenergetic DE subtraction framework was developed to calculate the DE signal intensity resulting from the logarithmic subtraction of the low- and high-energy signal intensities. A weighting factor is calculated to remove the dependence of the DE signal on the glandularity of the breast tissue. Using the DE signal intensity and weighting factor, the CNR for materials with atomic numbers (Z) ranging from 1 to 79 are computed for energy pairs between 10 and 50 keV. A group of materials with atomic numbers ranging from 42 to 63 were identified to exhibit the highest levels of CNR in the mammographic energy range. Several of these materials have been formulated as nanoparticles for various applications but none, apart from iodine, have been investigated as CEDE breast imaging agents. Within this group of materials, the necessary dose fraction to the LE image decreases as the atomic number increases. By reducing the dose to the LE image, the DE subtraction technique will not provide an anatomical image of sufficient quality to accompany the contrast information. Therefore, materials with Z from 42 to 52 provide nearly optimal values of CNR with energy pairs and dose fractions that provide good anatomical images. This work is intended to inspire further research into new materials for optimized CEDE breast functional imaging.

Guidelines and good clinical practice recommendations for Contrast Enhanced Ultrasound (CEUS) in the liver - update 2012: A WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS.

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging.

Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points • Tumour vascular function is key to tumour development and treatment • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function • Thus DCE-MRI with pharmacokinetic models can assess novel treatments • Many recent developments are advancing the accuracy of and information from DCE-MRI • Establishing common methodology across multiple centres is challenging and requires accepted guidelines.

Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography.

Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular support of tumours through analysis of temporal changes in attenuation in blood vessels and tissues during a rapid series of images acquired with intravenous administration of iodinated contrast material. Commercial software for DCE-CT analysis allows pixel-by-pixel calculation of a range of validated physiological parameters and depiction as parametric maps. Clinical studies support the use of DCE-CT parameters as surrogates for physiological and molecular processes underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of drug action in early phase trials for the treatment of a range of cancers. DCE-CT can be appended to current imaging assessments of tumour response with the benefits of wide availability and low cost. This paper sets out guidelines for the use of DCE-CT in assessing tumour vascular support that were developed using a Delphi process. Recommendations encompass CT system requirements and quality assurance, radiation dosimetry, patient preparation, administration of contrast material, CT acquisition parameters, terminology and units, data processing and reporting. DCE-CT has reached technical maturity for use in therapeutic trials in oncology. The development of these consensus guidelines may promote broader application of DCE-CT for the evaluation of tumour vascularity. Key Points • DCE-CT can robustly assess tumour vascular support • DCE-CT has reached technical maturity for use in therapeutic trials in oncology • This paper presents consensus guidelines for using DCE-CT in assessing tumour vascularity.

Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials.

Imaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points • DCE ultrasound can quantify and extract specific blood flow parameters, such as flow velocity, relative vascular volume and relative blood flow rate. • DCE ultrasound can be performed repeatedly and is therefore ideally suited for pharmacokinetic and pharmacodynamic studies evaluating vascular-targeted drugs. • DCE ultrasound provides a reproducible method of assessing the vascular effects of therapy in pre-clinical and early clinical trials, which is easily translatable into routine clinical practice.

USPIO-enhanced MRI of highly invasive and highly metastasizing transplanted human squamous cell carcinoma: an experimental study.

OBJECTIVE: The aim of this study was to investigate the signal intensity characteristics of highly invasive and highly metastasizing transplanted human squamous cell carcinoma using ultra-small super-paramagnetic iron oxide (USPIO)-enhanced MRI and to correlate them with USPIO distribution to tumour components revealed by histological examination. METHODS: 13 nude mice with transplanted human squamous cell carcinoma in the oral cavity were imaged before and 24 hours after intravenous administration of USPIO. The difference in signal intensity between pre-contrast and post-contrast MR images was visually evaluated. For quantitative analysis, signal intensity within a region of interest was measured. Histological findings were correlated with MR findings. The approximate USPIO concentration was evaluated using USPIO phantoms. RESULTS: Seven tumours had an area showing signal intensity increase on post-contrast T1 weighted images. Histopathologically, six of those tumours contained a small amount of iron particles in the stroma. The USPIO concentration was presumed low. Two tumours had an area showing signal intensity decrease on post-contrast T1 and T2 weighted images. The areas had a large amount of iron particles in the stroma and the USPIO concentration was presumed high. There was a minimal amount of iron particles in tumour parenchymal cells. CONCLUSIONS: The amount of USPIO accumulation into tumour stroma was considered to affect MR signal intensity. A small amount increases T1 weighted signal intensity, whereas a large amount decreases T1 and T2 weighted intensity. The USPIO accumulation into the tumour parenchyma was not thought to affect MR signal intensity.

