Imaging Metabolism and Hypoxia

Project title: Hyperspectral imaging for in vivo measurement of glucose uptake, mitochondrial membrane potential, and vascular oxygenation

Project Description: We are developing an optical toolbox that is able to distinguish tissue types based on differences in their metabolic phenotypes. A host of studies have indicated that measuring metabolic endpoints can be used to predict cancer metastasis or detect treatment resistance. Most studies are done in vitro with techniques such as Seahorse extracellular flux analysis which cannot be used in animal models. Current in vivo techniques such as PET and MRI offer valuable clinical information, but rely on expensive tracers and complicated instrumentation. Our technique is low-cost, and can be used with a wide range of microscopy systems. By imaging multiple key endpoints, our technique provides a more holistic view of metabolism than measurement of a single endpoint (traditionally, glucose). Our imaging toolbox uses both endogenous contrast from hemoglobin and exogenous contrast from metabolic fluorophores to characterize an in vivo region of tissue. This is illustrated in a dorsal skin flap model of normal tissues and tumors, as shown below.

Hyperspectral imaging of glucose uptake, mitochondrial membrane potential, and vascular oxygenation in tumor and normal window chambers.
Glucose uptake (2-NBDG60/RD), mitochondrial membrane potential (TMRE60), and vascular oxygenation (SO2) were measured in dorsal window chambers containing metastatic 4T1 tumors, non-metastatic 67NR and 4T07 tumors, or non-tumor tissue. 2-NBDG and TMRE fluorescence were measured 60 minutes after tail vein injection of the compound. Glucose uptake was increased in the metastatic relative to non-metastatic or non-tumor windows. However, mitochondrial membrane potential was increased in all tumor types relative to non-tumor. These alterations in metabolism were independent of SO2, which was comparable across all tissue types.