Visualizing Brain Pathology: Non-Invasive Imaging of Neuroinflammation

Taylor McKenzie Brinson, BA (Advisor: Federica Pisaneschi, PhD)

           Neuroinflammation, an inflammatory response in the central nervous system (CNS), has been demonstrated to be a key contributor to the pathogenesis and progression of neurological conditions and disorders. During an inflammatory response in the CNS, resident immune cells like microglia become activated, respond to pathological stimuli with a cascade of signaling molecules, engage local repair mechanisms, and can transition into disease-associated microglia (DAM) states through the upregulation of microglia-specific receptors, like triggering receptor expressed on myeloid cells-2 (TREM2). Although initially protective, sustained activation drives synaptic loss, neuronal death, and cognitive and functional deficits. Translatable imaging tools to track microglial activation is therefore essential for both early diagnosis and therapeutic development. To address these challenges, we aim to detect neuroinflammation in two pathological states using a novel positron emission tomography (PET) antibody-based tracer which is radiolabeled with zirconium-89 (⁸⁹Zr). Because of its characteristics as a bispecific antibody and subsequent ability to target transferrin receptors and selectively bind to TREM2, we hypothesize that we can utilize our tracer, ⁸⁹Zr-T2BA, as a specific tool for monitoring TREM2 upregulation and ensuing microglial activation across neuroinflammatory models, like lipopolysaccharide (LPS)-induced inflammation and cranial radiotherapy (CRT)-induced injury.

Advisory Committee:

• Federica Pisaneschi, PhD, Chair 
• Joya Chandra, PhD
• Niki Zacharias Millward, PhD
• Andrea Stavoe, PhD
• Long Jun Wu, PhD