Multiparametric ultrasound evaluation with CEUS and shear wave elastography for carotid plaque risk stratification.

PURPOSE: To assess the diagnostic effectiveness of Multiparametric ultrasound (MPUS), which includes color Doppler ultrasound (CDUS), CEUS and Shear wave elastography (SWE), for evaluating carotid plaque as compared with CT-angiography (CTA) and histology. MATERIALS AND METHODS: Forty-three consecutive patients scheduled to undergo carotid endarterectomy underwent MPUS. Then, after periods ranging from 2 days to 2 weeks, all underwent CTA. Each plaque was classified by means of dedicated scores for CEUS and SWE as compared with CTA features. At surgery, each plaque was removed in a single fragment to facilitate histological analysis, which evaluated 4 features: extension of the lipid core, thickness of the fibrous cap, inflammatory infiltrate (CD68 + and CD3 + markers) and the presence of intraplaque microvessels. For the CEUS, SWE and CTA, the following values for identifying plaque vulnerability were evaluated: sensitivity, specificity, accuracy, negative predictive value (NPV), positive predictive value (PPV) and Area under the curve (AUC). Cohen's kappa was used to evaluate the concordance between measurements in the different imaging methods. A p < 0.05 was considered statistically significant. RESULTS: At histology, 31 out of 43 plaques were identified as vulnerable because of the presence of at least one of the following criteria: fibrous cap < 200 µm, lipid core, intraplaque hemorrhage, inflammatory infiltrate or intraplaque neovascularization. CTA showed a sensitivity of 87.1%, a specificity of 100%, a PPV of 100%, an NPV of 75% and an AUC of 93.5%. SWE showed a sensitivity of 87.1%, a specificity of 66.7%, a PPV of 87.1%, an NPV of 66.7% and an AUC of 76.9%. CEUS showed a sensitivity of 87.1%, a specificity of 58.3%, a PPV of 84.4%, an NPV of 63.6% and an AUC of 72.7%. CONCLUSIONS: Multiparametric ultrasound is an effective modality to obtain comprehensive information on carotid plaques. Further studies are needed to determine whether it can be considered a diagnostic standard.

What is the role of contrast-enhanced ultrasound in the evaluation of the endoleak of aortic endoprostheses? A comparison between CEUS and CT on a widespread scale.

OBJECTIVE: To evaluate the accuracy of contrast-enhanced ultrasound (CEUS) in comparison to CT angiography (CTA) to identify and classify endoleaks following abdominal aortic aneurism repair with endoprosthesis. MATERIALS AND METHODS: A retrospective analysis of 181 patients treated with EVAR, from September 2009 to September 2014, was performed. Patients were evaluated with CEUS, CTA and angiography in the cases requiring treatment. Sac diameter, sac integrity, identification and classification of endoleaks were taken into consideration. Sensitivity, specificity, accuracy and negative predictive values were considered for each modality of endoleak identification. RESULTS: Forty-two endoleaks (23.2%; type II: 39 cases, type III: 3 cases) were documented. Sensitivity and specificity of CEUS and CT were, respectively, 97.6 and 90.5, 100 and 100%. In two cases, CEUS was able to better classify endoleaks compared to CT. CONCLUSIONS: CEUS accuracy to identify endoleaks following EVAR is similar to CT. CEUS should be considered as an effective modality for the long-term surveillance of EVAR because of its capability to correctly classify endoleaks with no ionizing radiation exposure.

Contrast-enhanced ultrasound in the evaluation of parotid gland lesions: an update of the literature.

High-resolution ultrasound is the first line examination for parotid gland diffuse disease and focal lesions, normally using grey-scale and colour-Doppler ultrasound. Unfortunately, grey-scale and colour-Doppler ultrasound features of benign and malignant salivary gland lesions may overlap, particularly with benign tumors, where pleomorphic adenomas are often indistinguishable from malignant lesions. With atypical lesions, contrast-enhanced magnetic resonance imaging is usually the second level imaging modality requested. The introduction of ultrasound contrast agents has opened further possible perspectives to improve the interpretation of parotid diseases, particularly the differentiation between benign and malignant lesions. We present a review of the current literature on contrast-enhanced ultrasound for the assessment of parotid gland lesions, considering all characteristics of the technique, evidence of usefulness, future perspectives and limitations.

