Evaluation of quantitative contrast harmonic imaging to assess malignancy of liver tumors:A prospective controlled two-center study

AIM: To establish the extent to which contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of hepatic tumors. METHODS: One hundred patients with histologically confirmed malignant or benign hepatic tumor (maximum size 5 cm) were analyzed. Contrast-enhanced ultrasound (bolus injection 2.5 mL SonoVue) was carried out with intermittent breath-holding technique using a multifrequency transducer (2.5-4 MHz). Native vascularization was analyzed with power Doppler. The contrast-enhanced dynamic ultrasound investigation was carried out with contrast harmonic imaging in true detection mode during the arterial,portal venous and late phases. Mechanical index was set at 0.15. Perfusion analysis was performed by post-processing of the raw data time intensity curve (TIC) analysis. The cut-off of the gray value differences between tumor and normal liver tissue was established using Receiver Operating Characteristic (ROC) analysis 64-line multi-slice computed tomography served as reference method in all cases. Magnetic resonance tomography was used additionally in 19 cases. RESULTS: One hundred patients with 59 malignant (43 colon,5 breast,2 endocrine metastases,7 hepatocellular carcinomas and 2 kidney cancers) and 41 benign (15 hemangiomas,7 focal nodular hyperplasias,5 complicated cysts,2 abscesses and 12 circumscribed fatty changes) tumors were included. The late venous phase proved to be the most sensitive for classification of the tumor type. Fifty-eight of the 59 malignant tumors were classified as true positive,and one as false negative. This resulted in a sensitivity of 98.3%. Of the 41 benign tumors,37 were classified as true negative and 4 as false negative,which corresponds to a specificity of 90.2%. Altogether,95.0% of the diagnoses were classified as correct on the basis of the histological classification. No investigator-dependency (P = 0.23) was noted. CONCLUSION: The results show the possibility of accurate prediction of malignancy of hepatic tumors with a positive prognostic value of 93.5% using advanced contrast-enhanced ultrasound. Contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics is a valuable tool to discriminate hepatic tumors.

1.5 Harmonic Imaging Sonography with microbubble contrast agent improves characterization of hepatocellular carcinoma

AIM： TO investigate the usefulness of 1.5 Harmonic Imaging Sonography with the use of the contrast agent Levovist for the diagnosis of hepatocellular carcinoma （HCC） and for the evaluation of therapeutic response. METHODS： Phantom experiments were performed to compare the contrast effects of 2^rd harmonic imaging and 1.5 Harmonic Imaging Sonography. 1.5 Harmonic Imaging Sonography was employed to examine 36 patients with HCC （42 nodules） before and after the treatment and to compare against the findings obtained using other diagnostic imaging modaUties. RESULTS： In 1.5 Harmonic Imaging Sonography, the tumor vessels of HCCs were clearly identified during the early phase, and late-phase images clearly demonstrated the differences in contrast enhancement between the tumor and surrounding hepatic parenchyma. Blood flow within the tumor was detected in 36 nodules （85.7%） during the early phase and in all 42 nodules （100%） during the late phase using 1.5 Harmonic Imaging Sonography, in 38 nodules （90.5%） using contrast-enhanced CT, in 34 nodules （81.0%） using digital subtraction angiography （DSA）, and in 42 nodules （100%） using US CO2angiography. Following transcatheter arterial embolization, 1.5 Harmonic Imaging Sonography detected blood flow and contrast enhancement within the tumors that were judged to contain viable tissue in 20 of 42 nodules （47.6%）. However, 6 of these 20 cases were not judged in contrastenhanced CT. 1.5 Harmonic Imaging Sonography was compared with the US CO2 angiography findings as the gold standard, and the sensitivity and specificity of these images for discerning viable and nonviable HCC after transcatheter arterial embolization were 100% and 100%,respectively. CONCLUSION： 1.5 Harmonic Imaging Sonography permits the vascular structures of HCCs to be identified and blood flow within the tumor to be clearly demonstrated. Furthermore, 1.5 Harmonic Imaging Sonography is potentially useful for evaluating the therapeutic effects of transcatheter arterial embolization on HCC. 2005 The WJG Press and Elsevier Inc. All rights reserved

Theory of higher harmonics imaging in tapping-mode atomic force microscopy

The periodic impact force induced by tip-sample contact in a tapping mode atomic force microscope （AFM） gives rise to the non-harmonic response of a micro-cantilever. These non-harmonic signals contain the full characteristics of tip-sample interaction. A complete theoretical model describing the dynamical behaviour of tip-sample system was developed in this paper. An analytic formula was introduced to describe the relationship between time-varying tip-sample impact force and tip motion. The theoretical analysis and numerical results both show that the timevarying tip-sample impact force can be reconstructed by recording tip motion. This allows for the reconstruction of the characteristics of the tip-sample force, like contact time and maximum contact force. It can also explain the ability of AFM higher harmonics imaging in mapping stiffness and surface energy variations.

