The aim of this study was to investigate the application value of thyroid puncture biopsy guided by contrast-enhanced ultrasound (CEUS). A total of 48 patients with 51 solid thyroid nodules (suspected papillary thyroid carcinoma, PTC) were enrolled in the study. Following detection by conventional ultrasonography and CEUS, puncture biopsy of the suspicious lesions guided by conventional ultrasonography and CEUS was conducted, respectively. Then, pathological diagnosis was performed. The number of PTC positive nodules and puncture points detected by the two methods were compared. In 51 nodules with 310 punctures, 44 nodules (86.3%, 44/51) and 240 punctures (77.4%, 240/310) were pathologically diagnosed as PTC. In the 44 nodules diagnosed as PTC, 43 and 34 nodules were detected by CEUS and conventional ultrasound, respectively, with a significant difference between the two methods (P=0.022). Eleven (25%) nodules were independently detected by CEUS. The sensitivity and accuracy of puncture point detection by CEUS (82.9 and 82.6%, respectively) were significantly higher compared with those of conventional ultra-sound (48.3 and 56.5%, respectively; P<0.001). The specificity of puncture points detected by CEUS (81.4%) was significantly lower compared with that by conventional ultrasound (84.3%; P=0.009). Compared with conventional ultrasound, a greater number of PTC-positive nodules were detected by CEUS, with increased sensitivity and accuracy of the puncture points.
contrast-enhanced ultrasound; ultrasound; papillary thyroid carcinoma; puncture biopsy
AIM: To assess the usefulness of contrast-enhanced ultrasound (CEUS) during follow-up after percutaneous ablation therapy for hepatocellular carcinoma (HCC).
METHODS: A total of 141 patients with HCCs who received percutaneous ablation therapy were assessed by paired follow-up CEUS and contrast-enhanced computed tomography (CECT). The follow-up scheme was designed prospectively and the intervals between CEUS and CECT examinations were less than 14 d. Both images of follow-up CEUS and CECT were reviewed by radiologists. The ablated lesions were evaluated and classified as local tumor progression (LTP) and LTP-free. LTP was defined as regrowth of tumor inside or adjacent to the successfully treated nodule. The detected new intrahepatic recurrences were also evaluated and defined as presence of intrahepatic new foci. On CEUS and CECT, LTP and new intrahepatic recurrence both were displayed as typical enhancement pattern of HCC (i.e., hyper-enhancing during the arterial phase and washout in the late phase). With CECT as the reference standard, the ability of CEUS in detecting LTP or new intrahepatic recurrence during follow-up was evaluated.
RESULTS: During a follow-up period of 1-31 mo (median, 4 mo), 169 paired CEUS and CECT examinations were carried out for the 141 patients. For a total of 221 ablated lesions, 266 comparisons between CEUS and CECT findings were performed. Thirty-three LTPs were detected on CEUS whereas 40 LTPs were detected on CECT, there was significant difference (P < 0.001). In comparison with CECT, the numbers of false positive and false negative LTPs detected on CEUS were 6 and 13, respectively; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of CEUS in detecting LTPs were 67.5%, 97.4%, 81.8%, 94.4% and 92.3%, respectively. Meanwhile, 131 new intrahepatic recurrent foci were detected on CEUS whereas 183 were detected on CECT, there was also significant difference (P < 0.05). In comparison with CECT, the numbers of false positive and false negative intrahepatic recurrences detected on CEUS were 13 and 65, respectively; the sensitivity, specificity, PPV, NPV and overall accuracy of CEUS in detecting new intrahepatic recurrent foci were 77.7%, 92.0%, 92.4%, 76.7% and 84.0%, respectively.
CONCLUSION: The sensitivity of CEUS in detecting LTP and new intrahepatic recurrence after percutaneous ablation therapy is relatively low in comparison with CECT.
Contrast-enhanced ultrasound; Contrast-enhanced computed tomography; Hepatocellular carcinoma; Radiofrequency ablation; Microwave ablation
To assess the value of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) from non-neoplastic lesion in cirrhotic liver in comparison with baseline ultrasound.
A total of 147 nodules (diameter ≤5.0 cm) in 133 cirrhotic patients (mean age±standard deviation: 52±13 years, range 20–82 years; gender: 111 males and 22 females) were examined with CEUS. There were 116 HCCs, 26 macroregenerative nodules and 5 high-grade dysplastic nodules. CEUS was performed with a real-time contrast-specific mode and a sulphur hexafluoride-filled microbubble contrast agent.
Hypervascularity was observed in 94.8% (110/116) HCCs, 3.8% (1/26) macroregenerative nodules and 60.0% (3/5) high-grade dysplastic nodules during arterial phase on CEUS. Detection rates of typical vascular pattern (i.e. hypervascularity during arterial phase and subsequent washout) in HCCs with a diameter of ≤2.0 cm, 2.1–3.0 cm and 3.1–5.0 cm were 69.2% (27/39), 97.1% (33/34) and 100.0% (43/43), respectively. CEUS significantly improved the sensitivity [88.8% (103/116) vs 37.1% (43/116), p<0.001], negative predictive value [70.5% (31/44) vs 31.5% (29/92), p<0.001], and accuracy [91.2% (134/147) vs 49.0% (72/147), p<0.001] in differentiating HCCs from non-neoplastic lesions when compared with baseline ultrasound. However, the sensitivity and accuracy of CEUS for HCCs ≤2.0 cm in diameter were significantly lower than those for HCCs of 2.1–3.0 cm and 3.1–5.0 cm in diameter.
CEUS improves diagnostic performance in differentiating HCCs from non-neoplastic nodules in cirrhotic patients compared with baseline ultrasound. Diagnosis of HCCs ≤2.0 cm diameter by CEUS is still a clinical concern, and thus needs further investigation.
