FRACTAL STRUCTURE ON GADOLINEUM-ENHANCED MRI SCANS CORRELATES WITH OXIDATIVE METABOLISM AND VEGF EXPRESSION IN GLIOBLASTOMA

AbstractIntroduction:In glioblastoma, VEGF expression promotes angiogenesis and has been reported to correlate with contrast enhancement on MRI scans. However, clinical results of anti-angiogenic therapy seem limited and there is a need to identify glioblastoma patients that might benefit from this treatment. Fractal structure is found throughout many processes in nature, and often arises from sets of simple growth rules. In this study, we examined the contrast enhancement patterns in MRI scans of glioblastoma patients for evidence of fractal structure and correlated these to biological tumor characteristics.Materials and Methods:For 39 glioblastoma patients, volumetric T1 post-contrast MRI scans were obtained before surgical resection. For each tumor, we calculated the fractal dimension (Minkowski-Bouligand dimension) using a box-counting (cubic scaling) approach. VEGF expression was determined with use of immunohistochemistry on tissue microarrays. RNA expression microarrays from fresh frozen tissue were explored with gene set enrichment analysis (GSEA).Results:We found robust evidence for fractal structure in the contrast enhancement pattern, with an average fractal dimension of 2.17 ± 0.10, with a visually apparent split at 2.10. High fractal dimension significantly correlated with increased VEGF expression. Additionally, GSEA analysis showed a clear association between high fractal dimension and a decrease of gene sets involved in oxidative phosphorylation.Conclusion:The presence of fractal dimensionality presents a new way to analyse classic gadolineum-enhanced T1 MRI scans of glioblastoma patients. The fractal dimension of the contrast enhancement pattern provides significant information on the tumor’s metabolism and might be used as a future biomarker for hypoxia or reponse to anti-angiogenic therapy.