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Imaging Approach for Evaluation of Focal Liver Lesions

2009; Elsevier BV; Volume: 7; Issue: 6 Linguagem: Inglês

10.1016/j.cgh.2009.03.024

1542-7714

Daniele Marin, Alessandro Furlan, Michael P. Federle, Massimo Midiri, Giuseppe Brancatelli,

Liver Disease and Transplantation

Focal liver lesions are common in the general population. Radiology (imaging) plays a pivotal role for the diagnosis, staging, treatment planning, and follow-up of focal liver lesions. To maximize lesion detection and characterization, imaging needs to be performed with appropriate equipment by using protocols carefully designed on the basis of the underlying clinical context. In addition, the decision of an imaging modality cannot be based on the diagnostic accuracy of an imaging test solely but must also consider patient safety and cost-effectiveness. Focal liver lesions are common in the general population. Radiology (imaging) plays a pivotal role for the diagnosis, staging, treatment planning, and follow-up of focal liver lesions. To maximize lesion detection and characterization, imaging needs to be performed with appropriate equipment by using protocols carefully designed on the basis of the underlying clinical context. In addition, the decision of an imaging modality cannot be based on the diagnostic accuracy of an imaging test solely but must also consider patient safety and cost-effectiveness. With the widespread use of cross-sectional imaging examinations, physicians from a wide array of specialties are becoming involved with questions regarding the management of patients with focal liver lesions. To formulate a practical approach to these patients, several factors must be incorporated into a clinical decision-making algorithm (Figure 1), including the particular clinical setting (eg, known comorbidities, underlying cirrhosis, or a known primary neoplasm), the presence of clinical signs and symptoms, the results of laboratory tests, and the critical information provided by imaging studies. In this article, we discuss the role of current imaging techniques for the management of focal liver lesions. The indications, major advantages, and shortcomings of different diagnostic methods are described and illustrated. The choice of an imaging modality for the study of focal liver lesions cannot be based solely on the diagnostic accuracy of the test but must also consider patient safety and cost-effectiveness. Because of a combination of high spatial resolution and inherent soft tissue contrast, lack of ionizing radiation, low cost, and wide availability, ultrasonography (US) is frequently the first-line imaging modality for the study of the liver. Operator dependency, substantial image degradation in obese patients, and limited field of view, however, represent major limitations of this modality compared with other cross-sectional imaging techniques. Common benign lesions, such as cysts and hemangiomas, usually have a characteristic appearance on US, often obviating other evaluation in non-oncology patients. More recently, with the introduction of microbubble contrast agents, contrast-enhanced US (CEUS) offers the unique capability to perform continuous, real-time assessment of normal hepatic parenchyma, hepatic vessels, and liver lesions.1Brannigan M. Burns P.N. Wilson S.R. Blood flow patterns in focal liver lesions at microbubble-enhanced US.Radiographics. 2004; 24: 921-935Crossref PubMed Scopus (166) Google Scholar This extends the temporal window of a dynamic imaging study beyond the limits of standard contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) examinations, which are able to display static views only. Although still under scrutiny, CEUS can be clinically useful in the investigation of rapidly enhancing hepatic tumors such as capillary hemangioma, focal nodular hyperplasia,2Kim T.K. Jang H.J. Burns P.N. et al.Focal nodular hyperplasia and hepatic adenoma: differentiation with low-mechanical-index contrast-enhanced sonography.Am J Roentgenol. 2008; 190: 58-66Crossref PubMed Scopus (130) Google Scholar hepatic adenoma,2Kim T.K. Jang H.J. Burns P.N. et al.Focal nodular hyperplasia and hepatic adenoma: differentiation with low-mechanical-index contrast-enhanced sonography.Am J Roentgenol. 2008; 190: 58-66Crossref PubMed Scopus (130) Google Scholar hepatocellular carcinoma,3Jang H.J. Kim T.K. Wilson S.R. Small nodules (1-2cm) in liver cirrhosis: characterization with contrast-enhanced ultrasound.Eur J Radiol. 