To develop an accelerated k-space shift calibration method for free-breathing 3D stack-of-radial MRI quantification of liver proton-density fat fraction (PDFF) and R2∗ .Accelerated k-space shift calibration was developed to partially skip acquisition of k-space shift data in the through-plane direction then interpolate in processing, as well as to reduce the in-plane averages. A multi-echo stack-of-radial sequence with the baseline calibration was evaluated on a phantom versus vendor-provided reference-standard PDFF and R2∗ values at 1.5T, and in 13 healthy subjects and 5 clinical subjects at 3T with respect to reference-standard breath-hold Cartesian acquisitions. PDFF and R2∗ maps were calculated with different calibration acceleration factors offline and compared to reference-standard values using Bland-Altman analysis. Bias and uncertainty were evaluated using normal distribution and Bayesian probability of difference (P < .05 considered significant).Bland-Altman plots of phantom and in vivo data showed that substantial acceleration was highly feasible in both through-plane and in-plane directions. Compared to the baseline calibration without acceleration, Bayesian analysis revealed no significant differences on biases and uncertainties of PDFF and R2∗ measurements with all acceleration methods in this study, except the method with through-plane acceleration equaling slices and averages equaling 20 for PDFF and R2∗ (both P < .001) for the phantom. A six-fold reduction in equivalent calibration acquisition time (time saving ≥25 s and ≥80.7%) was achieved using recommended acceleration factors for the in vivo protocols in this study.This proposed method may allow accelerated calibration for free-breathing stack-of-radial MRI PDFF and R2∗ mapping.
Objectives Ultrasound molecular imaging is increasingly used in preclinical studies to measure the expression of vascular markers during inflammation process. In this context, a new ultrasound contrast agent functionalized with a recombinant P-selectin glycoprotein ligand-1 analogue (rPSGL-Ig) was developed (MBrPSGL-Ig). This agent was assayed in vitro and in vivo to evaluate its binding performance and potential to image expression of inflammatory markers E- and P-selectin. Performance of this newly developed agent was compared with that of antibody (MBAb) or sialyl Lewis X (MBsLex) containing microbubbles and with control microbubbles (MBC). Materials and Methods The targeted ultrasound contrast agents were prepared by coupling biotin-conjugated ligands onto streptavidin-functionalized microbubbles. First, in vitro experiments were performed to measure the adhesion efficiency of these microbubble constructs under static or flow conditions (114 sec−1), on cell monolayer (human umbilical vein endothelial cells and bEnd.5), or coatings of E- or P-selectin of various animal species, respectively. Second, molecular imaging studies were performed in a rat inflammatory model 24 hours after intramuscular injection of lipopolysaccharide in the hind limb. Finally, immunohistochemistry staining of rat inflamed muscle tissue was performed to assess expression of E- and P-selectin. Results Microbubbles functionalized with rPSGL-Ig (MBrPSGL-Ig) displayed firm in vitro binding on the coating of both recombinant E- or P-selectin, with an efficiency similar to microbubbles comprising antibody specific for E-selectin (MBE) or P-selectin (MBP). In contrast, lower binding capacity was measured with MBsLex. At the surface of inflamed endothelial cells, MBrPSGL-Ig were able to interact specifically with E- and P-selectin. Binding specificity was demonstrated by performing blocking experiments with target-specific antibodies, resulting in an 80% to 95% decrease in binding. Ten minutes after microbubble injection, echo signal measured with MBrPSGL-Ig in the inflamed muscles was 20-fold higher compared with MBC. Moreover, the in vivo adhesion of MBrPSGL-Ig was 2- and 7-fold higher compared with P-selectin or E-selectin-specific microbubbles, respectively. Immunohistochemistry revealed a temporal coexpression of E- and P-selectin in the vascular bed of inflamed rat muscle 24 hours after lipopolysaccharide injection. Conclusion The molecular imaging study demonstrates that MBrPSGL-Ig provide imaging signal higher than those measured with antibody or sialyl Lewis X containing microbubbles. These results suggest that MBrPSGL-Ig is a powerful agent to image the expression of both E- and P-selectin in the context of an inflammatory process.