Contrast enhanced ultrasound (CEUS) is an imaging technique which appeared on the market around the year 2000 and proposed for the detection of liver metastases in gastrointestinal cancer patients, a setting in which accurate staging plays a significant role in the choice of treatment.
A total of 109 patients with colorectal (n = 92) or gastric cancer prospectively underwent computed tomography (CT) scan and conventional US evaluation followed by real time CEUS. A diagnosis of metastases was made by CT or, for lesions not visibile at CT, the diagnosis was achieved by histopathology or by a malignant behavior during follow-up.
Of 109 patients, 65 were found to have metastases at presentation. CEUS improved sensitivity in metastatic livers from 76.9% of patients (US) to 95.4% (p <0.01), while CT scan reached 90.8% (p = n.s. vs CEUS, p < 0.01 vs US). CEUS and CT were more sensitive than US also for detection of single lesions (87 with US, 122 with CEUS, 113 with CT). In 15 patients (13.8%), CEUS revealed more metastases than CT, while CT revealed more metastases than CEUS in 9 patients (8.2%) (p = n.s.).
CEUS is more sensitive than conventional US in the detection of liver metastases and could be usefully employed in the staging of patients with gastrointestinal cancer. Findings at CEUS and CT appear to be complementary in achieving maximum sensitivity.
The aim of the study was to evaluate the efficiency and feasibility of contrast-enhanced ultrasound (CEUS) with Sonovue in assessing of renal cell carcinomas (RCCs) following ultrasound (US)-guided percutaneous microwave ablation (MWA).
Patinets and methods
Seventy-nine patients (60 males and 19 females) with 83 lesions (mean size 3.2±1.6 cm) were treated by US-guided percutaneous MWA. The CEUS results of the third day after the ablation were compared with the synchronous contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) results and biopsy pathological results. The follow-up was performed by CEUS and CT/MRI after 1, 3, 6 months and every 6 months subsequently. The combination of clinical follow-up results and CT/MRI imaging findings was the reference standard of CEUS results for evaluating the therapeutic effect. The identification of residual or recurrence tumour was assessed by two blinded radiologists.
On the third day after MWA, CEUS showed 68 of 83 lesions (68/83, 81.9%) successfully ablated and 15 of 83 (18.1%) with residual tumours. Among residual tumours, 13 (86.7%) were confirmed by contrast-enhanced CT/MRI findings and biopsy results. The sensitivity, specificity, accuracy, positive and negative predictive value of CEUS evaluating the short-term MWA effectiveness were 100%, 97.1%, 97.6%, 86.7% and 100%, respectively. During the six years follow-up (median 26 months), the CEUS showed recurrence in 7 patients, and six of them achieved consistent results on CEUS and CT/MRI imaging. The sensitivity, specificity, accuracy, positive and negative predictive value for CEUS evaluating long-term MWA effectiveness were 85.7%, 98.7%, 97.6%, 85.7% and 98.7%, respectively.
The post-procedural CEUS demonstrated as an effective and feasible method in evaluating a therapeutic effect of RCCs following MWA.
contras enhanced ultrasound; microwave ablation; renal cell carcinoma
Ultrasound (US) is highly sensitive in the detection of renal masses. However, it may not be able to differentiate benign and malignant lesions in smaller masses. The purpose of this study was to determine the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) for small renal masses.
Materials and Methods
From January 2011 to December 2013, a total of 85 patients underwent CEUS for evaluation of renal masses. Of these patients, CEUS findings were retrospectively analyzed for small renal cell carcinoma (RCC) cases (n=38) and angiomyolipoma (AML) cases (n=11). The tumor echogenicity and enhancement patterns and degrees were evaluated. The diagnostic efficacy of CEUS in differentiating the two diseases was compared.
On CEUS, the findings of diffuse heterogeneous enhancement (observed in 78.9% of RCCs and 27.3% of AMLs, p=0.003), washout from hyperenhancement or iso-enhancement to hypoenhancement in late phase (73.7% of RCCs and 18.2% of AMLs, p=0.001), and perilesional rim-like enhancement (57.9% of RCCs and 9.1% of AMLs, p=0.006) were significantly different between AML and RCC cases. The corresponding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 86.8% (33/38), 63.6% (7/11), 89.2% (33/37), 58.3% (7/12), and 81.6% (40/49), respectively.
Our results suggest that the characteristic CEUS features could have diagnostic value in the evaluation of small renal mass. CEUS showed a higher diagnostic efficacy than conventional US for differentiating RCC and AML.
Angiomyolipoma; Contrast media; Renal cell carcinoma; Ultrasonography
To evaluate the response of breast cancers to neoadjuvant chemotherapy (NAC) with second-generation contrast-enhanced ultrasound (CEUS) and magnetic resonance (MR).
Materials and Methods
We studied 16 women aged 33–74 years (mean, 53 years; median, 38 years) with locally advanced breast carcinoma or large operable breast cancer (>2 cm; T2–T4, N0–N3, M0) that had been detected by mammography, conventional ultrasonography, and biopsy. CEUS (with SonoVue, 5 ml) and MR (with Gd-DTPA; 0.2 mM/kg) were performed under blinded conditions before, during, and after 6–8 cycles of NAC. Lesions were measured and time/signal intensity (T/SI) curves were calculated during both the examinations. The data obtained were analyzed in light of the results of surgical pathology.
Six patients had complete responses manifested by the disappearance of enhancement at both CEUS and MR. Six others had partial responses (reduction of lesion enhancement >50%). In 5/6, T/SI curves obtained with CEUS and MR were both indicative of malignancy (flat curves at CEUS, type I curves at MR); the sixth had a discontinuous curve at CEUS and a type II curve at MR. Four patients had lesional enhancement reductions of <50%. In 3, concordant pictures emerged from the analysis of T/SI curves (discontinuous curves in CEUS, type II and III curves in MR); the fourth had a flat CEUS curve and a type I MR curve. Responses to NAC classified on the basis of MR and CEUS findings showed good correlation with the pathological response.
