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Updated: Oct 9, 2025

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Effects of Multi-Shell Free Water Correction on Glioma Characterization
Lea Starck1,2, Fulvio Zaccagna3,4, Ofer Pasternak5,6
1Department of Physics and Technology, University of Bergen, N-5007 Bergen, Norway.
Abstract:
Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-naïve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p ≤ 0.003), whereas skewness is decreased (p ≤ 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity.
Insights
Free water (FW) elimination improves diffusion MRI analysis in brain tumors. This method enhances the accuracy of fractional anisotropy (FA) measurements, aiding in the characterization of tumor heterogeneity.
Area of Science:
- Neuroimaging
- Radiology
- Biomedical Engineering
Background:
- Diffusion MRI is crucial for brain tumor microstructure analysis.
- Edematous fluids can obscure tissue characteristics in diffusion MRI, complicating interpretation.
- Accurate quantitative evaluation of brain tumors using diffusion MRI is challenging.
Purpose of the Study:
- To apply a multi-shell regularized free water (FW) elimination model to diffusion MRI data from glioma patients.
- To investigate the diagnostic value of FW maps and FW-corrected fractional anisotropy (FA) measures.
- To assess the impact of FW elimination on quantitative diffusion MRI parameters for characterizing tumor heterogeneity.
Main Methods:
- A multi-shell regularized free water elimination model was applied to diffusion MRI data from 26 treatment-naïve glioma patients.
- Free water (FW) components were separated from tissue-related diffusion signals.
- Derived FW maps and FW-corrected tensor-derived fractional anisotropy (FA) maps were analyzed.
Main Results:
- Presumed necrotic tumor regions showed higher mean and variance of FW content.
- The area under the ROC curve for classifying necrotic and enhancing tumor volumes increased by 5% with FW correction.
- FW elimination increased FA entropy (p ≤ 0.003) and decreased skewness (p ≤ 0.004) in non-enhancing tumor parts.
- Kurtosis was significantly decreased (p < 0.001) in high-grade gliomas after FW elimination.
Conclusions:
- Eliminating free water (FW) contributions significantly improves quantitative estimations of fractional anisotropy (FA).
- FW correction aids in disentangling the heterogeneity within brain tumors.
- This approach enhances the diagnostic value and radiological interpretation of diffusion MRI in glioma patients.
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