Next Generation Chemical Exchange saturation transfer MRI

Magnetic resonance imaging (MRI) is an important medical imaging technique that combines excellent soft tissue contrast with high spatial resolution and can also provide functional information. However, pathological processes are often characterized by molecular or metabolic changes that can be observed before morphological effects. Some metabolites can be detected with the related method of MR spectroscopy, but the sensitivity of this method is relatively low and it is usually only used locally for a certain volumes. CEST MRI is a method that can produce images of the distribution of certain metabolites in tissue and therefore decisively broadens the application possibilities of MRI for precision medicine. The so- called "Chemical Exchange Saturation Transfer" of hydrogen nuclei is used for this purpose. With this effect, the high water content in tissue can increase the sensitivity for specific molecule groups up to a thousand times or even more. However, this promising technique still requires essential methodological developments for diagnostic applications in the clinic. Accordingly, this project aims to significantly advance CEST-MRI by combining new methods in image and contrast coding with current mathematical approaches for image reconstruction and data analysis. This should lead to fast and quantitative metabolic imaging on clinically usable MR systems. Established limits, such as those set by the Nyquist-Shannon sampling theorem, will be significantly exceeded. The project is divided into two overlapping work areas. On the one hand, the signal excitation for encoding metabolic information will be optimized. On the other hand, the development of new measurement and reconstruction methods will massively reduce the examination time. The newly developed methods are investigated at different magnetic field strengths, from 3T to the highest in- vivo field strengths of 9.4T. To achieve this goal, interdisciplinary international cooperation is required. The Austrian group (R. Stollberger, K. Bredies) has its strength in the development and implementation of new MRI methods based on mathematical optimization and variable image reconstruction techniques. The German group (M. Zaiss) has extensive experience in all aspects of CEST-MRI and also has access to state-of- the-art in vivo UHF systems. If the project is successfully implemented, a decisive contribution can be made to a better and more patient-friendly acquisition of metabolic information by MRI. This is an important basis for broader clinical application in biomarker imaging and precision medicine.

Pathological processes are typically characterized by molecular and metabolic changes. Therefore, the in vivo determination of these parameters is of great interest to medicine. In the field of MR tomography, the chemical exchange saturation transfer (CEST) method provides a means of determining molecular information in the form of an image. This method is still the subject of research and development. In this project, we have substantially improved essential elements of the existing challenges. We have succeeded in optimizing the pulsed encoding of CEST information so that the measured spectral information meets the theoretical requirements for quantification methods and can be obtained on standard clinical MR tomographs, while remaining robust in various applications. Another project area investigated how the dynamic equalization processes of water-bound proton magnetization and that of labile molecules can be used to integrate all necessary measurements into one procedure. Newly developed biophysical models make it possible to perform a quantitative evaluation of this data through model-based reconstruction. This approach yields the desired quantitative result in a single step. Additionally, this type of reconstruction achieves considerably better image quality with shorter measurement time. The reconstruction process uses mathematical optimization methods that are also an essential part of machine learning. As part of the international collaboration, measurements on ultra-high field systems revealed that assumptions about singular pools for specific CEST resonances were insufficient. It was found that a multipool model was necessary to optimize saturation pulses at these field strengths. As a result of this and by changing one of the boundary conditions of the optimization, pulsed saturation was able to achieve the desired performance in these cases as well. The project's international cooperation component also successfully researched strategies to ensure that the measurement sequences achieve the desired and modeled signal curves.