T/SI curves recorded during CEUS correlate with those obtained during MR and may be a valid index of response to the therapy.
Breast ultrasonography; Breast cancer; Contrast media; Contrast-enhanced US; MRI
AIM: To investigate the clinical role of contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CE-CT) or magnetic resonance imaging to improve the preoperative staging of hepatocellular carcinoma (HCC) and guide surgical decision-making.
METHODS: Sixty-nine patients who underwent liver resection for HCC in our center were enrolled prospectively in the study. CEUS and CE-CT/MRI were performed before surgery. Intraoperative ultrasound (IOUS) was carried out after liver mobilization. Lesions depicted by each imaging modality were counted and mapped. To investigate the impact of tumor size on the study, we divided the patients into two groups, the “Smaller group”(S-group, ≤ 5 cm in diameter) and the “Larger-group” (L-group, > 5 cm in diameter). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CE-CT/MRI, CEUS, IOUS, CEUS+CE-CT/MRI and the tumor node metastasis staging of tumors were calculated and compared. Changes in the surgical strategy as a result of CEUS and IOUS were analyzed.
RESULTS: One hundred and twenty-seven nodules, comprising 94 HCCs confirmed by histopathology and 33 benign lesions confirmed by histopathology and follow-up, were identified in 69 patients. The overall diagnostic sensitivity rates of CE-CT/MRI, CEUS, IOUS and CEUS+ CE-CT/MRI were 78.7%, 89.4%, 89.4% and 89.4%, respectively. There was a significant difference between CEUS + CE-CT/MRI and CE-CT/MRI (P = 0.046). Combining CEUS with CT or MRI increased, the diagnostic specificity compared with CT/MRI, CEUS and IOUS, and this difference was statistically significant (100%, 72.7%, 97.0%, and 69.7%, P = 0.004, P = 0.002, P = 0.002, respectively). The diagnostic accuracy was significantly higher for CEUS + CT/MRI compared with CT/MRI (92.1% vs 77.2%, P = 0.001). The TNM staging of tumors based on CEUS + CE-CT/MRI approximated to the final pathological TNM staging (P = 0.977). There was a significant difference in the accuracy of TNM staging when comparing CEUS + CE-CT/MRI with CE-CT/MRI (P = 0.002). Before surgery, strategies were changed in 15.9% (11/69) of patients as a result of CEUS. Finally, only 5.7% (4/69) of surgical strategies were changed because of IOUS findings. In the S-group, CEUS revealed 12 false positive lesions, including seven false positive lesions that were diagnosed by preoperative imaging examinations and five by IOUS. In contrast, in the L-group, IUOS revealed eight new malignant lesions; six of these lesions were true HCCs that were also identified by preoperative CEUS.
CONCLUSION: CEUS combined with CT or MRI improves the accuracy of preoperative staging for hepatocellular carcinoma and may help to guide individualized treatment for patients with HCC. CEUS may better identify non-malignant lesions in patients with small tumors and discover new malignant lesions in patients with large tumors.
Hepatocellular carcinoma; Contrast-enhanced ultrasound; Tumor node metastasis staging; Intraoperative ultrasound; Liver resection
The pre-surgical selection of thyroid nodules with indeterminate cytology (Thy 3 according to British Thyroid Association) after fine-needle aspiration biopsy (FNAB) is currently required in order to reduce unnecessary total thyroidectomy. The objective of our study was to use a surgical series of Thy 3 nodules to evaluate the predictive role of ultrasound elastosonography (USE) and contrast-enhanced ultrasonography (CEUS) in pre-surgical diagnoses of malignancy.
Subjects and methods
We enrolled 63 patients with Thy 3 nodules in which cytological–histological correlation was available. The ELX 2/1 strain index was obtained by means of semi-quantitative USE, which was performed before surgery in addition to conventional ultrasonography (US) and contrast-enhanced US (CEUS) on the Thy 3 nodules. The ELX 2/1 strain index, a five-item US score and both peak (P) index and time to peak (TTP) index from CEUS were correlated with the histological results. After surgical diagnosis, the data were analysed by using a receiver-operating characteristic (ROC) curve.
Histology was benign in 50 and malignant in 13 Thy 3 nodules. No difference in maximal diameter was noted between benign (22.8 ± 1.6 mm) and malignant (18.9 ± 2.9 mm) nodules. Significant correlations were found between histology and cumulative US findings (p=0.005), ELX 2/1 index (p=0.002), P index (p=0.01) and TTP index (p=0.02). On analysing data from US, USE and CEUS, significant ROC areas under the curve were observed (p<0.0001). A cut-off value was set for US (>2), ELX 2/1 (>0.95), P index (<0.99) and TTP index (>0.98) scores. The diagnostic power of the cumulative pre-surgical analysis of Thy 3 nodules with US, USE and CEUS, considering the experimental cut-off points obtained from the ROC curves was: sensitivity 64%, specificity 92%, PPV 75% and accuracy 84%.
The ELX 2/1 index in conjunction with the US score can be useful in orienting surgical strategies in Thy 3 nodules. The information added by CEUS is less sensitive than that provided by US and USE. The use of a cut-off based on histology can reduce thyroidectomy. Observation should be the first choice when not all instrumental results are suspect.
Thyroid nodules; Indeterminate cytology; Ultrasosonography; Ultrasound elastosonography; Strain index; Contrast-enhanced ultrasonography; Cytological–histological correlation; ROC analysis
To determine the potential application of contrast-enhanced ultrasound in the characterisation of focal liver lesions encountered in radiological practice at a district general hospital.
