Multimodal and multiparametric imaging for reliable preoperative localization of brain function in the border zone of brain tumors

• Applicants: Professor Dr. Arnd Dörfler; Professor Dr. Andreas Stadlbauer
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Medical Physics, Biomedical Technology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 286094343

Glioblastoma (GBM) is the most frequent and most devastating malignant primary brain tumor in adults. Surgical resection with reduction of tumor mass as radical as possible followed by radio-chemotherapy is considered the standard treatment for high-grade glioma (HGG). The rates of recurrence are significantly and inversely correlated with the extent of tumor resection. One aim of surgical treatment is therefore to remove as much tumor tissue as possible. A significant challenge in treatment of glioma is to strike a balance between maximizing the extents of tumor resection and minimizing postoperative neurologic deficits resulting from damage to intact, functioning brain structures. Preservation of eloquent cortical and subcortical structures of important brain functions in close proximity to the tumor is of crucial importance for clinical outcome and patients postoperative quality of life. Functional magnetic resonance imaging (fMRI) is the imaging method of choice for the preoperative localization of eloquent cortical areas. A major limitation of fMRI, however, is the lesion-induced neurovascular uncoupling (NVU) in the border zone associated with partial or complete suppression of the BOLD (blood oxygenation dependent) effect. This can lead to false-negative fMRI results, making fMRI unreliable for resection planning. This phenomenon is considered to be due to malfunction in autoregulation of blood flow and adaptation of blood oxygen content to neuronal activity although the cortical structure is still functioning. Metabolic and vascular factors caused by the glioma are under discussion. Innovative MR techniques enable the non-invasive quantification of metabolic and vascular imaging biomarkers, which may be useful for the detection and explanation of NVU. The aim of this project is to improve the reliability of imaging-based localization of cortical structures of important brain functions in the border zone of brain tumors and to investigate factors influencing the lesion-induced NVU. In work package 1, we will validate an innovative multiparametric MRI protocol for determination of metabolic and vascular imaging biomarkers with histopathologic parameters from intraoperatively collected tissue samples as well as with intraoperative measurements of blood and oxygen supply using a dedicated probe. In work package 2, lesion-induced NVU will be detected by functional measurements using magnetoencephalography (MEG) and by correlation of MEG results with fMRI localizations as MEG-fMRI mismatch. The real presence of NVU will be validated using intraoperative neurophysiological monitoring. By correlation of validated NVU with validated metabolic and vascular imaging biomarkers an explanatory model for NVU will be developed. This will finally (work package 3) result in a clinically applicable method for preoperative risk assessment for the presence of a lesion-induced NVU in the border zone of high-grade gliomas.

• DFG Programme: Research Grants