The liver is one of the most common targets for oncologic imaging. The organ may be the site of the primary tumor, but more often, the search is for metastases from cancers elsewhere.
At a symposium on Oncologic Imaging for the Practicing Radiologist, presented by the University of Texas MD Anderson Cancer Center in San Antonio, Tex, in September 2003, Chusilp Charnsangavej, MD, professor of diagnostic radiology at UTMDACC, discussed imaging of hepatocellular carcinoma (HCC), which is one of the world’s most common malignancies, causing an estimated 1 million deaths per year. Although in the past HCC was not seen frequently in the United States, Charnsangavej cautioned that this situation will change because of the increases in predisposing conditions such as alcohol abuse and chronic infection with the hepatitis B or, especially, hepatitis C viruses. In fact, the incidence of HCC has almost doubled in this country in the past 20 years. 1
An HCC usually develops in a cirrhotic liver, and the challenge for the radiologist is to differentiate the cancer from regenerative nodules and from other lesions such as hemangiomas and metastases.
The goals of imaging of a newly diagnosed HCC are to determine whether:
- The lesion is resectable;
- It has invaded the portal or hepatic vein;
- There are satellite lesions in other hepatic lobes;
- There is cirrhosis and portal hypertension;
- There are lymph node or distant metastases.
Sonography has been a popular method of looking for HCC. Typically, the cancer has a mosaic appearance with peripheral lucency, a lateral shadow, and posteriorenhancement. 1 Color Doppler scans often show a network of small blood vessels and a pulsatile waveform in the feeding artery. Dilation of the portal vein and thesplenic and superior mesenteric veins may be apparent in patients with portal hypertension. 1 Use of contrast medium can improve the differential diagnosis of HCC, metastases, hemangiomas, and abscesses. 2 Other techniques that improve the sensitivity and specificity for HCC are echo-enhanced power Doppler, 3 coded harmonic imaging with contrast enhancement, 4 and wideband harmonic gray-scale imaging with galactosepalmitic acid contrast. 5 All of these methods have problems identifying lesions smaller than 1 cm. 6
The diagnosis of HCC from CT scans is made on the basis of the hemodynamics of injected contrast medium, with multiphasic scans being acquired. 7 The hypervascularity of most of these tumors and their usual derivation of a blood supply from the hepatic artery means that they are best seen on early scans after rapid administration of a large bolus of contrast. The characteristic mosaic pattern and the tumor capsule are then visible, and any areas of necrosis or hemorrhage are apparent. The arterial phase is particularly good for identifying small lesions. 8 During the portal phase of the scan, on the other hand, the tumor may be hypodense or even isodense. The pattern of contrast uptake and washout can usually distinguish HCC from metastases, nodular hyperplasia, and other lesions 9 and may provide clues to the extent of tumor differentiation. 10 Multidetectorarray scanners are even more accurate, 11,12 and use of the data for multiplanar volume renditions and maximum intensity projections allows better measurement of the total tumor burden. 13
Magnetic resonance imaging with dynamic fast scanning after rapid intravenous administration of gadolinium contrast is another option. A useful protocol is T2-weighted fast spin-echo with fat saturation and multiphasic gadolinium-enhanced two- and threedimensional T1-weighted gradient echo. 14 The tumor capsule is better appreciated on T1-weighted images, whereas the internal architecture of the tumor, including any areas of hemorrhage or necrosis, are more visible on T2-weighted scans. Burrel and associates 15 have found MR angiography to be the best modality for staging of HCC measuring 1 to 2 cm, and Kanematsu and colleagues 16 reported that MR is capable of depicting diffuse HCC. For HCC of all types, an indication of the degree of malignancy can be obtained with superparamagnetic iron oxide (SPIO; ferumoxides), which is taken up by the Kupffer cells of the reticuloendothelial system. Such cells are present in well-differentiated, but not moderately and poorly differentiated, HCC. 1
Few studies have been done in HCC using positron emission tomography (PET) with fluorine 18-labeled deoxyglucose (FDG). This modality may distinguish well from poorly differentiated cancers and is a good method for detecting extrahepatic metastases. 1
IMAGING OF HEPATIC METASTASES
A radiologist in the United States is far more likely to be asked to image the liver of a patient with cancer to determine if there are any metastases than to search for HCC. As many as 30% of patients dying of cancer have hepatic metastases, and among patients with gastrointestinal cancers, 40% have liver lesions as their initial presentation.
