Diagnosing liver diseases with elastography

With India witnessing 10 lakh new patients being diagnosed in a year with liver ailments, there is an urgent need to detect and prevent liver diseases. Dr Manoj Sharma, Senior Consultant Radiologist, VPS Rockland Hospitals, talks about real-time elastography to prevent the disease

Every one in five Indians is estimated to be suffering from a liver ailment. The dynamics of liver diseases in the country has seen a paradigm shift with about 10 lakh new patients being diagnosed in a year.

Earlier caused by hepatitis B and C, the most common causes now are alcohol and other obesity-related disorders. Globally, hepatocellular carcinoma (HCC) – or a cancer in liver – is the second most common cause of death due to malignancy.

Early detection and prevention are the solutions. A healthy liver should be soft and elastic. A stiff liver means more scarring (fibrosis). The advanced stage of fibrosis is cirrhosis. Early detection of liver stiffness helps in better treatment planning and halting the disease process in beginning.

Common liver disorders include viral hepatitis, alcoholic and non-alcoholic fatty liver disease, drug-induced liver disease, primary biliary cirrhosis and immune hepatitis. Chronic liver disease causes increasing deposition of fibrous tissue within the liver, leading to development of cirrhosis with consequences like portal hypertension, hepatic insufficiency and hepatocellular carcinoma (HCC).

The process of liver fibrosis is dynamic. Studies show that regression is possible with treatment of the underlying condition. The stage of liver fibrosis is important to determine prognosis and surveillance, and to prioritise for treatment and explore potential for reversibility.

For a clinician, the most important question is whether or not the patient has cirrhosis. The diagnosis of decompensated cirrhosis (defined by presence of clinical complications like ascites, variceal haemorrhage, jaundice, and/ or encephalopathy) can be assigned clinically on the basis of patient history, physical examination and laboratory tests. However, the diagnosis of compensated cirrhosis is more challenging.

Although some findings like low platelet count and a nodular liver surface on images can indicate the presence of cirrhosis, these findings are often absent in a patient with compensated cirrhosis. Thus, a non-invasive study to confirm or exclude the presence of cirrhosis is needed.

Wave frequencies

Different histologic stages of progressive liver fibrosis range from no fibrosis (METAVIR stage F0) to cirrhosis stage (METAVIR stage F4). Using a combination of different blood markers and assessment of tissue elasticity based on transient elastography has shown promising results in determining the exact degree of liver fibrosis.

Transient elastography (FibroScan) is performed with an ultrasound transducer probe mounted on the axis of a vibrator. A vibration transmitted from the vibrator toward the tissue induces an elastic shear wave that propagates through the tissue. These propagations are followed by pulse-echo sonographic acquisitions and their velocity, which is directly related to tissue stiffness, is measured. The harder the tissue, the faster the shear wave propagates. Shear-wave elastography and acoustic radiation force impulse (ARFI) imaging allow for quantification of tissue stiffness, enabling more precise tissue characterisation. The shear waves created by the machine measure elasticity of liver in kilopascals (kPa). The higher the number, more advanced is the liver fibrosis.

The mean, maximum, minimum and standard deviation of a shear wave speed (in metres per second) or the young modulus (in kilopascals) within the region of interest are displayed. A strength of this technique is that it is performed with real-time imaging. So masses and large vessels can be avoided and areas with artifacts can be identified.

It can also be used to assess multiple regions of liver. The larger area of measurement allows for a larger region of interest for the averaging of measurements. Further, real-time two-dimensional shear wave elastography allows an operator to see generation of elastographic measures in a colour display as they are accumulated.

Real-time elastography is thus a new method to measure tissue elasticity integrated in a sonography machine and is technically different from transient elastography. With conventional ultrasound probes, echo signals before and under slight compression are compared and analysed.

As tissue elasticity cannot be measured directly from reflected ultrasound echoes, methods analysing the displacement of phases (for example cross-correlation method) can be investigated.

