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Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2018)

Recently, attention in chronic inflammation has been increasing since it is closely related to various diseases, such as rheumatoid arthritis, Huntington’s, Parkinson’s, Alzheimer’s diseases, and even in cancers. Inflammation is an immune response against pathogens, damaged cells or irritants. In the process, immune cells activate overproduction of reactive oxygen species (ROS) and decrease pH of the inflammatory area. Therefore, these two biomarkers are available as stimuli for controlled release of drug delivery system (DDS). DDS is intended to encapsulate conventional medicines in vehicles and safely transport the therapeutic agents only to disease area, minimizing adverse effects on normal tissue and maximizing the effect on the target. The ultimate goal of the DDS is to find optimized materials as a delivery vehicle. Polymers are proposed as suitable biomedical materials for several reasons. Firstly, both of hydrophobic conventional drugs and hydrophilic enzymes and proteins can be encapsulated according to polymer nature. Secondly, a wide range of chemical modification is applicable. The easy modification makes efficient delivery possible by controlling the release of cargo by disease-specific stimuli. Based on these advantages, inflammation-responsive polymeric carriers are introduced in here. In chapter 1, ROS-responsive polymeric degradation via chemical amplification is demonstrated. This polymer degraded 12 times faster compared with its control polymer by employing chemical amplification strategy. In chapter 2, anti-inflammatory drug conjugated polymer is introduced. To maximize drug delivery efficiency, an anti-inflammatory drug was conjugated onto dextran using a ROS-responsive linker. This polymeric material not only releases the anti-inflammatory drug in inflammatory cells but also increased drug efficacy by reducing ROS level in inflammation. In chapter 3, bioresponsive prophylaxis polymeric materials for acute inflammation is demonstrated both in vitro and in vivo.

    Cover page: Synthesis and Study of Inflammation Responsive Polymeric Particles
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2019)

    Purpose

    To develop a dynamic contrast-enhanced (DCE) MRI method capable of high spatiotemporal resolution, 3D carotid coverage, and T1-based quantification of contrast agent concentration for the assessment of carotid atherosclerosis using a newly developed Multitasking technique.

    Methods

    5D imaging with 3 spatial dimensions, 1 T1 recovery dimension, and 1 DCE time dimension was performed using MR Multitasking based on low-rank tensor modeling, which allows direct T1 quantification with high spatiotemporal resolution (0.7 mm isotropic and 595 ms, respectively). Saturation recovery preparations followed by 3D segmented fast low angle shot readouts were implemented with Gaussian-density random 3D Cartesian sampling. A bulk motion removal scheme was developed to improve image quality. The proposed protocol was tested in phantom and human studies. In vivo scans were performed on 14 healthy subjects and 7 patients with carotid atherosclerosis. Kinetic parameters including area under the concentration versus time curve (AUC), vp , Ktrans , and ve were evaluated for each case.

    Results

    Phantom experiments showed that T1 measurements using the proposed protocol were in good agreement with reference value ( R 2 = 0.96 ). In vivo studies demonstrated that AUC, vp , and Ktrans in the patient group were significantly higher than in the control group (0.63 ± 0.13 versus 0.42 ± 0.12, P < 0.001; 0.14 ± 0.05 versus 0.11 ± 0.03, P = 0.034; and 0.13 ± 0.04 versus 0.08 ± 0.02, P < 0.001, respectively). Results from repeated subjects showed good interscan reproducibility (intraclass correlation coefficient: vp , 0.83; Ktrans , 0.87; ve , 0.92; AUC, 0.94).

    Conclusion

    Multitasking DCE is a promising approach for quantitatively assessing the vascularity properties of the carotid vessel wall.
      Cover page: Quantitative 3D dynamic contrast‐enhanced (DCE) MR imaging of carotid vessel wall by fast T1 mapping using Multitasking
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2019)

      Purpose

      To develop a dynamic contrast-enhanced (DCE) MRI method capable of high spatiotemporal resolution, 3D carotid coverage, and T1-based quantification of contrast agent concentration for the assessment of carotid atherosclerosis using a newly developed Multitasking technique.

      Methods

      5D imaging with 3 spatial dimensions, 1 T1 recovery dimension, and 1 DCE time dimension was performed using MR Multitasking based on low-rank tensor modeling, which allows direct T1 quantification with high spatiotemporal resolution (0.7 mm isotropic and 595 ms, respectively). Saturation recovery preparations followed by 3D segmented fast low angle shot readouts were implemented with Gaussian-density random 3D Cartesian sampling. A bulk motion removal scheme was developed to improve image quality. The proposed protocol was tested in phantom and human studies. In vivo scans were performed on 14 healthy subjects and 7 patients with carotid atherosclerosis. Kinetic parameters including area under the concentration versus time curve (AUC), vp , Ktrans , and ve were evaluated for each case.

      Results

      Phantom experiments showed that T1 measurements using the proposed protocol were in good agreement with reference value ( R 2 = 0.96 ). In vivo studies demonstrated that AUC, vp , and Ktrans in the patient group were significantly higher than in the control group (0.63 ± 0.13 versus 0.42 ± 0.12, P < 0.001; 0.14 ± 0.05 versus 0.11 ± 0.03, P = 0.034; and 0.13 ± 0.04 versus 0.08 ± 0.02, P < 0.001, respectively). Results from repeated subjects showed good interscan reproducibility (intraclass correlation coefficient: vp , 0.83; Ktrans , 0.87; ve , 0.92; AUC, 0.94).

      Conclusion

      Multitasking DCE is a promising approach for quantitatively assessing the vascularity properties of the carotid vessel wall.
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