Accurate diagnosis, determination of the extension and stage of a tumor before therapy, and monitoring response after therapy are key requirements for successful treatment of cancer. Currently, pre- and post-contrast Tl-weighted and T2-weighted magnetic resonance imaging (MRI) is applied for non-invasive mapping of tissue features. Though MRI is valuable for visualizing regions where the blood-brain barrier has broken down, it is not specific for tumors and it does not show the extent of invading cells beyond the blood-brainbarrier leakage. Also, the extension of low-grade non-enhancing gliomas cannot unambiguously be determined using MRI alone. The first goal of this application is to consolidate the anatomical and structural information from MRI with the biochemical information from multi nuclear magnetic resonance spectroscopy (MRS) for clinical applications. To achieve this goal, unique MR hardware and software will be developed which are optimized for applications in children. Recently, it has been demonstrated that by means of quantitative feature analysis of tumor biopsies, neuroglial tumors of the same diagnostic name can be divided in subcategories that differ in their survival expectation. The second goal is to correlate MRS/MRI data with histological features and to explore whether a molecular pattern can be identified which correlates with these subclasses of neuroglial tumors and their survival distribution. The proposed research will focus on childhood brain tumor patients where MRI examinations are indicated and brain biopsies and/or surgical removal of tumor, guided by MRI, are part of the standard care. Considering the increased risk of long-term effects in children with a possibly very long survival time, imaging methods employing ionizing radiation, such as computer tomography (CT), single proton emission tomography (SPECT), or positron emission tomography (PET), should be applied only as a last resort and the entire information available by MR should be extracted first. We anticipate that patients benefit from the added non-invasive examinations by improved diagnoses, management, and monitoring of therapeutic response.