2008; ([Epub ahead of print])Google Scholar and metastases4Murphy-Lavallee J. Jang H.J. Kim T.K. et al.Are metastases really hypovascular in the arterial phase? The perspective based on contrast-enhanced ultrasonography.J Ultrasound Med. 2007; 11: 1545-1556Google Scholar (Figure 2). Multi-detector row CT (MDCT) has become the most commonly used modality in the preoperative diagnosis, staging, treatment planning, and follow-up of patients with known or suspected hepatic tumors.5Sahani D.V. Kalva S.P. Imaging the liver.Oncologist. 2004; 9: 385-397Crossref PubMed Scopus (72) Google Scholar With the recent advent of MDCT scanners, substantial anatomic volumes can be acquired within a short scan time, with submillimeter section thickness and virtually no penalty in increased radiation dose. Clinically, these technologic advances have led to image acquisition during peak vascular enhancement, with almost uniform enhancement along the entire scanned volume, reduced motion artifacts, and the capability to generate high-resolution reformations in any desired plane.6Saini S. Multi-detector row CT: principles and practice for abdominal applications.Radiology. 2004; 233: 323-327Crossref PubMed Scopus (48) Google Scholar In a single examination, MDCT provides detailed morphologic and hemodynamic information on the number, size, distribution, and vascularity of liver lesions, all of which are vital in guiding the clinical decision making and therapeutic plan. To maximize the detection and characterization of liver tumors, the CT protocol must be designed according to the diagnostic task. To increase the attenuation difference (ie, conspicuity) between the hepatic parenchyma and liver tumors,7Baron R.L. Understanding and optimizing use of contrast material for CT of the liver.Am J Roentgenol. 1994; 163: 323-331Crossref PubMed Scopus (279) Google Scholar several factors need to be optimized, including the volume and iodine concentration of contrast media, the injection rate (4–5 mL/s) (Figure 3), and the scanning delay from the start of contrast media administration. The CT sections are then obtained during the period of maximum vascular and/or hepatic parenchymal enhancement.8Foley W.D. Mallisee T.A. Hohenwalter M.D. et al.Multiphase hepatic CT with a multirow detector CT scanner.Am J Roentgenol. 2000; 175: 679-685Crossref PubMed Scopus (211) Google Scholar This requires application of contrast agent bolus timing methods, either automatic computer-assisted bolus tracking or test bolus, to correct for differences in circulation times in individual patients (Figure 4).Figure 4Images obtained in a 58-year-old man with HCV-related cirrhosis and hepatocellular carcinoma. (A) Transverse contrast-enhanced CT scan obtained during the early HAP without monitoring the contrast bolus circulation time demonstrates suboptimal timing (noted by absent enhancement of the portal vein [arrow] and spleen [S]). No arterial enhancing lesion can be identified. (B) Corresponding transverse MR image during the appropriate HAP performed with a bolus tracking technique (Smartprep; GE Healthcare, Chalfont St Giles, UK) reveals a 2.0-cm vividly enhancing hepatocellular carcinoma (curved arrow) in the right liver lobe.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Unlike hepatic parenchyma, predominantly fed by the portal vein, liver tumors receive blood supply from the hepatic arterial system. Most tumors are best seen during the hepatic venous phase (HVP), when the maximal difference in attenuation is attained between the vividly enhancing hepatic parenchyma and hypoattenuating lesions7Baron R.L. Understanding and optimizing use of contrast material for CT of the liver.Am J Roentgenol. 1994; 163: 323-331Crossref PubMed Scopus (279) Google Scholar (Figure 5). For certain specific clinical settings, the HVP of imaging must be preceded by a contrast-enhanced acquisition during the hepatic arterial dominant phase (HAP). This phase is crucial in the detection of those liver tumors (eg, focal nodular hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, and hypervascular liver metastases) that receive abundant arterial supply7Baron R.L. Understanding and optimizing use of contrast material for CT of the liver.Am J Roentgenol. 