Novel Simulation to Avoid Bias In Measurement of Hyperpolarized Pyruvate: Demonstrated In Phantom and In Vivo

<p>Dynamic nuclear polarization creates a transient hyperpolarized nuclear state that can dramatically increase the signal detected by magnetic resonance imaging. This signal increase allows real-time spectroscopic imaging of specific metabolites <em>in vivo </em>by magnetic resonance. Real-time imaging of both the spatial and chemical fate of hyperpolarized metabolites is showing great promise to meaningfully benefit clinical care of cancer patients. Imaging of hyperpolarized agents will have a larger clinical impact if it can function as a quantitative modality upon which clinical decisions can be made. However, quantitative measurement of hyperpolarized agents is currently difficult due to the restrictions imposed by the transient hyperpolarized state and the complexity inherent in biological systems. As more advanced imaging and measurement techniques are developed for imaging hyperpolarized substrates, it is critical to characterize their effect on any relevant quantitative measure. To assist in accurate quantitative measurement of hyperpolarized agents, an infrastructure where acquisition strategies can be developed, compared, optimized and validated was critically need. A novel simulation architecture was developed that combines classical chemical kinetics with the basic physics of nuclear magnetic resonance and couples them to multiple perfusion models. Simulation results showed that changes in the acquisition strategy used will affect the resulting quantification of chemical exchange rates and suggested that any bias that is imposed by the acquisition strategy can be avoided by using optimized pulse sequences. To validate these predictions, a phantom system was developed that allows controllable chemical conversion of hyperpolarized pyruvate into lactate with a variability less than 20%. Using this phantom system, studies showed that poorly optimized pulse sequences significantly reduced the measured value of the chemical exchange rates, whereas optimized pulse sequences showed no significant difference in chemical exchange measurements. In order to test simulation predictions for a perfused system, an animal cohort with orthotropic anaplastic thyroid cancer was scanned with multiple sequences. Again, optimized sequences showed no significant difference in measured exchange rates while poorly designed sequences significantly underestimated the exchange rates, which is consistent with the simulation results. These validation studies suggest that this simulation architecture will be a powerful tool for developing and optimizing acquisition and quantization methods for hyperpolarized magnetic resonance imaging.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2016

Author dc:creator

• Walker, Christopher M

Contributors dc:contributor

• James A. Bankson
• John Hazle
• Dawid Schellingerhout

• hyperpolarized
• pyruvate
• magnetic resoance
• simulation
• Analytical, Diagnostic and Therapeutic Techniques and Equipment
• Medicine and Health Sciences
• Other Physics

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/712

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1756