Late-phase pulse-inversion sonography using the contrast agent levovist: differentiation between benign and malignant focal lesions of the liver

OBJECTIVE: We assessed the ability of contrast-enhanced sonography to reveal differences between benign and malignant focal hepatic lesions. SUBJECTS AND METHODS: We examined 67 patients with focal hepatic lesions in a prospective study. The causes of the lesions were confirmed by histology, CT, MR imaging, or scintigraphy. The liver was screened for focal lesions using sonography. Thereafter, 2 g of Levovist (300 mg/mL; 1 mL/sec) was injected IV as a bolus. After a delay of at least 2.5 min without scanning, the liver was examined via three different scans using pulse-inversion sonography. RESULTS: For the discrimination of malignant versus benign liver lesions, contrast-enhanced sonography improved sensitivity from 85% to 100% and specificity from 30% to 63%, as compared with baseline sonography. Receiver operating characteristic analysis revealed a significant improvement in this discrimination (A(z) = 0.692 +/- 0.065 at baseline sonography, A(z) = 0.947 +/- 0.037 with contrast-enhanced sonography, p < 0.001). Furthermore, a lower interobserver variability was found for contrast-enhanced sonography (weighted kappa = 0.947), as compared with baseline sonography (weighted kappa = 0.469). All lesions that had homogeneous enhancement in the late phase of Levovist enhancement were benign. In distinction, 90% of lesions without contrast enhancement in the late phase were malignant. All lesions were malignant that were isoechoic (invisible) on baseline sonography but visible because of lack of enhancement after injection. CONCLUSION: Contrast-enhanced sonography has greater specificity and sensitivity than baseline sonography for the differentiation of benign and malignant liver lesions.     

Characterization of focal liver lesions with a new ultrasound contrast agent using continuous low acoustic power imaging: comparison with contrast enhanced spiral CT

PURPOSE: To evaluate the concordance of the enhancement patterns of a new ultrasound contrast agent (SonoVue) with those obtained with dual-phase contrast-enhanced spiral CT (CE-CT) in the characterization of focal liver lesions (FLLs). MATERIALS AND METHODS: Sixty-two patients with focal liver lesions discovered at ultrasound and also studied with CECT underwent contrast-enhanced ultrasound using continuous low acoustic power imaging after receiving a 2.4 ml bolus of the new US contrast agent SonoVue, consisting of a dispersion of sulphur hexafluoride microbubbles. The examinations were made using ATL HDI-5000, Acuson SEQUOIA and Aloka 5500 Prosound ultrasound systems with 5.2 MHz curved-array probes. The concordance between US and CE-CT images was evaluated on site by two radiologists blinded to CT RESULTS: The FLLs were assessed in the arterial (20 s after CM injection), portal (after 45-60 s) and late (after 120 s) phases for: 1) presence/absence of enhancement 2) distribution of enhancement (homogenous or target distribution, centripetal or centrifugal flow, and other), 3) qualitative enhancement pattern (hyperechoic, hypoechoic, or isoechoic) versus normal liver parenchyma. RESULTS: The concordance between SonoVue-enhanced US and CE-CT was 85%. Moreover during portal venous phase with CEUS it was possible to differentiate between malignancy or benignity of 91% of lesions. CONCLUSIONS: The preliminary data obtained in this study suggest that continuous low acoustic power imaging and contrast-enhanced US show similar results to CT in contrast distribution and contrast enhancement patterns.     

Characterization of focal liver lesions with contrast-specific US modes and a sulfur hexafluoride-filled microbubble contrast agent: diagnostic performance and confidence

PURPOSE: To assess whether characterization of solid focal liver lesions could be improved by using ultrasonographic (US) contrast-specific modes after sulfur hexafluoride-filled microbubble contrast agent injection, as compared with lesion characterization achieved with preliminary baseline US. MATERIALS AND METHODS: Four hundred fifty-two solid focal hepatic lesions that were considered indeterminate at baseline gray-scale and color Doppler US were examined after microbubble contrast agent injection performed by using low-acoustic-power contrast-specific modes during the arterial (10-40 seconds after injection), portal venous (50-90 seconds after injection), and late (100-300 seconds after injection) phases. Two readers independently and retrospectively reviewed baseline and contrast material-enhanced US scans and classified each depicted lesion as malignant or benign according to standard diagnostic criteria. Sensitivity, specificity, accuracy, and positive and negative predictive values and areas under the receiver operating characteristic curve (Az) were calculated by considering histologic analysis (317 patients) or contrast-enhanced helical computed tomography followed by serial US 3-6 months apart (135 patients) as the reference standards. RESULTS: Different contrast enhancement patterns were observed according to lesion characteristics. During the late phase, benign lesions were predominantly hyper- or isoechoic relative to the adjacent liver parenchyma, whereas malignant lesions were predominantly hypoechoic. Review of the contrast-enhanced US scans after baseline image review yielded significantly improved diagnostic performance (P <.05). Overall diagnostic accuracy was 49% before versus 85% after review of the contrast-enhanced scan for reader 1 and 51% before versus 88% after review of the contrast-enhanced scan for reader 2. Diagnostic confidence-that is, the Az-was 0.820 before versus 0.968 after review of the contrast-enhanced scan for reader 1 and 0.831 before versus 0.978 after review of the contrast-enhanced scan for reader 2. CONCLUSION: The use of contrast-specific modes with a sulfur hexafluoride contrast agent led to improved characterization of solid focal liver lesions.     

