Cancer Metabolism and Tumor Heterogeneity: Imaging Perspectives Using MR Imaging and Spectroscopy

Abstract

Cancer cells reprogram their metabolism to maintain viability via genetic mutations and epigenetic alterations, expressing overall dynamic heterogeneity. The complex relaxation mechanisms of nuclear spins provide unique and convertible tissue contrasts, making magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) pertinent imaging tools in both clinics and research. In this review, we summarized MR methods that visualize tumor characteristics and its metabolic phenotypes on an anatomical, microvascular, microstructural, microenvironmental, and metabolomics scale. The review will progress from the utilities of basic spin-relaxation contrasts in cancer imaging to more advanced imaging methods that measure tumor-distinctive parameters such as perfusion, water diffusion, magnetic susceptibility, oxygenation, acidosis, redox state, and cell death. Analytical methods to assess tumor heterogeneity are also reviewed in brief. Although the clinical utility of tumor heterogeneity from imaging is debatable, the quantification of tumor heterogeneity using functional and metabolic MR images with development of robust analytical methods and improved MR methods may offer more critical roles of tumor heterogeneity data in clinics. MRI/MRS can also provide insightful information on pharmacometabolomics, biomarker discovery, disease diagnosis and prognosis, and treatment response. With these future directions in mind, we anticipate the widespread utilization of these MR-based techniques in studying in vivo cancer biology to better address significant clinical needs.

Reliability of CT radiomic features reflecting tumour heterogeneity according to image quality and image processing parameters

“…Tumour heterogeneity is recognized as an important indicator of tumour growth and metastasis, as it is closely related to diverse genetic mutations, metabolic inhomogeneity, hypoxia, and acidosis 2 . Intratumoural heterogeneity can be spatially assessed using cross-sectional imaging data, and RF-based texture analysis can provide voxel-scale information about the compositional distribution profile within a tumour.…”

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

“…The controversy of quantitative imaging for clinical use and decision support depends on the ability to design robust methods that are likely multidimensional and multiparametric. Taking single modalities might bring the risk of oversimplifying the complex dynamics under investigation (heterogeneity, metabolism) [52]. However, quantitative phenotypes of tumors (such as tumor size, shape, margin, and blood flow kinetics) have been already successfully associated with corresponding molecular profiles (DNA mutation, miRNA, protein, pathway gene expression, and copy number variation) (see [53]).…”

How clinical imaging can assess cancer biology

“…Major approaches for pH imaging include MRS, MT methods, and pH-dependent relaxation agents, although with a limited clinical use [81]. Published preclinical data have evidenced the presence of an acidic extracellular pH and alkaline intracellular pH in tumors relative to normal tissues [76,82,83].…”