Materials & Methods
Retrospective analysis of 68 sequential patients undergoing contrast-enhanced ultrasound (CEUS) of liver. All patients were referred for CEUS following identification of 1 or more focal liver lesions on conventional ultrasound or CT imaging. After baseline US examination (Acuson), a bolus of 1.0-2.4 ml of SonoVue (Bracco, UK) was administered intravenously. CEUS images were obtained during arterial, portal venous and delayed phases. Patients were followed up for a mean period of 6 months. The CEUS diagnosis was compared to that indicated by other imaging modalities, histopathology, and clinical follow up.
CEUS correctly identified malignant liver lesions in 19 patients, with the final diagnosis confirmed by histopathology in 5 cases and clinico-radiological follow up in 14 cases. 47 patients were correctly identified with benign liver lesions on CEUS imaging, with all these cases confirmed on clinico-radiological follow up. In the detection of malignancy, the sensitivity was 95.0% and the specificity was 97.9%
In our experience to date, contrast-enhanced ultrasound imaging is highly accurate in characterising malignant and benign focal liver lesions. It therefore has significant potential for utilisation in most general radiology departments.
Ultrasound; Liver; Contrast
Percutaneous ablation using thermal or chemical methods has been widely used in the treatment of hepatocellular carcinoma (HCC). Nowadays, contrast-enhanced imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and contrast-enhanced ultrasound (CEUS) are widely used to evaluate local treatment response after ablation therapies. CEUS is gaining increasing attention due to its characteristics including real-time scanning, easy performance, lack of radiation, wide availability, and lack of allergy reactions. Several studies have documented that CEUS is comparable to CT or MRI in evaluating local treatment efficacy within 1 mo of treatment. However, little information is available regarding the role of CEUS in the follow-up assessment after first successful ablation treatment. Zheng et al found that in comparison with contrast-enhanced computed tomography (CECT), the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of CEUS in detecting local tumor progression (LTP) were 67.5%, 97.4%, 81.8%, 94.4% and 92.3%, respectively, and were 77.7%, 92.0%, 92.4%, 76.7% and 84.0%, respectively for the detection of new intrahepatic recurrence. They concluded that the sensitivity of CEUS in detecting LTP and new intrahepatic recurrence after ablation is relatively low in comparison with CECT, and CEUS cannot replace CECT in the follow-up assessment after percutaneous ablation for HCC. These results are meaningful and instructive, and indicated that in the follow-up period, the use of CEUS alone is not sufficient. In this commentary, we discuss the discordance between CT and CEUS, as well as the underlying mechanisms involved. We propose the combined use of CT and CEUS which will reduce false positive and negative results in both modalities. We also discuss future issues, such as an evidence-based ideal imaging follow-up scheme, and a cost-effectiveness analysis of this imaging follow-up scheme.
Hepatocellular carcinoma; Radiofrequency ablation; Ethanol ablation; Contrast-enhanced ultrasound; Follow-up; Treatment response; Computed tomography
Bladder cancer ranks 4th overall in the number of newly diagnosed cancers and 10th in causes of cancer deaths. More than 90% of all cases of bladder cancer are transitional cell carcinoma (TCC). The goal of this study is to confirm the usefulness of low mechanical index contrast-enhanced ultrasonography (CEUS), also in association with time–intensity curves, in the differentiation between high- and low-grade bladder malignant lesions.
Materials and methods
From February 2006 to February 2012 we recruited 144 patients. All patients underwent grayscale ultrasonography (US), color-Doppler ultrasonography (CDUS) and contrast-enhanced ultrasonography (CEUS). Subsequently all patients underwent cystoscopy and TURB.
Histological diagnoses were: 88 high-grade carcinomas (61.1%), and 56 low-grade carcinomas (38.9%). Sensitivity and specificity of CDUS were 87.5% (126/144) and 60%, respectively. Sensitivity and specificity of CEUS were 90.9% and 85.7%, respectively. Sensitivity and specificity of TIC were 91.6% (132/144) and 85.7%, respectively.
Discussion and conclusions
CEUS is a reliable noninvasive method for differentiating low- and high-grade bladder carcinomas since it provides typical enhancement patterns as well as specific contrast-sonographic perfusion curves.
Contrast-enhanced ultrasonography, CEUS; Bladder cancer; Time-intensity curves; Color-Doppler ultrasonography, CDUS
The aim of this study was to evaluate the imaging features of hepatic angiomyolipoma (AML) on contrast-enhanced ultrasound (CEUS). The imaging features of 12 pathologically proven hepatic AML lesions in 10 patients who had undergone baseline ultrasound (BUS) and CEUS examinations were evaluated retrospectively. The enhancement extent, pattern and dynamic change, along with the enhancement process, on CEUS were analysed. The diagnostic results of BUS and CEUS before pathological examination were also recorded. The results showed that 75% (9/12) of the AML lesions exhibited mixed echogenicity on BUS and most showed remarkable hyperechogenicity in combination with a hypoechoic or anechoic portion. Arterial flow signals were detected in 75% (9/12) of the lesions on colour Doppler imaging. On CEUS, 66.7% (n = 8) of the 12 lesions exhibited hyperenhancement in the arterial phase, slight hyperenhancement (n = 2) or isoenhancement (n = 6) in the portal phase, and slight hyperenhancement (n = 1) or isoenhancement (n = 7) in the late phase. Three (25%) lesions exhibited hyperenhancement in the arterial phase and hypoenhancement in both portal and late phases. One (8.3%) lesion exhibited hypoenhancement throughout the CEUS process. Before pathological examination with BUS, only 3 (25%) lesions were correctly diagnosed as hepatic AML. Conversely, on CEUS, correct diagnoses were made for 66.8% (8/12) of hepatic AMLs. Therefore, arterial hyperenhancement and subsequent sustained enhancement on CEUS were found in the majority of hepatic AMLs. The combination of BUS and CEUS leads to the correct diagnosis in the majority of hepatic AMLs, and is higher than the success rate achieved by BUS alone.
