Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

and a venous or interstitial sequence. Because most malignant liver neoplasms are supplied primarily by the hepatic artery, arterial (and capillary) phase images are more useful in this clinical setting than delayed images. Vessels and vascular tumors are also often best evaluated on early (capillary phase) contrastenhanced images.

Contrast Agents

Magnetic resonance imaging contrast agents useful in the liver are classified into four broad categories:

1.Gadolinium chelates (extracellular agents)

2.Macrophage-monocytic phagocytic system agents

3.Primarily hepatobiliary agents (intracellular agents)

4.Blood-pool agents

Some contrast agents overlap between categories. For instance, primarily hepatobiliary agents have an initial extracellular distribution; gadobenate dimeglumine (Gd-BOPTA) has dual contrast agent characteristics—it is both a nonspecific and a hepatobiliary agent.

All currently available MR contrast agents shorten tissue T1 and T2 relaxation times. The paramagnetic gadolinium and manganese contrast agents primarily shorten T1 and thus increase signal intensity of normal liver parenchyma on T1-weighted images; the superparamagnetic iron oxides shorten T2 and thus decrease signal intensity on T2-weighted images.While these metal ions are efficient, they are rather toxic and are thus chelated to other small molecular weight structures such as diethylenetriamine pentaacetic acid (DTPA) to reduce their toxicity.

The above four categories can be described as follows:

1.Nonspecific extracellular gadolinium chelates are currently the most often used MR contrast agents. The gadolinium feature most useful in MRI is its T1shortening time and thus increased signal intensity on T1-weighted images. Typically these agents are injected as a bolus and equilibrate with the extracellular (interstitial) space shortly after injection; as a result, liver lesions become isointense to liver on delayed views and thus to take

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full advantage of these contrast agents, dynamic imaging must be performed shortly after contrast injection (arterial phase to portal venous phase). After IV injection, their biodistribution is similar to that of iodine-containing contrast agents.

Gadolinium chelates have a much lower adverse contrast reaction rate than iodinated contrast agents, but anaphylactic reactions and cardiopulmonary arrests, including fatal ones, do occur. These agents are excreted by glomerular filtration but at the low doses used do not manifest iodinated agent’s nephrotoxicity.

2.Larger size superparamagnetic iron oxide (SPIO) particles are taken up by liver endothelial and Kupffer cells and result, among other effects, in a decrease in reticuloendothelial system (RES) enhancement on T2-weighted images. Ferumoxides is a commonly used SPIO agent consisting of a colloidal mixture of ferrous and ferric oxide. Because some well-differentiated tumors and normal liver contain RES cells and thus take up iron oxide particles, they show a considerable but similar signal loss and overall appearance, but tissues lacking RES cells, such as metastases, have little or no signal loss and thus appear hyperintense to the resultant hypointense normal RES-containing liver parenchyma. Normal liver signal intensity decreases and lesion-to-liver contrast ratio increases on T2-weighted images post-SPIO administration; as a result, not only are known tumors better identified, but, compared to unenhanced MR sequences, additional tumors are detected. These SPIO effects differ considerably among various tumors, suggesting an ability to achieve tissue characterization of different focal tumors.

The SPIO enhancement is impaired in a setting of diffuse liver disease. These agents have a longer intravascular half-life than gadolinium chelates. Their role in clinical imaging is not yet fully defined, but, as mentioned, they are useful in differentiating some benign from malignant tumors. A disadvantage is that the use of SPIO is time-consuming and involves an increased rate of false positive findings.

3.Several hepatobiliary specific paramagnetic contrast agents, such as Gd-

LIVER

(EOB)-DTPA and Gd-BOPTA initially act as extracellular agents and then undergo hepatocyte uptake. They are eliminated both by biliary and renal pathways. Gd- EOB-DTPA provides a biliary excretion rate of about 50% of the injected dose. Only several percent of Gd-BOPTA is taken up by hepatocytes; however, it has a high relaxivity and results in a prolonged increase in liver signal intensity. Man- ganese-DPDP is a hepatobiliary-specific paramagnetic contrast agent having an effect lasting for several hours. Thus delayed imaging is feasible. It also has a role in pancreatic imaging.