Characterization of renal tumours with pulse inversion harmonic imaging by intermittent high mechanical index technique: initial results

Our objective was to evaluate whether contrast-specific ultrasound (US) technique pulse inversion harmonic imaging (PIHI) with Levovist could reveal differential morphological features in solid and cystic renal masses. Twenty-six renal masses in 26 patients were evaluated by PIHI after Levovist injection with intermittent high mechanical index stimulation, performed every 10–15 s during arterial and delayed phase. Helical CT (HCT; n=6) or histological findings on surgical/bioptic specimen (n=20) were considered as the reference procedures for definitive diagnosis. Eleven solid renal cell carcinomas (RCCs), 1 embryonal matanephric adenoma (EMA), 7 angiomyolipomas (AMLs), 4 cystic RCCs and 3 complex inflammatory cysts were identified. Solid RCCs revealed a much higher (p<0.05) contrast enhancement than AMLs with typical pattern on conventional US (n=6). The EMA and AML with atypical pattern on conventional US (n=1) revealed intense contrast enhancement during arterial phase, progressively decreasing during delayed phase. Cystic RCCs and complex inflammatory cysts revealed intense contrast enhancement on the peripheral thick wall during arterial phase decreasing on delayed phase. The PIHI has been shown to differentiate solid RCC from typical AML by contrast enhancement assessment after Levovist injection, but differential diagnosis both in solid and in cystic renal masses still remains difficult. Electronic Publication     

Characterisation of focal liver lesions with unenhanced and contrast enhanced low MI real time ultrasound: on-site unblinded versus off-site blinded reading

Objective

To compare on-site and blinded off-site reading of baseline ultrasound (US) and contrast enhanced ultrasound (CEUS) for classification and characterisation of focal liver lesions.

Materials and methods

99 patients (57 women and 42 men, age range 18–89 years, mean age: 59 years) with 53 malignant and 46 benign liver lesions were studied with unenhanced US followed by contrast enhanced US after injection of 2.4 ml SonoVue^® (Bracco, Milano, Italy). Image interpretation was performed on-site with clinical information available by consensus of two readers and off-site by two independent blinded readers at two different centers. Comparison of pre and post contrast scans and of the different readers was performed. Reference examinations were histology, intraoperative US, MRI or CT.

Results

Sensitivity for malignancy improved from 81/89/66% (on-site/off-site reader 1/2) before to 100/96/96% post contrast administration (p < 0.05, except for reader 1). Specificity improved from 48/48/54% on baseline US to 89/80/76% on CEUS (p < 0.05). Accuracy for specific lesion diagnosis was 62/59/50% pre and 90/77/72% post contrast (p < 0.05). Classification and characterisation post contrast were mildly inferior for off-site reading. Agreement between on-site and off-site readers of unenhanced scans was fair (κ = 0.29–0.39) while it was good for CEUS (κ = 0.63–0.79).

Conclusions

CEUS improves classification and characterisation of focal liver lesions and interobserver agreement compared to conventional US. Classification and characterisation post contrast were mildly but statistically significantly better for on-site than for off-site reading.     