Parotid Gland Lesions: Multiparametric Ultrasound and MRI Features.

High-resolution ultrasound (US), as a readily available, cost-effective and harmless imaging technique, is appropriately the initial imaging modality for salivary gland lesions. Benign tumors are reported to present with regular and well-defined margins, a homogeneous hypoechoic structure and demarcated vessel distribution, whereas malignant lesions are irregular, heterogeneous and diffusely perfused. Ultrasound and color Doppler features of benign and malignant salivary gland lesions overlap, and many benign tumors, particularly pleomorphic adenomas, may appear irregularly shaped, with a heterogeneous echo-structure indistinguishable from a malignant lesion. Often skilled US operators are not always able to differentiate benign from malignant lesions. The introduction of US contrast agents has allowed further perspectives in the possible improvement of lesion characterization, and the emergence of US elastography, an innovative tool for assessing lesion stiffness/elasticity characteristics, has been advocated for differentiating salivary gland lesions. When lesions are atypical on US, contrast-enhanced magnetic resonance (MR) imaging is usually the definitive imaging modality. We present a current review of benign and malignant parotid gland tumors with emphasis on the role of multiparametric US and MR imaging.

Detection of small testicular masses in monorchid patients using US, CPDUS, CEUS and US-guided biopsy.

PURPOSE: Testis sparing surgery (TSS) is a well-known technique in the treatment of small testicular masses. Grayscale ultrasound (US), color/power Doppler US (CPDUS) and contrast-enhanced ultrasound (CEUS) are considered the best diagnostic imaging tools in those patients. Aim of this study was to assess the role of US imaging in the detection of small testicular masses in monorchid patients after orchiectomy for malignant neoplasm, and in guiding surgery to reach the target and also to differentiate lesions which presented vascular activity within the mass. METHODS: From January 2011 to October 2014, 18 patients were enrolled in this study. They had previously undergone orchiectomy and were investigated for suspected contralateral disease. During routine follow-up, all patients underwent grayscale US. If findings were positive, CPDUS and CEUS were performed and eventually all patients underwent surgery. After exteriorization of the testis, the small mass was identified by intraoperative US, and a needle was placed under US guidance. After excision of the mass, frozen section examination was performed. When malignancy was found, radical orchiectomy was performed; if histological outcome was negative, the healthy testis was conserved. RESULTS: All patients underwent grayscale US examination, which showed small hypoechoic masses. Each mass identified at US imaging was confirmed at surgery. All patients underwent CPDUS; 12/19 lesions showed blood flow while 7/19 showed absence of blood flow. At CEUS, 16/19 lesions showed enhancement and subsequent histological examination revealed that 8 were seminomas and 3 were Leydig cell tumors. In 5/19 cases CEUS showed the presence of lesions (focal inflammatory lesions) and in 3/19 cases CEUS was negative. CONCLUSIONS: TSS in monorchid patients may be a safe procedure leading to excellent results. We therefore consider it a valid alternative to radical orchiectomy, and US imaging is essential to guide the resection of non-palpable neoplasms and to exclude concomitant lesions.

CEUS Time Intensity Curves in the Differentiation Between Leydig Cell Carcinoma and Seminoma: A Multicenter Study.

