A system that acquires functional images of the brains of mice while they scamper about could provide unprecedented insight into diseases such as Alzheimer’s, autism and drug addiction. In most nuclear imaging studies, laboratory mice are drugged and bound in place to study changes in brain chemistry caused by the progression of disease or the application of a drug for treatment studies. Using anesthetics and restraints is not ideal because they can trigger brain activities that may alter the normal brain functions being studied. Functional images of the brains of conscious, unrestrained and unanesthetized mice are now being done by researchers from Thomas Jefferson National Accelerator Facility, Oak Ridge National Laboratory, Johns Hopkins Medical School and the University of Maryland using the AwakeSPECT system. The method documents, for the first time, the effects of anesthesia on the action of a dopamine transporter imaging compound in the mouse brain. Such compounds are used for Alzheimer's, dementia and Parkinson’s disease studies. In SPECT (single-photon emission computed tomography), a radionuclide is injected and collects in specific areas of the brain by function. The radionuclide emits gamma rays that are collected by a detector in separate scans from many different angles, which are combined in an algorithm to produce a 3-D image. “The AwakeSPECT system does regular SPECT imaging of mice,” said Jefferson Lab’s Drew Weisenberger, who led the multi-institutional collaboration and directed the SPECT system development effort. “SPECT is a nuclear medicine imaging technique that’s used in humans for various types of diagnostic studies. It’s also used in animal studies to facilitate the development and understanding of disease physiology.” The AwakeSPECT system uses two Jefferson Lab custom-built gamma cameras to image the radionuclide, as well as a system that processes the data to produce the 3-D images, Weisenberger said. An infrared camera system developed at Oak Ridge National Lab tracks movement of the mouse. Additional anatomical information is gathered using a commercially available CT system. To prepare a mouse for imaging with AwakeSPECT, it is first tagged with three markers that are glued to its head for the infrared system to track. Once the radionuclide is injected — in this case, DaTSCAN, provided by GE-Medical — the mouse can be imaged as it rests in a burrowlike, clear tube. The first mouse imaging studies were conducted at Johns Hopkins Medical School by Martin Pomper and colleagues. Three markers attached to the head of a conscious mouse enable the AwakeSPECT system to obtain detailed, functional images of its brain as it moves around. Courtesy of the Jefferson Lab. “We developed this system that, while acquiring SPECT images, uses infrared cameras that track the location and pose of the head,” Pomper said. “We use that information to then computationally remove motion artifacts from our SPECT imaging.” Researchers also imaged the action of a drug used to image dopamine transport in the brain — 123I-ioflupane — in awake and anesthetized mice. They discovered that the drug was absorbed less than half as well in awake mice, showing that the use of an anesthetic could potentially confound drug uptake studies. “We’ve shown the technology works,” Weisenberger said. “Now, you just have to make it a tool that more people will readily use.” Next, the investigators hope to improve the imager by upgrading the infrared tracking system, using newer technology for the SPECT imager, and by making the system more intuitive for animal researchers to operate. “With this work, we’re hoping to establish a new paradigm in noninvasive diagnostic imaging,” said Justin Baba, a biomedical engineer who heads the ORNL development team. Baba and colleagues envision development of new, more effective therapies for a variety of conditions and diseases while also contributing to pharmaceutical drug discovery, development and testing. The technology also could help with real-time stabilization and registration of targets during surgical intervention. The Jefferson Lab has received two patents for the technology associated with this system. The findings appeared in The Journal of Nuclear Medicine (doi: 10.2967/jnumed.112.109090). For more information, visit: www.jlab.org