Differential patterns of contrast enhancement in different focal liver lesions after injection of the microbubble US contrast agent SonoVue

PURPOSE: To identify differential contrast enhancement patterns in different focal hepatic lesions after injection of the microbubble contrast agent SonoVue using high or low acoustic power imaging. MATERIAL AND METHODS: Forty-seven focal hepatic lesions (1-8 cm) were detected in 45 patients at unenhanced gray-scale ultrasound (US) and evaluated by color Doppler (CD) US with spectral analysis of tumoral vessels. Lesions were subsequently evaluated by US contrast specific modes after IV bolus administration of 2,4-4,8 ml of SonoVue, by intermittent high acoustic power (18 patients) or by continous low acoustic power imaging (27 patients), during arterial, portal and late phase. Subjective evaluation of lesions appearance before and after SonoVue injection was performed. For final diagnosis multiphasic helical CT (21 patients) and/or fine needle US guided biopsy (24 patients) were considered as the reference procedures. RESULTS: Final diagnoses comprised 22 hepatocellular carcinomas (HCCs; 1,5-6 cm), 2 macroregenerative nodules (RNNs; 1-2 cm), 10 metastasis (2-3,5 cm), 10 hemangiomas (2-6 cm) and 3 focal nodular hyperplasias (FNHs; 1-3 cm). On CD evaluation HCCs revealed peripheral basket shaped (12/22) or intranodular (10/22) arterial pattern while, after SonoVue injection HCCs revealed diffuse contrast enhancement during arterial phase with contrast washout during portal and late phase. Metastases did not reveal flow signals on CD or contrast enhancement after SonoVue injection, except for 2 metastases which revealed peripheral and central vessels on CD and a diffuse contrast enhancement during arterial phase, appearing hypoechoic to the adjacent liver during portal and late phase. RNNs revealed dotted contrast-enhancement during portal and late phase with isoechoic appearance to the adjacent liver. Hemangiomas revealed some peripheral venous flows on CD and a peripheral nodular contrast enhancement during arterial phase with a centripetal fill-in during portal and late phase. FNHs revealed low resistance peripheral or central arterial vessels and a diffuse contrast enhancement during arterial phase, preceded or not by central spoke wheel shaped contrast enhancement, and a persistent iso-hyperechogenicity during portal and late phase. CONCLUSIONS: SonoVue injection has showed to identify differential contrast enhancement patterns in different focal hepatic lesions.     

Real-time contrast enhanced ultrasound imaging of focal splenic lesions

Objective

To investigate the imaging features of focal splenic lesions (FSLs) on contrast-enhanced ultrasound (CEUS).

Methods

Thirty two patients with FSLs proved by pathology were retrospectively analyzed. CEUS was performed using intravenous bolus injection of 2.4 ml sulfur hexafluoride-filled microbubble contrast agent and real time scanning. There were hemangioma (n = 7), lymphoma (n = 8), true cyst (n = 3), infarction (n = 4), hematolymphangioma (n = 2), metastasis tumor (n = 2), and one for each of the following entities extramedullary hemopoiesis, hamartoma, tuberculosis, Langerhans’ cell histiocytosis, inflammatory pseudotumor and myxofibrosarcoma.

Results

Among 21 benign lesions, 4 infarctions and 3 cysts presented non-enhancement throughout CEUS scanning, and the other 14 lesions displayed various enhancement levels with 6 (42.9%) hyper-enhancement, 2 (14.3%) iso-enhancement and 6 (42.9%) hypo-enhancement in arterial phase and 11 (78.6%) hypo-enhancement, 1 (7.1%) iso-enhancement and 2 (14.3%) hyper-enhancement in late phase, respectively. The enhancement pattern included 9 (64.3%) homogeneous, 4 (28.6%) heterogeneous and 1 (7.1%) rim-like enhancement. As for the malignant FSLs, all the lesions became completely or extensively hypo-enhancement during the late phase no matter their vascularity during arterial phase.

Conclusions

The CEUS features reported in this series may enrich the knowledge for CEUS characterization of FSLs.     

Characterization of liver hemangiomas with pulse inversion harmonic imaging

The purpose of this study was to determine if pulse inversion harmonic imaging (PIHI) can characterize liver hemangiomas. We retrospectively evaluated 39 consecutive patients with liver hemangiomas, 20 typical on conventional US (hyperechoic, homogeneous, or slightly inhomogeneous and with sharp margins) and 19 atypical (11 inhomogeneous with different echogenicity larger than 3 cm, 6 hypoechoic, and 2 isoechoic smaller than 3 cm). Each liver hemangioma was firstly evaluated by PIHI and then confirmed by dynamic helical CT (28 patients) or by 6 months of US follow-up (11 patients). The PIHI was performed by two distinct sweeps on a marker lesion, 30 s (vascular phase) and from 3 to 5 min (late phase) after bolus injection of Levovist (2.5 g, 300 mg/ml). Scans were digitally stored and reviewed using a dedicated software. Contrast enhancement features of marker lesion were subjectively evaluated. Typical hemangiomas on conventional US revealed on PIHI a characteristic rim-like or peripheral globular enhancement on 30-s scan in 4 of 20 cases (20%) and a characteristic isoechoic pattern on late phase in 16 of 20 cases (80%). On PIHI, all (11 of 11) atypical hemangiomas larger than 3 cm and 4 of 8 atypical liver hemangiomas smaller than 3 cm revealed a characteristic rim-like or peripheral globular enhancement on vascular phase with a characteristic centripetal fill-in on late phase. In 4 of 8 atypical liver hemangiomas smaller than 3 cm no characteristic pattern was revealed by PIHI. Pulse inversion harmonic imaging revealed a typical pattern in the majority of liver hemangiomas typical and atypical on conventional US. In few liver hemangiomas atypical on conventional US PIHI did not identify a characteristic pattern and helical CT was necessary for final characterization.     

