- Advances in magnetic resonance imaging (MRI) have provided the opportunity to revolutionize the evaluation of chronic liver diseases
- Two prominent examples are widespread use of hepatobiliary-specific contrast agents and ongoing development of molecularly targeted probes
- MRI techniques that allow imaging of molecular and cellular events go hand in hand with development of targeted therapies and selection of appropriate therapeutic candidates
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Magnetic resonance imaging (MRI) is routinely used to detect and stage liver diseases and assess response to treatment. It is the most versatile noninvasive method for visualizing and quantifying hepatic fat, hepatic iron content and fibrosis.
A wide range of contrast agents, including some that are currently in development, make it possible to add functional information to morphological images or greatly improve the distinction between normal and pathological tissues by targeting molecular and cellular events. Iris Y. Zhou, PhD, a researcher in the Martinos Center for Biomedical Imaging at Massachusetts General Hospital, Onofrio A. Catalano, MD, medical director of PET/MR at the center, and Peter Caravan, PhD, senior faculty member at the center and the co-director of the Institute for Innovation in Imaging, recently reviewed advances in functional and molecular MRI technologies in detail in the Journal of Hepatology. This summary discusses two prominent examples detailed below.
Imaging Hepatocyte Function
Hepatobiliary contrast agents, particularly gadoxetic acid, simultaneously provide morphologic and functional information about hepatobiliary systems. During the hepatobiliary phase, the liver parenchyma is enhanced but not the vessels, and impaired hepatocytes can be identified by their hypointensity.
Signal enhancement in hepatobiliary images also reflects the balance between uptake and excretory transporters and the total number of hepatocytes. A decreased relative liver enhancement may suggest a loss of functioning hepatocytes due to fibrotic replacement.
MRI enhanced by gadoxetic acid has been used to assess hepatobiliary function in liver fibrosis, cirrhosis and nonalcoholic steatohepatitis. Recently, a functional liver imaging score derived from gadoxetic acid was developed to predict hepatic decompensation and transplant-free survival in patients with chronic liver disease (as published in Radiology). The score requires no dynamic acquisition or signal modeling and is independent of MRI field strength and vendor, making it easier to implement in routine practice.
Over the past decade, gadoxetic acid–enhanced MRI has also been shown to accurately predict the risk of post-hepatectomy liver failure and graft liver dysfunction. One research group developed a scoring system that predicts graft survival for three years (as published in Investigative Radiology).
Imaging Molecular Processes
Molecularly targeted MRI probes are small molecules, peptides or antibodies that recognize a specific protein, receptor or biologic process. They are tagged with a contrast-generating agent such as gadolinium (Gd). Considerable effort is being devoted to developing targeted MRI probes for detection, staging, prognosis and treatment monitoring of progressive liver diseases, and the probes may also have a role in the discovery and validation of new drugs.
Here are examples of probes that have shown promise for imaging fibrogenesis, extracellular matrix (ECM) deposition and inflammatory response in chronic liver diseases:
- EP-3533: A cyclic peptide specific to type I collagen tagged with gadolinium for MRI detection; accurately staged fibrosis in various rodent models of liver fibrosis
- CM-101: A newer version of EP-3533 designed for faster blood clearance and for minimal retention of gadolinium in bone or tissue
- Gd-ESMA: Specific to elastin, which accumulates at advanced stages of fibrosis; successfully monitored ECM deposition in rats
- Gd-Hyd: Specific to extracellular aldehydes, which indicates the rate of deposition of ECM; monitored fibrogenesis in mice
- EP-2104R: A fibrin-specific, peptide-based gadolinium agent was used to measure extravascular fibrin deposition as a part of the inflammatory response in rat model of chronic liver disease
- Gd-MPO: Specific to myeloperoxidase, which is part of the inflammatory response to liver injury and is increased in non-alcoholic steatohepatitis; differentiated steatohepatitis from steatosis in mice
In this era of precision medicine, the need is growing to quantify liver function noninvasively and visualize cellular/molecular processes underlying liver diseases. Imaging could be used to select candidates for expensive new targeted anti-inflammatory/antifibrotic therapeutics and to monitor treatment response. The functional and molecular MRI approaches described here are the first steps towards these goals.
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