Doctor of Philosophy

dissertationMagnetic resonance imaging (MRI) techniques are widely applied in various disease diagnoses and scientific research projects as noninvasive methods. However, lower signal-to-noise ratio (SNR), B1 inhomogeneity, motion-related artifact, susceptibility artifact, chemical shift artifact and Gibbs ring still play a negative role in image quality improvement. Various techniques and methods were developed to minimize and remove the degradation of image quality originating from artifacts. In the first part of this dissertation, a motion artifact reduction technique based on a novel real time self-gated pulse sequence is presented. Diffusion weighted and diffusion tensor magnetic resonance imaging techniques are generally performed with signal averaging of multiple measurements to improve the signal-to-noise ratio and the accuracy of diffusion measurement. Any discrepancy in images between different averages causes errors that reduce the accuracy of diffusion MRI measurements. The new scheme is capable of detecting a subject's motion and reacquiring motion-corrupted data in real time and helps to improve the accuracy of diffusion MRI measurements. In the second part of this dissertation, a rapid T1 mapping technique (two dimensional singleshot spin echo stimulated echo planar image--2D ss-SESTEPI), which is an EPI-based singleshot imaging technique that simultaneously acquires a spin-EPI (SEPI) and a stimulated-EPI (STEPI) after a single RF excitation, is discussed. The magnitudes of SEPI and STEPI differ by T1 decay for perfect 90o RF pulses and can be used to rapidly measure the T1 relaxation time. However, the spatial variation of B1 amplitude induces uneven splitting of the transverse magnetization for SEPI and STEPI within the imaging FOV. Therefore, correction for B1 inhomogeneity is critical for 2D ss-SESTEPI to be used for T1 measurement. In general, the EPI-based pulse sequence suffers from geometric distortion around the boundary of air-tissue or bone tissue. In the third part of this dissertation, a novel pulse sequence is discussed, which was developed based on three dimensional singleshot diffusion weighted stimulated echo planar imaging (3D ss-DWSTEPI). A parallel imaging technique was combined with 3D ss-DWSTEPI to reduce the image distortion, and the secondary spin echo formed by three RF pulses (900-1800-900) is used to improve the SNR. Image quality is improved

Anderson Localization at the Subwavelength Scale and Loss Compensation for Surface-Plasmon Polaritons in Disordered Arrays of Metallic Nanowires

Using a random array of coupled metallic nanowires as a generic example of disordered plasmonic systems, we demonstrate that the structural disorder induces localization of light in these nanostructures at a deep-subwavelength scale. The ab initio analysis is based on solving the complete set of 3D Maxwell equations. We find that random variations of the radius of coupled plasmonic nanowires are sufficient to induce the Anderson localization (AL) of surface-plasmon polaritons (SPPs), the size of these trapped modes being significantly smaller than the wavelength. Remarkably, the optical-gain coefficient, needed to compensate losses in the plasmonic components of the system, is much smaller than the loss coefficient of the metal, which is obviously beneficial for the realization of the AL in plasmonic nanostructures. The dynamics of excitation and propagation of the Anderson-localized SPPs are addressed too.Comment: 5 pages, 4 figures, to appear in Phys. Rev.

Omega-3 Polyunsaturated Fatty Acids Antagonize Macrophage Inflammation via Activation of AMPK/SIRT1 Pathway

Macrophages play a key role in obesity-induced inflammation. Omega-3 polyunsaturated fatty acids (v-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert anti-inflammatory functions in both humans and animal models, but the exact cellular signals mediating the beneficial effects are not completely understood. We previously found that two nutrient sensors AMP-activated protein kinase (AMPK) and SIRT1 interact to regulate macrophage inflammation. Here we aim to determine whether v-3 PUFAs antagonize macrophage inflammation via activation of AMPK/SIRT1 pathway. Treatment of v-3 PUFAs suppresses lipopolysaccharide (LPS)-induced cytokine expression in macrophages. Luciferase reporter assays, electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation (ChIP) assays show that treatment of macrophages with v-3 PUFAs significantly inhibits LPS-induced NF-kB signaling. Interestingly, DHA also increases expression, phosphorylation and activity of the major isoform a1AMPK, which further leads to SIRT1 overexpression. More importantly, DHA mimics the effect of SIRT1 on deacetylation of the NF-kB subunit p65, and the ability of DHA to deacetylate p65 and inhibit its signaling and downstream cytokine expression require SIRT1. In conclusion, v-3 PUFAs negatively regulate macrophage inflammation by deacetylating NF-kB, which acts through activation of AMPK/SIRT1 pathway. Our study defines AMPK/SIRT1 as a novel cellular mediator for the anti-inflammatory effects of v-3 PUFAs

Construction of nano-assembly for mild photothermal therapy of tumors

Due to the high incidence and mortality rates of cancer, it is necessary to seek more targeted and effective treatment methods. Traditional cancer treatment methods have problems such as incomplete treatment and significant side effects. In recent years, photothermal therapy (PTT) has been considered one of the most promising treatment methods in the biomedical field. The treatment principle of PTT is to use materials with high photothermal conversion efficiency to absorb near-infrared light (NIR) and generate heat to ablate tumors. PTT has the advantages of low toxicity, non-invasiveness, strong specificity, and high controllability. However, the self-protective mechanism related to heat shock proteins (HSPs) gives cancer cells thermal tolerance. To minimize the thermal tolerance of cancer cells and improve the efficacy of PTT, a nano-assembly composed of Pluronic F-127 encapsulating the HSP inhibitor APO and the high photothermal conversion efficiency photosensitizer Cy7-TCF has been developed. The nano-assembly can accumulate at the tumor site and generate heat under near-infrared light irradiation. At the same time, it inhibits the expression of heat shock proteins, achieving the effect of mild photothermal therapy and reducing thermal damage to surrounding tissues