Characterization of unifocal liver lesions with pulse inversion harmonic imaging after Levovist injection: preliminary results

The aim of this study was to evaluate capabilities of pulse inversion harmonic imaging (PIHI) in characterization of unifocal liver lesions. We evaluated with PIHI (HDI5000, ATL, Bothell, Wash.) and spiral CT 46 consecutive patients with a single liver lesion identified by fundamental US [7 hepatocellular carcinomas (HCC), 2 cholangiocarcinomas, 7 focal nodular hyperplasias (FNH), 17 hemangiomas and 13 metastases]. The PIHI was performed before and 30 s, 2 and 4 min after bolus administration of Levovist (2.5 g, 300 mg/ml). Scans were digitally stored and reviewed using a dedicated software. Hepatocellular carcinoma was hyperechoic on 30-s scan, and hypoechoic (n = 5) or isoechoic (n = 2) on 2-min scan. Cholangiocarcinoma had inhomogeneous persistent enhancement. Focal nodular hyperplasia was hyperechoic (n = 5) or isoechoic (n = 2) on 30-s scan, hyperechoic (n = 4), isoechoic (n = 2) or slightly hypoechoic (n = 1) on 2-min scan. Large hemangioma revealed peripheral enhancement on 30-s scan which extended centripetally on 2-min scan. Small hemangioma appeared isoechoic on 2-min scan in all but two cases in which they were hypoechoic on 2-min scans and hyperechoic on 4-min scan. Metastasis was hypoechoic on all scans, 70% with rim enhancement. Similar changes in enhancement pattern have been observed at spiral CT. The 30-s and the 2-min scans revealed a conclusive importance in characterization of HCC, cholangiocarcinoma, and large hemangioma. The 2-min scan often furnished enough information for characterization of small hemangioma and metastasis. The 4-min scan allowed characterization of two hemangiomas which appeared hypoechoic on 2-min scans. In the other cases it did not provide further information. Diagnosis of FNH is usually reached with Colour Doppler US; PIHI should be used when colour Doppler is biased by artefacts or when colour Doppler findings are not characteristic. Our results seem to show that PIHI could be a valuable alternative diagnostic approach to spiral CT for unifocal liver lesion characterization. This hypothesis needs to be confirmed with an increased number of lesions.     

Characterization of focal liver lesions by ADC measurements using a respiratory triggered diffusion-weighted single-shot echo-planar MR imaging technique

The aim of this study was to determine apparent diffusion coefficients (ADCs) of focal liver lesions on the basis of a respiratory triggered diffusion-weighted single-shot echo-planar MR imaging sequence (DW-SS-EPI) and to evaluate whether ADC measurements can be used to characterize lesions. One hundred and two patients with focal liver lesions [11 hepatocellular carcinomas (HCC), 82 metastases, 4 focal nodular hyperplasias (FNH), 56 hemangiomas and 51 cysts; mean size, 16.6 mm; range 5–92 mm] were examined on a 1.5-T system using respiratory triggered DW-SS-EPI (b-values: 50, 300, 600 s/mm²). Results were correlated with histopathologic data and follow-up imaging. The ADCs of different lesion types were compared, and lesion discrimination using optimal thresholds for ADCs was evaluated. Mean ADCs (×10⁻³mm²/s) were 1.24 and 1.04 for normal and cirrhotic liver parenchyma and 1.05, 1.22, 1.40, 1.92 and 3.02 for HCCs, metastases, FNHs, hemangiomas and cysts, respectively. Mean ADCs differed significantly for all lesion types except for comparison of metastases with HCCs and FNHs. Overall, 88% of lesions were correctly classified as benign or malignant using a threshold value of 1.63 × 10⁻³mm²/s. Measurements of the ADCs of focal liver lesions on the basis of a respiratory triggered DW-SS-EPI sequence may constitute a useful supplementary method for lesion characterization.     

