Книги по МРТ КТ на английском языке / Advanced Imaging of the Abdomen - Jovitas Skucas

gives more complete coverage of a large organ such as the liver.

However, intraoperative US does have its detractors; one study found preoperative MRI to be almost as sensitive as intraoperative US in depicting liver tumors (2); intraoperative US altered surgery in only 4% of patients.

A current limitation of laparoscopic US is the considerable time required for a complete liver scan. Nevertheless, in selected patients laparoscopic US will detect small suspicious intrahepatic tumors and, if needed, provide biopsy guidance and influence surgery.

Doppler

Doppler US is readily performed at the patient’s bedside. Its primary value in the liver is in quantifying blood flow and detecting vascular lesions. Doppler US evaluates portal and hepatic venous systems for hypertension, obstruction, and presence of collaterals,and provides relative flow information in individual blood vessels. Each normal major hepatic vessel has a characteristic Doppler waveform.

Color Doppler US uses color to display a target frequency shift. Power Doppler US provides amplitude of the Doppler signal; it does not provide velocity information, but it is more sensitive in detecting flow in more structures than color Doppler US and is more sensitive and accurate in detecting tumor vascularity. One limitation of Doppler US is data reproducibility. A number of studies have documented significant interobserver and inter-equipment variability, although training does decrease the former.

Contrast Agents

Some authors use the term ultrasound angiography to describe contrast enhanced US.

The intravenous US contrast agent, Levovist (Schering, Berlin, Germany), consists of a suspension of micrometer-sized particles of galactose and gas bubbles. This agent passes readily through the lungs and enhances vascular signal intensity. Contrast-specific US techniques, such as phase or pulse inversion, are necessary; using this contrast agent with phase inversion harmonic mode US, normal liver parenchyma becomes hyperechoic; in most patients liver enhancement is sufficiently prolonged to allow lesion detection. Compared to conventional B-

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mode US, tumor conspicuity is improved and smaller tumors are detected and tumor characterization and overall diagnostic performance are significantly improved (3). Imaging can be performed during arterial (10–40sec after injection), portal venous (50–90sec) and late (>100sec) phases. Late-phase uptake of Levovist differs in different types of liver tumors; malignancies are mostly hypoechoic, uptake in hemangiomas is variable, and benign tumors are mostly hyperor isoechoic relative to liver parenchyma (4), differences aiding in separating benign tumors from malignancies.

Perflenapent emulsion (EchoGen, Sonus Pharmaceuticals, Bethell, WA), an intravascular US contrast agent, also provides liver parenchymal contrast enhancement (5).

A liver enhancing US contrast agent consists of direct injection of CO2 into the proper hepatic artery during arteriography (6); such a technique helps detect additional liver tumors during percutaneous ethanol therapy.

Magnetic Resonance Imaging

If a prediction is to be made based on theoretical considerations, MRI appears virtually certain to achieve future status as the dominant abdominal imaging modality, especially when investigating a specific problem. It loses some of its advantages to CT if a multiorgan screening study is required. The development of open high-field strength magnets and a simpler design should make MRI more readily available. Open MRI systems have obvious advantages, but their current limitation is a low field strength. Whether imaging with 3T (tesla) units will justify their extra complexity remains to be established. New techniques are necessary with 3T imaging—tissue relaxation times differ at 3.0T than at lower magnet strengths. Proton MR spectroscopy, including 3D MR spectroscopic imaging, shows promise but currently is mostly a research tool. Magnetic resonance spectroscopy using phosphorus 31 evaluates changes in phosphorus-containing liver metabolites and provides data on liver function. Although clinically useful in evaluating certain diseases, discussion of MR spectroscopy is beyond the scope of this work.

The discipline of MR interventional imaging is just beginning to be applied to clinical practice.

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Technique

An extensive literature exists comparing various MRI sequences in their detection of specific liver abnormalities. No universal set of sequences has emerged as an optimal study for liver disease. Optimal MR sequences for liver imaging are constantly changing and are not covered in this work. New hardware and software developments lead to new optimal sequences, making it difficult to generalize about specific techniques. Differences in equipment design between various manufacturers make comparison of some sequences moot. Thus a finding that a particular set of sequences produces better resolution images or detects more focal lesions in a shorter period of time is useful information, but may not apply to other units using different imaging parameters. Even with a similar MR unit, variations in repetition time, echo time, and acquisition time change the resultant information acquired.

One limitation of liver MRI, evident mostly with older units, is motion. A major decrease in motion artifacts is achieved when the scan acquisition time is shorter than a patient’s breath hold. Advances in MR coil design and the use of fast spin-echo pulse sequences designed to achieve short scan acquisition times minimize motion artifacts due to respiration and peristalsis, and yield high-resolution images.

