Translating preclinical MRI methods to clinical oncology

Abstract

The complexity of modern in vivo magnetic resonance imaging (MRI) methods in oncology has dramatically changed in the last 10 years. The field has long since moved passed its (unparalleled) ability to form images with exquisite soft‐tissue contrast and morphology, allowing for the enhanced identification of primary tumors and metastatic disease. Currently, it is not uncommon to acquire images related to blood flow, cellularity, and macromolecular content in the clinical setting. The acquisition of images related to metabolism, hypoxia, pH, and tissue stiffness are also becoming common. All of these techniques have had some component of their invention, development, refinement, validation, and initial applications in the preclinical setting using in vivo animal models of cancer. In this review, we discuss the genesis of quantitative MRI methods that have been successfully translated from preclinical research and developed into clinical applications. These include methods that interrogate perfusion, diffusion, pH, hypoxia, macromolecular content, and tissue mechanical properties for improving detection, staging, and response monitoring of cancer. For each of these techniques, we summarize the 1) underlying biological mechanism(s); 2) preclinical applications; 3) available repeatability and reproducibility data; 4) clinical applications; and 5) limitations of the technique. We conclude with a discussion of lessons learned from translating MRI methods from the preclinical to clinical setting, and a presentation of four fundamental problems in cancer imaging that, if solved, would result in a profound improvement in the lives of oncology patients. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1377–1392.

From Medical Imaging to Radiomics: Role of Data Science for Advancing Precision Health

“…Together with inter-patient heterogeneity, also intra-patient heterogeneity is a source of uncertainty that requires in depth investigation. Therefore, a shift of focus toward variability imposes looking at the specific weight of both repeatability (repeated testing of the same subject over time) and reproducibility (measure of the same subject with different instruments of the same type) of measurements [56][57][58]. Reliability of RAD approaches depends on validating stable models, that is, those in which features have been thoroughly assessed for consistency and generalizability [59].…”

Co-Clinical Imaging Resource Program (CIRP): Bridging the Translational Divide to Advance Precision Medicine

“…Image contrast can be sensitized to several properties of tissue water including nuclear relaxation rate, water diffusion, blood flow, or perfusion and chemical exchange. These properties can be quantitatively measured by magnetic resonance, resulting in numerous biometric markers of disease state ( 65 ). Typically, an MRI examination includes generation of a series of images with different contrast weighting, thereby facilitating multiparametric analysis ( 66 – 68 ) and improved specificity relative to single-parameter imaging techniques.…”

“…The reader is referred to numerous treaties describing MRI methodologies for additional details ( 69 – 71 ). Although a majority of MRI techniques available clinically may be applied in preclinical studies, there are a number of significant differences between the available tools and methodologies that pose challenges to the development of co-clinical studies ( 65 ).…”

Magnetic Resonance Imaging for Translational Research in Oncology

“…For example, the vascular endothelial growth factor receptor 2 (VEGFR2), which is a molecular marker of angiogenesis and is overexpressed on tumor vascular endothelial cells, is widely used in preclinical cancer research as a marker of therapy responsiveness [88,89,90,91,92]. Therefore, this modality could help enhance the translation of antiangiogenic agents and contribute positively to human patients’ treatments [93].…”