Magnetic Resonance Imaging of Tumor Growth and Leukocyte Infiltration in Brain Tumors after Stimulation of the Innate Immune System
| dc.contributor.advisor | Yong, Voon Wee | |
| dc.contributor.advisor | Dunn, Jeffrey F. | |
| dc.contributor.author | Yang, Run Ze | |
| dc.contributor.committeemember | Pike, G. Bruce | |
| dc.contributor.committeemember | Kelly, John James Patrick | |
| dc.date | 2018-11 | |
| dc.date.accessioned | 2018-07-03T15:53:20Z | |
| dc.date.available | 2018-07-03T15:53:20Z | |
| dc.date.issued | 2018-06-26 | |
| dc.description.abstract | Glioblastoma (GBM) is one of the deadliest brain cancers, and immunotherapy may be a promising treatment option. One of the challenges with immunotherapy in GBM is the lack of biomarkers that can be used to detect treatment response early on during treatment. The goal of this thesis is to use MRI to determine whether vitamin B3 (niacin) can suppress GBM growth, and develop a MRI method capable of detecting whether niacin stimulates monocyte trafficking to the brain tumor. We used human and animal derived brain tumor initiating cells for the studies. We used conventional anatomical MRI to show that niacin is capable of reducing tumor growth in the mouse. We showed that innate immune cells can be labeled by ferumoxytol, an iron based MRI contrast agent. This can be used to detect the effects of the innate immune stimulating drugs (Amphotericin B and niacin) in a mouse model of GBM. This is done by intravenously injecting ferumoxytol, and then quantifying iron changes in the tumor with susceptibility MRI. We expanded upon our results to investigate the mechanism of the iron changes after ferumoxytol injection. We used clodronate liposomes to deplete monocytes in the blood and Kupffer cells in the liver and showed that there is minimal passive leakage of ferumoxytol into the tumor, suggesting that ferumoxytol must be carried into the tumor by a phagocytic cell such as monocytes. We implemented another method of measuring ferumoxytol, quantitative susceptibility mapping (QSM), and used it in conjunction with T2* mapping to investigate whether the magnitude of ferumoxytol enhancement is related to future tumor control in niacin treated animals. We found that the degree of ferumoxytol enhancement is directly related to niacin’s ability to control tumor growth, with high ferumoxytol enhancement corresponding to smaller tumors. This thesis showed that niacin treatment can reduce tumor growth by stimulating monocytes. In addition, using ferumoxytol to track the innate immune system is a promising imaging tool to aid the assessment of immunotherapy treatment response in GBM. | en_US |
| dc.identifier.citation | Yang, R. (2018). Magnetic Resonance Imaging of Tumor Growth and Leukocyte Infiltration in Brain Tumors after Stimulation of the Innate Immune System (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32053 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/32053 | |
| dc.identifier.uri | http://hdl.handle.net/1880/106831 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Cumming School of Medicine | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Neuroscience | |
| dc.subject | Magnetic Resonance Imaging | |
| dc.subject | Cancer | |
| dc.subject | Neuroimmunology | |
| dc.subject.classification | Neuroscience | en_US |
| dc.title | Magnetic Resonance Imaging of Tumor Growth and Leukocyte Infiltration in Brain Tumors after Stimulation of the Innate Immune System | |
| dc.type | doctoral thesis | |
| thesis.degree.discipline | Neuroscience | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Doctor of Philosophy (PhD) | |
| ucalgary.item.requestcopy | true |