Most liver MR studies include both T1and T2-weighted sequences and a contrastenhanced sequence. In general, T1 sequences provide better anatomic orientation and lesion detection, but T2 sequences are superior for lesion characterization. An occasional lesion is identified with one but not the other sequence. A hyperintense signal on T1-weighted images is not specific for any disorder and is seen with such entities as fat, proteins, blood (hematoma), melanin, and contrast agents such as gadolinium. T2-weighted sequences result in a hyperintense signal from tissue containing increased amounts of fluid and a hypointense signal from fibrotic tissue. Iron results in a very hypointense signal on T2-weighted sequences.

Fast low-angle shot (FLASH) is a type of spoiled gradient-recalled echo (GRE) technique allowing the entire liver to be covered in a single breath-hold, thus reducing motion artifacts. Blood vessels appear as a signal void. This tech-

nique is useful in dynamic contrast-enhanced imaging.

Abnormal fluid or tissue is best identified if its MR signal intensity differs as much as possible from adjacent normal tissue; to some extent these signal intensity differences can be manipulated to achieve a desired result. For example, abnormal fluid and fibrotic tissue normally have a low T1-weighted signal intensity and are thus best identified against the normally high T1weighted signal intensity of adjacent fat. On the other hand, a hematoma, which most often has a high T1-weighted signal intensity, is better identified if, using a fat-suppression technique, fat is made to have a low T1-weighted signal intensity. Similar image manipulation is also useful with T2-weighted images.

The definition of precontrast MRI (occasionally called native phase MRI) is clear, as are con- trast-enhanced MRI and postcontrast MRI. MR angiography (MRA) implies that images are obtained sometime after intravenous contrast injection, but a more basic definition of MRA is a study using MR images sensitive to flowing blood, and thus MRA does not necessarily require the use of a contrast agent. Dynamic MRI implies that serial postcontrast images are obtained during specific arterial, capillary (parenchymal), portal venous, and delayed phases,but not necessarily all phases are imaged in any one study. Some authors use the terms dynamic MRI and MRA even when only the arterial phase is imaged. In the liver, postcontrast MR often implies MRI during portal venous or delayed phases unless a specific other postcontrast injection phase is identified.

Intravenous contrast is used with MRI for the same reasons as with CT: it improves lesion detection and characterization compared with precontrast images. Nevertheless, many lesions <1cm, regardless of histology, tend to have a similar MR contrast enhancement pattern. Breath-hold 3D MRA also aids lesion localization within specific liver segments.

Useful vascular contrast agents increase liver parenchyma-to-lesion signal intensity differences by their different effect on tissue proton relaxation. These differences vary with time and depend on the degree of tumor vascularity. One common technique consists of a rapid IV gadolinium contrast injection followed by several T1-weighted spoiled gradient echo (SGE) sequences, such as an arterial sequence

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-

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(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)

disease are prone to developing hepatocellular adenomas, with an occasional one progressing to hepatocellular carcinoma; one recommendation is that serum a-fetoprotein levels and yearly US be obtained in these patients.

Some of these patients undergo a portocaval shunt. Liver transplantation is an option in some with type Ia disease. In teenagers, transplantation restores normal metabolic balance, provides a growth spurt, and improves overall quality of life; liver transplantation does not, however, prevent focal glomerulosclerosis that is part of type Ia disease.

Type IV disease usually progresses rapidly, with death before 4 years of age, although a mild variant is seen in adults as a myopathy. Some of these infants undergo liver transplantation.

Computed tomography findings in patients with glycogen storage disease vary depending on activity. Glycogen deposition leads to a hyperdense liver, although associated steatosis often modifies the appearance. Once cirrhosis and hepatosplenomegaly develop, US reveals a hyperechoic liver.

13C MR spectroscopy using a whole-body MR is a noninvasive test for determining liver glycogen content.

Tyrosinemia

Tyrosinemia leads to progressive hepatocyte damage and regeneration, with surviving children developing dysplastic nodules and subsequent hepatocellular carcinoma. Imaging cannot reliably differentiate between regenerating nodules and neoplasms and, as a result, liver transplantation is recommended early in the course of this condition.

a1-Antitrypsin Deficiency

a1-Antitrypsin is a glycoprotein found in body fluids, serving mostly an inhibitory function. Some newborns manifest with cholestasis, which gradually clears. Some children with a homozygous deficiency develop chronic liver disease, which gradually progresses to liver failure and death, often by adolescence. Some adult cirrhotics have a1-antitrypsin deficiency, but the relationship is unclear. Some of these patients mimic hemochromatosis patients.

a1-ntitrypsin levels become normal after liver transplantation.