Objective: The aim of the study was to assess the role of contrast-enhanced ultrasound (CEUS) in treatment response evaluation after percutaneous bipolar radiofrequency ablation (BRFA) for liver tumors. Methods: From May 2012 to May 2014, 39 patients with 73 tumors were treated by BRFA. One month after the treatment, CEUS and CEMRI/CECT were conducted to evaluate the treatment response. The results of CEUS were compared with CEMRI/CECT. Results: Of the 73 tumors ablated, eight (11.0%) were found to have residual viable tumor tissue and 65 (89.0%) were successfully ablated based on CEMRI/CECT within 1-month after ablation. CEUS detected seven of the eight residual tumors and 63 of 65 completely ablated tumors. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 87.5% (7/8), 96.9% (63/65), 77.8% (7/9), 98.4% (63/64) and 95.9% (70/73), respectively. The complete ablation (CR) rates for the tumors ≤3.0 cm, 3.1-5.0 cm, and >5.0 cm were 96.6% (58/60), 63.6% (7/11), and 0% (0/2), respectively (P<0.001). CR rates were 94.7% (36/38) for primary liver tumors and 82.9% (29/35) for metastatic liver tumors (P=0.212), and were 97.4% (38/39) for the tumors with curative treatment intention and 79.4% (27/34) for those with palliative treatment intention (P=0.037). Major complication was not encountered in this series. Conclusions: BRFA is an effective technique of percutaneous ablation for liver tumors and CEUS can be used to assess its therapeutic effect accurately.
Contrast-enhanced ultrasound; contrast-enhanced MRI; contrast-enhanced CT; liver tumors; bipolar radiofrequency ablation
AIM: To assess the role of contrast enhanced ultrasonography in evaluation of hepatocellular carcinoma (HCC) at the first Indian tertiary liver center.
METHODS: Retrospective analysis of contrast enhanced ultrasound (CEUS) examinations over 24 mo for diagnosis, surveillance, characterization and follow up of 50 patients in the context of HCC was performed. The source and indication of referrals, change in referral rate, accuracy and usefulness of CEUS in a tertiary liver center equipped with a 64 slice dual energy computer tomography (CT) and 3 tesla magnetic resonance imaging (MRI) were studied. Sonovue (BR1, Bracco, Italy, a second generation contrast agent) was used for contrast US studies. Contrast enhanced CT/MRI or both were performed in all patients. The findings were taken as a baseline reference and correlation was done with respect to contrast US. Contrast enhanced MRI was performed using hepatocyte specific gadobenate dimeglumine (Gd-BOPTA). Iomeron (400 mg; w/v) was used for dynamic CT examinations.
RESULTS: About 20 (40%) of the examinations were referred from clinicians for characterization of a mass from previous imaging. About 15 (30%) were performed for surveillance in chronic liver disease; 5 (10%) examinations were performed for monitoring lesions after radiofrequency ablation (RFA); 3 (6%) were post trans-arterial chemo-embolization (TACE) assessments and 3 (6%) were patients with h/o iodinated contrast allergy. About 2 (4%) were performed on hemodynamically unstable patients in the intensive care with raised alpha fetoprotein and 2 (4%) patients were claustrophobic. The number of patients referred from clinicians steadily increased from 12 in the first 12 mo of the study to 38 in the last 12 mo. CEUS was able to diagnose 88% of positive cases of HCC as per reference standards. In the surveillance group, specificity was 53.3% vs 100% by CT/MRI. Post RFA and TACE specificity of lesion characterization by CEUS was 100% in single/large mass assessment, similar to CT/MRI. For non HCC lesions such as regenerative and dysplastic nodules, the specificity was 50% vs 90% by CT/MRI. The positive role of CEUS in imaging spectrum of HCC included a provisional urgent diagnosis of an incidentally detected mass. It further led to a decrease in time for further management. A confident diagnosis on CEUS was possible in cases of characterization of an indeterminate mass, in situations where the patient was unfit for CT/MRI, was allergic to iodinated contrast or had claustrophobia, etc. CEUS was also cost effective, radiation free and an easy modality for monitoring post RFA or TACE lesions.
CONCLUSION: CEUS is a valuable augmentation to the practice of ultrasonography, and an irreplaceable modality for confounding cases and interpretation of indeterminate lesions in imaging of HCC.
Hepatocellular carcinoma; Contrast ultrasound; Tertiary liver care; Triple phase contrast-enhanced computed tomography; Dynamic contrast enhanced magnetic resonance imaging
A key limitation of conventional ultrasound (US) includes poor differentiation of benign from malignant thyroid nodules. Contrast-enhanced US (CEUS) and acoustic radiation force impulse (ARFI) could provide better characterization of focal thyroid nodules; however, no studies have compared their efficacies.
To evaluate the diagnostic efficacy of conventional US,CEUS, ARFI, and their combined use in differentiating focal solid thyroid nodules.
One-hundred-forty-six Chinese patients with 175 thyroid nodules (119 benign and 56 malignant) were prospectively enrolled. Each patients underwent conventional US, CEUS and ARFI, respectively. The diagnostic performance of the conventional US, CEUS, ARFI, combined use of either CEUS or ARFI and combined use of the three modalities were assessed and compared using Pathological diagnosis (histological/cytological) as the reference method.