PURPOSE: Ultrasound (US) is the main imaging technique in the assessment of testicular masses, as it has proved to be highly accurate in the visualization of these pathologies. Identification of a Leydig cell tumor is essential since the lesion is benign in 90% of cases. The aim of this multicenter study is to assess the effectiveness of contrast-enhanced ultrasound (CEUS) in differentiating Leydig cell tumors from seminoma using qualitative and quantitative features. MATERIALS AND METHODS: From February 2011 to December 2013, 31 patients (mean age: 34 years; range: 25 - 52) were recruited for this prospective study. Three of them were monorchid. Therefore, a total of 59 testicles were assessed. All patients underwent grayscale US, color Doppler ultrasound (CDUS), CEUS and orchiectomy. The paired one-tailed Student's t-test was carried out to differentiate between Leydig cell tumors and seminomas. RESULTS: 31 lesions suspicious for malignancy were hypoechoic on grayscale US while they did not show a typical pattern on CDUS. CEUS qualitative analysis, based on contrast enhancement pattern, during the arterial and venous phases, did not allow discrimination of Leydig cell tumors from seminoma. Quantitative analysis of time-intensity curves (TICs) demonstrated that only three parameters presented statistical significance, i. e. wash-in rate (WiR) p = 0.014, peak enhancement (PE) p = 0.001 and time to peak (TTP) p = 0.003. CONCLUSION: The vascular bed of a Leydig cell tumor is wider and the blood flow velocity is higher than that of a seminoma due to more regular neovascularization. In contrast, a seminoma presents large areas of necrosis due to irregular neovascularization. This explains the different PE and WiR values. Further studies involving larger patient populations are mandatory to confirm these encouraging preliminary results.

Growing indications for CEUS: The kidney, testis, lymph nodes, thyroid, prostate, and small bowel.

Contrast enhanced ultrasonography (CEUS) is increasingly used for non-hepatic applications as well, so that nearly all organs have been investigated. Among them, there is a growing clinical use for a variety of pathologies of the kidney, testis, and small bowel. The possibility to differentiate benign from malignant nodes in cancer patients has been investigated. A new application is in the detection of sentinel nodes after intradermal microbubble injection. The need to distinguish thyroid nodules eligible for fine needle aspiration cytology has led to the use of CEUS in thyroid examinations as well. The potential of CEUS for prostate cancer detection has been extensively investigated, with encouraging initial results. Early promise, however, has not been fulfilled. New perspective regards evaluation of the extent of prostate tissue devascularization following ablative treatments.

Diagnostic accuracy and interobserver agreement of Quasistatic Ultrasound Elastography in the diagnosis of thyroid nodules.

PURPOSE: To assess the best technique and the diagnostic accuracy of Quasistatic Ultrasound Elastography (QUE) in thyroid nodules. Interobserver agreement was also evaluated. MATERIALS AND METHODS: A preliminary study of 50 patients with 54 thyroid nodules was performed with quantitative software in order to define the best cut-off value of different imaging methods. All patients underwent total thyroidectomy and histopathology findings served as the standard of reference. Thereafter, 154 nodules in 137 consecutive patients were prospectively evaluated by three operators. Findings at fine-needle aspiration cytology and histopathology (N = 60) served as the standard of reference. RESULTS: The most accurate technique was the axial peri-intranodular measurement method which achieved an area under the ROC curve of 0.961 (95 %CI 0.848 - 1.00) and had an optimal cut-off value of 3.00. QUE in the differentiation of thyroid nodules showed for operator 1: sensitivity 90 % (95 %CI 73.5 - 97.9 %), specificity 92.7 % (95 %CI 86.7 - 96.6 %), LR+ 12.40 (6.54 - 23.50), LR- 0.11 (0.04 - 0.32) and accuracy 91.4 % (95 %CI 85.4 - 97.3 %); for operator 2: sensitivity 86.7 % (95 %CI 69.3 - 96.2 %), specificity 87.1 % (95 %CI 79.9 - 92.4 %), LR+ 6.72 (4.16 - 10.80), LR- 0.15 (0.06 - 0.38) and accuracy 86.9 % (95 %CI 80.0 - 93.7 %); for operator 3: sensitivity 80 % (95 %CI 61.4 - 92.3 %), specificity 83.9 % (95 %CI 76.2 - 89.9 %), LR+ 4.96 (3.20 - 7.70), LR- 0.24 (0.12 - 0.49) and accuracy 81.9 % (95 %CI 74.0 - 89.9 %). Interobserver agreement values between operator 1 and operator 2 (k = 0.79) (p < 0.05, 95 %CI 0.684 - 0.904), between operator 1 and operator 3 (k = 0.73, 95 %CI: 0.607 - 0.854) and between operator 2 and operator 3 (k = 0.71, 95 %CI: 0.584 - 0.835) were significant. CONCLUSION: QUE provides accurate quantitative evaluation of thyroid nodules with low interobserver variability.

