MAKING A WORLD OF DIFFERENCE … TO RADIO-PHARMACEUTICAL IMAGING

Developing the next generation of complex equipment for imaging radio-pharmaceuticals in the body is the primary area of interest for Medical Physicist, Associate Professor Steven Meikle.

Such equipment is used by the 25-strong research team at the University of Sydney’s Brain and Mind Research Institute for the laboratory testing of new drugs and new imaging molecules in the various types of brain disorders, including neuro-degenerative diseases such as Alzheimer’s, and psychiatric diseases such as Schizophrenia and depression.

These experiments are often performed on small laboratory animals – typically mice and rats – that have had their genes manipulated to make them either more or less susceptible to disease, to see what happens to a specific drug in that particular animal. These techniques are used to shed new light on links between the disease process, genes and changes in the brain’s chemistry.

“One of the key areas of our research activity is not just using the best available equipment but, in fact, advancing the existing technology – that is, developing new instrumentation that will provide higher spatial resolution or better sensitivity for detecting radio-pharmaceuticals,” Professor Meikle said.

His research team is currently working on two major projects, each funded by the Australian Research Council.

The first project is to develop a small animal SPECT [Single Photon Emission Computed Tomography] camera that retains its high resolution, but also provides greater detection sensitivity.

“These instruments use the single photon technique to create images of animals at high resolution. The single photon refers to the fact that the isotope that we use decays by emitting a single photon at a time,” Professor Meikle explained.

“The SPECT cameras themselves are radiation detectors, but they work a little like an old Box Brownie camera, in that they have a tiny pinhole at the front. This is made of either lead or tungsten which absorbs almost all of the radiation coming from the animal, except for those photons which pass through the narrow pinhole before they hit the detector. That’s what gives us such a high resolution.

“But, the problem is, when you restrict the radiation detection to just this tiny pinhole the sensitivity is very poor – resulting in images that have good resolution, but are in fact quite grainy.

“At the moment we are exploring the use of multiple pinholes in different sized arrays and different configurations to let more of the radiation through to the detector. However, doing this creates a complex image reconstruction problem. That’s what we’re working on now,” he said.

The aim of the second major project is to enable researchers to obtain accurate, reliable radio-pharmaceutical images without the use of anesthesia.

“The problem researchers the world over face is that animals must keep perfectly still while they are being imaged – which is unrealistic without anesthetic, especially when you consider that the procedure can take anything up to ninety minutes,” Professor Meikle said.

“However, an anesthetic can alter the chemistry in the brain – and, sometimes, it alters the very thing we are trying to gain information about. This distorts our results and places limits on the research that we can successfully carry out.

“The alternative is to image the test animal without anesthesia while it is confined to a compact space within the scanner’s imaging field of view – but, even then, the animal’s head can move about.”

To overcome this obstacle, Professor Meikle and his collaborator in the School of Physics, Professor Roger Fulton, are working on developing new motion tracking technologies that will allow researchers to use an optical imaging system to detect the animal’s head motion in real time using reflective markers. Then this information, as well as the radio-pharmaceutical images, will be fed into a new image reconstruction algorithm, being developed by the research team. This new technology will take into account that the animal is moving all the time.

“We see these new technologies being used primarily in research environments, in facilities like the one we have for testing these types of molecules. But there is also the possibility that we can translate some of the new technologies we develop to the clinic, in which case they will be used in teaching hospitals for more accurate diagnosis of Alzheimer’s disease, and other neurological and psychiatric conditions,” Professor Meikle said.