7 Tesla MR spectoscopy in diffusely infiltrating gliomas

Proton magnetic resonance spectroscopic imaging (1H-MRSI) enables the non-invasive assessment of local changes in brain metabolism that underlie many brain diseases such as brain tumors. 1H-MRSI can improve brain tumor grading, differential diagnosis, detection of tumor foci, and assessment of tumor infiltration. This makes 1H- MRSI a valuable tool for treatment planning. However, available 1H-MRSI methods at clinical MR scanners (=3 Tesla) are restricted by several practical limitations. Our preliminary results show that novel 1H-MRSI methods at ultra-high magnetic field strength (i.e. 7 Tesla) can help to overcome these limitations (i.e. low spatial resolution). The aim of this project is to improve the quality of 1H-MRSI results by better hardware (i.e. 7T MR scanner and improved RF coils) and by improved acquisition methods. The further development of an improved 1H-MRSI sequence for 7T based on our initial results should enable 3D metabolic mapping of pathologic brain areas within reasonable scans times. After first validation of the technique in healthy volunteers, the additional value of high resolution 1H-MRSI will be explored in a selected group of 40 patients with diffusely infiltrating glioma (DIG). The extent of the infiltration area and tumor foci in DIG is difficult to assess by other imaging modalities. Hence, DIG are a suitable model to demonstrate the advantages of high resolution 1H-MRSI at 7T. Metabolic maps obtained by 1H-MRSI will be incorporated into the neuronavigation system. Stereotactic biopsies will be taken. A topographic correlation between metabolic maps and histopathology will be performed. After first successful application of high resolution 1H-MRSI, our method can be readily extended to investigations of other neurological diseases such as epilepsy, multiple sclerosis, Alzheimer`s disease, Parkinson`s disease, psychiatric and metabolic disorders.

The goal of the project was to develop a novel imaging method for the non-invasive investigation of the brain via 7 Tesla Magnetic Resonance Tomography (MRT), which is able to simultaneously image the concentration of different neurochemical compounds. This new MRT method should then be applied clinically for the first time in the scope of a pilot study. In particular it should be shown in a small cohort of patients with brain tumors, whether this new imaging method allows a better characterization of tumor-infiltrated and healthy tissue. Based on this information better therapy decisions could be possible. To reach this goal several development steps were necessary. First of all the MRT technique, which was the basis for the development, had to be modified in a way that allows its clinical application. For this, the following characteristics had to be improved: 1.) the coverage of the brain had to be improved to include the entire diseased brain region, 2.) the spatial resolution had to be improved to display pathological changes in more detail, 3.) the measurement time has to be reduced to clinically acceptable durations of ~5-6 minutes, 4.) the reproducibility had to be evaluated and negative influencing factors such as motion and hardware instabilities had to be largely compensated. Since the vast majority of the development work was conducted at a 7 Tesla MRT prototype, which is not yet approved for routine clinical use, we have additionally evaluated, how well the results of our new MRT technique can be translated to a routine clinical 3 Tesla MRT scanner. Finally, the newly developed neurochemical imaging method was applied in two first patient groups (brain tumors and Multiple Sclerosis), where first extremely promising results were obtained. Surprisingly, we could identify a new until now not used imaging biomarker, which are likely to results in new important findings both for brain tumors, but also in particular for Multiple Sclerosis. To conclude, this study has impressively shown both the clinical applicability and benefits of the new MRT imaging method, but also that substantial potential or improvement still remains and the application in other diseases will be of great promise.