CEUS in the study of bladder, method, administration and evaluation, a technical note.

PURPOSE: Contrast-enhanced ultrasound (CEUS) is the application of ultrasound contrast agents (UCAs) to traditional medical sonography. The development of UCAs allowed to overcome some of the limitations of conventional B-mode and Doppler ultrasound techniques and enabled the display of the parenchymal microvasculature. Purpose of this paper is to delineate the elements of a solid and science-based technique in the execution of urinary bladder CEUS. METHODS: We describe the technical execution of urinary bladder CEUS and the use of perfusion softwares to perform contrast enhancement quantitative analysis with generation of time-intensity curves from regions of interest. RESULTS: During CEUS, normal bladder wall shows a wash-in time of 13 s, a time to peak (TTP) >40 s, a signal intensity (SI) <45 % and a wash-out time >80 s; Low-grade urothelial cell carcinoma (UCC) shows a wash-in time of 13 s, a time to peak TTP >28 s, a SI <45 % and a wash-out time of 40 s; High-grade UCC shows a wash-in time of 13 s, a TTP >28 s, a SI >50 % and a wash-out time of 58 s. CONCLUSIONS: CEUS is a useful tool for an accurate characterization of bladder UCC although it has some drawbacks. To avoid misunderstandings, a widely accepted classification and a standardized terminology about the most significant parameters of this application should be adopted in the immediate future.

Reprint of "Update on ultrasound elastography: Miscellanea. Prostate, testicle, musculo-skeletal".

Nowadays ultrasound elastosonography is an established technique, although with limited clinical application, used to assess tissue stiffness, which is a parameter that in most cases is associated with malignancy. However, although a consistent number of articles have been published about several applications of elastosonography, its use in certain human body districts is still not well defined. In this paper we write on the use of elastosonography in prostate, testicle and musculo-skeletal apparatus. We report and compare the work of several authors, different type of elastosonography (shear wave, strain elastography, etc.) and instrumental data obtained in the study of both benign and malignant lesions.

Prospective comparative evaluation of quantitative-elastosonography (Q-elastography) and contrast-enhanced ultrasound for the evaluation of thyroid nodules: preliminary experience.

PURPOSE: To assess the effectiveness of semiquantitative elastosonography (Q-elastography) compared with contrast-enhanced ultrasound (CEUS) in differentiating the nature of thyroid nodules. METHODS AND MATERIALS: Forty-eight consecutive patients (35 males, 13 females, range: 34-69 years, mean: 49.4 years), candidate to surgery, previously detected at color-Doppler ultrasound (CDUS), were prospectively examined with elastosonography with dedicated semiquantitative software (Q-Elastography, Toshiba XG) and CEUS (Technos Mylab 70 Gold X, and Toshiba XG) before surgery. CEUS and elastosonography were evaluated by two investigators in consensus. Comparison between the CEUS pattern and elastonographic strain ratio observed and expected frequencies for the diagnoses was evaluated with χ(2) test or with Fisher exact test. RESULTS: Fifty-three nodules (19 papillary carcinoma, 32 hyperplasia, and 2 follicular adenoma) in 48 patients were available for analysis. Regarding echogenicity score, sensitivity, specificity, PPV and NPV of conventional US were 81%, 50%, 56%, 77%; according to Q-elastography, sensitivity, specificity, PPV and NPV were 95%, 88%, 97% and 91% respectively; whereas concerning CEUS, sensitivity specificity PPV and NPV were 79%, 91%, 83% and 89% respectively. Both CEUS and Q-elastography were more specific than US (p<0.01), with not statistical significant difference with regard to sensitivity. CONCLUSIONS: The results of the present study suggest that Q-elastography is a valuable tool in the characterization of thyroid nodules and it seems to be more sensitive than CEUS.

Update on ultrasound elastography: miscellanea. Prostate, testicle, musculo-skeletal.

