Dr Parul S Garde, Consultant Radiologist, Global Hospitals, Mumbai talks about new techniques revolutionising the diagnosis and management of chronic liver disease
Techniques
This MRI technique quantitatively evaluates tissue stiffness by propagating low frequency mechanical waves through the liver. It is performed using an MRI safe passive driver that is applied to the right upper abdomen and lower chest overlying the right lobe of the liver while the patient is being scanned in the MRI scanner. The MRE sequence is carried out with four short breath-holds and completed within one to two minutes, without the need for intravenous contrast injection.
An active driver generates low frequency mechanical waves (typically at 60 Hz) which are conducted to the passive driver through a long plastic tube. The passive driver vibrates and produces shear waves that are propagated across the liver. The wavelength of the propagating shear wave is directly proportional to the stiffness of the liver, that is, the stiffer the liver, the longer the wavelength.
By applying an inversion algorithm to the raw data, elastograms or stiffness maps that depict tissue stiffness are generated. Elastograms may be displayed in a gray scale or with a colour scale. The result is obtained by placing the region of interest on the processed images. It is measured in Kilo Pascals.
Applications
Staging of chronic liver disease: Regardless of the etiology, chronic liver disease can progress from inflammation to fibrosis (reversible in early stages) and finally cirrhosis (irreversible). Liver stiffness measured with MRE increases with increasing stage of fibrosis. The increase in stiffness increases significantly with advanced fibrosis and cirrhosis.
MR elastography can non invasively detect various stages of fibrosis and thus obviate the need for liver biopsy, which has been the gold standard for detection, till the past decade. Patients who are treated in early stages of fibrosis stand a better chance of survival compared to those untreated, particularly due to availability of effective antiviral treatment for chronic viral hepatitis.
Quantification of fat content of liver
Non alcoholic fatty liver disease is widely accepted as a cardiovascular and insulin resistance risk factor. Fatty liver is diagnosed when the intra-cytoplasmic fat deposition is found in greater than 5 per cent of hepatocytes. Till present times, histological fat analysis is a semi-quantitative method at best, with high rates of misdiagnosis due to sampling error.
Currently, there is no cutoff or limit where liver fat content is considered too much or harmful. However, it is foreseeable that as we understand this disease spectrum as there might arise a need to know the exact amount of fat in the liver for risk stratification or response assessment. Hence, there is a need for more precise quantitative methods of evaluating hepatic steatosis.
MRI based methods of hepatic fat quantification have proved to be able to reflect much smaller changes in the degree of steatosis. Besides, the results thus obtained can be correlated with the patients’ body weights and serum alanine aminotransferase and aspartate aminotransferase levels. This makes MRI ideal as an imaging biomarker for assessing response to treatment of fatty liver. In fact, recent papers have primarily used MRI as a means to quantify hepatic fat when studying the effects of prognostication and treatment of hepatic steatosis in relation to NASH and impaired glucose tolerance.
There are two primary methods of evaluation for estimation of hepatic fat fraction on MRI. The first is an imaging-based, Chemical Shift Imaging (CSI) method which takes advantage of the fact that protons (hydrogen atoms) in fat and water molecules are quite different in magnetic resonance properties and that the signal intensity of the liver at different time-points of image data acquisition (echo time) varies, depending on the concentration of water and fat. The second method is MR spectroscopy (MRS), a purely quantitative method that measures the concentration of water and fat metabolites based on their resonant frequencies.
Potentially, by combining the fat quantification information with MRE findings, one may be able to diagnosis simple hepatic steatosis from NASH and NASH with fibrosis.
Quantification of iron Content: Iron overload cannot be detected reliably on any other imaging technique except MRI. Iron is a paramagnetic substance and causes rapid decay of MRI signal and generally results in signal loss where it is found abundantly.
Quantification of the degree of iron deposition is important for two reasons: it influences the decision to treat and provides an objective means to monitor response to treatment. In patients with chronic hepatitis C, liver iron overload is associated with disease progression and resistance to antiviral therapy.
MRI can be used to estimate the degree of iron deposition in tissues by virtue of the fact that iron accelerates T2 and T2* signal decays in spin-echo and GRE pulse sequences respectively. In order to guide treatment initiation and therapy monitoring, a quantitative means of predicting the liver iron concentration (LIC) has been deviced.
Advantages
MR Elastography assesses the fibrosis by depicting the tissue stiffness over the entire liver cross section. This is unlike the ultrasound-based method of elastography, where in only a portion of the liver is interrogated. Similar drawback is with percutaneous needle biopsy, where in if a sample from the normal liver is obtained would give wrong results in a patient with cirrhosis/ fibrosis.
Besides elastography performed with ultrasound has its drawbacks in obese patients or when the patient has ascites or colonic interposition between the liver and the anterior abdominal wall.
Even after the injection of MRI contrast agents, there has been no influence on the liver stiffness measured with MR Elastography. Thus, it is considerably flexible in its use in the clinical liver MRI protocol.
As it is the quantitative technique, MR Elastography has an advantage due to the fact that it has excellent intra-observer and inter-observer reproducibility. Thus it can be used as a robust tool for monitoring the disease progression as well as assessing the response to treatment.
Limitation
Main limitation of the MR Elastography at the current time is that it may fail in patients having moderate to severe iron overload, where the liver MRI signal becomes very low and hence undetectable. Soon this limitation of MR Elastography would be overcome with newer MR sequence such as T1 mapping that are part of research at the moment.
Another major drawback of this technique at this point is that it cannot differentiate inflammation from fibrosis. 3D MR Elastography and multi – frequency MRE techniques are however underway, which would definitely help to overcome this drawback.
Future
At present MRE suffers from lower spatial resolution, especially compared to standard anatomic MR images of the liver. Hence, MRE technique is also undergoing several modifications and improvements.
Advancements in image acquisition technology would reduce scan time and minimise respiratory motion artifacts. Instead of using conventional gradient echo pulse sequences for image acquisition, spin echo, fast spin echo and echo planar imaging methods may increase signal to noise ratios, potentially reducing the limitation of hepatic iron overload.
The 3D MRE technique would be useful to estimate liver fibrosis burden and also focal liver lesions.
A multi-frequency MRE technique that can demonstrate changes in viscoelastic properties that can help separate inflammation, fibrosis and congestion is currently being developed.
MRE of the spleen is also underway with simultaneous evaluation of liver and spleen stiffness. Spleen stiffness correlates well with portal hypertension and is useful for prediction of significant varices.
Future role of MRE in combination with contrast enhanced MRI is likely to go beyond determining liver stiffness and will perhaps allow it to discriminate between the effects of inflammation, passive congestion and fibrosis.