Scientists at Technical University Munich (Germany) have developed a system that combines five molecular imaging techniques—including luminescence, fluorescence, and optical imaging—for multimodal imaging of both tissue models and live subjects.
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The preclinical and intravital molecular imaging system houses a window for tissue observation in addition to a larger imaging chamber. Together, they are being used to peer into the microenvironment of tumors and other tissues while learning about the co-registration of multiple lines of imaging data.
"This technology allows us to obtain in-depth knowledge of molecular imaging techniques, how to optimize them, and how to leverage data with statistical analysis while advancing new radiotracers and contrast agents for the imaging and treatment of a range of diseases," says Zhen Liu, PhD candidate and lead author of the study from the department of nuclear medicine at Technical University Munich.
Each technology within the system has its own strengths. Direct positron imaging is a nuclear medicine technique that allows researchers to gain physiological information from radiolabeled imaging agents that bind to targets in the body, which are then imaged with a specialized detector. The hybrid system applies both conventional and hyperpolarized magnetic resonance imaging (MRI). The former is ideal for soft-tissue contrast, and the latter has extremely fine imaging resolution due to a revolution in the technology called dynamic nuclear spin polarization, which is used to track minute biochemistry in the body--such as the transition of the naturally occurring chemical pyruvate to lactate. This exchange, which takes place throughout the body, has been found to be an excellent biomarker for disease. Finally, luminescence, fluorescence, and optical imaging can all be used to paint targets as small as a strand of DNA with glowing substances to make them stand out when scanned or observed under a very powerful microscope.
"Understanding the physiology behind multimodal imaging is very challenging due to discrepancies between macroscopic and microscopic images and between images of extracted or transplanted tissues versus images of a live subject," Liu says. "This establishment of high-resolution multimodal intravital imaging can bridge these discrepancies and offer a tool for the long-term observation of underlying physiology."
For this study, a tumor cell line was transplanted into a rat and imaged with each of the following: conventional MRI, the radiotracer carbon-13 (C-13) pyruvate and hyperpolarized MRI at a resolution of 2.5 mm, a Medipix positron detector, a luminescence sensor, and a fluorescence microscope.
Results of the study showed that increased lactate production was found by hyperpolarized MRI in areas of hypoxia (low oxygenation) and higher levels of fluorodeoxyglucose (FDG) binding represented areas of hypermetabolic activity surrounding the hypoxic areas. These are indications that areas of diseased tissue could be dying, while other parts of a tumor could be rapidly growing or becoming more aggressive. These details tell researchers about the heterogeneity of tumors, which is essential for developing appropriate research and drug protocols that can navigate all the inherent complexity of not just the anatomy and physiology being imaged, but also how imaging technologies intersect to capture as much information as possible.
The work was presented at the 2015 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in Baltimore, MD; for more information, please visit www.snmmi.org/am2015.
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