Milestones in microCT development - An interview with Dr. Alexander Sasov from Bruker MicroCT

Insights from industry

Please introduce yourself and tell us a bit about MicroCT.

My name is Alexander Sasov, I'm the founder and managing director of Bruker MicroCT, which was originally a separate company called SkyScan. Until now, all of our instruments have kept the SkyScan brand, because it’s a well-known trademark with more than 900 instruments installed around the world, being used for a variety of different applications in material science and life science. MicroCT (micron-scale computed tomography) technology was completely unknown when it began to be commercially available more than 15 years ago. It was actually part of my PhD in 1983, so to move from that to shipping our first system in 1997 is quite impressive – the technique has progressed very fast. Now, we are supplying around 100 systems a year, to researchers working in life science, materials science, and in-vivo imaging of small laboratory animals.

Can you share some of the key milestones in the development of microCT?

In life science, the most interesting milestone was in 2002, when we started to produce the first in-vivo MicroCT system in the world, which was designed for non-invasive small animal 3D imaging in model studies for human drug development. This changed the strategic landscape of drug development dramatically. Prior to 2002, all pharmaceutical companies and research groups working in drug development conducted their trials using a huge number of mice. They injected half of the mice with the drug, and used the other half as a reference group – each day, five or so mice from each group would be killed, and thin slices of tissue would be examined under a microscope in attempt to understand the differences between the two groups. Clearly, this type of study costs a lot of money, kills a lot of animals, and is very labour-intensive. Importantly, it only produces qualitative results, as it relies on experts comparing what they can see under the microscope from image to image. With micro-tomography, such trials became much simpler. Studies with microCT require just a single reference animal, and a single animal under investigation. Both are scanned (effectively virtually “sliced”) every day, and the information generated can be compared in quantitative ways - so conclusions can be generated faster, more easily and with higher precision.

What is the difference between CT and microCT?

Clinical CT has been well-known for 40 years, and is used in most hospitals and research centers. However, traditional CT scans are limited to a resolution of 1 millimeter, which is sufficient to image parts of the human body and provides enough detail for clinical use.

In the realms of materials science, and of course in small animal imaging, much better resolution is needed. Our scanners can work at the level of one micron, which is a thousandth of a millimeter. And that is better than is sounds - because we are working in 3D space, a cubic millimeter is 1000 x 1000 x 1000 cubic microns. In effect, this means our systems can resolve 109 cubic volumes within the smallest volume resolved by clinic CT.

There is also a major difference in the x-ray sources used – clinical CT uses a wide x-ray beam which would completely blur the micron-sized voxels in microCT. We need much sharper x-ray sources, with a spot size on the level of 1 micron – as a consequence, the power of the source is about 1000 times lower.

So in effect, we have lost 103 in the source, and 109 in the object – so we have lost 1012 overall in terms of information, but we are trying to achieve the same image quality as in clinical CT – this is our challenge as microCT developers.

An even more challenging task is to do the same thing within living animals, where we are limited by the x-ray dose we can safely apply to the animal to over the course of an investigation, to ensure it remains non-harmful.

What are the main benefits of microCT in practical use? Why is the potential of the technique so great?

MicroCT provides unique information on a unique scale. We’re talking about microns - that sort of resolution cannot be achieved in 3D imaging by any other non-destructive technology.

Even optical microscopy techniques capable of reaching that resolution can only work on the surface, or in a thin layer under the surface if the object can be made transparent. This is not a concern with x-rays – transparent or not, x-rays can pass through virtually any object and provide, non-destructively, 3D information about the internal microstructure or function of organs in living animals. This makes it different from any other technique.

It also allows us to get quantitative information. A two-dimensional image, even taken with x-rays, will not allow us to extract quantitative information. We will never be able to tell what’s at the front, what’s at the back, or what the volume of the object is, from a two dimensional image.

Virtual slicing by micro-tomography allows us to create a 3D digital model of the object, and measure any parameters that we might want to compare in a before-and-after study, or just create mathematical simulations of how the object or animal body will react under certain conditions.