Abstract
BACKGROUND: Protocol standardization and optimization for clinical translation of emerging quantitative multiparametric (mp)MRI biomarkers of high-risk prostate cancer requires imaging references that mimic realistic tissue value combinations for bias assessment in derived relaxation and diffusion parameters. PURPOSE: This work aimed to develop a novel class of hydrogel-based synthetic materials with simultaneously controlled quantitative relaxation, diffusion, and kurtosis parameters that mimic in vivo prostate value combinations in the same spatial compartment and allow stable assemblies of adjacent structures. METHODS: A set of materials with tunable T(2), diffusion, and kurtosis were assembled to create quantitative biomimetic (mp)MRI references. T(2) was controlled with variable agarose concentration, monoexponential diffusion by polyvinylpyrrolidone (PVP), and kurtosis by addition of lamellar vesicles. The materials were mechanically stabilized by UV cross-linked polyacrylamide gels (PAG) to allow biomimetic morphologies. The reference T(2) were measured on a 3T scanner using multi-echo CPMG, and diffusion kurtosis-with multi-b DWI. RESULTS: Agarose concentration controls T(2) values which are nominally independent of PVP or vesicle concentration. For agarose PVP hydrogels, monoexponential diffusion values are a function of PVP concentration and independent of agarose concentration. Compared to free vesicles, for agarose-PAG combined with vesicles, diffusion was predominantly controlled by vesicles and PAG, while kurtosis was affected by agarose and vesicle concentration. Both hydrogel classes achieved image voxel parameter values (T(2), D(a), K(a)) for relaxation (T(2): 65-255 ms), apparent diffusion (D(a): 0.8-1.7 μm(2)/ms), and kurtosis (K(a): 0.5-1.25) within the target literature ranges for normal prostate zones and cancer lesions. Relaxation and diffusion parameters remained stable for over 6 months for layered material assemblies. CONCLUSION: A stable biomimetic mpMR reference based on hydrogels has been developed with a range of multi-compartment diffusion and relaxation parameter combinations observed in cancerous and healthy prostate tissue.