Wilson’s Disease

Wilson’s disease is an autosomal-recessive disorder of copper metabolism affecting approximately 5 persons per million. The primary defect is in the liver and results in copper accumulation within liver parenchyma and other structures.

A brief digression into copper metabolism is in order. Copper is found in two forms in the human body: Cu+ and Cu2+. Cu+ is diamagnetic and normal amounts do not affect MR signals. Cu2+ is paramagnetic and decreases both T1 and T2 signals. Most normal liver copper is bound to metallothionein and is Cu+ and thus not paramagnetic, but evidence suggests that some oxidation to Cu2+ takes place, although the precise mechanisms in normal liver and tumors are poorly understood. Copper in hepatocellular carcinomas also appears to be bound to metallothionein. Distribution of copper does not correlate with intensity on T1-weighted images,

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and the paramagnetic effect of divalent copper accumulation is insufficient to affect results.

Clinically, Wilson’s disease is defined by several stages. First, asymptomatic copper accumulates within the liver, the liver enlarges, and steatosis develops. Next, copper is redistributed throughout the body and hepatocellular necrosis, fibrosis, and hemolysis ensue. Progression to cirrhosis leads to liver atrophy, while accumulation of copper in body tissues results in neurologic damage, at times irreversible.

Initially, either hepatic or neurologic findings tend to predominate. Fulminant hepatic failure, even in a child, is an occasional initial presentation. Copper levels in serum, urine, and liver tissue suggest the diagnosis. The ceruloplasmin level is low.

If detected sufficiently early, the use of chelating agents prevents copper overload and achieves homeostasis. When diagnosed later in its course, chelating agents may slow progression. When fulminant or advanced and the patient does not respond to conventional therapy, orthotopic liver transplantation is an option, realizing that liver transplantation only partially corrects the metabolic defect by converting a homozygous disease into a heterozygote condition.

In most Wilson’s disease patients imaging studies are noncontributory. Some children with Wilson’s disease and cirrhosis have marked hepatosplenomegaly and imaging evidence of portal hypertension. Although liver CT attenuation is mildly increased in many adults, sufficient overlap with normal livers makes this finding of limited use.

Imaging in one patient with Wilson’s disease revealed multiple, small, enhancing nodules during the early arterial phase (10); biopsy identified dysplastic nodules.

Not all elevated hepatic copper levels in children represent Wilson’s disease. An Indian childhood cirrhosis associated with excess copper ingestion exists. Excess copper ingestion in an occasional non-Indian child leads to cirrhosis, liver failure, and increased liver copper levels.

Gaucher’s Disease

Gaucher’s disease, an autosomal-recessive condition, is discussed in more detail in Chapter 15.

Hepatomegaly is common in patients with type 1 Gaucher’s disease, at times progressing to massive hepatic fibrosis and portal hypertension. Focal intrahepatic tumors develop in some; these are hypointense on T1and hyperintense on T2-weighted MR images.

Technetium-99m–red blood cell SPECT imaging in a patient with Gaucher’s disease revealed an appearance similar to that seen with a hemangioma, believed to be secondary to focal intrahepatic extramedullary hematopoiesis (11).

Niemann-Pick Disease

Niemann-Pick disease is a metabolic disorder that progresses to cirrhosis. Some of these children develop a hepatocellular carcinoma.

Sickle Cell Disease

Although uncommon, intrahepatic cholestasis does occur in sickle cell disease. These patients develop hepatomegaly, hyperbilirubinemia, coagulopathy, and, on rare occasion, acute liver failure. Exchange transfusion appears to be effective therapy.

These patients do not have excess iron absorption, and MR does not reveal excess liver iron. After blood transfusions, however, iron in organs containing reticuloendothelial cells results in low T2 signal intensity.

Polycystic Diseases

Autosomal Dominant

Although renal involvement in patients with adult polycystic disease leads to progressive loss of renal tissue, this does not hold true in the liver; liver function tends to remain normal in most individuals until late in the disease. In distinction to autosomal-recessive congenital hepatic fibrosis, little fibrosis is evident in this entity. Of note is that in some patients adult polycystic disease mostly spares the kidneys and primarily involves the liver. In this patient population the differential diagnosis also includes rare cystic neuroendocrine or gynecologic metastases.

Dilated small bile ducts surrounded by fibrous stroma, called von Meyenburg complexes, are common in patients with adult