Shulz_Nat_Methods_2011

Overview of PET Neuroimaging in Rodents

• Positron Emission Tomography (PET): A neuroimaging technique providing insights into molecular processes of neuronal communication and behavior analysis.

• Challenge: Traditional PET studies in animals require general anesthesia, limiting behavioral observation.

• Advancement: Introduction of ‘RatCAP’, a miniature portable PET scanner, allows imaging awake, behaving rats.

• Purpose of the Method: To correlate imaging data with behavioral data in real-time, enhancing understanding of brain functions and behaviors.

Key Components of the RatCAP

• Design: The scanner is mounted on the rat's head, ensures mobility and has radiotracer administration techniques.

• Specifications:

  • Weighs 250 g.

  • Inner diameter: 38 mm, outer diameter: 80 mm, axial extent: 25 mm.

  • Field of view: 38 mm diameter by 18 mm axially.

  • Spatial resolution: <2 mm full width at half maximum (FWHM).

  • Coincidence sensitivity: 0.76% at the center.

Methodological Framework

• Intensity of Study: This method allows simultaneous study of PET imaging and behavioral data, which is essential in exploring brain regions and molecular constituents.

• Electrophysiology and Other Techniques:

  • Traditional methods such as electrophysiology, fast-scan cyclic voltammetry, and microdialysis, while useful, are invasive and limited in scope.

Development Process of RatCAP

• Technical Innovations:

  • Utilizes scintillator lutetium yttrium oxy-orthosilicate (LYSO) and thin, solid-state avalanche photodiodes for efficient imaging.

  • Developed a custom front-end microchip for signal processing, requiring minimal power.

• Data Acquisition: Built a system that rapidly digitizes data for quantitative PET imaging.

• Performance Validation: Preliminary studies validated the quantification of PET images correlating with a rat brain atlas.

Behavioral Studies and Neurochemistry Correlation

• Dopamine D2 Receptor Focus: PET results indicate correlation between dopamine receptor binding and spontaneous behavior in open fields.

• Behavioral Assays: Explored the dopamine system but can extend to other neurotransmitter systems for broader applications.

Animal Mobility and Stress Assessment

• Mobility System Design: Implemented mechanical suspension on springs to allow natural movement with minimal stress to the rat.

• Corticosterone Measurement: Monitored stress hormone levels over time while wearing the scanner, documenting initial stress that tapers with acclimatization.

Behavioral Neuroimaging Comparisons

• Data Collection Method: Compared radiotracer uptake in awake versus anesthetized states, documenting the PET data correlation with behavior.

• Findings: Higher binding potential of dopamine D2 receptors observed in anesthetized rats; lower BPND in awake and behaving rats hints at dynamic neurochemistry associated with movement.

Implications for Neurobehavioral Studies

• Dopamine System Understanding: The findings present a model where lower receptor occupancy corresponds with higher behavioral activity, suggesting nuances in dopamine function.

• Future Exploration: The methodology allows for deeper investigations into the relationship between drug interventions, behavior, and imaging data.

Conclusion and Future Directions

• Advantage of Concurrent Acquisition: Combining PET techniques with behavioral studies in awake animals fosters a novel dimension in neuroscience research.

• Broader Applications: Future investigations may include various aspects of brain function and behavioral analysis across different neurotransmitter systems.