Role of contrast enhanced ultrasound in characterization of focal liver lesions

Aim

The purpose of the study was to describe the enhancement patterns of focal liver lesions (FLLs) on contrast enhanced sonography (CEUS), assessing the potential of this technique for characterizing the lesions and to compare its diagnostic accuracy with conventional baseline sonography including color Doppler.

Materials and methods

Between August 2009 and July 2010, 50 patients with FLLs underwent gray scale sonography, color Doppler and CEUS. The enhancement patterns of these FLL’s were analyzed throughout the arterial phase, the portal venous phase and the extended portal venous phase (the late parenchymal phase). The final diagnosis was established on the basis of histopathologic examination or CT/MRI imaging.

Results

Out of these 50 FLLs, 33 were malignant (4 hepatocellular carcinoma and 29 metastasis) and 17 were benign (5 hemangioma, 5 abscess, 2 cyst and 1 each of FNH, focal fat sparing area, focal fatty infiltration, adenoma and benign/granulomatous lesion). The enhancement patterns after injecting microbubble contrast agent allowed characterization of FLLs. The malignant lesions showed intratumoral and/or peritumoral vascularity during the arterial phase and perfusion defect during the late parenchymal phase. Contrast enhanced sonography improved sensitivity in detecting malignancy (CEUS vs. baseline sonography, 100% vs. 81.8%).

Conclusion

CEUS improves detection and characterization of FLLs. It should be used as problem solving tool in cases where conventional gray scale and color Doppler sonography are non-diagnostic.     

Real-time contrast-enhanced ultrasound imaging of focal liver lesions in fatty liver

PurposeThe objective of this study was to investigate the contrast-enhanced ultrasound (CEUS) imaging features of focal liver lesions (FLLs) in fatty liver.MethodOne hundred FLLs in 98 patients with fatty liver were evaluated with real-time CEUS.ResultsAll malignant FLLs showed hyperenhancement in arterial phase and contrast washout in portal and late phases. Among the FLLs, 3.3% of hemangiomas, 12.5% of focal nodular hyperplasias (FNHs), and 2.5% of focal fatty sparing lesions showed contrast washout in the late phase. The sensitivity and specificity for the characterization of hepatocellular carcinoma, metastasis, hemangioma, FNH, and focal fatty sparing lesions were 100% and 95.6%, 60% and 100%, 93.3% and 98.6%, 87.5% and 97.8%, and 92.6% and 100%, respectively.ConclusionsCorrect characterization of FLLs in fatty liver by CEUS is possible based on their typical enhancement patterns.     

Contrast enhanced ultrasound with second generation contrast agent in traumatic liver lesions

PURPOSE: To evaluate the accuracy of second generation contrast enhanced US (Sonovue) in the diagnosis and staging of traumatic hepatic lesions, compared with conventional US and spiral CT. MATERIAL AND METHODS: A total of 203 patients (127 males, 76 females, mean age 36 years) with isolated abdominal trauma were examined with conventional and contrast enhanced US (Sonovue, Bracco, Italy) between March 2002 and February 2003. The sonographic contrast agent was administered at a dose of 2 ml/10-15", repeated twice. CT examinations were performed with single- (Rhota, Esaote Biomedica, Italy) or multislice spiral CT with administration of contrast agent. The presence and number of lesions, hepatic capsular involvement, size and sonographic pattern were evaluated. RESULTS: Conventional US demonstrated hepatic lesions in 27 patients, in 3 cases it identified 2 foci (30 lesions, size 2-8 cm). Contrast enhanced US (CEUS) revealed another 2 lesions and in 4 patients it identified lesions not shown at conventional US (size 2-5 cm). Capsular involvement was detected in 14 cases (11 with conventional US). The sonographic pattern of the lesions at conventional US was hypo-anechoic in 19 cases, and hyperechoic in 11. In CEUS all the lesions appeared strongly hypoechoic against a strongly hyperechoic parenchyma, with clear borders and larger size as compared with conventional US. CONCLUSIONS: In isolated blunt abdominal trauma CEUS is more accurate than conventional US in determining the number and size of lesions and detecting capsular involvement. This has a strong impact on diagnosis as the number of false negatives is reduced and on prognosis as the lesions are more accurately graded, and there is close correlation with spiral CT. CEUS can be used as a first approach in mild isolated abdominal trauma, in paediatric patients and in the follow-up, whereas CT is the method of choice in severe trauma and in multiple traumas.