Prediction of normal brain extracellular spacings based on nanoparticle diffusion (A) Distribution of the logarithmic D eff of individual nanoparticles (■ PS-PEG5k and □ PSCOOH) at τ = 1 s. Data represents 4 independent experiments, with an average of n > 100 nanoparticles per experiment. (B) Normalized ensemble-averaged diffusivities (<D eff >/D W ) for different sized PEG-coated PS particles (60 nm (■), 110 nm (•), and 240 nm (▲)) at τ = 1 s, where D W is the theoretical diffusivities of neutral particles in PBS. The solid and dashed lines represent the range of theoretical <D eff >/D W ratios for various sized 60-, 110-, and 240-nm particles predicted by the obstruction scaling model. This leads to an estimated mesh spacing range in normal rat brain tissue of 20-230 nm obtained by maximum likelihood estimation fitting to experimental diffusivity ratios. <D eff >/D W from Thorne et al [34] are provided (3 nm (■), 14 nm (▲), and 35 nm(•)) for reference to previously estimated values. (C) Percent pores larger than 100-and 200-nm. Data represents the ensemble average of four independent experiments with n > 100 particles tracked for each experiment. 

Contexts in source publication

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... ensure that the observed rapid transport of PEGylated nanoparticles was not biased by a small fraction of fast moving outlier particles, we evaluated the heterogeneity in particle transport rates by examining the distribution of individual particle diffusivities at 1 s ( Figure 2A). The fastest 75 percent of 60-nm and fastest 65 percent of 110-nm PS-PEG particles exhibited uniformly rapid transport, compared to the fastest 15 percent of 240-nm PS-PEG particles. ...

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... on the determination that transport was limited due to steric obstruction for larger particles and not due to particle interaction with brain ECS components, diffusion rates for 240-nm PEG-PS particles were incorporated into this model. Using maximum likelihood estimation, the average pore size of normal rat brain ECS was estimated to be between 60-120 nm ( Figure 2B). More specifically, we calculated the pore size distribution to range from 20 nm to 230 nm. ...

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... specifically, we calculated the pore size distribution to range from 20 nm to 230 nm. The largest 20% of pore sizes experienced by particles were > 100 nm and 14% of pore sizes experienced by particles were > 200 nm ( Figure 2C). Overall approximately 60% of the pores sampled by probe particles were larger than 50 nm. ...

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... weighted MR images, which detect red blood cell leakage across the BBB, were taken 2-5 minutes postsonication at pressures ranging from 0.4 to 2.0 MPa. Hypointense regions indicating the presence of blood in the tissue appeared at 92% of locations (n=39) sonicated with pressures greater than or equal to 0.8 MPa, while only 16% of locations (n=43) sonicated with 0.6 MPa developed hypointensity ( Figure S2A). No erythrocyte leakage was detected at 0.4 MPa (n=3). ...

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... note, hypointense regions produced at 0.6 MPa were much smaller and fainter than those produced at higher pressures, and only occurred when sonications were performed close to the olfactory bulb. Additionally, MR thermometry indicated that no thermal rise occurred at the focal spot during the sonications ( Figure S2B). ...