CINEMA Research Projects

Current research projects within the research theme of Cardiometabolic Imaging (CINEMA) at CVS.

Steroid hormones circulate in blood and penetrate tissues where they have their actions. The amounts of steroids in tissue subregions can be modulated by local enzymes and transporters, making it vital to understand regional steroid amounts e.g. in inflamed sites, in tumours or in brain regions. Mass spectrometry imaging is a powerful technique used to localise molecules in tissue sections, providing molecular distribution. Research (funded by the BHF and MRC) has allowed development of approaches which reveal the tissue distribution of steroids in complex tissues.

Mass Spectrometry imaging offers the chance to identify molecules in tissue sections and create regional maps of their locations. In our lab we focus on small molecular species in the metabolome, many of which are present in isomeric forms e.g. leucine and isoleucine. Our particular interest lies with steroids, present as stereo-isomers, some of which are active and others inactive (e.g. testosterone and DHEA).

This project aims to develop 18F-LW223, the first fluorinated radiotracer targeting the 18kDa translocator protein (TSPO) with binding to human samples independent of the rs6971 genetic polymorphism. This novel radiotracer has major potential for clinical imaging for all patients.

Preclinical in vivo imaging modalities, such as positron emission tomography (PET) and computed tomography (CT) imaging, have empowered biomedical research because these techniques are less invasive than other techniques; by using the animals as their own controls, the number of animals to be used is reduced and the statistical power is improved; and diagnostic and therapeutic agents can be developed using identical platforms, thus providing a unique straightforward translational paradigm.

Absolute tissue sodium concentration is elevated in myocardial infarction and has been suggested as a biomarker for cell viability. We have developed a method to quantitatively measure cardiac sodium content in rats with good spatial resolution. This method offers a new tool for studying myocardial ion homeostasis in vivo and may be of interest for different areas of cardiovascular disease, e.g. myocardial infarction, myocardial hypertrophy, but could also be used to study other organs like kidney, liver or tumours.

This project aims to investigate the use of Positron Emission Tomography (PET) with 18F-Fluoro-Prolines for imaging and quantification of fibrosis.

Myocardial fibrosis is a pathological feature contributing to the progression of a wide range of cardiovascular diseases. In this project, we validate cardiovascular magnetic resonance imaging tools to assess myocardial fibrosis in a mouse model of pressure overload.

Zebrafish offer a valuable model system for in vivo imaging of adipose tissue dynamics. In particular, adipose tissue can be accurately quantified in live zebrafish using fluorescent lipophilic dyes - a technique applicable to large scale chemical and genetic screens to identify modifiers of adiposity and associated disease.  Although, this methodology offers considerable promise, the comprehensive identification and classification of zebrafish ATs has not been performed.