1994; 163: 323-331Crossref PubMed Scopus (279) Google Scholar (Figure 2, Figure 3, Figure 4). During the HAP, these lesions manifest as hyperattenuating foci relative to adjacent, poorly enhanced hepatic parenchyma but might not be detected during the HVP as a result of progressive liver enhancement from the portal vein (Figure 3B). By taking advantage of 2-dimensional reformation and 3-dimensional rendering techniques, the HAP images also enable noninvasive preoperative mapping of the normal hepatic arterial anatomy and common anatomic variants. This information is crucial in patients who are candidates for liver surgery (eg, transplantation, tumor resection, or laparoscopic hepatobiliary surgery),9Catalano O.A. Singh A.H. Uppot R.N. et al.Vascular and biliary variants in the liver: implications for liver surgery.Radiographics. 2008; 28: 359-378Crossref PubMed Scopus (147) Google Scholar transcatheter arterial chemoembolization10Sze D.Y. Razavi M.K. So S.K. et al.Impact of multidetector CT hepatic arteriography on the planning of chemoembolization treatment of hepatocellular carcinoma.Am J Roentgenol. 2001; 177: 1339-1345Crossref PubMed Scopus (37) Google Scholar (Figure 6), or hepatic arterial infusion chemotherapy.11Kapoor V. Brancatelli G. Federle M.P. et al.Multidetector CT arteriography with volumetric three-dimensional rendering to evaluate patients with metastatic colorectal disease for placement of a floxuridine infusion pump.Am J Roentgenol. 2003; 181: 455-463Crossref PubMed Scopus (38) Google Scholar In selected cases, the CT protocol should include additional acquisitions either before or after contrast material administration, during a more delayed phase of enhancement (ie, delayed phase), approximately 3–10 minutes after the start of contrast injection. The noncontrast acquisition might allow the characterization of liver lesions that have attenuation that is inherently higher (ie, hemorrhage, iron, glycogen, or calcification) (Figure 7) or lower (ie, fat, edema, and necrosis) (Figure 8) than liver parenchyma. As an adjunct to a post-contrast CT examination, the noncontrast phase is recommended in patients with cirrhosis12Baron R.L. Brancatelli G. Computed tomographic imaging of hepatocellular carcinoma.Gastroenterology. 2004; 127: S133-S143Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar and, at initial CT examination, in oncology patients.13Oliver 3rd, J.H. Baron R.L. Federle M.P. et al.Hypervascular liver metastases: do unenhanced and hepatic arterial phase CT images affect tumor detection?.Radiology. 1997; 205: 709-715Crossref PubMed Scopus (105) Google ScholarFigure 8Images obtained in a 78-year-old woman with HCV-related cirrhosis and hepatocellular carcinoma. (A) Transverse noncontrast CT scan shows a 3.5-cm lesion in the left lobe, with a focal area (curved arrow) of inherently lower attenuation (–50 HU) caused by intralesional fat deposition. (B, C) On corresponding dual gradient echo MR sequence with (B) in-phase (IP) and (C) opposed-phase (OP) acquisitions, the lesion's fat component (curved arrows) demonstrates marked signal intensity decrease on OP compared with IP image as a result of chemical shift artifact from intracellular fat.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The delayed phase of contrast enhancement plays a key role in the diagnosis of liver lesions with either a prominent fibrous component (eg, cholangiocarcinoma,14Lacomis J.M. Baron R.L. Oliver 3rd, J.H. et al.Cholangiocarcinoma: delayed CT contrast enhancement patterns.Radiology. 1997; 203: 98-104PubMed Google Scholar focal confluent fibrosis,15Ohtomo K. Baron R.L. Dodd 3rd, G.D. et al.Confluent hepatic fibrosis in advanced cirrhosis: appearance at CT.Radiology. 1993; 188: 31-35PubMed Google Scholar or a variety of liver tumors with a central scar) or a blood-pool effect (eg, cavernous hemangioma). On delayed phase images, these lesions demonstrate prolonged and more vivid contrast enhancement relative to the normal hepatic parenchyma. With the widespread use of fast imaging sequences that allow breath-hold imaging of the liver during short acquisition times (less than 20 seconds) and substantial reduction in the cost per examination, MRI has been advocated by some as the modality of choice in the noninvasive work-up of focal liver lesions.16Neto J.A. Elazzazzi M. Altun E. et al.When should abdominal magnetic resonance imaging be used?.Clin Gastroenterol Hepatol. 