Use of New Ultrasonography Methods for Detecting Neoplasms in Dogs and Cats: A Review.

The aim of this literature review was to present the novel imaging modalities elastography and contrast-enhanced ultrasonography. We provided an overview of the concepts and applications of each technique for the investigation of neoplastic and metastatic tumors in dogs and cats. Studies on elastography are based on the elasticity and deformation of the evaluated tissue. The information obtained from the different types of elastography can aid in the detection and differentiation of malignant and benign structures. Descriptions of elastography studies in several organs and tissue in veterinary medicine reported that, in general, malignant tumors tend to be more rigid and, therefore, less deformable than benign lesions or in comparison to the healthy parenchyma. Contrast-enhanced ultrasonography is based on the intravenous injection of contrast media constituted by microbubbles. This imaging modality can be performed in nonsedated animals and provides information on the tissue perfusion, allowing the investigation of macro- and micro-circulation. Studies on different organs and tissues were performed in dogs and cats and revealed a tendency of malignant tumors to present faster transit of the contrast media (time to wash-in, peak and wash-out). These advanced techniques can be associated with other imaging modalities, aiding important information to the well-established exams of B-mode and Doppler ultrasonography. They can be used as screening tests, potentially representing an alternative to the invasive sampling methods required for cytological and histopathological analysis.

Contrast-enhanced ultrasonography for the evaluation of malignant focal liver lesions.

In this review, the authors address the analysis of different types of malignant focal liver lesions (FLLs) using contrast-enhanced ultrasonography (CEUS). The specific enhancing patterns of hepatocellular carcinoma, cholangiocarcinoma, and metastases are discussed and exemplified with images. In addition, the use of CEUS in malignant portal vein thrombosis is discussed. The advantages and limitations of CEUS for the analysis of malignant FLLs are also discussed.

Can we replace computed tomography angiography by contrast-enhanced ultrasound in the surveillance of patients submitted to aortoiliac aneurysm repair?

OBJECTIVES: This study was designed for evaluation of CEUS (contrast-enhanced ultrasound) for the detection of endoleaks after EVAR (endovascular aortic aneurysms repair) as an alternative to CTA (computed tomography angiography), the gold standard in post-EVAR surveillance. METHODS: Post-EVAR surveillance of patients who underwent CEUS and CTA was retrospectively analyzed to compare the accuracy of CEUS compared to CTA. For that, the following parameters were analyzed: the largest aneurysm diameter, type of endoleaks, and the time elapsed after EVAR using both surveillance tests. RESULTS: The study involved 110 pairs of exams in patients with infrarenal aortoiliac or isolated iliac artery aneurysm, covering predominantly a male population (89%). The time elapsed after EVAR using CEUS or CTA exams were statistically similar, ranging from one to 58 months (mean 12.2) and one to 65 months (mean 9.7), respectively (p = 0.124). CEUS sensitivity was 75.5%, specificity 96.7%, false positives were 24.5%, and false negatives were 3.3%. The accuracy between the two exams was 87.3%. A secondary analysis, comparing CTA with CEUS as a reference standard, revealed CEUS sensitivity of 24.5%, higher than CTA for detecting endoleaks, with a concordance rate of true positive results of 75.5%. Among the endoleaks detected solely by CEUS (12 cases), one case was type Ia and eleven were type II, while those detected only by CTA (2 cases), one was type Ia and one type II. Additionally, a type II endoleak associated with type Ib, identified by CEUS, was seen as type II for CTA only. There was no difference between the pre-EVAR and the post-EVAR diameters of aortoiliac aneurysm (p = 0.058), both for CEUS and CTA. Computed tomography angiography, on the other hand, showed significant aneurysm diameter reduction compared to CEUS for isolated iliac artery aneurysms (p < 0.001). CONCLUSION: Contrast-enhanced ultrasound was more effective than CTA in identifying and characterizing endoleaks in patients undergoing EVAR, especially type II endoleaks. The advantages include efficacy and, particularly, safety, and must be considered in EVAR surveillance protocols so that its use becomes widespread. We understand that CEUS, as a surveillance exam, considerably reduces risks to patients compared to CTA.