Comparison study of harmonic imaging （HI） and fundamental imaging （FI） in fetal echocardiography

Objectives: To directly compare the quality of harmonic imaging (HI) and fundamental imaging (FI) in fetal echocardiography and to determine any differences in image quality between the two modalities. Methods: Fetal echocardiograms were performed with the use of FI and HI in 58 fetuses, image quality and visualization of left and right atria, left and right ventricles, mitral and tricuspid valves, aortic and pulmonary valves, left and right ventricular outflow tracts were evaluated and compared between FI and HI. Results: Mean HI scores were higher than mean FI scores (2.73±0.43 vs 2.16±0.69, P <0.001)for all the cardiovascular structures evaluated. Compared with FI, HI improved the image quality and visualization of fetal cardiac structures in subjects with both good (2.73±0.43 vs 2.88±0.32, P <0.001) and suboptimal (1.65±0.41 vs 2.58±0.47, P <0.001) echocardiographic windows. The interobserver correlation coefficient for the grading scores was 0.74 ( P <0.001). Conclusions: harmonic imaging enhances and improves the image quality of fetal echocardiography; and has important potential role in cardiac imaging in the fetus.

Cascading Enhancement of Reflected Optical Third-Harmonic Imaging in Bio-Tissues

A new nonlinear optical third\|harmonic imaging technology in reflected fashion in bio\|tissues by using cascading effect, a process whereby the second\|order effects combine to contribute to a third\|order nonlinear process, has been analyzed. The performance of the reflected optical third harmonic imaging enhanced by cascading effect in bio\|tissues is analyzed with the semi\|classical theory. The microscopic understanding of the enhancement of cascaded optical third\|harmonic imaging in reflected manner in bio\|tissues has been discussed.Some i deas for further enhancement is given.

IMAGING OF EEG BY SPHERICAL HARMONIC ANALYSIS

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Effect of viscoelasticity on nonlinear vibration of single microbubble

Based on the Church-Hoff model, the nonlinear oscillations of a single encapsulated microbubble with a finite thickness shell are theoretically studied. The effects of viscoelasticity on radial oscillations and the fundamental and harmonic components are researched. The peaks of radial oscillations and magnitudes of power spectra of the fundamental and harmonic components all increase gradually with the shear modulus of shell varying from 0 to 10 MPa by an interval of 0. 1 MPa at the same shear viscosity, while they decrease as the shear viscosity increases from 0 to 1 Pa · s by an interval of 0. 01 Pa · s at the same shear modulus. The fluctuation ranges of subharmonic and ultraharmonic signals are much larger than both the fundamental and second harmonic components. It means that the effect of viscoelasticity on the subharmonic and ultraharmonic signals is greater than that on the fundamental and second harmonic components. So adjusting the viscoelasticity of the shell is a potential method to obtain a perfect microbubble contrast agent used for the subharmonic and ultraharmonic imaging. Four points with significant fundamental and harmonic components are chosen as an example： a shear viscosity of 0. 39 Pa · s with shear modulus of 3.9, 6. 6, and 8.6 MPa, respectively; a shear modulus of 6.6 MPa with a shear viscosity of 0.42 Pa · s.

Differentiation between malignant and benign nodules in the liver: Use of contrast C^3-MODE technology

AIM: To investigate the value of contrast-enhanced C3-MODE technology in differentiating malignant nodules of liver from the benign ones. METHODS: Forty-six nodules in 36 patients (29 men and 7 women) were studied by contrast-enhanced C3-MODE technology and contrast-enhanced CT in 1 wk before the biopsy or operation. A low MI monitor and a high MI flash imaging were intermittently performed. After the injection of contrast agent, the period from 10 to 30 s and the time later than 100 s were respectively defined as early arterial phase and the late phase. The vascularities of the liver nodules in the two phases were combined for differential diagnosis. Corresponding to the pathological diagnosis, the accuracy, sensitivity and specificity of contrast-enhanced C3-MODE technology were compared to those of contrast-enhanced CT. RESULTS: By C3-MODE technology, 33 of the 46 liver nodules were demonstrated as defected area in the late phase and were diagnosed as malignant tumors. Of them, 28 with hypervascularity in the early arterial phase were assessed as hepatocellular carcinoma, the other five nodules with rim-like enhancement in the early arterial phase were diagnosed as metastatic tumors. Thirteen nodules were shown as iso or hypervascularity in the late phase as well as centripetal filling in the early arterial phase and we made a diagnosis of hemangioma. Corresponding to the pathological results, the sensitivity, specificity and accuracy of contrast-enhanced C3-MODE technology in differentiating malignant and benign nodules in the liver were 97.0%, 92.3% and 95.7%, respectively. With comparison to those of contrast CT (sensitivity, 94.1%; specificity, 91.7%; accuracy, 93.5%), the difference was not significant. CONCLUSION: Contrast-enhanced C3-MODE technology can effectively differentiate malignant liver tumors from the benign nodules. It highly agrees diagnostically with the pathology. We suggest that it provides a new approach for differential diagnosis of liver nodules in addition to contrast-enhanced CT.

