Distinguishing Closely Related Pancreatic Cancer Subtypes In Vivo by 13C Glucose MRI without Hyperpolarization

Abstract

Metabolic differences between patients and within the tumor itself can be an important determinant in cancer treatment outcome. However, methods for determining these differences non-invasively in vivo have been lacking. Using pancreatic ductal adenocarcinoma as a model, we demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of metabolism, as detected by imaging of uniformly 13 C labeled glucose tracers using a newly developed technique using tensor decomposition for noise suppression to bring the signal to a detectable level without hyperpolarization of the tracer. Using this method, cancer subtypes that appeared to exhibit similar metabolic profiles by other techniques that measured steady state metabolism can be distinguished.Tumor cells are metabolically flexible and redirect metabolites away from the citric acid cycle to the less energetically efficient aerobic glycolytic pathway to generate the biomass required for growth. 1 Beyond this metabolic phenotype, known as the Warburg effect, tumor growth is further aided by neo-angiogenesis for developing vasculature to support tumor growth. Compared to normal vasculature, which is well organized and structurally robust, the vascular network of tumors is chaotically organized and leaky resulting in poor delivery of oxygen and regions of both chronic and acute hypoxia. 2 Thus, the tumor microenvironment is typically distinguished by high uptake of glucose, high glycolytic flux and hypoxia and acidic conditions. This characteristic metabolic and physiologic phenotype is used to develop diagnostic imaging methods and to tailor appropriate therapies.

Application of low‐rank approximation using truncated singular value decomposition for noise reduction in hyperpolarized 13C NMR spectroscopy

“…In recent application, the use of singular value decomposition (SVD) gave good results for in vivo studies with hyperpolarized 1‐ 13 C‐pyruvic acid ( 13 C‐Pyr) using the real part of automatically phase corrected spectra: this required a phase correction before the noise reduction because the authors of References 4 and 5 chose to use only the real part of the signals.…”