DCE-MRI Biomakers Technology and Development

Colin G. Miller

An interesting imaging technology that I am actively involved with is Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI).  DCE-MRI is an imaging technique that combines the magnetic field and radio frequency imaging of MRI with the injection into a vein of a standard MRI contrast media that makes organs, tumors, and blood vessels easier to see. 

Essentially DCE-MRI provides the tracking of low molecular weight contrast agents through blood vessels, in particular the vasculature of tumors.  By analyzing the pharmacokinetics of the contrast agent into a specific tumor, it is possible to measure alterations in vascular permeability, blood flow, and extracellular volumes.   

This is of interest in the development of cancer drugs that inhibit new blood vessel formation (anti-angiogenesis) or disrupt existing blood vessels (vascular disrupting agents) for example. O’Connor et al in the British Journal of Cancer provide a good review of DCE-MRI imaging biomarkers in oncology clinical trials

Published data shows DCE-MRI biomarkers correlate with a decrease in tumor volume.  Outside of oncology, companies such as Amgen are evaluating the use of DCE-MRI as a biomarker to detect changes in the inflammation of synovial joints associated with rheumatoid arthritis (RA). They hope to be able to better detect changes associated with the treatment of their TNF inhibitor, etanercept (Enbrel). View clinical trial information here. 

 

DCE-MRI Imaging Biomarker Validation of Bi-Directional Transfer Coefficient K trans 

One of the DCE-MRI imaging biomarkers that the Quantitative Imaging Biomarker Alliance (QIBA) sub-committee, which I participate in, is looking to validate is the bi-directional transfer coefficient K trans.  We are aiming to make quantitative imaging results in clinical trials comparable in multi-center studies.    

One of the challenges in validation is ensuring that results from different sites in multi-center trials are comparable.  Central Review is one part of the quality control, but standardization of data acquisition is particularly important in DCE-MRI where there are a number of user associated parameters related to the time of contrast injection.   

There are also issues associated with the use of different MRI machines, which the QIBA group is addressing through the use of a standard phantom. DCE-MRI imaging biomarkers may have the ability to help companies assess the potential of their products in early phase drug development.   

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