| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 All authors: Sardinian Mediterranean Imaging Research Group, Via Gorizia no. 11, Sassari 07100, Sardinia, Italy.
Received August 8, 2003;
accepted after revision December 3, 2003.
Address correspondence to V. Migaleddu
(vmigale{at}tin.it).
Abstract
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
MATERIALS AND METHODS. Sixty-five patients (21 male and 44 female; age range, 8–82 years; mean ± standard deviation, 58.1 ± 14.5 years) were independently evaluated by two observers in a blinded manner using stored sonographic images. Seventy-five lesions were found: 15 hepatocellular carcinomas, nine focal nodular hyperplasias, two adenomas, 21 hemangiomas, 23 metastases, and five regenerative nodules. Nine patients were excluded (six because of technical failures, three with unproven diagnoses). New high-mechanical-index software was used to reveal power harmonic responses from contrast microbubble destruction. After a venous bolus injection of 4 g of Levovist at a strength of 400 mg/mL, delayed imaging was used to study lesion enhancement in the arterial, portal, and parenchymal phases. Two comparisons were made. The first was between the B-mode image and the first contrast-enhanced image after the flash. The second was between color Doppler sonograms and real-time contrast-enhanced perfusion images.
RESULTS. Contrast-enhanced images after the flash and real-time contrast-enhanced images revealed more information for the characterization of the lesion than did gray-scale and color Doppler images (p < 0.0001, Wilcoxon's signed rank test). Different types of lesions showed statistically significant differences in enhancement during each of the three vascular phases (p < 0.005, Kruskal-Wallis test). Lesions with lower contrast enhancement were metastases and regenerating nodules. Good agreement was present between the two observers; differences were not statistically significant (p > 0.05).
CONCLUSION. Agent detection imaging with Levovist increased diagnostic confidence in the characterization of focal hepatic lesions as compared with standard sonography.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Methodology
The contrast agent used was Levovist in doses of 4 g administered as a
bolus injection (in 2–3 sec) in a concentration of 400 mg/mL.
First, we performed conventional or tissue harmonic imaging of the lesion and color Doppler evaluation of its vascularity. To study a single lesion, images were acquired at various time intervals of 10–15 sec, 20–30 sec, and 1, 2, 3, 4, 5, and 6 min after injection. Using these time intervals, the arterial, portal, and parenchymal enhancement phases were visualized.
When agent detection imaging is activated, destruction of microbubbles occurs, resulting in an instantaneous flash contrast image. This step was followed by real-time observation of the macro- and microvessels for a minimum of 3 sec.
Patients
A total of 74 patients were examined, and of these, 65 were included in our
study (21 male and 44 female; age range, 8–82 years; average age
± standard deviation [SD], 58.1 ± 14.5 years). Nine patients
(12%) were excluded, six because their images were technically insufficient
and three because the diagnosis could not be confirmed. Technical failures in
the six patients who were excluded occurred only at the start of the study and
reflect our learning curve. The most common causes of failure were poor
cooperation from the patient or deep lesions. To eliminate unsuccessful
examinations, we used an intercostal approach that reduced the distance
between the transducer and the lesion and eliminated the deep respiration
necessary for subcostal examinations. Our findings were hemangiomas
(n = 21); adenomas (n = 2); focal nodular hyperplasias
(n = 9); hepatocellular carcinomas (n = 15); regenerating
nodules (n = 5); and metastases (n = 23) from colon
(n = 10), breast (n = 9), bladder (n = 1),
neuroendocrine (n = 2), and prostate (n = 1) cancer.
The diagnosis was confirmed on CT for the hemangiomas (except in one patient with a histologic diagnosis after laparoscopic nodulectomy of a suspected hepatocellular carcinoma in chronic liver disease); CT and percutaneous biopsy confirmed the diagnoses of the adenomas, focal nodular hyperplasias, hepatocellular carcinomas, and regenerating nodules. Two cases of colon metastases were confirmed with biopsy during surgery on the primary tumor. In one patient with hepatocellular carcinoma, CT was not performed because of the patient's intolerance for iodine contrast media; the diagnosis was confirmed only with percutaneous biopsy.
Image Analysis
Sonograms were evaluated by two double-blinded observers without knowledge
of the final diagnosis or the evaluation of the other observer.
We compared the baseline gray-scale image with the contrast-enhanced images. The first image was obtained 10–15 sec after the contrast injection, which resulted in a flash contrast image of the arterial phase. The second image was obtained 20–30 sec after injection, resulting in a flash contrast image of the portal phase. The next images were obtained at 1, 2, 3, 4, 5, and 6 min in the same manner to show the contrast enhancement in the early and late parenchymal phases.
The flash score consisted of the absence or presence of enhancement in the lesion compared with the surrounding parenchyma. Lack of enhancement, enhancement at the rim, homogeneity of the enhancement, and whether enhancement was less than, equal to, or greater than that of the surrounding parenchyma were also evaluated. Enhancement and homogeneity were assigned a numeric score from 0 to 4.5.
The vascular score consisted of comparison of baseline color Doppler images with those obtained in real time using contrast-enhanced harmonic imaging in the arterial, portal, and late phases. This set of data was subdivided into mild, medium, or high enhancement and regular or irregular appearance of the macro- and microvessels in and around the lesion. These evaluations were given a numeric score from 0 to 3.5 (Table 1).
|
The data were analyzed using Wilcoxon's signed rank test and the Kruskal-Wallis test [9, 10].
