Modified Perivascular Diffusivity in Glioblastoma: DTI-ALPS and Radiopathomic Correlations

Overview

This study demonstrates that glioblastoma (GBM) is associated with altered perivascular diffusivity as measured by the DTI-ALPS index, reflecting glymphatic dysfunction. Integration of DTI-ALPS metrics with radiopathomic maps reveals that tumor infiltration and increased cellularity beyond contrast-enhancing regions correlate with reduced perivascular fluid transport.

Background

Glioblastoma is the most common primary brain tumor in adults, characterized by rapid proliferation and resistance to therapy, with poor median survival despite standard treatment. Beyond tumor growth, GBM may disrupt the brain's glymphatic system, a pathway critical for waste clearance via perivascular spaces. The DTI-ALPS index, derived from diffusion tensor imaging, serves as a noninvasive marker of glymphatic function but has been underexplored in GBM. Combining advanced imaging with radiopathomic mapping allows assessment of tumor infiltration and its impact on perivascular fluid dynamics.

Data Highlights

Key Findings

• DTI-ALPS indices were lower in the hemisphere containing the GBM tumor, indicating disrupted perivascular diffusivity.
• Radio-pathomic maps detected hypercellular tumor infiltration beyond contrast-enhancing and FLAIR regions, correlating with reduced DTI-ALPS values.
• Perivascular invasion observed at autopsy corresponded spatially with areas of altered DTI-ALPS and radiopathomic tumor probability maps.
• Template-based ROI placement for DTI-ALPS calculation ensured reproducible and standardized measurement across patients.
• Lower DTI-ALPS indices serve as an indirect imaging biomarker of glymphatic dysfunction in GBM.

Clinical Implications

DTI-ALPS imaging combined with radiopathomic mapping offers a noninvasive approach to detect glymphatic impairment and microscopic tumor infiltration beyond conventional MRI boundaries in GBM. This may improve understanding of tumor microenvironment alterations and aid in identifying patients at risk for more aggressive disease. Incorporating these imaging biomarkers could enhance treatment planning and monitoring of therapeutic response.

Conclusion

Glioblastoma disrupts perivascular fluid dynamics as reflected by reduced DTI-ALPS indices, which correlate with tumor infiltration beyond contrast-enhancing regions. Integrating diffusion imaging with radiopathomic analysis provides valuable insights into glymphatic dysfunction in GBM.

References

1. Ostrom et al. 2020 -- CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States
2. Liu et al. 2021 -- DTI-ALPS as a Marker of Glymphatic Function
3. UCSF-Preoperative Diffuse Glioma MRI Dataset 2023 -- Imaging Data Source
4. Medical College of Wisconsin Neuro-oncology Brain Bank -- Autopsy Validation Case
5. Liu et al. 2020 -- Template-based ROI Method for DTI-ALPS Calculation