7
Liver
Technique
Computed Tomography
In a solid organ such as the liver, computed tomography (CT) reveals characteristic attenuation alterations and morphologic changes of diffuse disorders such as cirrhosis and fatty infiltration. Similar changes are also detected with magnetic resonance imaging (MRI). Currently the primary limitation of both CT and MRI is that a number of liver disorders have overlapping imaging findings, thus limiting specificity.
The terms helical CT and spiral CT are used interchangeably. In helical CT the patient table moves at a constant speed while the x-ray tube and detectors rotate continuously, and thus scanning is in a helix rather than a circle as with conventional CT. Images obtained with helical CT do not define a specific circular body slice and are not identical to those obtained with conventional CT. There is little argument that in evaluating abdominal disease in general, and liver disorders in particular, helical CT is preferred over conventional CT.
Initial helical CT scanners could cover either large body parts or thin sections of a limited volume, but not both, a limitation largely overcome by the introduction of multidetector CT (also known as multirow CT and multislice CT) in the late 1990s. As a basic concept, multidetector CT generates more than one slice per x-ray tube rotation. Multidetector CT, with 16
detectors being readily available, 32 detectors being tested, and 64 or more detectors on the drawing boards, offers several advantages: a larger volume scanned during a given time, reduced time required to scan a given volume, narrower collimation and thus increased resolution, and shorter enhancement intervals after contrast. Multidetector helical CT allows simultaneous acquisition of multiple slices, and complex, single breath-hold techniques are thus feasible (a breath-hold is typically defined as 20sec or less). Three-dimensional (3D) CT arteriograms without venous overlay are readily obtained by using first-pass data from a multirow detector CT scanner. One by-product of multidetector CT is a considerable increase in the number of images available for review, thus adding to study complexity. Simply decreasing the number of images evaluated is not a viable option because overlapping images at various phases of contrast flow improve disease detection.
In general, precontrast CT scanning identifies fewer liver lesions than postcontrast images. In many institutions precontrast CT is limited to specific indications such as in detecting calcifications or hemorrhage.
Correct arterial phase timing is obtained by using an initial test dose. Automatic bolus tracking initiates scanning after injection of contrast by monitoring a region-of-interest cursor placed in the abdominal aorta; a typical scenario is to set a threshold level at 100 Hounsfield units (HU) over the aortic baseline
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CT level and initiate scanning about 10 seconds later. A similar approach is to start arterial phase imaging when splenic enhancement reaches a certain HU value above baseline.
On average, CT arterial phase begins to enhance about 15 to 20 seconds after the start of intravenous (IV) contrast injection, followed by portal venous enhancement about 30 seconds later and parenchyma enhancement shortly after that. Images during the arterial phase map the major hepatic artery branches, and portal phase images outline portal and hepatic venous systems. Such a biphasic or dual-phase CT technique refers to the two discrete imaging sequences obtained and not to a biphasic contrast injection. For some indications, a liver parenchyma enhancement phase, also called an equilibrium phase, obtained several minutes after the start of contrast injection, is useful.
The literature is inconsistent about defining biphasic and triphasic CT imaging. Some authors include a precontrast phase as part of these terms, but others do not. In this book a precontrast phase is not included as part of either biphasic or triphasic imaging, and the use of these terms refers to postcontrast phases only. Even here confusion exists; does“biphasic” refer to the arterial, portal venous or equilibrium phases (or any other phase for that matter)? The term double arterial phase imaging signifies that early and late arterial phase images are obtained during a single breath-hold study. Some use quadruple phase to mean that images are obtained precontrast and at three times after the start of contrast injection. No sharp boundary exists between various phases. Ideally, authors should include the specific times after the start of injection when scanning is initiated.
Computed tomography CT data are viewed either as traditional transverse images or displayed in coronal, sagittal, or 3D projections. The latter allows a direct estimate of tumor size, information at times useful to the oncologist or surgeon.
Computed Tomography Angiography
Computed tomography angiography (CTA) is a general term used in a sense similar to conventional angiography but is often applied to a technique of injecting IV contrast and obtaining images during the arterial phase. Use of
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multidetector CT is especially well suited for such vascular studies.
Computed tomography angiography can also be performed with contrast injected through a catheter advanced into a major abdominal artery; whether one obtains CT arterial portography or CT hepatic arteriography (or any other specific vessel angiography) depends on the artery used and image timing.
