RESEARCH METHODS. Do you need MR (magnetic resonance) technology for your small animal studies? Well, in that case there’s an MR camera at your disposal on the ground floor of the EBM (Experimental Biomedicine) building at Medicinareberget. If your laboratory animals are at EBM, just take the elevator down to the ground floor and take advantage of the resources there.
In 2002, in connection with the Swegene initiative, Chalmers University of Technology and the University of Gothenburg bought an MR system for animal studies that was located at EBM. The system was used a lot when it was relatively new, but for some time the utilization declined due to reorganization and staff shortages. In recent years the equipment has been upgraded substantially, and now it is being used by several research teams.
The MR system previously belonged to the former CBI core facility (subsequently CPI), but now the facility is called the Experimental 7T MR Facility for Small Animals or Specimens (radfys.gu.se/animalMR). The person in charge of experiments carried out in the system is Mikael Montelius, who used the MR system in his dissertation and is now also responsible for its operation and maintenance:
“I know that there is a great interest among several research teams in using MR to address various issues, but few researchers know that the facility is again available for them,” he says.
Intresting results
This MR system was used for imaging of laboratory animals in a current study that produced results indicating that the body has a built-in bathroom scale that regulates body weight. The lead author was John-Olov Jansson in collaboration with Claes Ohlsson, and when their results were published in December, the media impact was great.
“We have made the MRIs of obese and lean mice that appear in the publication with the MR system at our facility,” says Mikael. He continues:
“We hope that more people will turn to us and use the technology so we can expand and develop the facility. For example, in the future we would like to be able to combine MR measurements with PET (positron emission tomography) to study metabolism in tissues in a thoroughly tested way. There are hybrid systems that include both technologies.”
The numerous advantages of MR
Advantages of MR technology are that it is a non-invasive technique – that is, you don’t need to poke or cut into the animal to obtain information. Unlike X-ray or computed tomography (CT), MR technology is not based on ionizing radiation either, which can be an advantage in certain types of studies.
“We have customized cradles and supports for animals or samples, and the 72-mm-diameter opening allows measurement of rodents weighing up to about 300 grams. Mice, rats, small guinea pigs, fish, birds or tissue biopsies from larger animals are some examples of what can be imaged,” says Mikael.
The MR system is powerful – its field strength is 7 Tesla. There is a broad selection of radio frequency coils (volume and surface RF coils). It’s possible to monitor temperature, respiration, electrocardiogram and blood pressure during measurement, which usually takes place on anesthetized animals.
The MR technology can provide high-resolution images, in which even very small details become visible. Higher resolution means longer measurement time, however. Preclinically, measurement time is limited by how long the animal can be anesthetized. An anatomical image with high contrast, low noise level and a resolution of around 100 µm × 100 µm × 500 µm takes a few minutes. If you need higher resolution or want to capture subtle, functional parameters, it’s not unusual for the measurement to take a half hour or longer. If you only require standard resolution, imaging can be very fast (milliseconds), which allows imaging of dynamic processes, such as movements of the heart.
“The MR methods available today offer qualitative and quantitative assessments of morphological and functional parameters, such as cell density, perfusion, metabolism, inflammation, hypoxia, suitable for diagnosis, therapy follow-up and much more,” says Mikael.
Tumors have a heterogeneous interior
Mikael is employed half-time at the MR unit to help other researchers. In his remaining time he teaches and conducts research. He publicly defended his doctoral thesis just over a year ago and uses MR technology in his own research. His research is a good example of what MR technology can offer: Using multiparametic MR methods – in other words, employing several MR methods in the same examination – he examines how tumors respond to treatment. He is a member of Professor Eva Forsell-Aronsson’s research team studying ways to optimize radionuclide therapy of cancer. With radionuclide therapy, you can reach tumors that have metastasized or tumors that cannot be surgically removed.
“One strength of MR is that the information in the different images of the tumor depends on how you acquire your image. Imagine that you take a photograph of your dog with a digital camera, and then you change the setting to ‘night vision,’ which captures thermal radiation, and take one more picture. In the first image you see the dog’s anatomy, in the second image you see which body parts are warmer than others, and you can then draw conclusions about, for example, how the superficial blood vessels are distributed in the dog,” Mikael explains.
With multiparametric MR methods, he acquires several images of the tumor, changing the settings between images. In this way he can see how different tissue parameters are distributed throughout the tumor without affecting the tumor. By repeating the experiment before and after treatment, he can study which parameters are affected, where in the tumor they are affected and which parts of the tumor are not responding to treatment. Parts that do not respond well must be treated with more aggressive methods so they can’t grow and produce a tumor that is even more difficult to treat.
Significantly faster feedback after treatment
Today there are no methods available for monitoring the tumor’s internal environment in clinical routine, and it can take months before the physician can see if a treatment is successful, or if it must be exchanged for a different treatment. Several of the MR parameters being studied by Mikael Montelius indicate whether the treatment is effective after only a few days or weeks after the treatment.
Another application is to guide biopsies to relevant parts of the tumor in cases where tissue samples from the tumor are needed to determine the tumor type and choose a treatment. If these biopsies miss the most aggressive parts of the tumor, it may lead to inadequate treatment.
Huge potential in MR methods
“Some MR methods are already used clinically, but there is a huge amount of additional information to be obtained. My research is about increasing the understanding of the connections between MR information and the underlying biological information in the tissue.”
MR is unparalleled in terms of soft-tissue contrast and image resolution. Since the method is non-invasive, measurement may be repeated several times. The method thus provides good images of functional or morphological parameters and anatomy and can also measure changes over time, without affecting what is being measured.
The facility has a website (https://radfys.gu.se/animalMR) that has already generated greater interest in MR on small animals among researchers at the university. Mikael now hopes that more researchers will discover the advantages of the MR technique and the expertise we can offer.
Future perspectives
“You still need histological classification methods in order to fully determine which type of tumor is being studied,” says Mikael. “But with histology and the complementary MR information, it’s possible to understand much more about the course of the disease and the effects of treatment, and I think that relatively soon we will be using MR to guide biopsies to the right places to a greater extent.”
In addition to the MR camera itself, there are laboratory benches, fume hoods and most of the equipment needed for additional experiments, dissection, etc. After the MR protocol is optimized for a particular study, you can usually learn to do your measurements yourself, which keeps the costs down. Some evaluation of the images can be done directly in the software of the camera, but if additional analysis is required, we will help, of course, to show what alternatives exist.
“Most issues can be resolved,” says Mikael in conclusion. Now he hopes that more research teams will make use of their resources.
Advantages of MR technology
- You can study tissue non-invasively and get a lot of information from a single imaging session
- You obtain spatial information, which can be helpful in taking biopsies and evaluating therapy response, for example
- It permits repeated measurements on the same animal, which means that the number of animals in a study can be reduced and that they become “their own control”
- It makes it possible to study tissue that is difficult to biopsy, such as the brain
- The method is translational – i.e., it’s relatively easy to adapt a method developed for animals to the clinic. Many techniques used in pre-clinical research are pre-installed and used in clinical systems, such as diffusion and perfusion measurements and anatomical imaging
- In addition to mice, you can also study fish, guinea pigs, rats, etc. – only your imagination and the space in the apparatus limits what can be studied
- It can be applied in most biomedical disciplines
TEXT: SUSANNE LJ WESTERGREN
