The Pautler Lab develops and applies methodologies that permit high-resolution images of the structure and function of the brain in intact, living animals.
Manganese Enhanced MRI (MEMRI) Neuronal Tract Tracing
Her current research efforts build upon the new technique that she developed known as Manganese Enhanced MRI (MEMRI) neuronal tract tracing. Manganese ion, Mn2+, is a calcium analogue and can enter neurons through calcium (Ca2+) channels. Furthermore, Mn2+ is transported along microtubules via fast axonal transport and is also paramagnetic, rendering it MRI detectable in spin-lattice (T1)-weighted MRI images. It is therefore possible to utilize MRI to repeatedly measure dynamic changes in signal intensity, reflective of fast axonal transport of Mn2+ ion, within the same animal before and during disease progression.
Alzheimer's Disease Research
One main project in Dr. Pautler's lab involves utilizing MEMRI to longitudinally elucidate in vivo changes in axonal transport rates in the central nervous system of mouse models of Alzheimer's Disease (AD) as symptoms evolve. Axonal transport deficits have been observed in flies and cultured rodent neurons exposed to excess amyloid precursor protein (APP) or amyloid-beta, but neither the molecular basis of the transport deficit nor the temporal relationship of the transport deficit and the acquisition of AD are known.
Novel 19F MRI Contrast Agent Development for Hypoxia Imaging
There is a need for positive contrast agents for magnetic resonance imaging (MRI) that respond to levels of hypoxia in heterogeneous environments like those found in many tumors for the purpose of predicting therapeutic outcomes, developing new therapies, and enabling the testing of hypotheses relevant to our collective fundamental understanding between hypoxia and human health.
Our long-term goal is to develop positive contrast agents for MRI to fill this void in diagnostic medicine by focusing on EuII-containing complexes that are among the most promising areas of study. The overall objective of this project is to establish the groundwork necessary for translation of our new 19F-EuII-based complexes into useful hypoxia-responsive contrast agents by studying the influence of the position of fluorine on ligands for europium and characterizing in vitro and in vivo indices of hypoxia.
The new 19F-EuII-based probes will be significant because they are expected to enable changes in hypoxia resulting from therapies to be imaged, consequently aiding in assessing therapeutic efficacy and influencing the care and management of cancer patients as well as a broad range of many other diseases. This work is in collaboration with chemist Dr. Matt Allen and pediatric oncologist Dr. Jason Yustein.