Dr. Ramos-Torres, a post-doctoral research fellow at the Gordon Center, was awarded an MGH Physician/Scientist Development award for “Imaging brain injury in animal models using PET.”
Dr. Ramos-Torres has broad training at the interface of chemical biology, organic and inorganic chemistry and is interested in the application of chemistry and chemical biology strategies to support the discovery and development of technologies for disease diagnosis, monitoring and treatment. Dr. Ramos Torres received her bachelor’s degree in Chemistry from the University of Puerto Rico, Río Piedras and earned her PhD in Chemistry and Chemical Biology at the University of California, Berkeley. Her research as a research fellow at the Gordon Center focuses on the development and application of new small molecule PET radiopharmaceuticals designed to better understand neurological disorders.
Abstract: Imaging brain injuries in animal models using PET
Disruptions to the myelin sheath, the protective layer that covers nerve cells in the brain and spinal cord, can affect neuronal ability to propagate action potentials needed for the proper function of motor, sensory and cognitive skills. Demyelination is a hallmark in a wide range of neurological pathologies, including multiple sclerosis, leukodystrophies, Alzheimer’s disease, traumatic brain (TBI) and spinal cord injury (SCI) and stroke, among others. However, demyelination is not a stand-alone feature in these disorders, being usually accompanied by other processes including neuroinflammation. It is therefore attractive to identify and develop methods that can accurately quantify and assess myelin status in order to diagnose and monitor disease progression and treatment.
Currently, myelin content in demyelinating diseases is evaluated with MRI. However, while MRI is highly sensitive to demyelination, it cannot discriminate between demyelination and other simultaneous processes present in these pathologies, such as inflammation and axonal loss. Due to its biochemical specificity and quantification ability, positron emission tomography (PET) can serve as a complementary technique to MRI. [18F]3F4AP, a recently developed 4-aminopyridine (4AP) based PET tracer that binds to voltage-gated K+ channels, has been proven to visualize demyelination in rodent models of multiple sclerosis (MS). The proposed research project seeks to assess the potential utility of this radiotracer to identify white matter injury in a variety of pathologies, namely models of brain injury, and distinguish between the progression of demyelination and inflammation.
The specific goals of this proposal are to study [18F]3F4AP, in combination with the known neuroinflammation tracer [11C]PBR28, as a tool to evaluate demyelination and inflammation with PET imaging in mouse brain injury models for open-head injury and stroke. Mice will be subjected to a well-characterized mouse model of TBI, open-head controlled cortical impact (CCI), and monitored in a longitudinal PET imaging study with both radiotracers to evaluate focal changes in myelin content and/or inflammation, followed by corroboration with histopathological and histochemical characterization of the brain tissue. Additionally, the study will expand to mouse models of stroke to study the pathologies of demyelination and neuroinflammation with imaging, histology and behavioral methodologies.
The Physician/Scientist Development Award (PSDA) provides transitional grant funding which aids the applicant (fellow or junior faculty) in becoming an independent investigator at MGH. The award is designed for those who are considered underrepresented in academic medicine.