2008; 6: 610-615Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Compared with CT, major advantages of MRI include higher soft tissue contrast resolution (Figure 9), greater sensitivity to intravenous gadolinium-based contrast agents (Figure 2C), excellent depiction of fluid-containing structures (eg, the biliary tree, gallbladder, or cystic lesions), and the absence of ionizing radiation. The latter attribute of MRI can be an effective strategy to limit the radiation burden from CT examinations, most importantly in children and young adults, or for patients undergoing serial examinations. When the imaging protocol is optimized, MRI enables accurate diagnosis of most focal liver lesions within a reasonable examination time (15–30 minutes).17Semelka R.C. Balci N.C. Op de Beeck B. et al.Evaluation of a 10-minute comprehensive MR imaging examination of the upper abdomen.Radiology. 1999; 211: 189-195PubMed Google Scholar For a comprehensive examination, the MRI protocol of the liver must include pulse sequences that assess T1 and T2 contrast characteristics of different tissues and a dynamic multiphase imaging study after rapid administration of gadolinium-based contrast media.18Semelka R.C. Martin D.R. Balci N.C. Magnetic resonance imaging of the liver: how I do it.J Gastroenterol Hepatol. 2006; 21: 632-637Crossref PubMed Scopus (28) Google Scholar Because of the absence of radiation hazards, multiple phases of contrast-enhanced images should be obtained routinely during the HAP, HVP, and delayed phase, with T1-weighted 3-dimensional volumetric sequences. These sequences enable the use of thin section reconstructions (typically 3.0 mm) along any desired plane, improving the assessment of liver lesions. By taking advantage of fat-sensitive imaging sequences such as chemical shift gradient-echo imaging with in-phase and opposed-phase acquisitions, MRI can improve readers' confidence for the diagnosis of either benign or malignant fat-containing liver lesions (Figure 8)19Basaran C. Karcaaltincaba M. Akata D. et al.Fat-containing lesions of the liver: cross-sectional imaging findings with emphasis on MRI.Am J Roentgenol. 2005; 184: 1103-1110Crossref PubMed Scopus (115) Google Scholar or liver lesions in the setting of diffuse fatty liver disease, as is often encountered in oncology patients after systemic chemotherapy (Figure 9).20Noone T.C. Semelka R.C. Balci N.C. et al.Common occurrence of benign liver lesions in patients with newly diagnosed breast cancer investigated by MRI for suspected liver metastases.J Magn Reson Imaging. 1999; 10: 165-169Crossref PubMed Scopus (20) Google Scholar More recently, the introduction into daily clinical practice of liver-specific MRI contrast media (ie, reticuloendothelial system-specific or hepatobiliary system-specific contrast agents) offers the possibility to combine information of a standard MRI examination with additional functional data, which in turn yields to improved detection and characterization of liver tumors (Figure 10).16Neto J.A. Elazzazzi M. Altun E. et al.When should abdominal magnetic resonance imaging be used?.Clin Gastroenterol Hepatol. 2008; 6: 610-615Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar With the widespread use of sensitive radiologic examinations, the incidental detection of a liver lesion in an asymptomatic patient has become a relatively common finding during radiologic examinations performed for indications other than evaluation for liver disease. The vast majority of these lesions are benign, so that the main goal of imaging is to firmly establish a diagnosis to avoid unnecessary, aggressive management and to minimize patient distress and anxiety.21Choi B.Y. Nguyen M.H. The diagnosis and management of benign hepatic tumors.J Clin Gastroenterol. 2005; 39: 401-412Crossref PubMed Scopus (15) Google Scholar, 22Heiken J.P. Distinguishing benign from malignant liver tumours.Cancer Imaging. 2007; 7: S1-S14Crossref PubMed Scopus (50) Google Scholar Along with clinical information (eg, age, sex, gender), imaging plays a leading role in the diagnosis of incidentally discovered liver lesions. The decision of the primary imaging test depends on a combination of factors, including personal preference of the referring physician, cost, availability of equipment, and individual experience of the radiologist. Some general recommendations, however, can be made. By avoiding the hazards of radiation exposure, US or MRI must be regarded as the modality of choice in the diagnosis of liver lesions in children and young adults. However, CT can display large and varied anatomic structures (eg, lung, abdominal viscera, and skeleton) in a study lasting only a few minutes, making it the preferred modality in older, less cooperative patients and in those considered to be at increased risk for cancer.5Sahani D.V. Kalva S.P. Imaging the liver.Oncologist. 