Principle of contrast-enhanced ultrasonography.

Sonazoid, an ultrasound contrast agent, has been covered by insurance in Japan since January 2007 for the diagnosis of hepatic mass lesions and is widely used for diagnosing not only primary liver cancer but also liver metastases such as those from breast cancer and colorectal cancer. Contrast-enhanced ultrasound for breast mass lesions has been covered by insurance since August 2012 after phase II and phase III clinical trials showed that the diagnostic performance was significantly superior to that of B-mode and contrast-enhanced magnetic resonance imaging. This paper describes the principles of imaging techniques in contrast-enhanced ultrasonography including the filter, pulse inversion, amplitude modulation, and amplitude-modulated pulse inversion methods. The pulse inversion method, which visualizes the second-harmonic component using the nonlinear scattering characteristics of the contrast agent, is widely used regardless of the contrast agent and target organ because of its high resolution. Sonazoid has a stiffer shell and requires a higher acoustic amplitude than Sonovue to generate nonlinear vibrations. The higher transmitted sound pressure generates more tissue harmonic components. Since pulse inversion allows visualization of the tissue harmonic components, amplitude modulation and amplitude-modulated pulse inversion, which include few tissue harmonic components, are primarily used. Amplitude modulation methods detect nonlinear signals from the contrast agent in the fundamental band. The mechanism of the amplitude modulation is considered to be changes in the echo signal's phase depending on the sound pressure. Since the tissue-derived component is minor in amplitude modulation methods, good contrast sensitivity can be obtained.

Simplified Wide-Range Ultrasonic Measurements Using the Sensor Three-Dimensional System.

We developed a simplified three-dimensional ultrasonic device that can scan a wide area and performed measurements in the scanned area. The system is more compact than magnetic resonance imaging (MRI) systems and can measure random cross sections by acquiring volume data over a wide range through freehand scanning with a magnetic sensor unit that detects the transducer position. The system was applied successfully to a case with a huge myoma. Our system, in ways similar to computed tomography or MRI systems, can support both the objective understanding of the pathology of huge tumors and follow-up determinations of tumor diameters at arbitrary cross sections in the volume data.

Virtual laparoscopy: Initial experience with three-dimensional ultrasonography to characterize hepatic surface features.

OBJECTIVE: To examine the potential utility of 3D-reconstructed sonograms to distinguish cirrhotic from non-cirrhotic livers by demonstrating hepatic surface characteristics. MATERIALS AND METHODS: A preliminary phantom study was performed to examine the potential resolution of 3D images, recognizing surface irregularities as a difference in height. In a prospective clinical study of 31 consecutive patients with ascites (21 cirrhosis, 10 non-cirrhosis), liver volume data were acquired by transabdominal mechanical scanning. The hepatic surface features of cirrhotic and non-cirrhotic patients were compared by 2 independent reviewers. Intra- and inter-operator/reviewer agreements were also examined. RESULTS: The phantom study revealed that 0.4mm was the minimum recognizable difference in height on the 3D sonograms. The hepatic surface image was successfully visualized in 74% patients (23/31). Success depended on the amount of ascites; visualization was 100% with ascites of 10mm or more between the hepatic surface and abdominal wall. The images showed irregularity of the hepatic surface in all cirrhotic patients. The surface appearance was confirmed as being very similar in 3 patients who had both 3D sonogram and liver resection for transplantation. The ability to distinguish cirrhotic liver from non-cirrhotic liver improved with the use of combination of 2D- and 3D-imaging versus 2D-imaging alone (sensitivity, p=0.02; accuracy, p=0.02) or 3D-imaging alone (sensitivity, p=0.03). Intra-/inter-operator and inter-reviewer agreement were excellent (κ=1.0). CONCLUSION: 3D-based sonographic visualization of the hepatic surface showed high reliability and reproducibility, acting as a virtual laparoscopy method, and the technique has the potential to improve the diagnosis of cirrhosis.

Preoperative RFA simulation for liver cancer using a CT virtual ultrasound system.

