Characteristics of glioma tumor perfusion in mice with BOLD-DSC MRI

다국어 초록 (Multilingual Abstract)

Glioblastoma is one of the most severe malignant primary brain tumors and is reported to have short survival duration. Therefore, early diagnosis and periodical monitoring are essential, which helps medical doctors to plan proper treatments for patients. Most tumor progression is mainly dependent on vasculature for continuous oxygen and nutrients supplies, such as co-option, angiogenesis, vasculogenic, etc., Since then, vessel system within tumor must change to adapt for tumor needs. Vasculature in tumor appears to be abnormal in structure and function with disorganized, tortuous and leaky vessels. This leads to heterogeneous perfusion within any tumor environment. Consequently, investigating perfusion has potential for indirect assessing and understanding glioma tumor development, specifically its characteristics such as Cerebral Blood Volume (CBV), Cerebral Blood Flow (CBF), Mean Transit Time (MTT), etc. Among well-known perfusion imaging techniques is Dynamic Susceptibility Contrast (DSC), which requires a short bolus injection of gadolinium-based contrast agent (GBCA, approved by FDA). Although this method is popular in clinical uses but still there remains some limitations, such as the ability of within-body deposition, allergies, unbeneficial for children, long waiting time for total wash-out of contrast agent, etc. This raises a need for critical techniques which obsess high sensitivity (like DSC) using endogenous contrast agents. To overcome this, we incorporated new Blood Oxygenation level-dependent (BOLD)-DSC techniques using deoxyhemoglobin as an alternative for traditional contrast agents. Deoxyhemoglobin is a paramagnetic which can cause local magnetic field changes and affect surrounding protons. The change of deoxyhemoglobin concentration within blood vessel, manipulated by introducing a short 5 second (s) inhalation of nitrogen (N2) gas, allows the measurement of perfusion parameters. This technique can interchangeably call “BOLD-DSC” or “transient hypoxic gas challenge” following previous publishes. In this study, BOLD-DSC is used to 1) investigate how glioma tumor perfusion dynamically alters during progression after implantation (GL261 cell lines); then 2) vasculature morphology is determined through mean vessel size calculation using data acquired from both Gradient-Echo (GE) and Spin-Echo (SE) Echo Planar Imaging (EPI). In conclusion, this preliminary study confirmed the ability and sensitivity of BOLD-DSC for perfusion in glioma tumor models and provided critical insight into tumor progression.

목차 (Table of Contents)

• Chapter 1. Introduction 1
• 1.1. Glioma tumor and related MRI methods for evaluation 1
• 1.2. Imaging technique in perfusion study 3
• 1.3. Perfusion imaging in MRI 4
• 1.3. Challenges and New approach 6
• 1.4. Aims of this study 7
• Chapter 2. Characteristics of glioma tumor perfusion in mice with BOLD-DSC MRI in 9.4T 8
• 2.1. Introduction 8
• 2.2. Materials and Methods 10
• 2.3. Results 18
• 2.4. Discussion 27
• Chapter 3. Conclusion 29
• References 30
• 논문요약 33