Whole brain, PET-based molecular neuroimaging of fos expression – a new tool for imaging neurocircuitry involved in complex behavior

"Whole brain, PET-based molecular neuroimaging of Fos expression - a new tool for imaging neurocircuitry involved in complex behavior," is led by the Molecular and Cellular Imaging Laboratory (MCIL), which operates at the intersection of chemistry, physics and biology and emphasizes molecular and cellular imaging modalities for regenerative medicine and early disease detection. Although MCIL's core expertise has historically centered on magnetic resonance imaging (MRI) and x-ray computed tomography (CT), the lab's mission to develop novel molecular probes and targeted contrast agents forms a direct conceptual foundation for extending into whole-brain PET-based approaches to map immediate early gene activity such as Fos. PET imaging of Fos expression is a means to capture, across the entire brain, patterns of neuronal activation and ensemble dynamics that underlie complex behaviors.

Shapiro's laboratory comprises three main cores: development of novel nanoparticle contrast agents for MRI and CT; application of molecular and cellular imaging techniques to monitor cell migration (for example, after stem cell transplants); and the use of targeted contrast agents to detect specific molecular epitopes, such as those found in cancer. These established capabilities emphasize probe chemistry, sensitivity to molecular targets, and in vivo imaging strategies that support translation of molecular markers into whole-organ imaging readouts. Leveraging this infrastructure, a whole-brain PET-based method for imaging Fos expression would integrate targeted radiotracer chemistry with high-sensitivity PET detection to visualize immediate early gene activity indicative of neuronal activation. Such a tool would enable researchers to move beyond localized or invasive assays of Fos and toward noninvasive, brain-wide mapping of circuit engagement during complex behaviors and experimental manipulations.

The value of whole-brain PET imaging of Fos lies in its ability to reveal distributed networks and the relationships among regions recruited by behavior, pharmacologic challenge, or disease processes. By adapting strategies from MCIL's targeted-contrast-agent work, radioligands or reporter systems could be designed to bind or report on Fos protein expression, allowing PET cameras to quantify regional Fos dynamics with whole-brain coverage. This approach complements existing MCIL strengths in tracking cell migration and detecting molecular epitopes, extending those competencies to functional molecular neuroimaging. As such, the project sits naturally within the lab's translational aims: developing molecular imaging tools that can probe biological phenomena at the systems level, inform mechanistic understanding, and ultimately guide interventions.

While MCIL's prior efforts have emphasized MRI and CT contrast agent innovation and cellular imaging applications, the formulation of a PET-based Fos imaging platform would broaden the laboratory's methodological repertoire and create a new capability for neuroscience research at Michigan State University. By coupling expertise in probe development, molecular targeting, and whole-organ imaging, the initiative aims to deliver a sensitive, specific, and scalable imaging modality to map neurocircuitry involved in complex behavior, with potential applications ranging from basic circuit discovery to preclinical studies of neuropsychiatric and neurodegenerative disorders.