On T1-weighted images these agents selectively enhance both normal liver parenchyma and such hepatocyte-containing tumors as focal nodular hyperplasia,regenerative nodules, and hepatocellular adenomas and carcinomas, but show little or no enhancement of metastases or hemangiomas. One exception is metastatic neuroendocrine tumors—an occasional one will enhance with Mn-DPDP. For the vast majority of tumors, however, these hepatobiliary agents differentiate between hepatocyte-containing and nonhepatocytecontaining tumors, and thus are useful in differentiating hepatocellular carcinomas from metastases, with nonhepatocyteorigin metastases becoming more conspicuous due to the increased signal from surrounding normal liver parenchyma. Duration of liver parenchymal enhancement varies, being up to several hours for some. Both early and delayed scans are useful as these agents are excreted by the biliary tract. One use is during MR-guided thermal tumor ablation procedures when prolonged tumor visualization is desired (7); Mn-DPDP identifies more focal tumors both in cirrhotic and noncirrhotic livers than precontrast images. Excretion of manganese is decreased in a setting of biliary stasis, and thus the use of this agent in cholangiography is limited, but it appears useful for defining intrahepatic biliary anatomic variants, such as in pretransplantation liver lobe donors. Its diagnostic impact is not yet clear.

4.Ultrasmall SPIO particles, unlike most MR contrast agents, shorten both T1 and T2 relaxation times. These agents have a blood

half-life measured in hours and thus appear useful as blood-pool MR contrast agents. Small iron oxide particles (<10nm) pass through capillaries and eventually are taken up by lymph nodes and thus are also called MR lymphographic agents. Ferumoxtran consists of dextran-coated iron oxide particles about 30nm in size. After IV injection, ferumoxtran is taken up by liver, spleen, and lymph node reticuloendothelial cells and results in a homogeneous loss of signal in these structures. In distinction to gadolinium where preand postcontrast images can be obtained at the same session, post-ferumoxtran scans are obtained roughly 1 day after contrast injection, and thus two scanning sessions are required.

This class of contrast agents potentially aids in differentiating highly vascular lesions, such as hemangiomas, from solid neoplasms. Traditional MRA is not feasible with these agents. Some of these bloodpool agents reduce intravascular T1 values for several hours, and thus appear useful for MR angiographic interventional procedures without the need for repeat contrast injection. They have their own problems such as superimposition of arterial and venous structures, possibly solved by more extensive 3D imaging.

Refinements in MR contrast agent use include a combination of two such agents. Thus by combining information about RES status obtained with a superparamagnetic iron oxide agent with the perfusion data of a gadolinium chelate agent, more specific information is obtained about some liver tumors than with a single agent alone.

Serum levels of patients on hemodialysis show that about 80% of gadolinium is dialyzed after the first and essentially all after the fourth dialysis; no contraindications exist to normal-dose contrast use in these patients.

Scintigraphy

The primary role of liver scintigraphy is to provide tissue characterization. Scintigraphy relies primarily on specific physiologic and biochemical properties of a lesion as compared to normal liver parenchyma. For focal liver disease

scintigraphy aids primarily in narrowing a differential diagnosis.

Radiopharmaceutical Agents

Currently two main types of radiopharmaceutical agents are used in hepatobiliary imaging; both rely on labeling with technetium-99m (Tc-99m):

1.The iminodiacetic acid (IDA) derivatives evaluate hepatocyte function and patency of the bile ducts. These lipophilic radiopharmaceuticals are extracted from blood by hepatocytes, excreted into bile, and thus outline the gallbladder and bile ducts and eventually flow into the intestine. Urinary excretion is minimal if liver function is reasonably intact. In contrast to bilirubin, the IDA compounds are excreted without being conjugated. Bilirubin, however, competes with IDA derivatives for hepatocyte receptor binding sites and excretion pathways, and there is poor image quality in a setting of hyperbilirubinemia.

The IDA radiopharmaceuticals are useful in infants and children in evaluating neonatal jaundice, trauma, and complications developing after transplantation.

2.Colloid particles—sulfur colloid and albumin colloid—are taken up by reticuloendothelial cells, with most of these being in the liver, about 5% to 10% in the spleen, and smaller amounts in bone marrow. The particles are permanently deposited in the liver. Nonvisualization of the liver with Tc-99m–sulfur colloid scintigraphy is uncommon, occurring in severe acute hepatitis and similar diffuse parenchymal disorders.

