A Novel Z-Spectrum MRI For The Detection Of Brown And Browning Adipose Tissue

Brown adipose tissue (BAT) is one of the brightest hopes in the fight against the obesity epidemic. This peculiar subtype of fat tissue, in fact, when activated in response to cold exposure, breaks down triglycerides and glucose and dissipates the chemical energy into heat (“nonshivering thermogenesis”), therefore increasing energy expenditure and reducing the lipid buildup. Key to the understanding and management of BAT is the establishment of a noninvasive imaging method to unbiasedly detect and monitor brown and browning adipose tissue. The current imaging approaches are either invasive or lack a comprehensive capability to assess the structural and functional aspects of the tissue. Z-Spectrum MR Imaging (ZSI) can bridge this gap. In this dissertation, it is presented how ZSI can produce both structural and functional contrasts, which can be used to study brown and browning adipose tissue. In the first Aim, it is shown how ZSI can measure fat water fraction and how such measurement can be used to characterize BAT. By fitting the Z-spectrum it is possible to extract the relative contribution to the overall signal, summarized in the fat water fraction. The technique was validated in vitro and in vivo and compared to conventional Dixon MRI. It was then tested in a clinically relevant scenario, by characterizing the reduced functionality of BAT in polycystic ovary syndrome (PCOS) patients. It was then demonstrated the efficacy of Z-spectrum MRI in detecting adipose tissue activation through changes in FWF in a transgenic mouse model treated with a stimulating drug. FWF was significantly lower over time in the treated group compared to the controls, suggesting that lipid consumption, associated with adipose tissue activation, has occurred. After demonstrating how the FWF contrast can characterize BAT mass and function, it was the aim in this thesis to show how ZSI can produce a marker of BAT very own thermogenesis. Here was then proposed a new sequence based on the ZSI platform, with a fine spectral selectivity that can monitor temperature-induced changes in the water resonance frequency. The proof of concept was carried out in PBS solution exposed to hot air flow. The technique was then tested on a whipped cream phantom, used as a proxy for biological fatty tissue. The temperature measurement was successful and correlated well with the results form the electrode sensor probe inserted in the phantom. Finally, the feasibility of the binomial-ZSI technique implementation in vivo was assessed. The protocol was tested in healthy mice undergoing thermal challenge and compared to infrared and MRI standard methods. Results correlated well in both muscle and fat tissues. These studies, taken together, show how Z-spectrum Imaging is capable of producing varied contrasts for a comprehensive characterization of brown and browning adipose tissue.