The impact of the relationship between tumor boundaries and adjacent white matter on surgical outcomes in diffuse gliomas

Introduction and Aim: Diffuse gliomas are common primary tumors of the central nervous system, especially exhibiting an infiltrative behavior pattern in the brain. Due to this characteristic, they are closely associated with the brain's white matter. The primary treatment for these tumors is surgical resection, and the most commonly used method for preoperative diagnosis is FLAIR-weighted magnetic resonance imaging. However, the relationship between the tumor and the adjacent white matter can affect surgical outcomes and is closely linked to the patients' functional and oncological outcomes. The infiltrative nature and heterogeneity of tumor burden within the tumor raise challenges in defining tumor boundaries and better identifying peritumoral areas. This study aims to better elucidate the cellular heterogeneity of diffuse gliomas and the tumor boundaries, as well as peritumoral areas, using diffusion tensor imaging. Materials and Methods: The main hypothesis of the study is that tumor cell infiltration is also present in the peritumoral areas that do not appear hyperintense on FLAIR imaging. Additionally, the cellular heterogeneity of these tumors and the decrease in cellular density from the tumor center toward the tumor periphery can be revealed through correlates based on diffusion-weighted imaging and diffusion tensor imaging. For this purpose, preoperative FLAIR-weighted MR images of 90 patients with grade 2 and grade 3 diffuse gliomas, classified according to the World Health Organization criteria, were segmented into four areas: tumor center, tumor periphery, peritumoral area, and normal brain tissue in the contralateral hemisphere. The changes in tumor burden across these areas were investigated by measuring major DWI and DTI metrics, including ADC, FA, OD, RD, and AD. Additionally, the major white matter tracts located near the tumor in four cadavers' eight hemispheres were identified through central core and white matter dissection and standardized according to the relevant brain lobe. Subsequently, tractographic techniques were applied preoperatively in 90 patients and postoperatively in 19 patients, and DTI metrics were measured. In this patient group, evaluations and examinations regarding the surgical process were performed and reported in the preoperative, early postoperative and late postoperative periods by faculty members who are experts in 4 fields: motor and movement, language and speech, sensation and perception, and also neuropsychometry.Case-based analyses also examined patients' postoperative functional outcomes in relation to the association between the tumor and white matter tracts. Results: The measurements of ADC, FA, OD, RD, and AD in the four segmented areas showed a statistically significant change from the tumor center toward the periphery and normal brain tissue, which was explained by the tumor's cellular heterogeneity. Moreover, the metric differences between the peritumoral area, which appeared normal on FLAIR imaging, and normal brain tissue suggested that tumor cell infiltration might be present in the peritumoral regions not detected on FLAIR imaging. In measurements performed on 90 patients targeting the white matter tracts that were found to occupy a wide area in the cadaver dissections, significant metric differences were observed between the affected hemisphere and the contralateral hemisphere. No significant changes in DTI metrics were found in postoperative tract analyses. In preoperative, early postoperative and late postoperative examinations and evaluations, it was reported that although partial disorders were observed in the early postoperative period, these disorders improved to a great extent in the late postoperative period. Conclusion: Diffuse gliomas can exhibit cellular heterogeneity, and tumor infiltration may also be present in the peritumoral regions seen on preoperative surgical-radiological evaluations. In this case, it may be necessary to evaluate the extent of surgical resection individually for each patient, and considering the options for supratotal resection may emerge as a viable approach. Keywords: diffuse glioma, peritumoral area, heterogeneity, DTI, tractography