In a patient with newly diagnosed cancer, the physician wants to know whether there are metastases and, if so, how many and where. The physician is then in a position to determine if the disease is resectable and whether any of the newer treatment techniques such as percutaneous ablation are appropriate. Later, the radiologist will be asked to determine whether the cancer has recurred.
Ultrasonography is usually considered the modality of choice for detecting hepatic metastases, although it is operator dependent and may overlook lesions smaller than 1 cm. 17 Contrast-enhanced helical CT is 70% to 85% sensitive in detecting hepatic metastases of colorectal carcinoma; CT arterial portography increases the sensitivity to as much as 93%. 17
Another option is MRI. 17,18 Characteristically, metastases show an enhancing peripheral ring immediately after gadolinium contrast administration. 18 Colorectal cancer metastases are moderately hyperintense on T2-weighted images and hypointense on T1-weighted images. The sensitivity of MRI to this type of metastasis can be improved by dynamic contrast-enhanced studies. Typically, the metastases, which derive their blood supply from the hepatic artery, display high signal during the arterial phase and lower signal during the portal venous phase, when the normal hepatic parenchyma, supplied primarily by the portal vein, becomes prominent. A newer option is ferumoxides, which are not taken up by metastases. 19 Such tissue-specific contrast agents may aid in preoperative planning. 20
FDG-PET and radioimmunoscintigraphy with technetium Tc 99m or indium In111 labeled monoclonal antibodies against carcinoembryonic antigen (CEA) are being explored as tools for identifying colorectal cancer metastases. Many of the reported studies of PET are compromised by small patient numbers or lack of histopathologic confirmation of the diagnosis, but the technique appears useful in identifying extrahepatic metastases in patients being considered for partial hepatic resection. 21 Radioimmunoscintigraphy with 111In-labeled antibodies, in which metastases appear as areas of low uptake, has proved less accurate than CT. 22 Scans with 99mTc-labeled monoclonal antibodies against CEA-derived antigens, in which metastases appear as areas of increased isotope uptake, have shown a sensitivity as high as 75% and a specificity exceeding 90% 23 but have not found wide acceptance.
At the September meeting, Paul M. Silverman, MD, professor of diagnostic radiology at MD Anderson and the symposium organizer, spoke of the several advantages of multidetector array CT scanners for identifying and assessing hepatic metastases. These scanners can cover the same area with thinner sections or depict a larger area with thinner sections in the same time, thus making whole-organ imaging a practical reality. Contrast enhancement can be optimized for each patient with computer automated scan technology (CAST), and threephase imaging is predictably possible: hepatic arterial, late arterial (portal venous inflow), and hepatic (portal) venous. The first phase images are the template for constructing CT angiograms. The second set of images is best for depicting hypervascular tumors, while the third is best for hypovascular tumors. Arterial-phase studies will reveal 30% more lesions than are depicted by classic CT scans, and 6% of metastases are visible only on arterial-phase images. Finally, the greater speed of multidetector scanners makes the procedure more acceptable to patients and increases department throughput.
Imaging of the liver is frequently called for in the cancer patient. Numerous options are available, and the choice depends on the particular clinical situation and the equipment available.
Judith Gunn Bronson, MS, is a contributing writer for Decisions in Axis Imaging News.
- Kamel IR, Bluemke DA. Imaging of hepatocellular carcinoma. J Vasc Intervent Radiol. 2002;13(suppl):S173S184.
- Youk JH, Kim CS, Lee JM. Contrastenhanced agent detection imaging: value in the characterization of focal hepatic lesions. J Ultrasound Med. 2003;22:897910.
- Rickes S, Schulze S, Neye H, Ocran KW, Wermke W. Improved diagnosing of small hepatocellular carcinomas by echoenhanced power Doppler sonography in patients with cirrhosis. Eur J Gastroenterol Hepatol. 2003;15:893900.
