Dual contrast microvascular MRI

Abstract

The fundamental magnetic resonance angiography (MRA) has been used for obtaining vascular information, such as vessel size and structure. For many decades, MRA techniques with contrast agent have been developed and implemented in research and the clinical area for in vivo applications. Especially, the longitudinal (T1) and transverse (T2 or T2*) contrasts in MRA provide diverse and different information of same subject’s vasculature. The assessments of vascular structure and function by using two types of contrast are important for monitoring vascular behavior. Generally, the two types of contrast agent are T1- and T2-contrast agents. In recent years, several efforts have been focusing on synthesizing hybrid nanoparticles to achieve T1- and T2-contrast, simultaneously. The MR images with both positively and negatively enhanced contrast over the same anatomical region offer complementary information. The benefits of dual contrast with a single agent for in vivo experiments are obvious. In this study, instead of synthesized hybrid contrast agents or multiple contrast agents, simultaneous acquisitions of in vivo dual contrast with size-controlled superparamagnetic iron oxide nanoparticles (SPION) in MRA were obtained and evaluated. As this method is successful for preclinical investigations, dual contrast has a great potential to directly help to compensate vascular information by positively and negatively enhanced contrast. The results of obtained dual contrast in in vivo images were apparent, the smaller vessels in the head region of rodents were distinctively visible from negatively enhanced contrast MRA, while positively enhanced contrast MRA eliminated false contrasts in regions of airways and bone from negatively enhanced contrast MRA. Based on advantages of dual contrast in in vivo MRA, we systematically compared the strengths and weaknesses of dual contrast-enhanced MRAs with SPION in cerebral micro-vessels of the rodent brain. The vasculatures in rodent brain with positively enhanced contrast were visualized well without any artifact, but smaller vessels than given spatial resolution were hardly detected. On the other hand, negatively enhanced contrast based MRA provided good sensitivity for micro-vessels. However, negatively enhanced vessels and specific regions suffered from susceptibility-induced artifacts. Consequently, dual contrast enhanced MRAs were combined for compensation of those short-comings and visualization of whole-brain micro-MRA. The other subject of this thesis is a feasibility evaluation of newly developed contrast agent for in vivo applications at high magnetic field. From MR perspective, the behavior of higher magnetic field (> 7T) is attractive, as it is expected to drastically increase SNR, resolution and susceptibility contrast, which improves lesion detection and quantifications. Also the reduction of inherent T1 relaxation time of contrast agent at high magnetic field is important to increase positively enhanced contrast with limited MR acquisition parameters. The developed contrast agent used in this study was observed to maintain its favorable positive relaxivity even at 7 T magnetic field without drastic reductions of r1 relaxivity. The developed contrast agent was characterized by this phantom and in vivo experiments. The results of 3D MRA proved the feasibility of vascular imaging within 2 hours after intravenous injection of the contrast agent. And a significant reduction of T1 values was observed in the tumor region 7 hours after contrast agent injection in the tumor mouse model.