The purchase of a microCT scanner for computational imaging research has been a boon for Blacksburg-based biomedical studies ranging from birth defects caused by diabetes to bone strength and tissue engineering. This past fall, ECE’s Chris Wyatt, director of the BioImaging Systems Laboratory, set up the new medical imaging machine for a research effort involving biomechanical modeling of bone strength. The $300,000 microCT scanner can accommodate small animals, such as rodents and small material samples.
The first of several planned imaging systems, it was purchased with funding from the State Council of Higher Education for Virginia (SCHEV) and the Virginia Tech/Wake Forest School of Biomedical Engineering and Sciences (SBES).
The mini CT scanner has a diameter of 8 cm and fits small quantities of materials or small animals, such as mice.
“Our initial purpose for the machine was to study bone development in small animals,” Wyatt explained. “The soft tissue contrast is poor, but the machine is excellent at imaging hard tissue. We can see the very fine structure of bones — even the micro structure or matrix of the bone,” he added.
The project involves scanning bones from different animals being treated with different drugs, and using the information to build biomechanical models of the bone strength. The models would be used to determine the effects of different drug treatments on bone. “This way, we hope to follow the course of osteoporosis, or look at calcium and see how it is metabolized in the bone,” Wyatt explained.
All drug studies start with small animals, then move forward to human testing, according to Wyatt. “Medical researchers are always looking for ways to reduce the numbers of animals needed,” he explained. “From microCT images, we build virtual models, so that we can simulate exactly what happens mechanically to different bones,” Wyatt said. “This way, with one bone, we can do hundreds of studies, and greatly reduce the usage of animals.”
In addition to the bone modeling, Wyatt has used the imaging equipment to help a variety of research projects. “We have scanned a turtle head, solid samples, chicken bones, and aggregate materials.”
Another ongoing project involves a tissue engineering effort by Aaron Goldstein in chemical engineering. “We are analyzing the mechanical structures of the scaffolds that the tissue is built on,” Wyatt explained. “The scanner allows us to image the actual scaffold structure. We hope to identify when the bone starts to develop and calcify on the scaffold, then image where and experimentally determine the rate at which it forms.”
ECE's mini CT scanner is helping biomedical researchers in several areas and is responsible for forming a highly experienced, multidisciplinary team for studies on bone strength and bone deformities. From left: Jeryl Jones, associate professor of radiology; Renee Prater, research assistant professor of biomedical science; Chris Wyatt, assistant professor of ECE; and Cindy Hatfield, assistant professor of anesthesiology.
One of the laboratory’s largest projects has been related to birth defects in mice. Soon after the equipment was set up in its home at the Virginia-Maryland Regional College of Veterinary Medicine on Tech’s Blacksburg campus, Renee Prater, a research assistant professor, wanted to conduct bone scans on fetal mice. Prater, who holds a joint appointment as an assistant professor of microbiology at the Virginia College of Osteopathic Medicine, was working on a study of birth defects in babies of diabetic mothers, a syndrome called diabetic embryopathy.
Mothers who have diabetes before and during pregnancy have a higher risk of birth defects. Although keeping the diabetic mother’s metabolism and diabetes regulated reduces birth defects, it does not totally eliminate them. Prater was studying whether non-specific immune stimulation of diabetic mice could reduce diabetes-induced defects of the craniofacial, or head and face area, of their babies.
Instead of scanning the dead fetus, Prater was interested in being able to study pregnancies in vivo, or live, and being able to follow pregnancies throughout the process to detect exactly when different defects occur.
Prater and Wyatt soon tapped Jeryl Jones, a veterinary radiologist and associate professor at the vet school, and Cindy Hatfield, an assistant professor and expert in veterinary anesthesiology. The team is working on a system of scanning pregnant mice with the least possible discomfort. “This gives us quantitative data. We can determine how many fetuses have cleft palette, or spina bifida, without sacrificing as many animals. This experimental model gives us conclusions that are more statistically significant than the histomorphometry methods currently used,” Wyatt said.
“Based on this experience, we are developing proposals for future efforts, including mouse models of osteoporosis,” he said. “The big story on their side is they now have a new tool for their studies. Renee can now look at things she hasn’t been able to study before and has a way to measure total bone volume. Without this equipment, the four of us would never have formed a team.”
Wyatt brings his technical and engineering expertise to the team. His biggest interests with the microCT scanner are in reconstruction of images, image processing, and developing efficient image analysis systems. “The scanner takes projections of an object, like you are looking at different angles,” he said. “The projections are then reconstructed into 3-D images, which is a mathematical/computer problem. We take the data from the projections and reconstruction to get images.”
The scanner comes with general software for the image computation, but his team is developing computational software specific for extremely low doses of radiation. “We’re trying to use the lowest dose of radiation possible, because we are imaging fetal mice and do not want to introduce problems,” he said. Lower doses means more noise in the images, which they are compensating for in the reconstruction stage. “There is always a tradeoff between dose and noise. We have to rely on our clinical collaborators to monitor the animals and help us find the ideal balance,” he said.
In addition to noise and quantitative issues, Wyatt is tackling one of the biggest issues in medical research today — too much data. “The good news about these scanners is they generate a lot of data,” he said. “And the bad news is, these scanners generate a lot of data. If we scan at 15 microns, each mouse image is 2048 x 2048 x 600 pixels. That’s about 5 gigabytes of data. Somebody must sit down and go through all that.”
Whether dealing with animal studies or human drug trials, one of the biggest time and cost factors is reading and analyzing data from diagnostic images, according to Wyatt. “If you are evaluating a new drug and you scan 1,000 animals three times, you have 3,000 sets of data to process by hand. It is a difficult, time-consuming process that right now is done manually.”
Wyatt’s team is working to automatically extract the necessary information from the data on the fetal bone studies. “We are working on software to count ribs, estimate if any are fused or not, measure the total bone volume, or density, or just measure the skull or arms and limbs. We are trying to automate that process so it is consistent and fast.” Wyatt’s ultimate goal is to release the software as an open-source package so other biologists with access to such a scanner has the appropriate tools for analysis.
The microCT scanner is the first of several diagnostic imaging pieces that Wyatt hopes to have in the laboratory. “With the microCT scanner, we are able to show researchers in other areas how our expertise can further their studies,” he said. Virginia Tech’s associated biomedical laboratories have a number of research projects that can be helped with imaging tools, he added. “We anticipate that as the laboratory develops, we will be able to add capabilities and specialized computational tools that can help further the research of both basic scientists and clinicians, whose research impacts human and animal health.”