Mirko D’Onofrio

EFSUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography. Part 2: Clinical Applications

The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way.

Acoustic Radiation Force Impulse (ARFI) technique in ultrasound with Virtual Touch tissue quantification of the upper abdomen

Purpose. Virtual Touch tissue quantification is an implementation of ultrasound (US) Acoustic Radiation Force Impulse (ARFI) imaging that provides numerical measurements (wave-velocity values) of tissue stiffness. The aim of this study was to define the normal values of shear-wave speed for the healthy liver, gallbladder, pancreas, spleen and kidneys. Materials and methods. Thirty-five young healthy volunteers underwent Virtual Touch tissue quantification after having signed an informed consent form. All upper abdominal organs were examined by two independent operators. A phantom fluid model was also evaluated. All mean wave-velocity values were analysed and compared. Results. One hundred and forty measurements of liver, pancreas, spleen and kidneys, and 70 measurements of the gallbladder lumen were performed. Twenty measurements on the phantom were also performed. Comparing all measurements separately made by each operator in different parts of the organs, no statistically significant differences were observed. A “XXXX/0” value was always obtained from all measurements performed on the gallbladder lumen and on the phantom fluid model. Liver, pancreas, spleen and kidney mean values were 1.59 m/s, 1.40 m/s, 2.44 m/s and 2.24 m/s, respectively. Conclusions. Virtual Touch tissue quantification is a new, promising implementation of the US ARFI technique, which provides numerical measurements of tissue stiffness. The mean shear-wave speed is lower in the pancreatic parenchyma than in the liver and kidney, whereas the spleen is characterised by the highest mean value. In Riassunto Obiettivo. Il Virtual Touch tissue quantification è una applicazione quantitativa della tecnica ecografica Acoustic Radiation Force Impulse (ARFI) che fornisce valori numerici dell’elasticità dei tessuti. Lo scopo dello studio è definire i valori di normalità di fegato, colecisti, pancreas, milza e reni. Materiali e metodi. Sono stati studiati 35 giovani volontari sani. Un consenso informato è stato ottenuto prima dell’esame. Gli organi addominali superiori sono stati studiati da due operatori indipendenti. È stato inoltre studiato un phantom contenente acqua. Tutti i valori medi di velocità di propagazione dell’onda sono stati analizzati e confrontati. Risultati. Sono state effettuate 140 misurazioni su fegato, pancreas, milza e reni, 70 nel lume della colecisti e 20 nel phantom. Confrontando tutte le misurazioni eseguite da ciascun operatore in differenti parti dei vari organi addominali, non sono risultate differenze statisticamente significative. Tutte le misurazioni effettuate su colecisti e phantom hanno fornito un valore definito “XXXX/0”. Fegato, pancreas, milza e reni avevano valori medi rispettivamente di 1,59 m/s, 1,40 m/s, 2,44 m/s e 2,24 m/s. Conclusioni. Il Virtual Touch tissue quantification è una promettente applicazione della tecnica ecografica ARFI, che consente una valutazione espressa in numeri della durezza dei tessuti. Il valore medio della velocità di propagazione dell’onda nel parenchima pancreatico è inferiore rispetto a quella misurata nel fegato e nei reni, mentre la milza è caratterizzata da valore medio più alto. Nei fluidi semplici, come l’acqua, viene sempre riscontrato ABDOMINAL RADIOLOGY RADIOLOGIA ADDOMINALE Radiol med (2010) 115:889–897 DOI 10.1007/s11547-010-0504-5 Acoustic Radiation Force Impulse (ARFI) technique in ultrasound with Virtual Touch tissue quantification of the upper abdomen Tecnica Acoustic Radiation Force Impulse (ARFI) nello studio ecografico con Virtual Touch tissue quantification dell’addome superiore A. Gallotti • M. D’Onofrio • R. Pozzi Mucelli Istituto di Radiologia, Policlinico G. B. Rossi, Università di Verona, Piazzale L. A. Scuro 10, 37134 Verona, Italy Correspondence to: M. D’Onofrio, Tel.: +39-045-8124301, Fax: +39-045-8027490, e-mail: mirko.donofrio@univr.it Received: 19 May 2009 / Accepted: 28 July 2009 / Published online: 15 January 2010

