Characterizing diffusion‐controlled release of small‐molecules using quantitative MRI in view of applications to orthopedic infection.

Calcium sulfate is an established carrier for localized drug delivery, but a means to non‐invasively measure drug release, which would improve our understanding of localized delivery, remains an unmet need. We aim to quantitatively estimate the diffusion‐controlled release of small molecules loaded into a calcium sulfate carrier through a gadobutrol‐based contrast agent, which acts as a surrogate small molecule. A central cylindrical core made of calcium sulfate, either alone or within a metal scaffold, is loaded with contrast agents that release into agar. Multi‐echo scans are acquired at multiple time points over 4 weeks and processed into R2* and quantitative susceptibility mapping (QSM) maps. Mean R2* values are fit to a known drug delivery model, which are then compared with the decrease in core QSM. Fitting R2* measurements of calcium sulfate core while constraining constants to a drug release model results in an R2‐value of 0.991, yielding a diffusion constant of 4.59 × 10−11 m2 s−1. Incorporating the carrier within a metal scaffold results in a slower release. QSM shows the resulting loss of susceptibility in the non‐metal core but is unreliable around metal. R2* characterizes the released gadobutrol, and QSM detects the resulting decrease in core susceptibility. The addition of a porous metal scaffold slows the release of gadobutrol, as expected. [ABSTRACT FROM AUTHOR]