Nano-CT Imaging Visualizes Nanostructure of Bones

A novel nanotomography method developed by a team of Europeans paves the way for computed tomography (CT) imaging of miniscule structures at nanometer resolutions. Using this technique, three-dimensional (3D), detailed imaging of fragile bone structures becomes a reality.

The investigators involved with the project were from Technische Universitaet Muenchen (TUM; Germany), the Paul Scherrer Institute (Switzerland), and the ETH-Zurich (Villigen PSI, Switzerland). Their first nano-CT images were published in the journal Nature on September 23, 2010. This new technique should, according to the scientists, advance developments in both life sciences and materials sciences.

Osteoporosis, a medical disorder in which bones become brittle and fragile from a loss of density, is among the most common diseases in aging bones. In Germany, approximately 25% of the population aged over 50 is affected. Patients' bone material shrinks rapidly, leading to a considerably increased risk of fracture. In clinical research to date, osteoporosis is detected almost exclusively by establishing an overall reduction in bone density. This approach, however, gives little data about the associated, and of equal importance, local structure and bone density changes.

Dr. Franz Pfeiffer, professor of biomedical physics at TUM and head of the research team, has resolved the predicament, "With our newly developed nano-CT method it is now possible to visualize the bone structure and density changes at high resolutions and in 3D. This enables us to do research on structural changes related to osteoporosis on a nanoscale and thus develop better therapeutic approaches.”

During the development process, Dr. Pfeiffer's team built on X-ray CT technology, which in the process, the human body is X-rayed while a detector records from different angles how much radiation is being absorbed. A number of such images are then used to generate digital 3D images of the body's interior using image processing.

The newly developed method measures not only the overall beam intensity absorbed by the object under examination at each angle, but also those parts of the X-ray beam that are diffracted. Such a diffraction pattern is generated for every point in the sample. This supplies additional data about the precise nanostructure, as X-ray radiation is particularly sensitive to the tiniest of structural changes. "Because we have to take and process so many individual pictures with extreme precision, it was particularly important during the implementation of the method to use high-brilliance X-ray radiation and fast, low-noise pixel detectors--both available at the Swiss Light Source [SLS],” said Oliver Bunk, who was responsible for the requisite experimental setup at the PSI synchrotron facilities in Switzerland.

The diffraction patterns are then processed using an algorithm developed by the team. TUM researcher Martin Dierolf, lead author of the Nature article, explained, "We developed an image reconstruction algorithm that generates a high-resolution, three-dimensional image of the sample using over one hundred thousand diffraction patterns. This algorithm takes into account not only classical X-ray absorption, but also the significantly more sensitive phase shift of the X-rays.”

An example of the new technique was the examination of a 25-μm, superfine bone specimen of a laboratory mouse--with amazingly precise results. These phase contrast CT images reveal even smallest variations in the specimen's bone density with extremely high precision: Cross-sections of cavities where bone cells reside and their about 100-nm-fine interconnection network are clearly visible.

"Although the new nano-CT procedure does not achieve the spatial resolution currently available in electron microscopy, it can--because of the high penetration of X-rays--generate three-dimensional tomography images of bone samples,” commented Roger Wepf, director of the Electron Microscopy Center of the ETH Zurich (EMEZ). "Furthermore, the new nano-CT procedure stands out with its high precision bone density measurement capacity, which is particularly important in bone research.”

This method should help create studies more precise on the early phase of osteoporosis, in particular, and assessment of the therapeutic outcomes of various treatments in clinical studies. The new technique is also very interesting for nonmedical applications: additonal fields of application include the development of new materials in materials science or in the characterization of semiconductor components. Eventually, the nano-CT procedure may also be transferred to laser-based X-ray sources, such as the ones currently under development at the Cluster of Excellence Munich-Center for Advanced Photonics (MAP) and at the recently approved large-scale research project Center for Advanced Laser Applications (CALA) on the TUM-Campus Garching near Munich.

Related Links:
Technische Universitaet Muenchen
Paul Scherrer Institute
ETH-Zurich