Ongoing Research
One-shot morphologic, hemodynamic and metabolic MR imaging of brain tumors
Dr. Maheshwaran Duraiyarasu, Lakshmisree Damodaran
Rapid proliferation of cancer cells combined with unbalanced levels of pro and anti-angiogenic factors lead to abnormal vasculature which results in regions of hypoxia in solid tumors. MRI provides a powerful platform for generating 3-D spatial maps of hypoxia and targeted, non-invasive in vivo imaging with the use of a novel hypoxia targeted Gadolinium (Gd3+) contrast agent called GdDO3NI (developed in our lab), which could immediately impact the therapeutic choices. We have conducted in-vitro and in-vivo analysis of GdDO3NI and correlate with immuno-histochemical staining of hypoxia. The goal of this study is to establish GdDO3NI as a potential hypoxia and perfusion mapping contrast agent that would aid in studying the physiological properties of individual patient’s tumor and hence help direct the treatment decisions and study tumor’s response to treatments.
Optimizing macroencapsulation devices transplantation via magnetic resonance oximetry
Yuka Sugamura, Charmayne Seaton
Clinical islet transplantation is a promising treatment for insulin-dependent diabetic patients, with the potential to eliminate long-term secondary complications by restoring native insulin signaling. As a result, much research has explored the development of macroencapsulation devices to isolate transplanted cells from the recipient immune system. To date, these devices demonstrate limited clinical efficacy, due in large part to limited oxygen delivery to encapsulated cells.
We seek to approach macroencapsulation device design using computational modeling to optimize device oxygen distribution prior to fabrication and testing, and evaluate device oxygenation in vitro and in vivo via a novel, siloxane probe-based magnetic resonance (MR) oximetry technique, originally developed by Prof. Vikram Kodibagkar for cancer applications. We hypothesize that MR oximetry, via siloxane core probe device labelling, will enable the first precise tracking and evaluation of macroencapsulation device oxygenation in a spatiotemporal manner. We anticipate that MR imaging will validate in silico finite element modeling predictions of oxygen distribution within varied macroencapsulation device designs, and enable non-invasive, real-time tracking of macroencapsulation device oxygenation levels in vivo.
HDO Imaging as a Quantitative Marker of Cerebral Glucose
Samantha McClendon, Chavalchart Herabut
Deuterium magnetic resonance imaging, DMI, has demonstrated ability to identify changes in brain metabolism associated with cancer. However, downstream products of glucose metabolism, glutamate/glutamine (glx) and lactate, have intrinsically low signal to noise ratios that make detection challenging. This work posits that imaging of HDO following metabolism of [2H7]glucose will produce a more sensitive means of detecting glycolysis and glucose oxidation in the Krebs cycle. Towards this end we will establish optimal dosing levels of substrate as well as the impact of insulin sensitivity on cerebral metabolism of the glucose substrate. We will compare our new methods to 18F-deoxyglucose – positron emission tomography (FDG-PET) to determine if the two techniques provide complementary information about metabolism in animal models of brain cancer. The overall goal in this projest is to establish HDO imaging as a robust marker of cerebral glucose metabolism.
Development of a radio frequency coil for magnetic resonance imaging of hypoxia in micro-scale tumor spheroids
Chavalchart Herabut
Current commercial RF coils do not offer adequate RF field sensitivity and homogeneity to image tumor spheroids because of their small diameter (600-800µm). In order to image the spheroid samples, there is a need for a custom transmitting and receiving RF coil capable of providing high quality images of minute hypoxic regions. Our goal is to design and build an RF coil that can provide high quality magnetic resonance imaging (MRI) data when imaging oxygenation levels in tumor spheroids. By providing a quantitative measure of oxygenation, it is the hope that MRI can be used to gauge the efficacy of cancer therapies and to better identify and treat cancer based on unique, personalized data.