Feasibility and Safety of Contrast-Enhanced Ultrasound of the Neonatal Brain: A Prospective Study Using MRI as the Reference Standard.

BACKGROUND. MRI is the reference standard for neonatal brain imaging, but it is expensive, time-consuming, potentially limited by availability and accessibility, and contraindicated in some patients. Transfontanelle neonatal head ultrasound is an excellent alternative but may be less sensitive and specific than MRI. Contrast-enhanced ultrasound (CEUS) has the potential to improve the capabilities of ultrasound. OBJECTIVE. The purpose of this study is to prospectively evaluate the feasibility, safety, and diagnostic performance of transfontanelle neonatal brain CEUS, with MRI used as the reference standard. METHODS. Neonates in the institutional neonatal ICU who were undergoing MRI as part of their clinical care were prospectively recruited to undergo portable brain ultrasound and CEUS for research purposes. Brain ultrasound and CEUS were performed portably without moving the patient from the isolette or crib in the neonatal ICU. Adverse events were recorded. Two radiologists independently evaluated ultrasound and CEUS images for abnormalities and then reached consensus regarding discrepancies. A separate radiologist reviewed MRI examinations. Sensitivity, specificity, and interreader agreement were evaluated, with MRI used as the reference. Qualitative post hoc image review was performed. RESULTS. Twenty-six neonates (nine boys and 17 girls; mean [± SD] age, 15.2 ± 14.0 days) were included. No significant alteration in patient vital signs or adverse reaction to the ultrasound contrast agent (UCA) occurred. The mean duration of the examination was significantly shorter for combined ultrasound and CEUS than for MRI (21.1 ± 4.7 vs 74.2 ± 34.8 minutes; p < .001). Interrater agreement for any abnormality was almost perfect for both ultrasound and CEUS (κ = 0.92 and 0.85, respectively). Sensitivity for any abnormality was 86.7% for ultrasound and 93.3% for CEUS; specificity was 100.0% for both. CEUS had sensitivity of 87.5% for acute or subacute ischemia and 100.0% for chronic ischemia; its specificity was 100.0% for acute or subacute ischemia and chronic ischemia. For both ultrasound and CEUS, sensitivity for subdural and intraparenchymal hemorrhage was poor (22.2-50.0%). On CEUS but not on MRI, post hoc review showed a case of postischemic hyperperfusion, which was confirmed by subsequently performed contrast-enhanced CT. CONCLUSION. The use of portable brain CEUS in neonates is feasible, safe, and more rapid than MRI. CLINICAL IMPACT. The potential diagnostic utility of brain neonatal CEUS relative to conventional ultrasound, particularly for ischemia, warrants further investigation.

Correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value.

PURPOSE: To analyze the correlation between contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value. METHODS: In this study, 64 patients with axillary lymph node metastasis of primary breast cancer diagnosed and treated in our hospital from February 2011 to March 2013 were collected as an observation group, and 54 patients without axillary lymph node metastasis were collected as a control group. All patients underwent a contrast-enhanced ultrasound examination, and the correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis and its diagnostic value were analyzed. They were divided into two groups according to their survival conditions: the group with good efficacy and group with poor efficacy, and the prognostic factors of breast cancer in the two groups were analyzed. RESULTS: There were statistical differences in the peripheral acoustic halo, blood flow classification, ratio of length to diameter (L/D), maximum cortical thickness, and enhancement mode of lymph nodes between the two groups (p < 0.05). The area under ROC curve for diagnosis of axillary lymph node metastasis by contrast-enhanced ultrasound was 0.854, sensitivity was 83.33%, and specificity was 87.5%; L/D and enhancement mode were independent prognostic factors for breast cancer. CONCLUSIONS: Contrast-enhanced ultrasound image features have diagnostic and prognostic value for axillary lymph node metastasis of breast cancer.

