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Wearable PET Scanner Ready To Roam Print E-mail
SciMed - Neuroscience
TS-Si News Service   
Monday, 14 March 2011 03:00
Upton, NY, USA.Scientists have demonstrated the efficacy of a portable (i.e., wearable) PET scanner, a new tool for simultaneously studying brain function and behavior in fully awake, moving animals.

In neuropsychology and cognitive neuroscience, positron emission tomography (PET) is a powerful tool for studying the molecular processes that occur in the brain. The PET scanner is a nuclear technology that produces 3D images or picture of functional processes in the body.


CT X-ray scans are often combined with PET during the same session, in the same machine, to provide a more comprehensive mapping of the patient. Scientists can use the wearable scanner, available now for rat laboratory models, alone or in combination with other tools to links between specific psychological processes and brain activity, allowing integrated and simultaneous study of behavior and brain function in animals.



The new portable scanner was developed for rats by Paul Vaska, head of PET physics at the Brookhaven National Laboratory (BNL) with a joint appointment at Stony Brook University, who led development with Brookhaven colleagues David Schlyer and Craig Woody.

The researchers describe the tool and validation studies in the journal Nature Methods.
PET studies in animals at Brookhaven and elsewhere have required general anesthesia or other methods to immobilize the animals. "Immobilization and anesthesia make it impossible to simultaneously study neurochemistry and the animals' behavior — the actions resulting from what goes on in the brain," Schlyer said. "Our approach was to eliminate the need for restraint by developing a PET scanner that would move with the animal, thus opening up the possibility of directly correlating the imaging data with behavioral data acquired at the same time."

After several years of development, the scientists have arrived at a design for a miniature, portable, donut-shaped PET scanner that can be "worn" like a collar on a rat's head for simultaneous studies of brain function and behavior. Weighing only 250 grams, the device — Rat Conscious Animal PET (RatCAP) — is counterbalanced by a system of springs and motion stabilizers to allow the animal significant freedom of movement. Measurements of the rats' stress hormones indicated only moderate and temporary increases. "Rats wearing the device appear to adapt well and move freely about their environment," Woody said.

To validate the use of the wearable scanner for simultaneous studies of brain function and behavior, the scientists conducted tests with 11C-raclopride, a commonly used PET radiotracer, which incorporates a radioactive, positron-emitting isotope of the element carbon. When the positrons interact with electrons in ordinary matter, they immediately annihilate one another, emitting back-to-back gamma rays. Detectors in the circular PET scanner pick up the signals from these back-to-back gamma rays to identify the location and concentration of the tracer in the body.

The tracer 11C-raclopride binds to receptors for dopamine, a brain chemical involved in movement, reward, and memory formation. A higher signal from the tracer means that less natural dopamine is in that particular part of the brain; a low signal indicates that that particular part of the brain has released dopamine (which binds to its receptors, thus blocking the tracer from binding).

The main test was to see if the wearable scanner could be used to correlate dopamine levels with behavior — in this case, the rats' activity (i.e., movement) within their chambers. Surprisingly the level of activity was inversely related to dopamine levels — that is, the more active the animals were, the lower the level of dopamine (as indicated by a stronger tracer signal).

"This is perhaps a counterintuitive result because behavioral activation is typically associated with an increase in dopamine release," said Daniela Schulz, a Brookhaven behavioral neuroscientist and lead author of the paper. "So our method provides data which may challenge traditional paradigms and ultimately improve our understanding of the dopamine system."

"But regardless of the direction, the results clearly demonstrate that RatCAP can correlate brain function measurements with behavioral measures in a useful way," she said.

The scientists also present results comparing RatCAP-wearing rats moving freely about their cages with animals that had been anesthetized, as well as comparisons of two methods of administering the tracer — injecting it all at once and in a steady infusion to maintain a constant concentration in the blood.

"These measurements will help us further refine the technique and aid in our assessment of results obtained with RatCAP in comparison with other study techniques," Schulz said.

The researchers' next step will be to use RatCAP to explore distinct behavioral expressions that can be correlated with simultaneously acquired PET data.

Animal research protocols

Development of RatCAP was a joint effort between the Medical, Chemistry and Physics Departments, Instrumentation Division at Brookhaven National Laboratory (BNL) and the Biomedical Engineering Department at Stony Brook University.

All research involving laboratory animals at Brookhaven National Laboratory is conducted under the jurisdiction of the Lab's BNL Institutional Animal Care and Use Committee (IACUC), in compliance with the Public Heath Service (PHS) Policy on Humane Care and Use of Laboratory Animals, the U.S. Department of Agriculture's Animal Welfare Act, and the National Academy of Sciences' Guide for the Care and Use of Laboratory Animals.

Funding
The research was funded by the DOE Office of Science.
ParticipationCo-authors on the paper include: Daniela Schulz (Brookhaven National Laboratory (BNL)), Sudeepti Southekal (Brigham & Women's Hospital, Boston),Sachin S. Junnarkar (Brookhaven National Laboratory (BNL)), Jean-François Pratte (Université de Sherbrooke, Sherbrooke, Canada), Martin L. Purschke (Brookhaven), Paul O'Connor (Brookhaven National Laboratory (BNL)), Sean P. Stoll (Brookhaven National Laboratory (BNL)), Bosky Ravindranath (Stony Brook University), Sri Harsha Maramraju (Stony Brook University), Srilalan Krishnamoorthy (Stony Brook University), Fritz A. Henn (Brookhaven National Laboratory (BNL) and Cold Spring Harbor Laboratory), Craig L. Woody (Brookhaven), and David J. Schlyer and Paul Vaska (Brookhaven and Stony Brook University).
CitationSimultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph. Daniela Schulz, Sudeepti Southekal, Sachin S Junnarkar, Jean-François Pratte, Martin L Purschke, Sean P Stoll, Bosky Ravindranath, Sri Harsha Maramraju, Srilalan Krishnamoorthy, Fritz A Henn, Paul O'Connor, Craig L Woody, David J Schlyer, Paul Vaska. Nature Methods 2011; ePub ahead of print. doi:10.1038/nmeth.1582

Abstract

Positron emission tomography (PET) neuroimaging and behavioral assays in rodents are widely used in neuroscience. PET gives insights into the molecular processes of neuronal communication, and behavioral methods analyze the actions that are associated with such processes. These methods have not been directly integrated, because PET studies in animals have until now required general anesthesia to immobilize the subject, which precludes behavioral studies. We present a method for imaging awake, behaving rats with PET that allows the simultaneous study of behavior. Key components include the 'rat conscious animal PET' or RatCAP, a miniature portable PET scanner that is mounted on the rat's head, a mobility system that allows considerable freedom of movement, radiotracer administration techniques and methods for quantifying behavior and correlating the two data sets. The simultaneity of the PET and behavioral data provides a multidimensional tool for studying the functions of different brain regions and their molecular constituents.

TS-Si News ServiceThe TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. The sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates.

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Last Updated on Sunday, 13 March 2011 19:54
 
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