contrast dynamic imaging techniques and recognized by the presence of intratumoral non-enhanced areas. local response to treatment is defined as: a. complete response, defined as complete disappearance of all known lesions (absence of tumor enhanced areas, reflecting total tumor necrosis) and absence of other new lesions determined by two observations not less than 4 weeks apart; b. partial response, defined as more than 50% reduction in total tumor enhancement in all measurable lesions, determined by two observations not less than 4 weeks apart c. stable disease (is not described by a, b, or d) d. progressive disease, defined as 25% increase in size of one or more measurable lesions or the appearance of new lesions. techniques for evaluating the efficiency of therapy the efficiency of 2d ultrasound is low in assessing the effects of hcc or metastasis therapy, as it is unable to differentiate viable tumor tissue from post-therapy tumor necrosis. however, it is able to detect the appearance of new lesions and to assess the occurrence of any complications of disease progression (ascites or portal vein thrombosis). color doppler ultrasound can be useful sometimes being able to show the presence of intratumoral vasculature as a sign of incomplete therapy or intratumoral recurrence. the absence of doppler signal does not exclude the presence of viable tumor tissue. ceus exploration, by its ability to enhance intra-lesion microcirculation, has proved its utility in monitoring therapeutic efficacy. its indications are defined for hcc ablative treatments (pre, intra and post-therapy), while monitoring of systemic therapies of hcc and metastases are not validated indications at this time, but with proved efficacy in extensive clinical trials (claudon et al., 2008). ceus examination cannot completely replace the other imaging diagnostic methods currently in use because of the known limitations of the ultrasound method (operator/ equipment dependent, ultrasound examination limitations). in addition to bloating, in cancer patients post-therapy steatosis occurs, which prevent deep visibility. spiral ct scan remains the method of choice in monitoring cancer therapies because it provides an overview of tumor extension and it is not limited by bloating or steatosis. gadolinium mri examination is a procedure used more and more often, and its advantages are the absence of irradiation and its high sensitivity in tumor vasculature detection, especially in smaller tumors. however it remains an expensive and not a very accessible procedure, although it has a high specificity. currently, ceus and mri are considered complementary methods to ct scan. ultrasound monitoring ablative therapies (alcoholization – pei, radiofrequency ablation – rfa) ablative therapies are considered curative treatments for hcc together with surgical resection and liver transplantation and they are indicated for early tumor stages in patients with good liver function. also they are successfully applied in the treatment of liver metastases, where surgical resection is contraindicated. they are chemical (intratumoral ethanol injection) or thermal (radiofrequency, laser or microwave ablation). they are applied in order to obtain a full therapeutic response, without affecting liver function. complete response is locally proved by complete tumor necrosis with a safety margin around the tumor. 2d ultrasound, doppler ultrasound and especially ceus can play an important role in pretherapeutic staging, particularly when sectional imaging investigations (ct, mri) provide uncertain results or are contraindicated. during the interventional procedure, ultrasound allows guidance of the needle into the tumor. ceus allows guidance in areas of viable tissue and avoids intratumoral necrotic areas. ceus also allows assessment of therapeutic effect immediately post-procedure (with the possibility of reintervention in case of partial response) . to accurately assess the effectiveness of treatment it is mandatory to compare the tumor diameter before therapy with the ablation area. the volume of damaged tissue must be higher than the initial tumor volume. ceus appearance is that of central nonenhanced area showing a peripheral homogeneous hyperenhanced rim due to post-procedure inflammation. 24 hours after the procedure the inflammatory peripheral rim is thinning and the necrotic area appears larger than at the previous examination. thus, a possible residual tumor may appear more evident. residual tumor has poorly defined edges, irregular shape, and the tumor diameter is unchanged. residual tumor tissue is evidenced at the periphery of the tumor as an eccentric area behaving as the original tumor at ceus examination, with arterial hyperenhancement and portal and late wash-out. ultrasound examination 24 hours after the procedure, including ceus, can show apart from the character of the lesion any potential post-intervention complications (e.g. active bleeding). in the first days after rfa both ceus and spiral ct have low sensitivity in assessing therapeutic efficacy. ct