However, these measurements are associated with strong aliasing. To overcome these restrictions, real-time elastography based on the combined auto-correlation method and 3D tissue model can be deployed to determine phase displacement in real time without aliasing.

Promising results

In elastic or soft tissue, the amount of displacement is high because soft tissue can be compressed more than hard tissue. In addition, with the combined auto-correlation method, echo-frequency patterns of parallel ultrasound echoes are compared to detect possible lateral evasion of hardened tissue areas. In a second step, a strain field is reconstructed from the measured displacements (strain image). Conclusions concerning the elasticity of the underlying tissue can be drawn from these reconstructions abutted to a spring model. Areas of high elasticity (that is soft tissue) appear as places of high strain, areas with low elasticity (that is hard tissue) appear as places of low strain.

By using the 3D tissue model (finite-element method), the examined tissue is divided in up to 30,000 finite elements of equal stiffness before compression. During compression, the displacement of each element is measured. The finite-element method can then determine the tissue elasticity from the calculation of each element.

The calculation of tissue elasticity distribution is performed in real time, and the examination results are represented as colour-coded images with the conventional B-mode image in the background.

It is likely that diagnostic accuracy of real-time elastography can be improved by further optimisation of images using different ultrasound probes, refined selection of liver tissue’s analysed area and more refined statistical assessment of elasticity images for a larger data set or a larger number of images for each patient. Especially, the diagnosis of cirrhosis seems to be improvable if more reliable assessments of variability between single images are available. Results of further studies are needed before real-time elastography can be introduced widely in clinical practice. In addition, the combination of real-time elastography with other blood tests such as FibroTest may further improve specificity and sensitivity for the non-invasive estimation of liver fibrosis.

Reducing biopsies

A head-to-head comparison of transient elastography (FibroScan) and real-time elastography will be of future interest as well. This is state-of the-art technology for diagnosis of liver disease and provides immediate, non-invasive and painless measurement of liver health. It is useful in patients with fatty liver in order to identify those with fibrosis who have progressive disease. The technique has the potential to decrease the number of liver biopsies and offer safe, more repeatable tests to follow patients with liver diseases. The biopsy complications are high including pain and bleeding, often requiring hospitalisation. A liver biopsy samples only a very small piece of the liver which can lead to incorrect staging.

Key learnings

• Research is needed to better understand the performance of elastography for monitoring longitudinal changes in fibrosis. Emerging indications of elastography include detection of hepatic inflammation, assessment of portal hypertension, characterisation of focal liver lesions, and evaluation of other abdominal organs.
• Potential confounders when using stiffness for assessment of liver fibrosis include technical and instrument-related factors and biologic and patient-related factors. The former include location and depth of measurements, wave frequencies, and device dependencies. The latter include concomitant hepatic steatosis, inflammation, and cholestasis; breathing; right heart failure and hepatic venous congestion; and fasting versus post-prandial state.
• Measured stiffness is frequency dependent. In general, measured stiffness increases as the frequency of the shear waves increases. Different techniques use different frequencies. Hence, observed stiffness values are technique dependent.
• Various elastography techniques have advantages and limitations. No single technique currently can be recommended as optimal for all indications and circumstances. Depending on the indication, different modalities may be preferred. Ultrasound elastography techniques are relatively inexpensive, portable, increasingly available, and generally provide good diagnostic accuracy for advanced fibrosis. Nevertheless, they sample relatively small portions of the liver and they may be unreliable in obese patients and those with narrow intercostal spaces. Magnetic resonance elastography samples larger portions of the liver and offers excellent diagnostic accuracy that probably slightly exceeds that of ultrasound-based techniques, but quality may be degraded in patients with marked iron deposition. Finally elastography techniques integrated to clinical ultrasound and MRI systems can assess mechanical properties in vivo. Radiologists should be familiar with these exciting new technical capabilities to examine by imaging what once could be examined only by direct palpation.