Contrast-Enhanced Ultrasound of Congenital and Infantile Hemangiomas: Preliminary Results From a Case Series.

OBJECTIVE. The contrast-enhanced ultrasound (CEUS) imaging features of hepatic vascular tumors in infants, including infantile hemangioma (IH) and congenital hemangioma (CH), are not well reported. Frequent inaccurate use of lesion terminology in the literature has created diagnostic confusion. The purpose of this study is to describe the CEUS features of IH and CH. MATERIALS AND METHODS. Ten patients, ranging in age from 8 days to 16 months, with hepatic vascular tumors were included for retrospective analysis. Gray-scale ultrasound, color Doppler ultrasound, and CEUS features were reviewed, and interobserver kappa coefficients were calculated. Final diagnoses were clinically determined by a pediatrician with expertise in vascular anomalies except in one patient who underwent surgical excision. RESULTS. Of the 10 patients, five had CHs and five had IHs. All 10 lesions were hyperenhancing in the early arterial phase. In the portal venous phase, four of five (80%) CHs showed hyperenhancement relative to normal liver parenchyma, whereas four of five (80%) IHs showed isoenhancement. In the late phase, washout of contrast material was seen in three of five (60%) IHs, whereas one IH remained isoenhancing and one IH was hyperenhancing. None of the CHs showed late washout. Interobserver kappa coefficients for CEUS features ranged from 0.60 to 1.00. CONCLUSION. Except for the CEUS feature portal venous phase enhancement (κ = 0.60), good to excellent (κ = 0.74-1.00) agreement about CEUS features of IHs and CHs was observed. A significant proportion of IHs (60%) showed washout at delayed phase imaging, which has also been reported with malignancies. Recognition of the overlap in imaging appearance of these two entities is vital to preventing misdiagnosis of malignancy.

Untargeted contrast-enhanced ultrasound versus contrast-enhanced computed tomography: a differential diagnostic performance (DDP) study for kidney lesions

OBJECTIVES: Histopathology is the 'gold standard' for diagnosing renal cell carcinoma but is limited by sample size. Contrast-enhanced ultrasound can differentiate malignant and benign lesions, but the Chinese guidelines on the management of renal cell carcinoma do not include this method. The purpose of this study was to compare the diagnostic parameters of contrast-enhanced ultrasound against those of contrast-enhanced computed tomography for detecting kidney lesions, with histopathology considered the reference standard. METHODS: Patients with suspected kidney lesions from prior grayscale ultrasonography and computed tomography were included in the analysis (n=191). The contrast-enhanced ultrasound, contrast-enhanced computed tomography, and histopathology data were collected and analyzed. A solid, enhanced mass was considered a malignant lesion, and an unenhanced mass or cyst was considered a benign lesion. The Bosniak criteria were used to characterize the lesions. RESULTS: Contrast-enhanced ultrasound and contrast-enhanced computed tomography both detected that 151 patients had malignant tumors and 40 patients had benign tumors. No significant differences in the tumors and their subtypes were reported between contrast-enhanced ultrasound and histopathology (p=0.804). Chromophobe renal cell carcinoma was detected through contrast-enhanced computed tomography (n=1), but no such finding was reported by contrast-enhanced ultrasound. A total of 35 cases of papillary renal cell carcinoma were reported through contrast-enhanced ultrasound while 32 were reported through histopathology. CONCLUSIONS: Contrast-enhanced ultrasound might be safe and as accurate as histopathology in diagnosing kidney lesions, especially renal cell carcinoma. Additionally, this study provides additional information over histopathology and has an excellent safety profile. Level of evidence: III.