sensitivity 24 hours post-therapy is reported to be even lower than ceus. difficulties in ceus examination result from post-lesion hyperemia, presence of intratumoral air, ultrasound limitations (too deep lesion or the presence of fatty liver) or lack of patient's cooperation (immediately after therapy). for this reasons contrast imaging (ct or ceus) control should be performed one month after ablation to confirm the result of the therapy. local recurrence is defined as recurrence of a hyperenhanced area at tumor periphery in the arterial phase, with portal and late wash-out. sometimes, especially for hcc treated by alcoholization (pei) hyperenhanced septa or vessels can be shown inside the lesion. in case of successful treatment, us monitoring using ceus is performed every three months. although ce-ct and/or mri are considered the method of choice in post-therapy monitoring, ceus can be used in follow-up protocols, its diagnostic accuracy being equivalent to that of ce-ct or mri. fig. 13. assessment of therapeutic efficacy on ultrasound (2d, cfm, ceus). us exam shows vascular doppler signal at cfm (left) and ceus examination reveals incomplete therapy (right). ultrasound monitoring of tace therapy (transarterial chemoembolization) transarterial chemoembolization (tace) is part of palliative therapies for hcc used in intermediate stages of the disease. it consists of selective angiographic catheterization of the hepatic artery and injection of chemotherapeutic agents (usually adriamycin, but other molecules are currently the subject of clinical trials), followed by embolization of hepatic artery with gelfoam, alcohol or metal rings. a similar procedure is transarterial embolization but without chemotherapeutic agents injection, used in the treatment of hypervascular liver metastases. these therapies are based on the predominantly arterial vasculature of hcc and hypervascular metastases, while the remaining liver parenchyma has a dual vascular intake, predominantly portal. their efficacy is high only for lesions who are hyperenhanced during arterial phase. the role of us is limited in the first few days after the procedure, and refers only to its complications, due to lipiodol retention mainly intratumoral, but also diffusely intrahepatic. on ultrasound, lipiodol appears intensely hyperechoic inside the tumor, with significant posterior attenuation which make us examination more difficult. on the other hand, ce-ct is also limited by the presence of lipiodol (iodine oil), therefore the evaluation of therapeutic efficiency is currently made by indirect assessing lipiodol binding to the tumor using nonenhanced ct. ce-mri is not influenced by the presence of lipiodol, but it is an expensive method and still difficult to reach. several studies have proved similar efficacy, even superior, of ceus compared to ce-ct and ce-mri for the evaluation of post-tace treatment results, while other studies have shown the limitations of ceus especially for deep or small lesions. given the ceus limitations, currently some authors consider ct as standard method for the evaluation of tace and local ablative therapies and ceus and ce-mri as complementary methods. monitoring tace therapeutic results by contrast imaging techniques is performed as for ablative therapies initially after one month then after every 3 months post-tace. given that tace is indicated only for hyperenhanced lesions during arterial phase, ceus plays a very important role in monitoring the dysplastic nodules to identify the moment when changes occur in arterial vasculature, being able to have an early therapeutic intervention in order to limit tumor progression, to increase patient survival, and thus to create a bridge to liver transplantation. fig. 14. small hcc is seen at top (nodule in nodule). efficient chemoembolization of the nodule (bottom). ceus examination shows no circulatory signal within the nodule. ultrasound monitoring of systemic therapies systemic therapies are procedures based on the affinity of certain molecules to inhibit either tumor cell replication or multiplication of neoplastic vasculature (antiangiogenic therapies). they are intravenously administered and are indicated in advanced stages of liver tumor diseases, when there are no other effective therapeutic solutions. among ultrasound techniques, ceus is the one that brought a significant benefit not only by increasing the sensitivity and specificity of ultrasound in detecting liver metastases, but also by assessing the efficacy of systemic therapy for hcc and metastases. the method has been adopted by oncologists since 2003 because it involves no irradiation and has no hepatic or renal toxicity, and it is now currently used in tumor therapeutic evaluation. it is currently used in large clinical trials aimed at determining the efficacy of different types of anti-angiogenic molecules by quantifying intratumoral perfusion based on the statistical analysis performed using specific software during post-processing in order to assess therapeutic efficacy as early as possible.