Ultrasonography of the pancreas. 4. Contrast-enhanced imaging

The introduction of contrast-enhanced ultrasonography (CEUS) has lead to great developments in the diagnostic capabilities of ultrasound. Second generation contrast media, characterized by harmonic responses at low mechanical index of the ultrasound beam, have already proven usefulness in the study of the liver but other abdominal organs can take advantage from the dynamic study during continuous ultrasonographic scans. The dynamic observation of the enhancement allows the perfect evaluation of the abdominal organs perfusion. The perfusion of the pancreas is well correlated to the semeiology of the gland parenchymography at CEUS. The study of the pancreas is a new and promising application of CEUS. CEUS can be used to better identify pancreatic lesions respect to conventional Ultrasound (US) or to characterize pancreatic lesions already visible at US. Moreover the staging of some pancreatic lesions can be improved by the use of contrast media. This article will review the clinical application of CEUS in the different pancreatic pathologies.

Acoustic Radiation Force Impulse (ARFI) ultrasound imaging of solid focal liver lesions

OBJECTIVE The aim of this paper was to evaluate the application of ARFI ultrasound imaging and its potential value for characterizing focal solid liver lesions. MATERIALS AND METHODS In this multicentric prospective study, over a total non-consecutive period of four months, all patients underwent ARFI US examination. Two independent operators performed 5 measurements per each lesion and 2 measurements in the surrounding liver. According to the definitive diagnosis, a mean velocity value and standard deviations were obtained in each type of focal solid lesion, compared by using t-test, and the inter-operator evaluation was performed by using the Students t-test. A comparison between the total mean values of each type of lesion and the mean value of the parenchyma was performed. RESULTS 40 lesions were evaluated and a total of 400 measurements were obtained. The lesions were: 6/40(15%) hepatocellular carcinomas, 7/40(17.5%) hemangiomas, 5/40(12.5%) adenomas, 9/40(22.5%) metastases and 13/40(32.5%) focal nodular hyperplasias. The total mean values obtained were: 2.17 m/s in HCCs, 2.30 m/s in hemangiomas, 1.25 m/s in adenomas, 2.87 m/s in metastases and 2.75 m/s in FNHs. The inter-operator evaluation resulted non-statistically different (p>0.05). A significant difference (p<0.05) was always found by comparing adenomas to the other lesions. 160 measurements were obtained in the surrounding parenchyma, with a no significant difference between values measured in adenomas and in the surrounding liver. CONCLUSIONS ARFI technology with Virtual Touch tissue quantification could non-invasively provide significant complementary information regarding the tissue stiffness, useful for the differential diagnosis of focal solid liver lesions.

Contrast-enhanced ultrasonography better identifies pancreatic tumor vascularization than helical CT.

Background: Contrast-enhanced ultrasonography (CEUS) is a recently introduced field of ultrasonography (US). To assess the ability of CEUS to identify the vascularization of solid pancreatic tumors in comparison to helical CT. Methods: Forty-two resected pancreatic tumors, found at US, were studied with CEUS and helical CT. The tumor enhancement at CEUS was scored in comparison to the baseline aspect of the lesion and/or the extralesional pancreatic parenchyma together with the adjacent vessels during the dynamic study. All the lesions underwent pathological examination using H&E stains and CD34 markers with an evaluation of the microvessel density (MVD). The correlation of CEUS and helical CT with the MVD of the lesions was established with Spearman’s test. Results: The correlation of CEUS with the MVD of the lesions was significantly superior (Rs = 0.914; p < 0.0001) to that of helical CT (Rs = 0.635; p < 0.0001). Conclusions: CEUS is better than helical CT in the identification of the vascularization of solid pancreatic tumors. CEUS, when the pancreatic gland is optimally visualized, should be therefore considered a complementary imaging modality in the characterization of pancreatic tumors. CEUS can be a valid onco-imaging modality for quantifying tumoral vascularization in a noninvasive and accurate way.

