Biomarkers in Imaging: Realizing Radiology’s Future

Abstract

Modern pharmaceuticals and medical devices have provided substantial benefits to patients throughout the world. These benefits come at a high and increasing cost, with development of the typical pharmaceutical requiring 12 years and hundreds of millions of dollars before gaining U.S. Food and Drug Administration marketing approval. Appropriate use of imaging biomarkers--defined as anatomic, physiologic, biochemical, or molecular parameters detectable with imaging methods used to establish the presence or severity of disease--offer the prospect of smaller, less expensive, and more efficient preclinical studies and clinical trials. Scientists, government regulators, and industry have all recognized the potential of biomarkers in imaging. Although real, this promise can only be realized with the rigorous application of science to their use. Success is most likely when (a) the presence of an imaging marker is closely linked with the presence of a target disease; (b) detection and/or measurement of the biomarker is accurate, reproducible, and feasible over time; and (c) measured changes are closely linked to success or failure of the therapeutic effect of the product being evaluated. By applying this paradigm to the array of imaging modalities, the radiology community is poised to become a major force in preclinical and clinical evaluations of new medical treatments.

Final Cerebral Infarct Volume Is Predictable by MR Imaging at 1 Week

“…9 Recently, Gaudinski et al 8 demonstrated that infarct volume did not vary significantly between days 30 and 90. This finding raised the question of whether it was possible to predict this fixed stage as early as days [3][4][5][6]. Following this hypothesis, we found a good correlation between subacute and chronic volumes in line with previous work, 20,21 which nevertheless failed to take into account whether statistical conditions of a linear relationship were met for the full spectrum of volumes.…”

“…4 Therefore, our study dealt with the relationship between volumes and clinical outcomes. We found that FLAIR volumes were significant and independent predictors of clinical outcomes.…”

“…Infarct volume has been proposed as an alternative (surrogate end point) to classic disability or handicap scales, 2,3 being able to improve the efficacy of phase II trials by increasing their statistical power and, therefore, their ability to reach conclusions about the potential benefits of therapy. 4 The same marker is also frequently used in conceptual studies, particularly in penumbra proof-of-concept studies, which consider the fate of "at risk" tissue as an outcome variable. 5 Nevertheless, there is currently no consensus as to the appropriate timing for final infarct volume measurements.…”

In Vivo magnetic resonance techniques and drug discovery

“…Clinical drug studies, in particular those addressing chronic disease, are time consuming and expensive. Similarly to the preclinical phase, biomarkers are a means to obtain early information on drug effectiveness and safety in clinical studies, which can lead to a substantial reduction in costs and development time [28,29]. More important is patient management: the time lost for a patient, who is not responsive to treatment, can be significantly reduced.…”

Magnetic resonance imaging as a biomarker in renal cell carcinoma

“…Preliminary results using some of these techniques are encouraging and support their incorporation into clinical practice as well as into clinical trials. 12 In this article, we review the role of magnetic resonance imaging (MRI) as a biomarker, defined as a tool to noninvasively detect intratumoral anatomic, physiologic, biochemical, or molecular parameters, 13 to characterize primary and metastatic RCC as well as its response to antitumor therapy. We present some of the MRI findings used for the determination of the histologic subtype in RCC, including imaging findings on conventional MRI and enhancement patterns on dynamic contrast-enhanced (DCE) MRI.…”