We developed a computed tomography (CT) virtual ultrasound system (CVUS) as an imaging system to support treatment under percutaneous ultrasound (US) guidance. This prototype clinical system, produced in collaboration with Tokyo Medical University, uses display software developed by Toshiba Medical Systems. We examined the utility of this system by scheduling treatment plans preoperatively and simulating puncture and radiofrequency ablation (RFA) for liver cancer. The study enrolled 51 liver cancer patients with 66 nodules 0.8-8cm in diameter in which RFA was performed between June 2004 and December 2004. Virtual US and multiplanar reconstruction (MPR) images were constructed on the basis of DICOM CT data and puncture and ablation of liver cancer were simulated. The following were evaluated: (1) how to avoid complications and determine an appropriate puncture route by simulating puncture with C-mode MPR images; (2) determination of the three-dimensional location of the tumor for ablation, as well as the adjacent organs and vessels, by MPR rotation 360 degrees around the center of the tumor (center lock); and (3) how to determine the center and volume of ablation and avoid injuries to nearby organs and vessels by simulating ablation procedures. C -mode MPR images were effective for (1) determining and modifying the puncture route in 35 of 51 cases (69.6%) and (2) determining the spatial location of vessels and nearby organs in 50 of 51 cases (98.0%) by the center lock; and (3) simulating the ablation helped determine the center and volume of ablation by avoiding injuries to vessels and nearby organs in 45 or 51 cases (88.2%). Taken together, the CVUS allowed easy simulation of local treatment of liver cancer under US guidance using CT data alone and the preoperative simulation predicted an improvement in the safety of local therapy of liver cancer.

Sonographic shift of hypervascular liver tumor on blood pool harmonic images with definity: time-related changes of contrast-enhanced appearance in rabbit VX2 tumor under extra-low acoustic power.

We elucidated the features of the time-related contrast-enhanced ultrasound appearance of hypervascular liver tumor using Definity, which has no accumulation activity in the liver. Ten rabbits with VX2 tumors broadcast into the liver were used. Changes in contrast-enhanced sonograms were evaluated by real-time observation (FR 15 Hz) of harmonic imaging under extra-low MI (MI 0.065) with Definity, and their intensity changes were analyzed. Hepatic angiography (4/10) and histopathological examination (10/10) were performed to investigate the tumor vascularity. VX2 tumors were hypervascular on angiogram (4/10) and histology (10/10). They showed time-related sonographic appearance changes from hyperechoic to hypoechoic, which were confirmed by quantitative intensity analysis. Hypervascular VX2 tumors showed characteristic time-related shift on contrast-enhanced sonograms in real-time and extra-low MI harmonic images with Definity. These findings may be useful for the ultrasound diagnosis of human hypervascular liver tumor like hepatocellular carcinoma with blood-pool contrast agent.

Different behaviors of microbubbles in the liver: time-related quantitative analysis of two ultrasound contrast agents, Levovist and Definity.

The differences in time-related changes of liver images were compared quantitatively between Levovist and Definity. A total of 40 rabbits were assigned to eight groups according to the timing of taking enhanced liver images at 1, 3, 5, 7, 9, 11, 13 and 15 min by intermittent harmonic imaging using Levovist or Definity (30 microL/kg) and another 40 rabbits for Definity (50 microL/kg). Intensity changes between before and after enhancement in the portal vein (I-PV) and liver parenchyma (I-LP) were analyzed. I-PV was greater than I-LP at the 1- and 3-min phases of enhancement and I-LP became greater than I-PV with Levovist after 5 min. However, I-PV was higher than I-LP in all phases with Definity. Different time-intensity curves of these two agents will indicate discrete behaviors of microbubble hemodynamics in the liver; Levovist becomes accumulated in the liver, whereas Definity acts as a blood pool contrast agent, without accumulation.

Extra-low acoustic power harmonic images of the liver with perflutren: novel imaging for real-time observation of liver perfusion.

OBJECTIVE: The features of images below the extra-low mechanical index level were studied to elucidate a suitable mechanical index level for observing real-time and continuous harmonic images of rabbit livers with VX-2 tumors with the use of perflutren. METHODS: Eight New Zealand White rabbits, 2 with healthy livers and 6 with VX-2 tumors, were examined by harmonic imaging (1.85 and 3.7 MHz) at a frame rate of 17 Hz under various mechanical index levels. RESULTS: Real-time enhanced images of the liver were observed continuously in all rabbits. Vascular images were more clearly visualized at the low mechanical index level (mechanical index, 0.18) than at any other level. However, predominant enhanced images of the whole liver were observed only at the extra-low mechanical index level (mechanical index, 0.06). In VX-2 tumors, tumor vessels were shown more clearly at a low acoustic power level than at an extra-low level. The histologically proved area of viable tumor was enhanced as a stain in the tumor nodule at an extra-low mechanical index level. CONCLUSIONS: Harmonic imaging under extra-low mechanical index levels with perflutren could provide real-time and continuous enhanced images of the liver, which would contribute to improvement of the diagnostic ability of contrast-enhanced sonography in liver diseases.