2004; 9: 385-397Crossref PubMed Scopus (72) Google Scholar In the great majority of cases, imaging provides a confident diagnosis of benign lesions, including cysts, hemangiomas, focal steatosis, and focal nodular hyperplasia. In some cases, imaging findings might remain indeterminate or suggestive of malignancy. In these cases, liver biopsy is often warranted to clarify the nature of a liver lesion.23Anders R.A. Kamel I.R. Biopsy considerations in the diagnosis of hepatic masses.Clin Gastroenterol Hepatol. 2007; 5: 541-544Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar The liver is a common site of metastatic disease, with metastases being the most common hepatic malignant neoplasm. Although liver metastases are generally indicative of an advanced tumor stage and poor prognosis, patient survival can be improved substantially by accurate identification of patients with limited disease. These individuals are eligible for a variety of potentially curative therapies, including hepatic resection and percutaneous tumor ablation techniques (eg, radiofrequency, laser, or alcohol ablation).24Dodd 3rd, G.D. Soulen M.C. Kane R.A. et al.Minimally invasive treatment of malignant hepatic tumors: at the threshold of a major breakthrough.Radiographics. 2000; 20: 9-27Crossref PubMed Scopus (541) Google Scholar Thin-section contrast-enhanced MDCT is the preferred imaging modality for the preoperative detection, staging, treatment planning, and follow-up of patients with liver metastases, with reported sensitivity ranging from 73% to 85%.25Valls C. Andía E. Sánchez A. et al.Hepatic metastases from colorectal cancer: preoperative detection and assessment of resectability with helical CT.Radiology. 2001; 218: 55-60Crossref PubMed Scopus (211) Google Scholar Smaller hepatic lesions (1.5 cm in diameter or smaller), however, which are increasingly detected with the routine use of submillimeter section acquisitions, can be difficult to characterize at CT.26Jones E.C. Chezmar J.L. Nelson R.C. et al.The frequency and significance of small (less than or equal to 15 mm) hepatic lesions detected by CT.Am J Roentgenol. 1992; 158: 535-539Crossref PubMed Scopus (175) Google Scholar The detection of such diminutive findings frequently poses a diagnostic dilemma during the work-up of oncology patients (Figure 11), although these are usually benign.27Khalil H.I. Patterson S.A. Panicek D.M. Hepatic lesions deemed too small to characterize at CT: prevalence and importance in women with breast cancer.Radiology. 2005; 235: 872-878Crossref PubMed Scopus (73) Google Scholar Depending on potential impact on management, such "too small to characterize" lesions might be subjected to additional imaging28Morana G. Cugini C. Mucelli R.P. Small liver lesions in oncologic patients: characterization with CT, MRI and contrast-enhanced US.Cancer Imaging. 2008; 8: S132-S135Crossref PubMed Scopus (7) Google Scholar or close interval imaging follow-up (eg, 3–6 months),29Robinson P.J. Arnold P. Wilson D. Small "indeterminate" lesions on CT of the liver: a follow-up study of stability.Br J Radiol. 2003; 76: 866-874Crossref PubMed Scopus (28) Google Scholar because they are generally too small to biopsy. In this clinical setting, MRI is typically used as a problem-solving modality. Compared with contrast-enhanced CT, MRI provides additional useful information for the characterization of liver lesions, such as lesion signal intensity on T2-weighted sequences (Figure 12), improved visualization of lesion-specific contrast-enhancement patterns (as a result of the inherently higher sensitivity of MRI to gadolinium-based contrast media), and functional information with the use of liver-specific contrast agents (Figure 10). The incidence of hepatocellular carcinoma has gradually increased during the past 2 decades. Cirrhosis from various etiologies is the single most important predisposing factor for hepatocellular carcinoma, with approximately 80% of these tumors developing in a cirrhotic liver.30El-Serag H.B. Epidemiology of hepatocellular carcinoma in USA.Hepatol Res. 2007; 37: S88-S94Crossref PubMed Google Scholar Because of the widespread practice of surveillance in patients who are at increased risk for the development of hepatocellular carcinoma, an increasing number of tumors are being identified at an earlier stage, when liver function is still preserved and potentially curative therapies, including surgery or percutaneous tumor ablation techniques, can be performed with a curative intent.31El-Serag H.B. Marrero J.A. Rudolph L. et al.Diagnosis and treatment of hepatocellular carcinoma.Gastroenterology. 