MRI method development
Ph.D. in Chemistry, National Taiwan University
Our research focuses on the development of new MRI methods for use in biomedical applications.
Real-time glucose MRI by Chemical Exchange Saturation (CEST) imaging
It is a challenge to image changes in specific metabolites in vivo. In this research project, we use CEST images to observe changes in glucose metabolism.The brain mainly relies on glucose as an energy source for its metabolism. Traditionally, FGD-PET is an imaging method to study glucose metabolism in the brain. In recent years, a chemical exchange saturation transfer (CEST) method using proton exchange between glucose and water as a contrast mechanism has been proposed to study dynamic glucose enhancement (DGE). DGE can be used to understand the dynamic metabolism of glucose over time. However, the blood flow in the dynamic system will affect the saturation efficiency of the studied slice, resulting in a decrease in DGE performance. In this study, the DGE signals of tumors and Huntington's disease over time were studied and analyzed through theoretical models. The results indicate that there is a significant correlation between DGE signal and disease progression.
Machine learning for semiautomated classification of glioblastoma in Dynamic Glucose-Enhanced MRI (DGE MRI)
Differentiating glioblastoma, brain metastasis, and central nervous system lymphoma (CNSL) on conventional magnetic resonance imaging (MRI) can present a diagnostic dilemma due to the potential for overlapping imaging features. In this project, we utilize DGE MRI and integrate it into artificial intelligence (AI) to classify the the tumor microenvironment.
NMR spectroscopy the superior analytical tool has been proven to play pivotal role in structure elucidation, bioanalysis and screening of numerous metabolites that can be used as potential therapeutic candidates in drug discovery and development. The recent and fast progressing developments in NMR data acquisition and processing increase the ability to directly observe metabolites / biomolecules with high-resolution, high sensitivity and reproducibility. Qualitative and quantitative informations that NMR provide benefits numerous disciplines in drug discovery, including natural products research, metabolism studies, drug design, quality control and synthetic medicinal chemistry. On coming recent exciting applications of NMR in the drug discovery process holds out the promise of further improvements in the field of drug development.
MRI contrast agent
Gadolinium-based contrast agents (CAs) that enhance the quality of magnetic resonance imaging (MRI) are extensively used to achieve précised diagnosis and treatment of tumors. Rising prevalence of tumors, triggered the development of novel gadolinium probes with high biocompatibility, selective targeting, and clearance as key challenges. Ligand mediated targeting of tumors with high specificity and affinity is an attractive strategy for increasing the efficiency of MRI assisted diagnostic imaging and chemotherapies. In recent years, boronic acid and their derivatives, especially phenyl boronic acid (PBA) that selectively recognizes the overexpressed sialic acid on the surface of cancer cells have attracted great attention in diverse applications, including medical diagnosis, drug delivery and imaging. Therefore, we developed PBA functionalized gadolinium probe and investigated its effect both in vitro and in vivo on highly metastatic B16F10 murine melanoma cells overexpressing sialic acid on their surface. Our results showed efficient targeting of Gd-DO3A-Am-PBA to SA moieties on tumor surface, with increased cellular intake in vitro and enhanced tumor retention in vivo compared to that of the commercially available contrast agent, Gadovist. This prolonged retention of Gd-DO3A-Am-PBA at the tumor site after injection suggests the possibility of using Gd-DO3A-Am-PBA in early tumor detection and also in tumor treatment after labeling with specific anti-tumor drugs. In addition, this study could also be extended to other type of tumors that are known to exhibit sialic acid expression. Research along these line is currently under way.
A Gadolinium DO3A Amide m-Phenyl Boronic Acid MRI Probe for Targeted Imaging of Sialated Solid TumorsBiomedicines, Oct 13, 2021