- Furuse J, Nagase M, Ishii H, Yoshino M. Contrast enhancement patterns of hepatic tumours during the vascular phase using coded harmonic imaging and Levovist to differentiate hepatocellular carcinoma from other focal lesions. Br J Radiol. 2003;76:385392.
- Isozaki T, Numata K, Kiba T, et al. Differential diagnosis of hepatic tumors by using contrast enhancement patterns at US. Radiology. 2003;229:798805.
- Gritzmann N. Small hepatocellular carcinomas in patients with liver cirrhosis: potentials and limitations of contrastenhanced power Doppler sonography [comment]. Eur J Gastroenterol Hepatol. 2003;15:881883.
- Valls C, Andia E, Roca Y, Cos M, Figueras J. CT in hepatic cirrhosis and chronic hepatitis. Semin Ultrasound CT MR. 2002;23:3761.
- Zhou KR, Yan FH, Tu BW. Arterial phase of biphase enhancement spiral CT in diagnosis of small hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2002;1:6871.
- Liu WY, Jin Y, Rong RH, Ta X, Zhu XS. Multi-phase helical CT in diagnosis of early hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2003;2:7376.
- Karahan OI, Yikilmaz A, Isin S, Orhan S. Characterization of hepatocellular carcinomas with triphasic CT and correlation with histopathologic findings. Acta Radiol. 2003;44:566571.
- Kopp AF, Heuschmid M, Claussen CD. Multidetector helical CT of the liver for tumor detection and characterization. Eur Radiol. 2002;12:745752.
- Zhao H, Zhou KR, Yan FH. Role of multiphase scans by multirow-detector helical CT in detecting small hepatocellular carcinoma. World J Gastroenterol. 2003;9:21982201.
- Kamel IR, Georgiades C, Fishman EK. Incremental value of advanced image processing of multislice computed tomography data in the evaluation of hypervascular liver lesions. J Comput Assist Tomogr. 2003;27:652656.
- Hussain SM, Semelka RC, Mitchell DG. MR imaging of hepatocellular carcinoma. Magn Reson Imaging Clin North Am. 2002;10:3152.
- Burrel M, Llovet JM, Ayuso C, et al. MRI angiography is superior to helical CT for detection of HCC prior to liver transplantation: an explant correlation. Hepatology. 2003;38:10341042.
- Kanematsu M, Semelka RC, Leonardou P, Mastropasqua M, Lee JK. Hepatocellular carcinoma of diffuse type: MR imaging findings and clinical manifestations. J Magn Reson Imaging. 2003;18:189195.
- Saunders TH, Mendes Ribeiro HK, Gleeson FV. New techniques for imaging colorectal cancer: the use of MRI, PET and radioimmunoscintigraphy for primary staging and follow-up. Br Med Bull. 2002;64:8199.
- Pedro MS, Semelka RC, Braga L. MR imaging of hepatic metastases. Magn Reson Imaging Clin North Am. 2002;10:1529.
- Takahama K, Amano Y, Hayashi H, Ishihara M, Kumazaki T. Detection and characterization of focal liver lesions using superparamagnetic iron oxideenhanced magnetic resonance imaging: comparison between ferumoxidesenhanced T1-weighted imaging and delayed-phase gadolinium-enhanced T1-weighted imaging. Abdom Imaging. 2003;28:525530.
- Sica GT, Ji H, Ros PR. Computed tomography and magnetic resonance imaging of hepatic metastases. Clin Liver Dis. 2002;6:165179.
- Zealley IA, Skehan SJ, Rawlinson J, Coates G, Nahmias C, Somers S. Selection of patients for resection of hepatic metastases: improved detection of extrahepatic disease with FDG PET. Radiographics. 2001;21(spec no.)S55S69.
- Corman ML, Galandiuk S, Block GE, et al. Immunoscintigraphy with 111-Insantumomab pendetide in patients with colorectal adenocarcinoma: performance and impact on clinical management. Dis Colon Rectum. 1994;37:129137.
- Moffat FL Jr, Pinsky CM, Hammershaimb L, et al. Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab’ antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal phase three trial. J Clin Oncol. 1996;14:22952305.