2008; 134: 1752-1763Abstract Full Text Full Text PDF PubMed Scopus (874) Google Scholar Imaging (ie, CEUS, CT, or MRI) plays a pivotal role in the diagnosis of hepatocellular carcinoma and assessment of tumor burden. The imaging features that differentiate hepatocellular carcinoma from other benign, cirrhosis-associated hepatocellular nodules (eg, regenerative nodules and low- or high-grade dysplastic nodules) are increased vascularity of the tumor compared with the adjacent hepatic parenchyma during the HAP and "washout" (decreased attenuation relative to liver) on later phases of imaging (Figure 7).32Baron R.L. Oliver 3rd, J.H. Dodd 3rd, G.D. et al.Hepatocellular carcinoma: evaluation with biphasic, contrast-enhanced, helical CT.Radiology. 1996; 199: 505-511PubMed Google Scholar Both signs are required for a definite diagnosis of hepatocellular carcinoma with 1 (lesions >2 cm) or 2 (lesions 1–2 cm) concordant imaging techniques.33Bruix J. Sherman M. Practice Guidelines CommitteeAmerican Association for the Study of Liver DiseasesManagement of hepatocellular carcinoma.Hepatology. 2005; 42: 1208-1236Crossref PubMed Scopus (5017) Google Scholar Unlike overt hepatocellular carcinoma nodules, small well-differentiated tumors receive relatively little arterial supply, thus being rarely detected at imaging during the HAP. These tumors tend to be hypovascular relative to the liver during the HVP and delayed phase (Figure 13).34Bolondi L. Gaiani S. Celli N. et al.Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma.Hepatology. 2005; 42: 27-34Crossref PubMed Scopus (357) Google Scholar In addition, although arterial enhancement is a very sensitive sign for the diagnosis of hepatocellular carcinoma, several other entities such as nontumorous arterioportal shunts or hemangioma might manifest with a similar appearance and, thus, mimic hepatocellular carcinoma during the HAP, particularly if smaller than 2 cm in diameter.35Brancatelli G. Baron R.L. Peterson M.S. et al.Helical CT screening for hepatocellular carcinoma in patients with cirrhosis: frequency and causes of false-positive interpretation.Am J Roentgenol. 2003; 180: 1007-1014Crossref PubMed Scopus (115) Google Scholar Clinically, these false-positive findings might expose the patient to the risk of either unnecessary invasive procedures (eg, biopsy or percutaneous ablation) or, for patients on the liver transplant waiting list, might increase inappropriately the assignment priority.36Said A. Lucey M.R. Liver transplantation: an update.Curr Opin Gastroenterol. 2006; 22: 272-278Crossref PubMed Scopus (13) Google Scholar Unlike hepatocellular carcinoma, early enhancing pseudolesions demonstrate persistent enhancement during the HVP and/or delayed phase, thus being isoattenuating or hyperattenuating/intense compared with the adjacent liver parenchyma. When imaging findings are equivocal, lesion biopsy or, in the case of a lesion smaller than 1 cm, imaging follow-up is warranted to confirm or rule out the diagnosis of hepatocellular carcinoma in patients with cirrhosis.33Bruix J. Sherman M. Practice Guidelines CommitteeAmerican Association for the Study of Liver DiseasesManagement of hepatocellular carcinoma.Hepatology. 2005; 42: 1208-1236Crossref PubMed Scopus (5017) Google Scholar Contrast-enhanced CT and MRI play a pivotal role during imaging follow-up of patients with treated liver tumors. When therapy is performed with a curative intent, such as in the case of liver surgery (ie, hepatic resection or transplantation) or percutaneous tumor ablation techniques, the goal of imaging is early diagnosis of procedure-related complications37Latteri F. Sandonato L. Di Marco V. et al.Seeding after radiofrequency ablation of hepatocellular carcinoma in patients with cirrhosis: a prospective study.Dig Liver Dis. 2008; 40: 684-689Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar (Figure 14) and incomplete treatment or recurrence of the tumor (Figure 15).38Catalano O. Esposito M. Nunziata A. et al.Multiphase helical CT findings after percutaneous ablation procedures for hepatocellular carcinoma.Abdom Imaging. 