Defect Reperfusion Imaging with Sonazoid®: A Breakthrough in Hepatocellular Carcinoma

Abstract

The detection of small nodular lesions in coarse liver parenchyma is difficult by B-mode US alone, although dynamic CT or dynamic MRI can detect arterial enhancing nodules with venous washout. Approximately 10% of HCC nodules that are not detected by B-mode US can be clearly identified by defect reperfusion imaging with Sonazoid®. The false positive rate increases when the technique is confined to Kupffer phase scanning. In addition to the Kupffer defect, information on arterial vascularity, i.e., the reinjection method, increases the diagnostic accuracy to 100% even in deeply seated nodules. This breakthrough method allows the detection of nodules that cannot be visualized by B-mode US, as defects on Kupffer images in the stable Kupffer phase. The presence of arterial blood flow in nodules with Kupffer defects is subsequently determined by the reinjection technique, making this method a breakthrough in diagnostic imaging [4,5]. CEUS with Sonazoid® reinjection requires no special apparatus or analysis, and is the result of a change in the way of thinking regarding CEUS. For the typical CT image (so-called early enhancement with late washout nodules), defects are easily detected in the Kupffer phase, and arterial perfusion within the defect is subsequently demonstrated by the reinjection test (visualization of staining within the Kupffer defects, which is the reverse phenomenon of early enhancement with late washout). The introduction of this technique has allowed almost 100% accuracy in the detection of lesions observed on CT images that are not visualized on B-mode US images. If the reinjection test shows no enhancement of a Kupffer defect, this defect differs from the nodule detected by CT. This method then serves to guide needle insertion. In surveillance, this procedure facilitates screening because Sonazoid® US can be performed in the setting of a routine examination. In addition, operators only need to concentrate on the delineation of Kupffer defects in the Kupffer phase in contrast to routine B-mode US, in which regenerative nodules or dysplastic nodules may mimic malignant ones. If defects are detected, HCC can be confirmed by Sonazoid® reinjection, which provides information on both Kupffer cell function and arterial blood flow on the same cross-sectional image. This dual phase fusion imaging allows detection and definitive diagnosis of HCC with 100% confidence. As a result, Sonazoid® has markedly improved the efficiency of HCC detection. In the past, CEUS was considered only for nodules previously depicted by B-mode US and was not used as a screening tool. However, this concept changed with the introduction of defect reperfusion imaging using Sonazoid®. Defect reperfusion imaging is also useful for the localization of recurrent lesions at a previously ablated area, which is difficult by B-mode US because of the inhomogeneous echo pattern mixed with viable lesions, the ablated area, and ablated surrounding liver. In this setting, even skilled operators have difficulties determining the viable area on B-mode US images alone, which corresponds to the enhancing area on CT because of numerous US cross-sections [50]. This problem has been readily overcome by defect reperfusion imaging with Sonazoid®. Defect reperfusion imaging is particularly useful for needle insertion guidance in the treatment of HCC. For invisible nodules on B-mode US, needle insertion can be performed under the guidance of either fusion imaging [51,52] or SonoVue®-enhanced US. However, fusion imaging requires CT/MRI volume data and special apparatus. In addition, complete concordance of synchronized images from B-mode US that correspond to the cross-sectional plane of CT/MRI volume data is sometimes difficult. Similarly, under SonoVue®-enhanced US, puncture should be performed in a very short time in the early arterial phase. Conversely, in Sonazoid®-enhanced US, Kupffer defects are detected easily, and whether blood flow is present in defective areas can be determined by the reinjection technique (defect reperfusion imaging) in all cases. Therefore, needle insertion can be easily performed during a stable period in the Kupffer phase, and accurate needle placement followed by sufficient treatment is possible with Sonazoid®-enhanced US.