Renal safety in pediatric imaging: randomized, double-blind phase IV clinical trial of iobitridol 300 versus iodixanol 270 in multidetector CT.

BACKGROUND: It is debated whether iso-osmolar and low-osmolar contrast media are associated with different incidences of contrast medium-induced nephropathy (CIN) in patients with renal insufficiency. OBJECTIVE: To compare the incidence of CIN in children undergoing contrast-enhanced multidetector computer tomography (MDCT) with intravenous injection of low-osmolar (iobitridol, Xenetix® 300) or an iso-osmolar (iodixanol, Visipaque® 270) iodinated contrast medium. MATERIALS AND METHODS: One hundred forty-six children with normal renal function were included in this multicenter trial and underwent contrast-enhanced MDCT. The primary endpoint was the relative change in creatinine clearance from 48 h pre- to 72 h postcontrast medium administration using a noninferiority analysis in the intent-to-treat (ITT, n = 128) and per protocol (n = 68) populations. Secondary endpoints were incidence of CIN, global image quality, diagnostic efficacy and clinical safety. RESULTS: In the ITT population, the noninferiority of iobitridol over iodixanol was demonstrated. CIN incidence was 4.8% (three cases) with iobitridol and 10.6% (seven cases) with iodixanol (not significant). No statistically significant differences were observed for the secondary endpoints. CONCLUSION: Comparable satisfactory safety profiles were confirmed for both contrast media, with no significant difference in the incidence of CIN in children with normal renal function.

Magnetic labeling of non-phagocytic adherent cells with iron oxide nanoparticles: a comprehensive study.

Small particles of iron oxide (SPIO) and ultrasmall particles of iron oxide (USPIO), inducing a strong negative contrast on T(2) and T(2)*-weighted MR images, are the most commonly used systems for the magnetic labeling of cultured cells and their subsequent detection by magnetic resonance imaging (MRI). The purpose of this work is to study the influence of iron incubation concentration, nanoparticle size and nanoparticle coating on the magnetic labeling and the viability of non-phagocytic adherent cells in culture. The magnetic labeling of 3T6 fibroblasts was studied by T(2)-weighted MRI at 4.7 T and by dosing-or cytochemical revealing-of iron through methods based on Perl's Prussian blue staining. Cells were incubated for 48 h with increasing iron concentrations of SPIO (25-1000 microg Fe/ml Endorem. Sinerem, a USPIO (20-40 nm) coated with neutral dextran, and Resovist (65 nm), a SPIO bearing an anionic carboxydextran coating, were compared with Endorem (dextran-coated, 80-150 nm) as magnetic tags. The iron loading of marrow stromal cell primary cultures (MSCs) isolated from rat femurs was compared with that of 3T6 fibroblasts. The SPIO-labeling of cells with Endorem was found to be dependent on the iron incubation concentration. MSCs, more sparsely distributed in the culture, exhibited higher iron contents than more densely populated 3T6 fibroblast cultures. A larger iron loading was achieved with Resovist than with Endorem, which in turn was more efficient than Sinerem as a magnetic tag. The magnetic labeling of cultured non-phagocytic adherent cells with iron oxide nanoparticles was thus found to be dependent on the relative concentration of the magnetic tag and of the cells in culture, on the nanoparticle size, and on the coating type. The viability of cells, estimated by methods assessing cell membrane permeability, was not affected by magnetic labeling in the conditions used in this work.