PURPOSE: Focused ultrasound-induced blood-brain barrier (BBB) opening is a promising method for neurotherapeutic delivery. The standard for quantifying induced BBB permeability is the K trans $$ {K}^{\mathrm{trans}} $$ parameter, which reflects both permeability and plasma flow. The influence of plasma flow can be eliminated by estimating the PS parameter. However, this parameter has been largely unexplored in this application. This study aims to compare permeability estimates based on K trans $$ {K}^{\mathrm{trans}} $$ and PS in focused ultrasound-induced BBB opening experiments. METHODS: We used the extended Tofts model (ETM) and the two-compartment exchange model (2CXM) to estimate K trans $$ {K}^{\mathrm{trans}} $$ and PS parameters, respectively. Permeability estimates were compared using simulated concentration curves, simulated DCE-MRI data, and real datasets. We explored the influence of spatially-regularized model fitting on the results. RESULTS: For opened BBB, K trans $$ {K}^{\mathrm{trans}} $$ was minimally influenced by plasma flow under the tested conditions. However, fitting the ETM often introduced outliers in K trans $$ {K}^{\mathrm{trans}} $$ estimates in regions with closed BBB. The 2CXM outperformed the ETM at high signal-to-noise ratios, but its higher complexity led to lower precision at low signal-to-noise ratios. Both these issues were successfully compensated by spatially-regularized model fitting. CONCLUSION: Both K trans $$ {K}^{\mathrm{trans}} $$ and PS seem to be eligible options for the quantification of BBB opening, and the correct choice depends on the specifics of the acquired DCE-MRI data. Additionally, spatial regularization has demonstrated its importance in enhancing the accuracy and reproducibility of results for both models.

Department of Pharmacology Faculty of Medicine Masaryk University Brno Czechia

Faculty of Electrical Engineering and Communication Brno University of Technology Brno Czechia

Institute of Scientific Instruments Czech Academy of Sciences Brno Czechia

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Focused ultrasound-induced blood-brain barrier opening: A comparative analysis of permeability quantification based on K trans and PS