Dynamic Assessment of the Focal Hepatic Lesion in Rats Using Ultrasonic Contrast Agent

The focal hepatic lesion caused by local injection of absolute alcohol in rats was evaluated with ultrasonic contrast agent and pathologic examination. Twenty adult Wistar rats weighing about 200 g were injected with absolute alcohol （0. 05-0. 1 mL each one） on the exterior left lobe of the liver under the monitoring of ultrasound. Pulse inversion harmonic imaging was used to evaluate the focal lesion after bolus injection of ultrasonic contrast agent （0. 05 mL/200 g） through caudal vein. Seven days later, the focal lesion was studied again as before. The exterior left lobe of liver with focal lesion was incised and underwent pathologic examination. The results showed that all of the focal lesions could be defined clearly after bolus injection of the ultrasonic contrast agent under the mode of pulse inversion harmonic imaging. There was good correlation between the size of the focal lesion measured by ultrasound on the 7th day after the ＂ablation＂ under the mode of pulse inversion harmonic imaging and that gotten by pathologic examination （P=0.39）. The focus size measured by ultrasound right after the ablation was larger than that gotten by pathologic examination （P=0. 002）. It was concluded that ultrasonic contrast agent plus pulse inversion harmonic imaging could be used to assess the size of the focal hepatic lesion caused by local injection of absolute alcohol in rats.

Comparison of the veracity of real-time perfusion, harmonic angio, and ultraharmonic myocardial contrast imaging modes in evaluation of acute myocardial infarction area

Background Innovative advancements in ultrasound instrumentation present a number of imaging modalities for myocardial contrast echocardiography （MCE） in ischemic syndromes. How well they compare to each other in diagnostic accuracy in the detection of acute myocardial infarction is unclear. The purpose of this study was to assess the relative accuracy of 3 different imaging modes of MCE, low mechanical index （MI） real-time perfusion imaging （RTPI）, triggered harmonic angio mode （HA）, and ultraharmonic imaging mode （UH） in the detection of acute experimental myocardial infarction within the time frame suitable for potential reperfusion. Methods MCE was performed in 10 open-chest dogs using RTPI, triggered HA and triggered UH modes at baseline and one hour after occlusion of left anterior descending coronary artery. Presence or absence of peffusion defects, and the perfusion defect size when present, were analyzed and compared with the infarct size delineated by triphenyltetrazolium chloride （TTC） staining. Results The infarct area was （15.8-2.4）% by TTC staining; Peffusion defect area by MCE was similar to anatomic infarct area in all the three MCE approaches： （16.1-2.7）% by RTPI mode, （15.5-2.9）% by HA mode, and （15.5-3.0）% by UH mode. The sensitivity, specificity and overall diagnostic accuracy in the detection of myocardial infarction were 100%, 88%, and 94% for RTPI mode, 88%, 100%, and 94 % for HA mode, and 100%, 75%, and 88% for UH mode. Conclusion All modes of MCE, RTPI, triggered HA mode and triggered UH mode have excellent diagnostic accuracy in the immediate hour of acute coronary occlusion within the optimal time frame suitable for reperfusion therapy.

Improving contrast and sectioning power in confocal imaging by third harmonic generation in SiOx nanocrystallites

We present a new optical microscope in which the light transmitted by a sample-scanned transmission confocal microscope is frequency-tripled by SiOx nanocrystallites in lieu of being transmitted by a confocal pinhole. This imaging technique offers an increased contrast and a high scattered light rejection. It is demonstrated that the contrast close to the Sparrow resolution limit is enhanced and the sectioning power are increased with respect to the linear confocal detection mode. An experimental implementation is presented and compared with the conventional linear confocal mode.