Low-grade gliomas do not grow along white matter tracts: evidence from quantitative imaging

Low-grade gliomas are infiltrative brain tumors that can lead to significant neurological deficits due to their invasive nature. The prevailing belief is that low-grade gliomas primarily disseminate along white matter tracts, but quantitative in vivo evidence supporting this concept is lacking. Clarifying their true growth patterns is essential for optimizing therapeutic strategies. We conducted a quantitative analysis of tumor growth patterns in a longitudinal cohort of 43 untreated patients with unigyral World Health Organization grade 2 or 3 gliomas, stratified by their anatomical locations within the neocortex, mesocortex and allocortex. Serial MRI scans were used to generate vector deformation fields, providing detailed three-dimensional representations of tumor evolution over time. These vector deformation fields were compared with diffusion tensor imaging data to assess the alignment of tumor growth with white matter pathways. Quantitative analysis revealed that low-grade gliomas do not predominantly expand along white matter tracts. Instead, they remain confined within specific anatomical boundaries, in respect to their topology of origin. Angular measurements and heat map analysis indicated that tumor growth is directed towards the subventricular zone and may follow their respective radial units. These consistent observations across different anatomical regions challenge the traditional model of glioma progression, suggesting that early-stage glioma expansion is closely governed by ontogenetic factors. In conclusion, this study provides the first quantitative evidence that phenotypical low-grade gliomas do not primarily follow white matter tracts but may instead be influenced by ontogenetic mechanisms. These insights necessitate a re-evaluation of existing models of glioma progression and underscore the importance of incorporating developmental aspects into treatment planning to enhance patient outcomes.