Quantitative Susceptibility Mapping Shows Size-dependent Focused Ultrasound-mediated Therapeutic Delivery to Naive Brain and Gliomas in Mice.

Abstract

Background Focused ultrasound US (FUS)-mediated disruption of the blood-brain barrier (BBB) and blood-tumor barrier (BTB) augments therapeutic delivery; however, relationships between dose, agent size, and delivery to both healthy and tumor tissue with FUS remain poorly defined. Purpose To evaluate quantitative susceptibility mapping (QSM) for quantifying delivery of iron oxide nanoparticles (IONPs) after FUS-mediated BBB and BTB disruption and investigate how delivery efficiency varies with particle size in naive and glioma-bearing mice. Materials and Methods FUS-mediated BBB and BTB disruption was performed on 8-11-week-old naive (n = 31) or GL261 glioma-bearing (n = 26) female C57BL/6 mice using albumin-shelled microbubbles and acoustic feedback control. Four contrast agents were delivered: 2.3-nm gadobenate dimeglumine and 15-, 23-, and 45-nm IONPs. Multi-echo gradient-echo MRI scans acquired before and after FUS were reconstructed into susceptibility maps and then converted to concentration maps. Tumor measurements were performed for 2.3- and 45-nm agents. Results FUS-mediated delivery to naive brain varied with contrast agent size. Compared with 2.3-nm gadobenate dimeglumine (mean, 0.007 percentage injected dose [%ID] ± 0.001 [SD]), delivery increased 2.6-fold at 15 nm (mean, 0.017 %ID ± 0.002; P = .008) and was similar at 23 nm (mean, 0.015 %ID ± 0.002; P = .94) but decreased 2.5-fold at 45 nm (mean, 0.006 %ID ± 0.001; P =.004) relative to 23 nm. In gliomas, FUS increased delivery 1.9-fold for gadobenate dimeglumine (mean, 0.56 %ID/g ± 0.07 vs 1.08 %ID/g ± 0.16; P = .032) and 3.6-fold for 45-nm IONPs (mean, 0.39 %ID/g ± 0.06 vs 1.41 %ID/g ± 0.32; P = .001). Compared with naive brain, glioma delivery was similar for both gadobenate dimeglumine (mean, 0.87 %ID/g ± 0.06 vs 1.08 %ID/g ± 0.16; P = .26) and for 45-nm IONPs (mean, 1.76 %ID/g ± 0.34 vs 1.41 %ID/g ± 0.32; P = .47). Conclusion QSM after MRI and FUS revealed that FUS-mediated delivery of contrast agents of therapeutically relevant sizes to naive murine brain varied with contrast agent size. Delivery to gliomas was similar to that to naive brain. Supplemental material is available for this article. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license.