Several additional agents are occasionally useful in liver imaging:

1.Tc-99m–labeled red blood cells study blood-pool distribution and aid in diagnosing cavernous hemangiomas.

2.After inhalation, fat-soluble xenon 133 accumulates in fatty liver tissue. Although xenon-133 scintigraphy appears theoretically worthwhile in evaluating questionable fatty infiltration, clinical application has been controversial.

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3.Gallium 67 citrate is useful in abscess detection. Its value in liver abscesses is compromised by uptake in normal liver tissue. It is also taken up by some hepatocellular carcinomas, lymphomas, and metastases.

4.Normally Tc-99m–methylene diphosphonate (MDP) is used for bone scintigraphy and not liver. After IV iron therapy some patients have liver uptake of Tc-99m-MDP, presumably due to phagocytosed iron within hepatic reticuloendothelial cells.

Positron Emission Tomography

Positron emission tomography (PET) is useful for detecting early primary and metastatic liver tumors and in staging. The information obtained with PET differs from other imaging modalities: PET images metabolic activity (i.e., uptake of a specific radioisotope), rather than providing an anatomic roadmap. The primary advantage of PET is that abnormal metabolic activity is often detected before anatomic changes are evident. In clinical practice, however, PET provides complementary information to more conventional imaging.

Two types of PET-based systems are used: dedicated PET and single photon emission computed tomography (SPECT). The basic principles underlying PET and SPECT are similar: a positron emitted by a radionuclide interacts with an electron, the resultant annihilation reaction produces two 511-keV photons in opposite directions and imaging detectors placed opposite to each other then detect these photons. In a dedicated PET system the detectors are fixed in position; with SPECT the detectors rotate around the body. Positron emission tomography imaging is faster and provides higher quality images than SPECT but at considerably higher cost. Rather than being dedicated to a particular type of study, a SPECT system is also useful for other nuclear medicine imaging. Both 2D and 3D PET systems are available. Fused PET/CT units combine functional with anatomic information.

Positron emission tomography is based primarily on an increased uptake of glucose by cancer cells; thus it depends on presence of viable tumor cells. A high uptake of fluorine- 18–labeled fluorodeoxyglucose (FDG) is evident in numerous neoplasms, and this agent is most

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often employed clinically; PET-FDG imaging detects not only liver tumors but also tumor recurrence at primary sites. Whole-body imaging is readily performed. False-positive uptake is by brain, cardiac muscle, and inflammatory cells. FDG uptake is decreased in a setting of hyperglycemia due to competition with unlabeled glucose. FDG is excreted by kidneys and pools in the bladder, thus limiting its use in the pelvis.

For certain applications, 18F-fluoromethyl- choline is more advantageous than FDG. Fluorine-18 labeled a-methyl tyrosine (FMT) is a less often employed PET tracer. Although preliminary results indicate that, compared with FDG, FMT liver uptake is less, differences in uptake between benign and malignant tumors are significantly greater with FMT-PET (8).

Monoclonal Antibody

Both preoperative and intraoperative probe scintimetry are potential monoclonal antibody techniques.

A radiotracer-labeled monoclonal antibody designed against a specific neoplasm should potentially improve tumor detection. The antibody Tc-99m–anti–carcinoembryonic antigen (CEA) is available for the study of colon cancer metastases to the liver. This antibody is also taken up by normal liver parenchyma, thus limiting tumor detection.

Angiography

Conventional angiography and digital subtraction angiography (DSA) are well-established techniques generally requiring multiple contrast injections and multiple views to outline liver vascular anatomy.

Digital rotational subtraction angiography consists of rotating an X-ray tube around the patient during contrast injection, with resulting 3D images providing easier visualization of the course and direction of major vessels and their branches than is feasible with conventional 2D imaging.

Biopsy

Most liver biopsies are performed at the bedside and do not require imaging. Whether laparoscopic liver biopsy has any advantages is un-

certain, except possibly in the patient with mild- to-moderate coagulation abnormalities where a fibrin plug at the biopsy site may decrease bleeding.

Imaging is helpful when tissue from a specific focal tumor is desired. The choice of imaging used varies; US is more common in Europe and Japan, while CT is more often preferred in the United States, although considerable local variation exists.

Ultrasonography-guided liver biopsies are performed on an outpatient basis, with patients generally discharged after an observation period. These biopsies achieve a sensitivity of over 90% and specificity of 100%; false-negative results are more common in cirrhotic nodules.

