A Study on Contrast-enhanced Ultrasonography with Second-generation Contrast Agent Sonazoid® for Diagnosis of Liver and Splenic Nodules in Dogs

Ultrasonography is one of the first modalities that has high sensitivity for detection of the abdominal mass lesion. In many patients, however, ultrasonographic characterization of masses is not possible because of poor specificity. In human medicine, contrast-enhanced ultrasonography with Sonazoid®, a second-generation contrast agent incorporated by the reticuloendothelial system, allows an accurate diagnosis of hepatic tumors. In veterinary medicine, although contrast-enhanced ultrasonography has been performed for many organs, the utility of Sonazoid® has been uncertain. The principal aim of this thesis was to investigate the clinical utility of Sonazoid®-enhanced ultrasonography in veterinary medicine. Firstly, the author evaluated the usefulness of Sonazoid®-enhanced ultrasonography in differentiating between malignant and benign hepatic nodules with clinical patients (Chapter 1). Secondly, the author evaluated the usefulness of Sonazoid®-enhanced ultrasonography in differentiating between malignant and benign splenic nodules with clinical patients (Chapter 2).In chapter 1, contrast-enhanced ultrasonography using Sonazoid® was performed in 6 normal beagles and 27 dogs with 28 hepatic nodules. An appropriate protocol for the evaluation of all 3 phases (arterial, portal, and parenchymal) was established based on the results for normal beagles. By evaluation of the echogenicity of hepatic nodules during the arterial and parenchymal phases it was possible to differentiate malignant tumors from benign nodules with very high accuracy. In 15 of 16 nodules diagnosed as malignant tumors, nodules were clearly hypoechoic to the surrounding normal liver during the parenchymal phase. Additionally, malignant tumors had different echogenicity compared to the surrounding normal liver during the arterial phase in 14 of 15 nodules. In the portal phase, there were no characteristic findings. In chapter 2, contrast-enhanced ultrasonography using Sonazoid® was performed in 6 normal beagles and 29 dogs with spontaneous focal or multifocal splenic lesions. An appropriate protocol for the evaluation of all 3 phases (early vascular, late vascular, and parenchymal) was established based on the results for normal beagles. In 29 dogs with splenic lesions, qualitative assessment of the enhancement pattern was performed in the early vascular, late vascular, and parenchymal phase. In the early vascular phase, a hypoechoic pattern was significantly associated with malignancy (P = 0.02) with sensitivity of 38% [95% CI, 25-38%], and specificity of 100% [95% CI, 84-100%]. In the late vascular phase, a hypoechoic pattern was significantly associated with malignancy (P = 0.001) with sensitivity of 81% [95% CI, 66-90%], and specificity of 85% [95% CI, 65-95%]. There was no significant difference between malignant and benign lesions during the parenchymal phase.In conclusion, the result of the present study demonstrated that Sonazoid®-enhanced ultrasonography could differentiate benignancy and malignancy of liver and splenic lesions in dogs. For liver lesions, the arterial and parenchymal phase imaging could be useful for the differentiation. For the splenic lesions, the early vascular and late vascular phase imaging could be useful for the differentiation. This thesis could be a huge first step towards making definitive diagnosis with this noninvasive diagnostic method, Sonazoid®-enhanced ultrasonography.