There were no significant differences between individual groups (CEUS vs US, P = 0.279, ARFI vs US, P = 0.372, CEUS vs ARFI, P = 0.849), combined use of US and CEUS or combined use of US and ARFI yielded significant difference compared to US. (combination of US & CEUS vs US, P = 0.021; combination of US & ARFI vs US, P = 0.036). The combination of three modalities significantly improved the diagnostic accuracy compared with either combination of conventional US and CEUS or combination of conventional US and ARFI (P = 0.045 and P = 0.027, respectively).
CEUS and ARFI can be used as an additional tool in the diagnostic work up of thyroid nodules. The combination of CEUS with ARFI can significantly improve the diagnostic accuracy.
The commercially available Navigator system© (Esaote, Italy) allows easy 3D reconstruction of a single 2D acquisition of contrast-enhanced US (CEUS) imaging of the whole liver (with volumetric correction provided by the electromagnetic device of the Navigator©). The aim of our study was to compare the efficacy of this panoramic technique (Nav 3D CEUS) with that of conventional US and spiral CT in the detection of new hepatic lesions in patients treated for hepatocellular carcinoma (HCC).
Materials and methods
From November 2006 to May 2007, we performed conventional US, Nav 3D CEUS, and spiral CT on 72 cirrhotic patients previously treated for 1 or more HCCs (M/F: 38/34; all HCV-positive; Child: A/B 58/14) (1 examination: 48 patients; 2 examinations: 20 patients; 3 examinations: 4 patients). Nav 3D CEUS was performed with SonoVue© (Bracco, Milan, Italy) as a contrast agent and Technos MPX© scanner (Esaote, Genoa, Italy). Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values (PPV and NPV, respectively) were evaluated. Differences between the techniques were assessed with the chi-square test (SPSS release-15).
Definitive diagnoses (based on spiral CT and additional follow-up) were: 6 cases of local recurrence (LocRecs) in 4 patients, 49 new nodules >2 cm from a treated nodule (NewNods) in 34 patients, and 10 cases of multinodular recurrence consisting of 4 or more nodules (NewMulti). The remaining 24 patients (22 treated for 1–3 nodules, 2 treated for >3 nodules) remained recurrence-free. Conventional US correctly detected 29/49 NewNods, 9/10 NewMultis, and 3/6 LocRecs (sensitivity: 59.2%; specificity: 100%; diagnostic accuracy: 73.6%; PPV: 100%; NPV: 70.1%). Spiral CT detected 42/49 NewNods plus 1 that was a false positive, 9/10 NewMultis, and all 6 LocRecs (sensitivity: 85.7%; specificity: 95.7%; diagnostic accuracy: 90.9%; PPV: 97.7%; NPV: 75.9%). 3D NAV results were: 46N (+9 multinodularN and 6 LR), 3 false-negatives, and one false-positive (sensitivity: 93.9; specificity: 97.9%; diagnostic accuracy: 95.6; PPV: 97.9; NPV: 93.9).
3D Nav CEUS is significantly better than US and very similar to spiral CT for detection of new HCCs. This technique revealed the presence of lesions that could not be visualized with spiral CT.
Hepatocellular carcinoma; Liver; Detection; SonoVue; Three-dimensional ultrasound; Contrast-enhanced ultrasound; Spiral CT
AIM: To investigate contrast-enhanced ultrasound (CEUS) findings in portal venous system aneurysms (PVSAs).
METHODS: In this multi-center, retrospective, case series study, we evaluated CEUS features of seven cases of PVSAs that were found incidentally on conventional ultrasound in the period 2007-2013. Three Ultrasound Centers were involved (Chieti, Italy, Bad Mergentheim, Germany, and Cluj-Napoca, Romania). All patients underwent CEUS with Sonovue® (Bracco, Milan, Italy) at a standard dose of 2.4 mL, followed by 10 mL of 0.9% saline solution. The examinations were performed using multifrequency transducers and low mechanical index. We considered aneurysmal a focal dilatation of the portal venous system with a size that was significantly greater than the remaining segments of the same vein, and that was equal or larger than 21 mm for the extrahepatic segments of portal venous system, main portal vein and bifurcation, and 9 mm for the intrahepatic branches.
RESULTS: After contrast agent injection, all PVSAs were not enhanced in the arterial phase (starting 8-22 s). All PVSAs were then rapidly enhanced in the early portal venous phase (starting three to five seconds after the arterial phase, 11-30 s), with persistence and slow washout of the contrast agent in the late phase (starting 120 s). In all patients, CEUS confirmed the presence of a “to-and-fro” flow by showing a swirling pattern within the dilatation in the early portal venous phase. CEUS also improved the delineation of the lumen, and was reliable in showing its patency degree and integrity of walls. In one patient, CEUS showed a partial enhancement of the lumen with a uniformly nonenhancing area in the portal venous and late phases, suggesting thrombosis.
CONCLUSION: In our case series, we found that CEUS could be useful in the assessment and follow-up of a PVSA. Further studies are needed to validate its diagnostic accuracy.
Venous system; Portal vein; Aneurysm; Contrast-enhanced ultrasound; Computed tomography; Magnetic resonance imaging
The purposes of this paper were to present the current status of contrast-enhanced transrectal ultrasound imaging and to discuss the latest achievements and techniques now under preclinical testing.
Although grayscale transrectal ultrasound is the standard method for prostate imaging, it lacks accuracy in the detection and localization of prostate cancer. With the introduction of contrast-enhanced ultrasound (CEUS), perfusion imaging of the microvascularization became available. By this, cancer-induced neovascularisation can be visualized with the potential to improve ultrasound imaging for prostate cancer detection and localization significantly. For example, several studies have shown that CEUS-guided biopsies have the same or higher PCa detection rate compared with systematic biopsies with less biopsies needed.
