Practical Dynamic Contrast Enhanced MRI in Small Animal Models of Cancer: Data Acquisition, Data Analysis, and Interpretation

Abstract

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) consists of the continuous acquisition of images before, during, and after the injection of a contrast agent. DCE-MRI allows for noninvasive evaluation of tumor parameters related to vascular perfusion and permeability and tissue volume fractions, and is frequently employed in both preclinical and clinical investigations. However, the experimental and analytical subtleties of the technique are not frequently discussed in the literature, nor are its relationships to other commonly used quantitative imaging techniques. This review aims to provide practical information on the development, implementation, and validation of a DCE-MRI study in the context of a preclinical study (though we do frequently refer to clinical studies that are related to these topics).

Imaging biomarker roadmap for cancer studies

“…Repeatability estimated from studies using rodents can seem unfavourable because, in some models, tumours can grow considerably within a few hours78, but useful data can be gained in slow-growing rodent models. Definitive repeatability analysis is best assessed in studies with humans, and should be performed at each centre that evaluates the IB anew, because reliance on historical or literature values is a source of error.…”

Comparison of region-of-interest-averaged and pixel-averaged analysis of DCE-MRI data based on simulations and pre-clinical experiments

“…In principal, heterogeneity can produce a ‘plateau’ or ‘persistent’ kinetic curve, due to a large range of K trans and v e values within a ROI. Please note that the necrotic tissue could also produce a curve with larger v e , but in this case, a smaller K trans would be expected (Barnes et al, 2012), and this was not the case in the examples shown in Fig. 9.…”

MR Imaging Biomarkers in Oncology Clinical Trials

“…These fundamental challenges can be potentially solved through the use of less expensive hyperpolarization techniques (e.g., SABRE vs. d-DNP) or through innovation in hyperpolarization hardware (116) or through the invention of HCAs with long-lived proton sites vs. heteronuclear-based HCAs (e.g., hyperpolarized 1H-propane vs. hyperpolarized 129Xe). Moreover, heteronuclear-based HCAs can also potentially be detected via indirect proton detection (38); the latter would require a relatively minor clinical MRI scanner upgrade, and would therefore enable this technology on most clinical MRI scanners.…”

“…DCE-MRI is a class of techniques characterized by whether a qualitative, semi-quantitative, or quantitative approach is used for data analysis. A qualitative analysis examines the shape (e.g., plateau or persistent) of the time-intensity curve (38,39), while a semi-quantitative analysis provides values such as the area under the curve (AUC), enhancement, time to peak, and wash-in/wash-out slopes (38,40). A quantitative analysis fits the time-intensity curve to pharmacokinetic models to extract parameters that reflect physiological characteristics such as tumor vessel perfusion and permeability and tissue volume fractions (40).…”