Perinodal fibrosis developed after ultrasonography-guided core-needle biopsy of a contrast-enhanced ultrasound-detected sentinel axillary node interferes with subsequent surgical sentinel node dissection.

OBJECTIVE: To evaluate perinodal fibrosis after 14-gauge staging core-needle biopsy (CNB) of the axillary sentinel lymph node (SLN) identified using contrast-enhanced ultrasonography (CEUS) and its interference with subsequent surgical SLN dissection in breast cancer patients. METHODS: Frequencies or means of main clinical, sonographic, pathological, and surgical characteristics were calculated. We also compared patient groups with and without perinodal pathological fibrosis. RESULTS: Forty-eight patients who underwent CEUS + CNB and axillary surgery were eligible for this cross-sectional study. Axillary surgical specimens showed perinodal fibrosis in 9/48 (18.7%) patients. Interference with SLN dissection was reported in 4/48 (8.3%) patients (two hematomas, three abnormal palpation findings, and four difficult dissections). The overall surgical detection rate of SLN was 43/48 (89.6%). In the majority of cases, perinodal fibrosis was described as moderate (4/9 [44.4%]) or severe (4/9 [44.4%]). The mean time elapsed between CEUS + CNB and axillary dissection was shorter in patients with perinodal fibrosis (P = .04). Interference with SLN dissection was only reported in patients with perinodal fibrosis (P < .001). Surgical SLN detection was successful in all nine cases in which perinodal pathological fibrosis or interference with SLN dissection was reported. CONCLUSION: Perinodal fibrosis may impair the surgical SLN dissection in early stage breast cancer patients who were staged using CEUS + CNB using a14-gauge needle.

Characterization of Malignant Portal Vein Thrombosis with Contrast-Enhanced Ultrasonography.

We prospectively evaluated the effectiveness of contrast-enhanced ultrasonography (CEUS) for differentiation of benign versus malignant portal vein thrombosis (PVT). We studied a total of 43 patients with chronic liver disease, hepatocellular carcinoma-suggestive nodules and confirmed PVT, in whom the nature of the PVT was confirmed by follow-up imaging (US, computed tomography and/or magnetic resonance imaging) performed up to 6 mo after CEUS. PVT was assessed by US, Doppler US and CEUS with respect to vessel wall disruption and/or invasion, color Doppler vascularization, pulsed Doppler vascularization pattern and CEUS enhancement and vascularization pattern, and thrombi were classified as benign or malignant based on these findings. Follow-up studies revealed malignant PVT in 22 of the 43 patients (51%) and benign PVT in 21 patients (49%). CEUS findings were consistent with follow-up studies in 41 of the 43 patients (95%), with κ = 0.903 (p < 0.0001), sensitivity = 91% and specificity = 100%, indicating that CEUS can be confidently used to differentiate benign from malignant portal vein thrombosis in the setting of chronic liver disease.

Accuracy of four ultrasonography techniques in predicting histopathological classification of canine mammary carcinomas.

Due to the importance of presurgical, noninvasive, and accurate diagnostic tools in mammary carcinoma characterization, this prospective secondary observational cohort study was designed to evaluate and compare the diagnostic accuracy of B-mode, Doppler, contrast enhancement ultrasonography, or acoustic radiation force impulse-elastography in identifying mammary carcinomas types with high degree of malignancy. A total of 246 mammary carcinomas from 141 female dogs were analyzed using B-mode, Doppler, contrast enhancement ultrasonography, and acoustic radiation force impulse ultrasonography prior to their histopathological classification according to types (simple, complex, or special) and grade (I, II, or III). Qualitative and quantitative variables were compared between carcinoma types and grades by Fisher's or analysis of variance. Diagnostic performance was estimated by receiver-operating characteristic analysis, using histopathological classification as a reference. Deformability (acoustic radiation force impulse) had a diagnostic specificity of 100% and sensitivity of 12% in identifying special carcinomas. A width:length ratio greater than 0.53 can be suggestive of special carcinoma, with 80% sensitivity and 76% specificity. Contrast wash-in and peak enhancement times lower than 7.5 and 13.5 s, respectively, were indicative of complex carcinoma at 62% sensitivity and 60% specificity. Contrast wash-in, peak enhancement, and wash-out times greater than 6.5, 12.5, and 64.5 s, respectively; were indicative of grade II and III carcinoma at 68% sensitivity and 62% specificity. In conclusion, B-mode ultrasonography, contrast enhancement ultrasonography, and acoustic radiation force impulse-elastography enabled the identification of some of the characteristics of high-grade mammary carcinoma types and grades in female dogs with limited accuracy. The findings from this study may contribute to oncology research and clinical management canine patients.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Advantages of contrast-enhanced ultrasonography over computed tomography for the detection of persistent type II endoleak after embolization: A case report.

