Label-free hypoxia measurement in a xenograft multiple myeloma model using optical-resolution photoacoustic microscopy

Abstract

In cancer research, regions of increasingly lowered oxygenation in tissue (hypoxia), which are due to tumor development, are considered to play an important role in activating various signaling pathways that facilitate further development of the cancer. However, devising a minimally invasive method to monitor tissue oxygenation has remained a challenge. Photoacoustic microscopy has been posed as a solution in a variety of preclinical research studies. Here, using optical-resolution photoacoustic microscopy (OR-PAM), for the first time, we non-invasively measured oxygenation and vascularization in vivo caused by multiple myeloma (MM) progression. Mice injected with MM cells tagged with green fluorescent protein were monitored with a fluorescence microscope for tumor progression over the course of 28 days. OR-PAM evaluated the oxygen saturation (sO2) and the blood vessel density in the cerebral bone marrow, where MM cells home. At 28 days after the injection of MM cells, the total sO2 had dropped by 50% in the developing tumor regions, while in the non-tumor developing regions it had dropped by 20% compared with the value at one day after MM injection. The blood vessel density had dropped by 35% in the tumor developing regions, while in the non-tumor developing regions it had dropped by 8% compared with the value at one day after MM injection. In summary, non-invasive measurement by OR-PAM correlated the development of hypoxia with to MM progression. It revealed decreased vascularization surrounding the tumor areas, which we feel can be ascribed to the rapid tumor progression.

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