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Contrast-enhanced harmonic imaging with systems using a high mechanical index requires an imaging delay to allow reperfusion of the lesion and the surrounding parenchyma after the destruction of the microbubbles; therefore, using a system with a high mechanical index requires a longer learning period than a system using a low mechanical index. In our experience, agent detection imaging with real-time observation of contrast enhancement in the macro- and microvessels reduces the learning curve.
Agent detection imaging uses both fundamental echoes and contrast-enhanced harmonic echoes in the formation of the image. Unlike the low mechanical index technique in which the fundamental gray-scale image is absent, agent detection imaging software offers the possibility of visualizing the fundamental gray-scale image, the contrast-enhanced harmonic image by itself, or both together. At the start of the examination, an optimal baseline gray-scale image can be obtained so that the lesion is perpendicular to the ultrasound beam and in the center of the box in which the contrast-enhanced harmonic image is formed.
Visualization of contrast enhancement in the intrahepatic macro- and
microvessels permits the determination of the arterial and the portal
contributions to a lesion, which allows one to modify the time intervals of
the examination according to the vascular pattern of the lesion. For example,
because of the hyperkinetic circulation of cirrhosis in hepatocellular
carcinoma, it is necessary to obtain the first scan at 10–15 sec. In
focal nodular hyperplasias and adenomas, it is best to choose scanning
intervals to study the arterial and early portal phases. Hemangiomas and
metastases require particular attention in the portal and the early and late
parenchymal phases. The quantity and the concentration of the contrast agent
we used (4 g and 400 mg/mL) were sufficient to obtain information from both
the early and the late phases (
6 min).
Our results show that the information acquired with contrast imaging both in the flash phase and during real-time vascular observation is clearly superior to that obtained with conventional sonography and color Doppler sonography. The observation in real time of the peri- and intralesional vessels seen after the first flash of microbubble destruction added diagnostically important information such as the regularity or irregularity of the vasculature. Other static contrast-enhanced imaging technologies that use a high mechanical index and intermittent scanning, such as pulse inversion, flash echo, and combined contrast chain, do not reveal the same clear information that is possible with real-time scanning. In our experience, real-time contrast-enhanced imaging technologies that use a low mechanical index, such as coherent contrast-enhanced imaging, contrast-tuned imaging, and helical biphasic or triphasic CT, also do not readily show these findings.
Image interpretation (from contrast-enhanced CT experience) is simple, sufficiently objective, and not operator-dependent, as seen by the results of our two observers.
In the characterization of focal liver lesions, this method can improve diagnostic specificity because of observing different contrast enhancement for different disorders. These statistically significant results are achieved both by evaluating the contrast-enhanced flash images and through real-time evaluation.
The contrast-enhanced examination was less useful than conventional and color Doppler sonography in regenerating nodules and metastases. For the latter, the characteristic appearance is the lack of enhancement in the parenchymal phase. Clinical and laboratory evaluations are important in chronic liver disease because hypovascular hepatocellular carcinomas can be confused with regenerating nodules. When lesions are found that do not enhance in the arterial phase and that present internal irregular small vessels at real-time evaluation, sonographically guided biopsy is recommended. In our experience, hepatocellular carcinomas were found in two cases with this contrast pattern.
The central spider sign visualized in real time in the nodules of focal nodular hyperplasia strongly suggests the diagnosis. Arterial and venous vessels can be visualized in the center of high-flow hemangiomas. Rim enhancement visualized in the arterial phase can help in the diagnosis of high-flow hemangiomas.
In conclusion, agent detection imaging with Levovist achieves a high specificity in the diagnosis of focal liver lesions. Such imaging may reduce the need for more costly and invasive examinations such as CT, MRI, and biopsy.
Acknowledgments
We thank Matteo Bottai of the Consiglio Nazionale delle Ricerche in Pisa,
Italy, for providing the statistical analysis.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Ricci, V. Cantisani, M. D'Onofrio, D. Sahani, E. Pagliara, F. Calliada, E. Mehmet, K. Sanjeva, N. Faccioli, R. Pozzi-Mucelli, et al. Behavior of Hepatocellular Adenoma on Real-time Low-Mechanical Index Contrast-Enhanced Ultrasonography With a Second-Generation Contrast Agent J. Ultrasound Med., December 1, 2008; 27(12): 1719 - 1726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Catalano, V. Migaleddu, E. Quaia, and G. Caruso Terminology for Contrast-Enhanced Sonography: A Practical Glossary J. Ultrasound Med., June 1, 2007; 26(6): 717 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Catalano, F. Sandomenico, A. Nunziata, M. M. Raso, P. Vallone, and A. Siani Transient Hepatic Echogenicity Difference on Contrast-Enhanced Ultrasonography: Sonographic Sign and Pitfall J. Ultrasound Med., March 1, 2007; 26(3): 337 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Minami, M. Kudo, H. Chung, T. Kawasaki, Y. Yagyu, T. Shimono, and H. Shiozaki Contrast Harmonic Sonography-Guided Radiofrequency Ablation Therapy Versus B-Mode Sonography in Hepatocellular Carcinoma: Prospective Randomized Controlled Trial Am. J. Roentgenol., February 1, 2007; 188(2): 489 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Leen, P. Ceccotti, C. Kalogeropoulou, W. J. Angerson, S. J. Moug, and P. G. Horgan Prospective multicenter trial evaluating a novel method of characterizing focal liver lesions using contrast-enhanced sonography. Am. J. Roentgenol., June 1, 2006; 186(6): 1551 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Catalano, A. Nunziata, R. Lobianco, and A. Siani Real-Time Harmonic Contrast Material-specific US of Focal Liver Lesions RadioGraphics, March 1, 2005; 25(2): 333 - 349. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
