**3.2 Dysplastic nodules (DN)**

These lesions have various patterns (hypo or hyperechoic) with at least 1 cm diameter. They are hepatocytes with dysplastic changes, but without clear histological criteria for malignancy. They are divided into low-grade dysplastic nodules, where cellular atypia are mild and high-grade dysplastic nodules with moderate or severe cellular atypia, but without any established signs of malignancy. Occasionally, well-differentiated HCC foci can be identified in high-grade dysplastic nodules (appearance called "nodule in nodule") (Minami & Kudo, 2010). Most authors accept the carcinogenesis process as a progressive transformation of DN from low-grade to high-grade and into HCC. The nodule's vasculature changes progressively, correlated with the degree of malignancy, and it is characterized by decrease until absence of portal venous input and by increase of arterial intratumoral input. Neoformation vessels occur with increasing degree of dysplasia. Arterial neovascularization is enhanced in a chaotic and explosive way, while normal, arterial and portal vasculature continues to decline. High-grade dysplastic nodules are hypovascularized both arterial and portal phases, while early HCC nodules may have similar arterial pattern with the surrounding parenchyma or exacerbated, and portal hypovascularization. In moderate or poorly differentiated HCC (classic HCC) tumor nutrition is performed only by neoformation vessels (abundant), the normal arterial and portal vasculature completely disappearing (Matsui 2004). This behavior of intratumoral vascularization is typical for HCC and is the key to imaging diagnosis (Lencioni et al 2008).

liver segments. They can crowd resulting in large pseudo tumors. At Doppler examination, these nodules have no circulatory signal. CEUS exploration is indicated when a nodule is different against the general pattern of restructured liver either by different echogenity or by a different size than the majority of nodules. During the arterial phase, the signal is weak or absent. During the portal venous and late phase, the appearance is persistently isoechoic. Generally, RN is not distinct from the surrounding parenchyma. CEUS examination is useful to exclude an active lesion at the moment of exploration but does not have absolute prognostic value; therefore the patient should be periodically examined at short intervals (Kojiro, 2004; Bolondi et al, 2005). Correlation with clinical status and AFP measurements is

Fig. 9. Regenerative nodule (CEUS). One can see the hypovascular pattern of the solid

These lesions have various patterns (hypo or hyperechoic) with at least 1 cm diameter. They are hepatocytes with dysplastic changes, but without clear histological criteria for malignancy. They are divided into low-grade dysplastic nodules, where cellular atypia are mild and high-grade dysplastic nodules with moderate or severe cellular atypia, but without any established signs of malignancy. Occasionally, well-differentiated HCC foci can be identified in high-grade dysplastic nodules (appearance called "nodule in nodule") (Minami & Kudo, 2010). Most authors accept the carcinogenesis process as a progressive transformation of DN from low-grade to high-grade and into HCC. The nodule's vasculature changes progressively, correlated with the degree of malignancy, and it is characterized by decrease until absence of portal venous input and by increase of arterial intratumoral input. Neoformation vessels occur with increasing degree of dysplasia. Arterial neovascularization is enhanced in a chaotic and explosive way, while normal, arterial and portal vasculature continues to decline. High-grade dysplastic nodules are hypovascularized both arterial and portal phases, while early HCC nodules may have similar arterial pattern with the surrounding parenchyma or exacerbated, and portal hypovascularization. In moderate or poorly differentiated HCC (classic HCC) tumor nutrition is performed only by neoformation vessels (abundant), the normal arterial and portal vasculature completely disappearing (Matsui 2004). This behavior of intratumoral vascularization is typical for HCC and is the key to imaging diagnosis (Lencioni et al 2008).

required.

nodule, with a size <10 mm.

**3.2 Dysplastic nodules (DN)** 

B-mode ultrasonography is unable to distinguish between regenerative nodules and "borderline" lesions such as dysplastic nodules and even early HCC. Doppler examination also has a low sensitivity in differentiating dysplastic nodules from early HCC. Doppler signal may be absent in both regenerative and dysplastic nodules. Some authors indicate the presence of venous type Doppler flow which reflects the portal venous nutrition of the nodule as a characteristic feature of dysplastic nodules and early HCC (Minami & Kudo, 2010). Other authors noticed the presence of an arterial flow with small frequency variations and a normal resistivity index (RI) (Lencioni et al 2008).

On CEUS examination both RN and DN may have quite a variable enhancement pattern. Generally, both nodules enhances identically with the surrounding liver parenchyma after UCAs injection. Dysplastic nodules are hypovascular in the arterial phase. In case of highgrade dysplastic nodule sometimes a hypervascularization can be detected, but without associating "wash out" during portal and late CEUS phases. In these cases, biopsy may clarify the diagnosis.

Fig. 10. Dysplastic nodule (2D, CFM, CEUS). The nodule is well-defined with a size between 10- 20 mm, lacks vessels in CFM and CEUS exploration.
