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.

Effective magnetic susceptibility of 3D-printed porous metal scaffolds.

PURPOSE: 3D-printed porous metal scaffolds are a promising emerging technology in orthopedic implant design. Compared to solid metal implants, porous metal implants have lower magnetic susceptibility values, which have a direct impact on imaging time and image quality. The purpose of this study is to determine the relationship between porosity and effective susceptibility through quantitative estimates informed by comparing coregistered scanned and simulated field maps. METHODS: Five porous scaffold cylinders were designed and 3D-printed in titanium alloy (Ti-6Al-4V) with nominal porosities ranging from 60% to 90% using a cellular sheet-based gyroid design. The effective susceptibility of each cylinder was estimated by comparing acquired B0 field maps against simulations of a solid cylinder of varying assigned magnetic susceptibility, where the orientation and volume of interest of the simulations was informed by a custom alignment phantom. RESULTS: Magnitude images and field maps showed obvious decreases in artifact size and field inhomogeneity with increasing porosity. The effective susceptibility was found to be linearly correlated with porosity (R2  = 0.9993). The extrapolated 100% porous (no metal) magnetic susceptibility was -9.9 ppm, closely matching the expected value of pure water (-9 ppm), indicating a reliable estimation of susceptibility. CONCLUSION: Effective susceptibility of porous metal scaffolds is linearly correlated with porosity. Highly porous implants have sufficiently low effective susceptibilities to be more amenable to routine imaging with MRI.