Materials and methods
This paper describes the current status of CEUS and discusses novel quantification techniques that can improve the accuracy even further. Furthermore, quantification might decrease the user-dependency, opening the door to use in the routine clinical environment. A new generation of targeted microbubbles is now under pre-clinical testing and showed avidly binding to VEGFR-2, a receptor up-regulated in prostate cancer due to angiogenesis. The first publications regarding a targeted microbubble ready for human use will be discussed.
Ultrasound-assisted drug delivery gives rise to a whole new set of therapeutic options, also for prostate cancer. A major breakthrough in the future can be expected from the clinical use of targeted microbubbles for drug delivery for prostate cancer diagnosis as well as treatment.
Contrast-enhanced ultrasound; Prostate cancer; TRUS; Targeted microbubbles; Quantification
Purpose. Bladder cancer is a frequent cause of haematuria in elderly patients, and bladder ultrasound (US) is a valuable tool in diagnosing these malignancies. We examined the accuracy of 3D bladder US in diagnosing bladder tumors in patients with haematuria. Patients and Methods. Twenty-one patients observed in the emergency department for haematuria underwent a kidney and bladder US. Patients with normal or uncertain bladder US findings underwent a 3D US and a cystoscopy. Results. In 5 (23.8%) patients, the 3D US detected bladder tumours not seen in 2D US. All these patients were found to have bladder tumours on cystoscopy. Another 5 (23.8%) patients with uncertain findings on 2D US had normal 3D US and cystoscopy. 3D US showed a sensitivity of 83.3% and a specificity of 100% with a positive predicted value and negative predictive values of 100% and 93.8%, respectively. Conclusion. 3D US was more sensitive than 2D US in diagnosing bladder tumours in patients with haematuria.
To assess the usefulness of contrast–enhanced ultrasound (CEUS) in differentiating malignant from benign gallbladder (GB) diseases.
This study had institutional review board approval. 192 patients with GB diseases from 9 university hospitals were studied. After intravenous bonus injection of a phospholipid-stabilized shell microbubble contrast agent, lesions were scanned with low acoustic power CEUS. A multiple logistic regression analysis was performed to identify diagnostic clues from 17 independent variables that enabled differentiation between malignant and benign GB diseases. Receiver operating characteristic (ROC) curve analysis was performed.
Among the 17 independent variables, multiple logistic regression analysis showed that the following 4 independent variables were associated with the benign nature of the GB diseases, including the patient age, intralesional blood vessel depicted on CEUS, contrast washout time, and wall intactness depicted on CEUS (all P<0.05). ROC analysis showed that the patient age, intralesional vessels on CEUS, and the intactness of the GB wall depicted on CEUS yielded an area under the ROC curve (Az) greater than 0.8 in each and Az for the combination of the 4 significant independent variables was 0.915 [95% confidence interval (CI): 0.857–0.974]. The corresponding Az, sensitivity, and specificity for the age were 0.805 (95% CI: 0.746–0.863), 92.2%%, and 59.6%; for the intralesional vessels on CEUS were 0.813 (95% CI: 0.751–0.875), 59.8%, and 98.0%; and for the GB wall intactness were 0.857 (95% CI: 0.786–0.928), 78.4%, and 92.9%. The cut-off values for benign GB diseases were patient age <53.5 yrs, dotted intralesional vessels on CEUS and intact GB wall on CEUS.
CEUS is valuable in differentiating malignant from benign GB diseases. Branched or linear intralesional vessels and destruction of GB wall on CEUS are the CEUS features highly suggestive of GB malignancy and the patient age >53.5 yrs is also a clue for GB malignancy.
Bladder cancer presents as a spectrum of different diatheses. Accurate assessment for individualized treatment depends on initial diagnostic accuracy. Detection relies on white light cystoscopy accuracy and comprehensiveness. Aside from invasiveness and potential risks, white light cystoscopy shortcomings include difficult flat lesion detection, precise tumor delineation to enable complete resection, inflammation and malignancy differentiation, and grade and stage determination. Each shortcoming depends on surgeon ability and experience with the technology available for visualization and resection. Fluorescence cystoscopy/photodynamic diagnosis, narrow band imaging, confocal laser endomicroscopy and optical coherence tomography address the limitations and have in vivo feasibility. They detect suspicious lesions (photodynamic diagnosis and narrow band imaging) and further characterize lesions (optical coherence tomography and confocal laser endomicroscopy). We analyzed the added value of each technology beyond white light cystoscopy and evaluated their maturity to alter the cancer course.
Materials and Methods
Detailed PubMed® searches were done using the terms “fluorescence cystoscopy,” “photodynamic diagnosis,” “narrow band imaging,” “optical coherence tomography” and “confocal laser endomicroscopy” with “optical imaging,” “bladder cancer” and “urothelial carcinoma.” Diagnostic accuracy reports and all prospective studies were selected for analysis. We explored technological principles, preclinical and clinical evidence supporting nonmuscle invasive bladder cancer detection and characterization, and whether improved sensitivity vs specificity translates into improved correlation of diagnostic accuracy with recurrence and progression. Emerging preclinical technologies with potential application were reviewed.
Photodynamic diagnosis and narrow band imaging improve nonmuscle invasive bladder cancer detection, including carcinoma in situ. Photodynamic diagnosis identifies more papillary lesions than white light cystoscopy, enabling more complete resection and fewer residual tumors. Despite improved treatment current data on photodynamic diagnosis do not support improved high risk diathetic detection and characterization or correlation with disease progression. Prospective recurrence data are lacking on narrow band imaging. Confocal laser endomicroscopy and optical coherence tomography potentially grade and stage lesions but data are lacking on diagnostic accuracy. Several emerging preclinical technologies may enhance the diagnostic capability of endoscopic imaging.