Computed Tomography
Arterial Portography
Computed tomography arterial portography consists of angiographic placement of a catheter in the superior mesenteric artery or splenic artery, transfer of the patient to a CT suite, injection of a contrast bolus through the intraarterial catheter, followed by liver imaging during the portal venous phase. This technique maximizes attenuation differences between a neoplasm having a primarily arterial blood supply and normal liver parenchyma primarily supplied by the portal vein. It is superior to the usual intravenous contrast-enhanced CT imaging; over 80% of tumors <1cm in diameter are imaged. It is used in some centers preoperatively for anatomic localization of lesions and in evaluating whether a patient is indeed a surgical candidate. A refinement of this technique consists of a dual-phase study: during the first phase images are obtained about 30 seconds after the start of the contrast injection, and second-phase images are obtained at 70 seconds.
In general, there is no difference in hepatic enhancement whether CT arterial portography is performed via the superior mesenteric artery or the splenic artery. In the presence of an anomalous right hepatic artery originating from the superior mesenteric artery, the catheter needs to be positioned distal to this site. Computed tomography arterial portography is of limited use in patients with portal hypertension and collateral portal blood flow away from the liver.
Altered blood flow anomalies result in a number of artifacts during arterial portography. Inhomogeneous perfusion is most common near the porta hepatis, falciform ligament, and gallbladder. Perfusion defects can either resemble a neoplasm or even mask the presence of one. A liver zebra pattern, consisting of alternating regions of hyperand hypoperfusion,
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LIVER
is identified in some patients, regardless of whether the splenic artery or superior mesenteric artery is injected.
Computed tomography arterial portography is an invasive procedure and was more in vogue during the 1990s. It has a high sensitivity for detecting lesions but a low specificity for diagnosis due to numerous false-positive findings. Currently, it is gradually being supplanted by other advances in CT and magnetic resonance (MR) technology.
Computed Tomography
Hepatic Arteriography
Computed tomography hepatic arteriography consists of contrast injected through a catheter placed in the hepatic artery and arterial phase images obtained. Tumors having primarily an arterial blood supply are thus enhanced compared to liver parenchyma, which obtains a large part of its blood supply from the portal vein. This technique is also prone to artifacts because liver parenchyma tends not to enhance homogeneously, mostly due to blood supply anomalies. These artifacts (often called pseudolesions), especially around the gallbladder fossa, can be minimized by first injecting prostaglandin into the superior mesenteric artery (1).
An additional refinement is combined CT arterial portography and CT hepatic angiography in an attempt to improve lesion detection.
Contrast Agents
A biphasic CT study typically consists of continuous IV injection of 60 to 200mL of a contrast agent at a rate of up to 5mL per second. In general, a uniphasic injection is superior to biphasic injection. The degree of liver enhancement depends on the amount of iodine delivered. Ionic and nonionic contrast agents provide the same degree of contrast enhancement. The nonionic agents, however, are associated with less patient discomfort, fewer motion artifacts, and fewer side effects, and are preferred over ionic agents, especially for more complex examinations such as 3D reconstruction where minimizing patient motion is paramount.
Portal venous blood flow increases after a meal. Thus an indirect method of increasing liver CT portal contrast enhancement would be
to perform a study shortly after a meal, but this adds further complexity.
How common is hepatobiliary excretion of vascular contrast media? Functioning hepatocytes excrete small amounts of contrast material into the biliary system. Several-hour delayed images obtained after arterial portography result in enhancement of normal liver parenchyma; non–iodine-excreting neoplasms tend to appear hypodense. Gallbladder opacification is occasionally seen after CT angiography in patients with cirrhosis or other liver disease.
The use of iodized oil during CT is essentially limited to the study of hepatocellular carcinomas, and this topic is covered later (see Hepatocellular Carcinoma).
Ultrasonography
Conventional (Gray Scale)
Most ultrasonography (US) imaging consists of real-time, gray-scale, B-mode display, with the reflected signal amplitude displayed as a variation in brightness. This technique is referred to as gray-scale US or simply as US to distinguish it from Doppler US. The transducer is most often in contact with a patient’s skin (conventional US), although it can be placed in body cavities (endoluminal US) either directly or endoscopically (endoscopic US or endosonography).
As with CT and MR, it is hoped that continued advances in US equipment design will lead to more accurate diagnoses. For instance, the introduction of tissue and contrast harmonic imaging with stimulated acoustic emission has resulted in clearer images and improved tumor detection compared to more conventional US.
One novel approach is the use of two frequencies. Preliminary data suggest that metastases have an increase in contrast-to-noise ratios at higher frequencies, in distinction to hemangiomas, which have a decreased ratio.
Intraoperative
Special transducers are available for laparoscopic US. Introduced through a 10-mm laparoscopic port, a flexible transducer tip allows contact with the curved liver surface. The oftenused 7-MHz transducer provides only limited penetration of the liver; a 5-MHz transducer
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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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LIVER
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