Liver cancer and focal liver lesions

Liver cancer ranks as the third-leading cause of cancer-related deaths worldwide.^[5] The dominant form of liver cancer is hepatocellular carcinoma (HCC), accounting for 80% of primary liver cancers.^[6] HCC is a type of FLL; however, FLLs also encompass other malignant lesions, such as intrahepatic cholangiocarcinoma and hepatic metastasis, as well as benign lesions such as hepatic haemangioma and focal nodular hyperplasia. Early detection and accurate characterization of FLLs are crucial for optimal treatment decisions and prognostic predictions.^[7]

FLLs are often found incidentally during imaging for other purposes, such as the assessment of abdominal pain or during surveillance for liver metastases in patients with non-liver cancer.^[8] Three main imaging modalities are used for the detection and characterization of FLLs: conventional ultrasound is often the modality to first detect FLLs, after which contrast-enhanced computed tomography (CECT), contrast-enhanced magnetic resonance imaging (CEMRI), or contrast-enhanced ultrasound (CEUS) are used for FLL characterisation.^[8][9][10]

Key modalities used for liver imaging

Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are non-invasive imaging modalities, and each relies on different underlying physical principles (Figure 1). Ultrasound uses sound waves that pass into the body and bounce back from the tissues inside, like an echo. Different tissue types reflect the sound waves differently and software is used to process these echoes to create images of the body.^[11][12]

CT uses a series of X-rays to build images by acquiring multiple projections of the same location from different orientations. Tomographic reconstruction then generates 3D cross-sectional images of the body. The individual X-ray images quantify the reduction in X-ray intensity as they pass through tissues. Different tissue types absorb different levels of radiation (e.g. bones absorb the most) and the resulting differential generates contrast.^[11][12]

MRI employs strong magnets to create a magnetic field in which protons (mostly hydrogen atoms in water molecules) in the body will preferentially align with the magnetic field. By pulsing a specific radiofrequency through the patient’s body, the protons can be forced to spin out of alignment with the magnetic field. After the radiofrequency is turned off, the protons relax back to their resting alignment and release energy. Different tissue types have different relaxation properties, and the released energy can be measured to create an image.^[11][12]

Figure 1: Non-invasive modalities for liver imaging

Enhancing contrast to enhance categorisation

For all three imaging modalities, contrast agents can be used to improve their diagnostic capability. Contrast agents for CEUS consist of microbubbles containing an inert gas stabilized by a shell, enhancing the echo (and thus signal intensity) from the blood.^[13][14] Contrast agents for CECT typically contain iodine atoms that increase image contrast by absorbing X-rays.^[15] CEMRI often uses gadolinium-based contrast agents that shorten the relaxation times of proton nuclei in the tissues, improving signal intensity from contrast-enhanced tissues.^[16][17]

For characterization of FLLs, particularly in patients at high risk of HCC, a Liver Imaging Reporting and Data System (LI-RADS) has been developed to categorize FLLs from LR-1 (definitely benign) to LR-5 (definitely HCC). LI-RADS algorithms specific to CECT/CEMRI and CEUS are available.^[18] Categorization considers factors such as the lesion size and flow of contrast agent through the liver. Because the liver has a dual blood supply (from the hepatic artery and the portal vein), three distinct phases can be assessed during imaging, in which the injected contrast agents (for any of the modalities) ‘wash in’ and ‘wash out’ of the liver: the arterial phase, portal venous phase, and late phase. Depending on the pattern of contrast enhancement of FLLs compared with the surrounding liver parenchyma, the FLLs can be categorized by CEUS, CECT and/or CEMRI.^{[19][20][21][22]}

Advantages and limitations of modalities for liver imaging

All three contrast-enhanced modalities play a role in charactering FLLs, and each has advantages and limitations. For example, CEUS offers real-time imaging, has wide accessibility, can be performed with the clinician/radiographer at the patient’s bedside and is relatively inexpensive.^[10][23][24] However, CEUS has limited penetration depth, affecting imaging in overweight/obese patients, and only one lesion can be studied at a time. ^[22][23][24] Conversely, CECT and CEMRI can visualize deep structures and enable evaluation of the whole liver. ^{[10][15][23][24]} A limitation of CECT is that it uses ionising radiation, and contrast agents for both CT and MRI have restricted use in patients with renal impairment due to nephrotoxic effects.^[10][23][25] CECT and CEMRI cannot be performed in real-time and imaging is performed at predetermined times following contrast agent administration.^[22] They are also performed in a dedicated room, where the patient is confined to a large scanner on their own and may experience discomfort.^[24]

Depending on multiple factors, one modality may be preferred over the other, or multiple modalities may be used, complementing each other.^[8][10][22] Understanding the benefits and limitations of these techniques is necessary to guide the selection of the most appropriate imaging modalities for specific individuals, and assist in accurate characterization and diagnosis of FLLs to avoid delays in diagnosis and treatment, thereby improving patient outcomes.^[4] Such insights can also help optimize medical workflows, and ultimately reduce healthcare utilisation.^[9][24][26]

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This post was written by Ulrike Jahnke, Medical Writer, and Paul Cowling, Medical Writer.

References

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^[2]World Liver Day website.

^[3]European Association for the Study of the Liver (EASL) press release

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^[19]Bargellini I, Battaglia V, Bozzi E, Lauretti DL, Lorenzoni G, Bartolozzi C. Radiological diagnosis of hepatocellular carcinoma. J Hepatocell Carcinoma. 2014;1:137-48

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