Nowadays ultrasound elastosonography is an established technique, although with limited clinical application, used to assess tissue stiffness, which is a parameter that in most cases is associated with malignancy. However, although a consistent number of articles have been published about several applications of elastosonography, its use in certain human body districts is still not well defined. In this paper we write on the use of elastosonography in prostate, testicle and musculo-skeletal apparatus. We report and compare the work of several authors, different type of elastosonography (shear wave, strain elastography, etc.) and instrumental data obtained in the study of both benign and malignant lesions.

Elastographic and contrast-enhanced ultrasound features of a benign schwannoma of the common fibular nerve.

Differential diagnosis of a mass in the popliteal fossa includes a number of pathologies, such as Baker's cyst, extra-articular ganglia cyst, hematoma, proliferation of adipose tissue, aneurysm of the popliteal artery, thrombosed varicose vein, gouty tophi and benign or malignant soft tissue tumors. Schwannoma is the most common benign peripheral nerve tumor. However, only a few authors have so far reported on schwannomas located on the common fibular nerve. The aim of this paper is to present contrast-enhanced ultrasound and ultrasound elastographic features of a rare case of schwannoma of the common fibular nerve as well as imaging features of a schwannoma of the peripheral nerve.

3D cone beam (CBCT) in evaluation of frontal recess: findings in youth population.

BACKGROUND: Frontal recess is the anatomical region most difficult to manage in endoscopic frontal sinus surgery due to the extreme variability of the cell patterns that may be observed in this area. CT has always been the gold standard in preoperative evaluation, but especially in the assessment of the causes of frontal recess obstruction and surgical failure. In recent years, this accredited and reliable method has been complemented by computed tomography cone beam (CBCT), which provides similarly detailed anatomical information with a lower dose of radiation. AIM: The purpose of this paper is to analyze and validate the use of CBCT in the study of frontal recess, and especially its anatomical variants in a youth population. MATERIALS AND METHODS: We analyzed 500 CBCT images of paranasal sinuses of young subjects with sinus inflammation pathology between 2009 and 2011. RESULTS: We observed that the method is very sensitive in detecting anterior and posterior recess cells, also in a youth population and then report on some significant images. CONCLUSIONS: We confirm the validity of CBCT, which by virtue of its sensitivity and specificity may be used in the analysis of frontal recess pathologies, especially when a young population is involved.

Measurement of inflammatory mediators of mast cells and eosinophils in native nasal lavage fluid in nasal polyposis.

BACKGROUND: Nasal polyposis (NP) often coexists with asthma, rhinitis and sinusitis. Polyp histology typically shows chronic, eosinophilic inflammation. The inflammatory cell infiltrate generally includes eosinophils, lymphocytes, plasma cells and mast cells. OBJECTIVE: To gain insight into the natural history of NP, we analysed mediator levels and leukocyte values in nasal fluids and eosinophil cationic protein (ECP), total IgE levels and eosinophils in the blood in several groups of both allergic and non-allergic patients with nasal polyps and in patients with allergic rhinitis (AR). METHODS: Thirty-two patients with nasal polyps entered the study. As a control group, we studied 55 patients with AR, i.e. 20 patients with seasonal AR to grass pollen, 24 with AR sensitive to Parietaria and 11 with AR sensitive to house dust mite (HDM). Eighteen patients with nasal polyps were also allergic patients (8 were sensitive to Parietaria and 10 were sensitive to HDM), whereas 14 were non-allergic patients. Tryptase and histamine values were assayed in nasal fluids, whereas total IgE was determined in serum. ECP values were assayed both in nasal fluids and serum. Eosinophils were quantified both in the blood and nasal fluids. RESULTS: Tryptase levels were significantly higher in the nasal lavages from patients with NP than in those from patients without NP (4.7 vs. 3.5 U/l, p < 0.001) and correlated with symptom scores (r(s) = 0.42, p < 0.0001). The median levels of histamine in nasal fluids from patients with NP were also significantly higher than those observed in patients without NP (50.0 vs. 21.3 ng/ml, p < 0.001), but did not correlate with symptom scores. Finally, the median levels of ECP in nasal fluids from patients with NP were significantly higher than those observed in patients without NP (38.1 vs. 16.1 ng/ml, p < 0.001) and correlated with symptom scores (r(s) = 0.38, p < 0.001). Analysis of variance showed that, among the variables studied, the presence of nasal polyps was the factor responsible for the higher levels of tryptase, histamine and ECP in nasal fluids. With regard to leukocyte counts in nasal fluids, no significant differences were observed between rhinitis patients with NP and those without NP. With regard to serum ECP and serum total IgE, no significant differences were detected between the two groups under study. Blood eosinophil levels in patients with NP were significantly higher than those observed in patients without NP (5.8 vs. 5.6, p = 0.002). Analysis of variance showed that both the presence of nasal polyps and the type of sensitisation were important. Considering the total symptom scores, no significant differences were observed between rhinitis patients with NP and those without NP. CONCLUSIONS: The present findings are consistent with the view that chronic eosinophil mucosal inflammatory disease in NP involves a self-sustaining mechanism, i.e. local release of inflammatory mediators, independent of allergen stimulation of nasal mucosa. Increased release of inflammatory mediators contributes to the development of nasal polyps, determining oedema and an increased recruitment of inflammatory cells. Besides eosinophils, mast cells also play a key role in this process.