2000; 25: 607-614Crossref PubMed Scopus (49) Google Scholar With prompt recognition, the latter events might be amenable to effective secondary treatments.39Yang W. Chen M.H. Yin S.S. et al.Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy: therapeutic efficacy on early- and late-phase recurrence.Am J Roentgenol. 2006; 186: S275-S283Crossref PubMed Scopus (53) Google ScholarFigure 15CT images obtained in a 74-year-old woman with hepatocellular carcinoma who underwent radiofrequency ablation. (A) Transverse contrast-enhanced CT scan obtained during the HAP shows a 3.5-cm lesion (arrows) in left hepatic lobe. (B) On corresponding image obtained 1 month after the ablation procedure, the lesion demonstrates uniform hypoattenuation caused by tumor necrosis, except for a peripheral enhancing nodule indicative of residual vital tumor tissue (curved arrow). On the basis of the latter finding, the patient underwent repeat radiofrequency ablation procedure with successful tumor ablation, shown on a subsequent scan (C).View Large Image Figure ViewerDownload Hi-res image Download (PPT) In patients who have had palliative therapies such as local or systemic chemotherapy or transarterial chemoembolization, imaging follow-up can provide an accurate assessment of tumor response to therapy. A prompt identification of nonresponder patients enables timely discontinuation or change of chemotherapy regimen, with improved patient survival and/or quality of life. By avoiding artifacts caused by high concentrations of iodized oil, MRI is generally preferred over CT for the follow-up of patients who have had conventional transarterial chemoembolization (Figure 16). For evaluation of treatment response of hypervascular neoplasms (eg, hepatocellular carcinoma and certain metastases), decreased vascularity or even necrosis might indicate a positive response to therapy, often predating a reduction in tumor size.40Murakami T. Nakamura H. Hori S. et al.Detection of viable tumor cells in hepatocellular carcinoma following transcatheter arterial chemoembolization with iodized oil: pathologic correlation with dynamic turbo-FLASH MR imaging with Gd-DTPA.Acta Radiol. 1993; 34: 399-403PubMed Google Scholar With the trend toward personalized medicine (ie, patient-specific diagnosis and drug treatment), imaging is becoming increasingly important as a biomarker of drug response. This has led to investigation of a variety of functional biomarkers that might be integrated with anatomic information to predict tumor response to treatment. By assessing regional and global alterations in liver blood flow, perfusion CT and MRI41Pandharipande P.V. Krinsky G.A. Rusinek H. et al.Perfusion imaging of the liver: current challenges and future goals.Radiology. 2005; 234: 661-673Crossref PubMed Scopus (263) Google Scholar hold promise as quantitative tools to measure vascularity and angiogenesis of liver tumors, which have become crucial in the evaluation of tumor response to new molecular targeted antiangiogenetic agents (eg, sorafenib).42Llovet J.M. Ricci S. Mazzaferro V. et al.Sorafenib in advanced hepatocellular carcinoma.N Engl J Med. 2008; 359: 378-390Crossref PubMed Scopus (8551) Google Scholar Diffusion-weighted MRI is an emerging tool for the investigation of focal liver lesions. This technique has the potential to increase the conspicuity of liver tumors. In addition, on the basis of the lesion's apparent diffusion coefficient, diffusion-weighted MRI might be helpful in differentiating benign from malignant liver tumors or assessing tumor response to therapy. Although positron emission tomography (PET) and CT, or PET/CT, play a key role in the initial staging and follow-up of patients with a variety of tumors, with a sensitivity of approximately 90% for the detection of liver metastases, its clinical utility in the diagnostic work-up of primary liver tumors is still debated. Because of a combination of high safety profile, low cost, and wide availability, US is the first-line imaging modality for the study of the liver and might be sufficient to exclude hepatic disease or to diagnose with confidence common lesions such as cysts and hemangiomas. Contrast-enhanced CT and MRI remain the reference techniques in the assessment of focal liver lesions. To maximize lesion detection and characterization, CT and MRI need to be performed with equipment capable of obtaining thin-section large anatomic coverage with fast acquisition times. Even more importantly, imaging protocol must be carefully designed on the basis of the underlying clinical concern.