Improved quantification of in vivo metabolic kinetics using hyperpolarized 13C magnetic resonance spectroscopic imaging
Abstract/Contents
- Abstract
- With signal-to-noise ratio enhancements on the order of 10,000-fold, hyperpolarized 13C MRSI allows the study of both the injected substrate and downstream metabolic products in vivo within the target organ, with the appearance of the 13C labels on the various metabolites resulting from a combination of isotopic exchange and metabolic flux. Although hyperpolarized [1-13C] pyruvate has been extensively researched as an in vivo biomarker for disease diagnosis and response to therapy, efficient and robust quantification still remains important areas of investigation. Recently, a new quantification paradigm called the saturable kinetics of 13C labeling process was proposed. This method utilized a Mechaelis-Menton-like mathematical formulation with the estimated apparent Vmax to directly quantify the dose dependence (i.e., the saturation effects) of lactate and alanine reaction velocities following one hyperpolarized 13C pyruvate injection. However, to obtain the apparent Vmax, the current quantification method repeats the multi-site exchange model fitting with different pyruvate doses and each data point corresponds to one independent pyruvate injection. Therefore, the process needs multiple injections and multiple subjects to obtain one single saturation curve. Such an intense injection pattern is almost impossible for clinical trials. Also, the estimated apparent Vmax inevitably involves the inter-subject variability due to the multi-subject requirement. Therefore, it is necessary to have an efficient quantification method for the saturable kinetics and apparent Vmax measurement. First, we developed an inflow-based single-slice quantification method which can measure saturable kinetics in one slice efficiently. The experiment time can be reduced from multiple injections with multiple animals to one injection. We demonstrated our quantification method on healthy models (rat kidney and liver) and disease models (mouse prostate tumor). Second, we applied our proposed inflow-based single-slice quantification method and demonstrated the relative change of apparent Vmax of the lactate 13C labels was well correlated with the gold-standard ALDH2 enzymatic activity in rat liver. It may serve as a potential noninvasive in vivo indicator for ALDH2 activity and provide an alternative way to research the related diseases including alcoholism and ischemia. Finally, we extended our proposed inflow-based quantification method to the 3D case so that the saturable kinetics in multiple slices can be measured efficiently following one single pyruvate injection. This extension further improved the quantification efficiency and is useful in the case of the heterogeneous in vivo saturable kinetics. We demonstrated our 3D quantification method in healthy rat models.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Xu, Tao |
|---|---|
| Associated with | Stanford University, Department of Electrical Engineering |
| Primary advisor | Pauly, John (John M.) |
| Primary advisor | Spielman, Daniel (Daniel Mark) |
| Thesis advisor | Pauly, John (John M.) |
| Thesis advisor | Spielman, Daniel (Daniel Mark) |
| Thesis advisor | Pfefferbaum, Adolf |
| Advisor | Pfefferbaum, Adolf |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Tao Xu. |
|---|---|
| Note | Submitted to the Department of Electrical Engineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2011. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Tao Xu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...