New optical imaging technologies may improve bladder cancer detection and characterization, and transurethral resection quality. While data on photodynamic diagnosis are strongest, the clinical effectiveness of these technologies is not proven. Prospective studies are needed, particularly of narrow band imaging, confocal laser endomicroscopy and optical coherence tomography. As each technology matures and new ones emerge, cost-effectiveness analysis must be addressed in the context of the various bladder cancer types.
urinary bladder neoplasms; fluorescence; cystoscopy; lasers; tomography; optical coherence
AIM: To assess the value of contrast-enhanced ultrasound (CEUS) in diagnosing splenic artery complications (SACs) after acute pancreatitis (AP).
METHODS: One hundred and eighteen patients with AP were enrolled in the study. All patients were examined by CEUS and contrast-enhanced computed tomography (CECT). CECT was accepted as a gold standard for the diagnosis of SACs in AP. The diagnostic accuracy of splenic CEUS and pancreatic CEUS was compared with that of CECT. Splenic infarction was the diagnostic criterion for splenic artery embolism and local dysperfusion of the splenic parenchyma was the diagnostic criterion for splenic arterial stenosis. The incidence of splenic sub-capsular hemorrhage, splenic artery aneurysms, and splenic rupture was all lower than that of SACs.
RESULTS: Nine patients were diagnosed as having SACs after AP by CECT among the 118 patients. The patients with SACs were diagnosed with severe acute pancreatitis (SAP). Among them, 6 lesions were diagnosed as splenic artery embolism, 5 as splenic artery aneurysms, and 1 as splenic arterial stenosis. No lesion was diagnosed by pancreatic CEUS and 5 lesions were diagnosed by splenic CEUS. By splenic CEUS, 4 cases were diagnosed as splenic artery embolism and 1 as splenic arterial stenosis. The accuracy of splenic CEUS in diagnosis of SACs in SAP was 41.7% (5/12), which was higher than that of pancreatic CEUS (0%).
CONCLUSION: Splenic CEUS is a supplementary method for pancreatic CEUS in AP patients, which can decrease missed diagnosis of SACs.
Acute pancreatitis; Severe acute pancreatitis; Contrast enhanced ultrasound; Splenic artery complications; Splenic contrast-enhanced computed tomography
Hepatocellular carcinoma (HCC) is the leading cause of death amongst cirrhotic patients. Its diagnosis and discrimination from non-HCC malignant lesions in cirrhosis includes contrast enhanced computed tomography (CECT), contrast enhanced magnetic resonance imaging (CEMRI), or, in selected cases, liver biopsy. The role of contrast-enhanced ultrasonography (CEUS) is still controversial.
To evaluate whether, by selecting an appropriate ‘time to wash-out’ cut-off value, CEUS capability of discriminating between HCC and non-HCC malignancies in cirrhotic patients may be enhanced.
We enrolled 282 cirrhotic patients who underwent CEUS at our institute, from January 2008 to January 2012, for focal liver lesions (FLLs) detected at ultrasound (US). We used liver biopsy and subsequent histological evaluation as the gold standard for correct classification of FLLs. We calculated the area under receiver operator characteristic curves for CEUS to distinguish patients with HCC from those with non-HCC malignancies. The best ‘time to wash-out’ cut-off values were selected.
Histological diagnosis of FLLs was as follows: 34 benign lesions (i.e. 25 regenerative nodules and 9 dysplastic nodules) and 248 malignant lesions (223 well-to-moderately differentiated HCCs; 7 poorly-differentiated HCCs; 5 intrahepatic colangiocellular carcinomas (ICCs); 5 primary non-Hodgkin B-cell lymphomas (NHBLs); and 8 metastatic liver tumors). A time to wash-out > 55 s identified patients with HCC with the highest level of accuracy (92.7%). Similarly, a time to wash-out ≤ 55 s correctly identified the vast majority of the non-HCC malignancies (100% sensitivity, 98.2% specificity and diagnostic accuracy of 98.3%).
CEUS is an accurate and safe procedure for discriminating FLLs in cirrhotic patients, especially when a cut-off time to wash-out of 55 s is chosen as a reference value.
Biopsy; cirrhosis; cholangiocellular carcinoma; contrast enhancement; focal liver lesions; hepatocellular carcinoma; liver; ultrasound
AIM: To evaluate whether contrast enhanced ultrasound (CEUS) might also be used for response prediction and early response evaluation in patients receiving bevacizumab based chemotherapy for metastasized colorectal cancer.
METHODS: Thirty consecutive patients with non primary resectable liver metastases from colorectal cancer underwent CEUS before treatment (CEUS date 1) and before the second (CEUS date 2) and fourth (CEUS date 3) cycle of bevacizumab based chemotherapy. Three parameters [PEAK, Time to peak (TTP) and RISE RATE]were correlated with radiological response.
RESULTS: For neoadjuvant purpose a reduction of tumour mass was required to assume clinical response. Based on these response criteria there was a significant (P < 0.001) correlation in TTP between metastases of responders (9.08 s) and non-responders (14.76 s) archived on CEUS date 1. By calculating a standardized quotient (metastases divided by normal liver tissue) we were able to define a cut off, predicting response with a sensitivity of 92.3 % and a specificity of 100 %. To reflect a palliative intention only those patients with progressive disease were classified as non-responders. In this stetting TTP was also significantly (P < 0.01) different between responders and non-responders. In contrast, Peak and Rise rate did not show any significant difference between responder and non-responder.
CONCLUSION: CEUS might serve as a surrogate marker to predict treatment response in patients with metastasized colorectal cancer who receive antiangiogenic therapy.
Colorectal cancer; Liver metastases; Response prediction to chemotherapy; Contrast-enhanced ultrasound; Bevacizumab