Abstract
Purpose: To build a mathematical model based magnetic resonance (MR) method to simulate drug anisotropic distribution in vivo in the interstitial space (ISS) of the brain.Materials and Methods: An injection of signal intensity-related gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), which is an exogenous drug, was administered, and its diffusion was traced in the ISS of the brain using MRI. Dynamic MRI scans were performed to monitor and record the changes in signal intensity in each pixel of the region of interest. The transport parameters were calculated using the modified equation to simulate three-dimensional anisotropic diffusion, which was resolved using a Laplace transform and a linear regressive model.Results: After Gd-DTPA was introduced into the caudate nucleus, its distribution was demonstrated in real time. As the Gd-DTPA gradually cleared, the associated hyperintensity attenuated over time. The average diffusion coefficient (D) and the clearance rate constant (k) were (1.305 ± 0.364) × 10−4 mm2/s and (1.40 ± 0.206) × 10−5 s−1, respectively.Discussion: The combination of trace-based MRI and modified diffusion mathematical models can visualize and measure the three-dimensional anisotropic distribution of drugs in the ISS of the brain.
Highlights
Despite rapid progress in neuroscience, traditional oral or intravenous administration for brain diseases have consistently shown low efficiency (Fisher et al, 2009; Wolak and Thorne, 2013) and much more research needed to understand the brain activity underlying emotion, behavior, etc. (Yan et al, 2017a,b)
Real-time monitoring of the distribution of Gd-DTPA in the interstitial space (ISS) revealed that after the Gd-DTPA tracer was injected into the ISS, signal intensity in the caudate nucleus increased
Drug diffusion and clearance in the ISS of the brain can be monitored in real time using multi-view MR images
Summary
Despite rapid progress in neuroscience, traditional oral or intravenous administration for brain diseases have consistently shown low efficiency (Fisher et al, 2009; Wolak and Thorne, 2013) and much more research needed to understand the brain activity underlying emotion, behavior, etc. (Yan et al, 2017a,b). Administering therapeutics through the interstitial space (ISS) of brain is considered a promising method of treating brain diseases based on the fluid dynamics of the interstitial fluid (ISF) in the ISS (N’djin et al, 2014; Lonser et al, 2015). Modeling on Diffusion in ISS has demonstrated certain advantages compared with traditional drug delivery, including the ability to bypass the bloodbrain barrier, wider targeted distributions throughout the brain volume, and reduced side effects (Xi et al, 2014). An appropriate mathematical model, which can stimulate drug distribution in ISS, is crucial to the emerging achievements and applications of the promising administration
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