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Research Focus C

Biomedical imaging and radiation therapy with brilliant x-rays and particle beams

In the previous funding period of MAP a strategic alliance between physics and medicine was established in order to advance a compact laser-driven X-ray and particle sources for non-invasive medical applications in imaging and therapy. This outstanding alliance led to the successful application for funding of a new, dedicated building and the required laser infrastructure in Garching - the Centre for Advanced Laser Applications (CALA).

Based on the main physical and biomedical achievements made in the previous funding period of MAP, i.e. the development of phase-contrast based imaging methods and the breakthroughs in laser-driven ion beam generation, we intend to further advanced instrumentation and biomedical applications. CALA provides an optimal plattform to develop laser-driven technologies with the primary objective to improve the cure rates of cancer patients by combining early tumour detection with targeted particle therapy.

Thus, the research plan proposed for the next funding period derives from the long-term vision of CALA. Yet, the spectrum of biomedical research in MAP also includes severe chronic diseases such as osteoarthritis, atherosclerosis and diffuse lung diseases, which, like cancer, show increased provalence due to the demographic development. The novel technological modalities will enable more sensitive diagnosis by substantially improved tissue characterisation at lower radiation exposure. Early detection of cancer and chronic diseases is of enormous advantage with regard to treatment and treatment results. The localisation of primary tumours at a non-metasised stage would allow for implementation of high-precision laser-driven radiotherapy and higher cure rates.

Overall, laser-driven techniques hold promise of substantially improving current diagnostic and therapeutic strategies and may reduce the socioeconomic burden of chronic diseases. The interdisciplinary Research Area C focuses on the application of novel laser-driven X-ray and particle sources (as developed in Research Area A) for biomedical diagnosis and image-guided radiation therapy. This involves both technological developments and the translation into pre-clinical and - in the long run - clinical applications.

Fig. C.1: The research projects in Focus C are closely connected to the development

Grand challenges and questions in Research Focus C

1) How can brilliant X-ray sources yield microscopic insights into tumour cells and tissue samples?
We pursue the development of novel coherent X-ray nanoscopy and nano-tomography methods to yield high-resolution insights into tumour cells and tissue samples. The availability of this instrumentation will provide tools to study the underlying micro-morphological changes associated with the clinical diagnostics and radiotherapy research projects.

2) How can the enhanced brilliance of novel laser-driven X-ray sources be best employed for early diagnosis in a pre-clinical setting?
We pursue the development of novel X-ray imaging modalities that yield improved contrast in radiographic and tomographic diagnostic imaging applications. These new experimental and algorithmic approaches provide the basis for the clinical diagnostics and radiotherapy research projects.

3) Which are clinical indications for phase-contrast imaging with the highest diagnostic yield?
We will explore the potential of phase-contrast imaging in different clinically relevant settings (osteoarthritis, breast cancer, diffuse lung diseases and atherosclerosis). Analysis and development will comprise (i) in vitro assays and (ii) in vivo animal models at large and small laboratory scale and large-scale synchrotron radiation sources.

4) Is there additional diagnostic information gained by phase-contrast imaging as compared to established techniques?
In all phase-contrast imaging experiments image resolution and characteristics and radiation dose will be closely monitored and compared to established imaging techniques, such as conventional computed tomography (CT), magnetic resonance imaging (MRI) and histopathology as the gold standard. Also, we will compare results obtained from smaller beam sources in CALA with results obtained from large scale synchrotron facilities to simulate ideal set-ups. Suitable contrast agents and multispectral properties and their application for specific indications or organ systems will be characterised.

5) Can laser-driven proton, ion and X-ray sources provide the basis for compact, cost-efficient instrumentation for high-precision image-guided radiation therapy?
We pursue the development of the required beamline instrumentation (e.g. beam transport and monitoring) for laser-driven proton, ion and brilliant X-ray beams in order to translate these radiation sources to first pre-clinical applications for radiotherapy research in small animals.

6) Why are carbon ions radiobiologically more effective than protons and how can this be exploited to improve radiation therapy?
We pursue radiobiological experiments with cells, three-dimensional tissue models and tumour models in small animals using a well defined, conventionally accelerated ion microbeam as well as laser-driven beams to compare and evaluate the biological effects of protons and carbon ions.