Effect of fluticasone propionate on soluble CD30 release in patients with severe allergic asthma.

Previous studies have demonstrated improvements in health-related quality of life in asthmatic patients after treatment with fluticasone propionate. CD30 is a marker of Th2 lymphocytes, which are key cells in the pathogenesis of allergic inflammation. There is also a soluble form of CD30 (sCD30) released by CD30+ cells. Since serum sCD30 levels are high in allergic patients, in our study we examined the possible role of fluticasone propionate in modulating sCD30 release in patients with severe allergic asthma. In addition, we evaluated a possible correlation between sCD30 and FEV1 in these patients. To this end two groups of subjects were enrolled: 20 healthy nonatopic control subjects (group A) and 20 atopic patients with severe bronchial asthma receiving fluticasone propionate at the total dosage of 1 mg/day for 8 weeks (group B). Serum samples were examined before and after the treatment period. sCD30 serum levels were determined by the commercial ELISA-kit (Dako). The limit of detection of the assay was 1 U/ml. Our data show that sCD30 basal serum levels were significantly (p <0.05) higher in patients of group B respect to group A subjects (8.35+/-4.88 vs. <1 IU/ml, respectively). In addition, we found that sCD30 serum levels were undetectable in patients of group B after fluticasone propionate therapy. In group B a positive correlation between serum sCD30 levels and FEV1 values before fluticasone propionate treatment was noted (Rho = -0.644, p <0.005). The fluticasone propionate inhibition of sCD30 release may partly explain how fluticasone propionate exerts its antiinflammatory activity, through the modulation of Th2 cells.

Burning mouth syndrome due to cadmium in a denture wearer.

We report the case of a female denture wearer who was referred to our service due to burning of the lips and tongue but with no visible oral lesions. Her biochemical data, complete blood cell count, sedimentation rate, thyroid and sex hormones were normal. Tongue culture was negative. Patch tests, performed with a panel of 20 potential denture allergens, gave positive results (+++) only to a 2% petrolatum cadmium sulfate, which was present in the denture. Removal of the denture led to the clearing up of oral symptoms in 3 days. In light of these findings, carrying out patch tests with the allergens related to denture materials should be considered in these cases.

In vitro effect of lithium chloride on interleukin-15 production by monocytes from IL-breast cancer patients.

Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer. Interleukin-15 (IL-15) is a cytokine which possesses promoting activities on hematopoiesis and is also involved in antitumor response, activating NK, CTL and LAK cells. In this study we analyzed IL-15 production by monocyte cultures treated with lithium chloride (LiCl). Monocytes were obtained from patients affected by non-metastatic and metastatic breast cancer. LiCl treatment induced IL-15 production by monocytes mainly from non-metastatic patients. Combined lipopolysaccharide/LiCl treatment of monocyte cultures up-regulated IL-15 release compared to those treated with LPS alone (p<0.0001). The modulation of LiCl-induced IL-15 could counteract the immunosuppression state of cancer patients, which should be taken into account when developing new immunotherapeutic strategies.