Pancreatic multicenter ultrasound study (PAMUS)

AIM To describe the typical CEUS pattern of pancreatic lesions and to evaluate the diagnostic accuracy of Contrast-enhanced ultrasound (CEUS) in their characterization. MATERIALS AND METHODS All US and CEUS examinations of focal pancreatic masses performed in six centers during a period of five years were reviewed. Inclusion criteria were: focal pancreatic mass pathologically proved, visible at ultrasound (US) and studied with CEUS. All lesions were then evaluated for size, aspect and enhancement pattern. Sensitivity, specificity, positive and negative predictive values with 95% CIs were calculated to define diagnostic accuracy of CEUS in respect to pathology. Diagnostic confidence of US and CEUS, discerning between benign and malignant lesions, were represented by using ROC (receiver operating characteristics) curves. Agreement was evaluated by means of k statistics. RESULTS 1439 pancreatic lesions were included. At CEUS the lesions were divided into solid (89%) and cystic (12%) masses and classified into six and eight categories, respectively. Among the solid lesions, adenocarcinomas were characterized with an accuracy of 87.8%. Among the cystic lesions, cystic tumors were diagnosed with an accuracy of 97.1%. ROC curve area increased from 0.637 for US to 0.877 for CEUS (p<0.0001). Inter-observer agreement was slightly higher for solid (k=0.78) than cystic (k=0.62) lesions. In none of the centers side effects were reported. CONCLUSION CEUS is accurate in the characterization of pancreatic lesions. CEUS should be considered as a complementary imaging method for pancreatic lesions characterization.

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms.

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.

Focal liver lesions: sinusoidal phase of CEUS

Ultrasound examination is the first imaging modality for hepatic study in neoplastic and chronic liver diseases. Focal liver lesions frequently cause diagnostic problems in terms of characterization, especially when small and hypoechoic to the rest of the parenchyma. Contrast- enhanced ultrasonography (CEUS) has shown its value in the characterization of focal liver lesions. This study assessed the value of the sinusoidal phase of CEUS with a second-generation contrast agent in the characterization of focal liver lesions to distinguish benign from malignant. Two hundred hepatic lesions with suspicious features at baseline ultrasound were prospectively studied with CEUS. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of the sinusoidal phase in the characterization of benign versus malignant liver lesions were evaluated. Hypoechogenicity of the focal liver lesion, during the sinusoidal phase of CEUS, allowed the diagnosis of malignancy with a sensitivity of 85%, specificity of 88%, positive predictive value of 92%, negative predictive value of 77%, and diagnostic accuracy of 86%. The diagnostic confidence in the diagnosis of malignancy significantly increased, with receiver operating characteristic curve areas from 0.536 for baseline ultrasound to 0.902 for the sinusoidal phase of CEUS.

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: A retrospective multicentre study

BACKGROUND Acoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis. AIM To evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography. METHODS A multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients. RESULTS The best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels>5 × the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively. Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively. For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa. CONCLUSION Liver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels.

Acoustic radiation force impulse (ARFI) ultrasound imaging of pancreatic cystic lesions

PURPOSE To evaluate the ARFI ultrasound imaging with Virtual Touch tissue quantification in studying pancreatic cystic lesions, compared with phantom fluid models. MATERIALS AND METHODS Different phantom fluids at different viscosity or density (water, iodinate contrast agent, and oil) were evaluated by two independent operators. From September to December 2008, 23 pancreatic cystic lesions were prospectively studied. All lesions were pathologically confirmed. RESULTS Non-numerical values on water and numerical values on other phantoms were obtained. Inter-observer evaluation revealed a perfect correlation (rs=1.00; p<0.0001) between all measurements achieved by both operators per each balloon and fluid. Among the pancreatic cystic lesions, 14 mucinous cystadenomas, 4 pseudocysts, 3 intraductal papillary-mucinous neoplasms and 2 serous cystadenomas were studied. The values obtained ranged from XXXX/0-4,85 m/s in mucinous cystadenomas, from XXXX/0-3,11 m/s in pseudocysts, from XXXX/0-4,57 m/s in intraductal papillary-mucinous neoplasms. In serous cystadenomas all values measured were XXXX/0m/s. Diagnostic accuracy in benign and non-benign differentiation of pancreatic cystic lesions was 78%. CONCLUSIONS Virtual Touch tissue quantification can be applied in the analysis of fluids and is potentially able to differentiate more complex (mucinous) from simple (serous) content in studying pancreatic cystic lesions.