Magnetic resonance–guided liver biopsies are feasible and are most useful when a tumor is identified by MRI but not CT or US or if other image-guided biopsies are incomplete. Magnetic resonance–compatible needles are available.An 18-gauge needle provides enough tissue for diagnosis with few complications. From a pathologist’s viewpoint, most diagnostic dilemmas with aspiration biopsies occur with well-

or ascites. Use of combined fluoroscopic and US guidance during biopsy improves visualization, increases operator confidence and is advantageous in smaller patients and in children (9). Several studies have achieved a histopathologic diagnosis in over 95% using either 18or 19gauge transjugular biopsy needles. An occasional such biopsy contains unusual tissue, such as duodenal mucosa or renal tissue.

Wedge-shaped transient subsegmental parenchymal enhancement is occasionally found along the needle tract on postbiopsy CT; subsegmental arterioportal shunting is responsible for this finding.

Complications of transjugular liver biopsy include an occasional subcapsular hematoma, intrahepatic arteriovenous fistula, liver capsule puncture, hemobilia, and those complications related to the neck puncture site (Fig. 7.1). Complications occur both with percutaneous and laparoscopically guided liver biopsies.

Percutaneous biopsy complication rate appears to be less if US provides guidance. The presence of perihepatic ascites does not appear

to affect either major of minor complication rates. Hemobilia is not uncommon after a percutaneous biopsy, and postbiopsy hemobilia is a rare cause of pancreatitis, cholecystitis, or even portal vein thrombosis. Infective complications include a liver abscess and peritonitis.

Malignant needle tract and abdominal wall implantation are known biopsy complications, found in up to 2% of biopsies. Abdominal wall implantations have also developed after drainage of a cancer-associated abscess, transhepatic bile drainage in a setting of a hilar cholangiocarcinoma, and laparoscopic cholecystectomy in patients with unsuspected gallbladder cancer.

Congenital Abnormalities

Some congenital abnormalities manifest primarily through liver parenchymal damage while others lead to cholestasis and suggest a biliary anomaly; these latter ones are covered in Chapter 8.

Some errors of metabolism, such as hemochromatosis, manifest primarily in adulthood; they are discussed later (see Metabolic and Related Disorders).

than usual in the heterotaxic syndromes; this includes both asplenia and polysplenia.

Although rare, hepatolithiasis can develop in a setting of situs inversus.

Lobe Atresia/Agenesis

Agenesis of the right lobe and associated portal hypertension are not common. Presumably growth arrest develops during fetal life. At times lobe agenesis is associated with other anomalies such as an ectopic gallbladder, aberrant hemidiaphragm, hammock stomach appearance, and Chilaiditi’s syndrome. Congenital absence of a lobe can be associated with fibrosis.

Not all apparent absences of the right lobe are due to agenesis and agenesis of a hepatic duct should be differentiated from lobe atresia. Grossly, a similar appearance is seen in cirrhosis, malignant infiltration, or previous surgical resection. Likewise, lobar agenesis should not be confused with lobar atrophy. In lobe agenesis the right portal vein, hepatic duct, and hepatic vein are not present, but these structures are identified in an atrophied lobe (Figs. 7.2 and 7.3). Lobar atrophy is often associated with biliary obstruction. A hypoplastic right lobe can be associated with a retrohepatic gallbladder.

With situs inversus, the liver is located in the left upper quadrant. It is more midline in location

Accessory liver lobes are not uncommon. Torsion of an accessory lobe can lead to

volvulus and an acute abdomen, even in infants.

Glycogen Storage Disease

A number of glycogen storage diseases (GSDs) have been described, with several involved in overt liver abnormalities (Table 7.1). Some define a group of disorders that have been subsequently subdivided into subtypes. Most have an autosomal-recessive inheritance.

Type I (von Gierke’s disease) is the most common and involves a defect in the microsomal glucose-6-phosphatase system, which controls glucose homeostasis. In neonates with type I disease, glycogen is deposited in hepatocytes and eventual hepatomegaly develops. Imaging reveals diffuse fatty infiltration. Some patients with type I disease develop focal nodular hyperplasia, with almost half of these patients having had a previous portacaval shunt. Surviving patients with type I (and, less often, type III)