The aim of this case report is to describe the use of contrast-enhanced ultrasonography in the detection of a type II endoleak after prior embolization with Onyx. A 74-year-old male patient with hypertension previously underwent endovascular repair of a 7.1-cm infrarenal aortic aneurysm. CT angiography surveillance revealed a type II endoleak associated with aneurysm sac expansion. Selective transarterial embolization of the endoleak was performed, but it was not possible to detect the persistent endoleak using CT angiography because of image artifacts caused by Onyx. Contrast-enhanced ultrasonography enabled us to detect the persistent endoleak in this patient. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:522-526, 2016.

Yield of Contrast-Enhanced Power Doppler Endoscopic Ultrasonography and Strain Ratio Obtained by EUS-Elastography in the Diagnosis of Focal Pancreatic Solid Lesions.

OBJECTIVE: Although endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is the gold standard for diagnosing pancreatic lesions, its negative predictive value is suboptimal. Our aim was to evaluate the yield of contrast-enhanced EUS (CED-EUS) and of strain ratio EUS-elastography (SR-E-EUS) for differentiating pancreatic solid lesions. METHODS: Forty-seven patients (27 men, 20 women, 70 ± 11 years) were consecutively involved in this single-center, prospective study. They were submitted to EUS, SR-E-EUS, CED-EUS with Sonovue(®), and EUS-FNA. The final diagnosis was based on the histological assessment of EUS-FNA and/or surgical specimens when available, and on follow-up of at least 6 months. RESULTS: From the 47 focal pancreatic lesions included, 13 (28%) were benign and 34 (72%) malignant. Patients with malignancy were older (70 ± 11 vs. 61 ± 8, P = 0.003), and had larger lesions (34 ± 12 mm vs. 22 ± 11 mm, P = 0.03). Malignant lesions had higher SR-E-EUS (31 ± 32 vs. 8 ± 9, P = 0.001) and more hypovascular pattern (93% vs. 33%, P < 0.001). Logistic regression determined that only hypovascularity (OR = 2.6, 95%CI: 1.5-130, P = 0.02) was independently predictive of malignancy. ROC analysis for SR-E-EUS yielded an optimal cutoff of 8 (AUC 0.91, 95%CI: 0.74-0.98) for the best power distinction for malignancy. There was no significant difference concerning sensitivity (79%, 90%, 93%) and specificity rates (85%, 75%, 67%) of EUS-FNA, SR-E-EUS, and CED-EUS, respectively. By analysis of the inconclusive EUS-FNA subset (9 patients, 19%), SR-E-EUS > 8 and hypovascularity showed sensitivity of 80% and 100%, and specificity of 67% and 67%, respectively. CONCLUSION: The clinical utility of CED-EUS and SR-E-EUS remains questionable. The accuracies of CED-EUS and SR-E-EUS are similar to EUS-FNA. Hypovascularity was independently predictive of malignancy. Patients with inconclusive EUS-FNA could benefit from CED-EUS due to the high sensitivity of hypovascularity for diagnosing malignancy.