Technical note: hydrogel-based mimics of prostate cancer with matched relaxation, diffusion and kurtosis for validating multi-parametric MRI.

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 T2, diffusion, and kurtosis were assembled to create quantitative biomimetic (mp)MRI references. T2 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 T2 were measured on a 3T scanner using multi-echo CPMG, and diffusion kurtosis-with multi-b DWI. RESULTS: Agarose concentration controls T2 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 (T2, Da, Ka) for relaxation (T2: 65-255 ms), apparent diffusion (Da: 0.8-1.7 µm2/ms), and kurtosis (Ka: 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.

Evaluating Variability of Commercial Liver Fibrosis Elastography Phantoms.

OBJECTIVE: Liver fibrosis has been found to increase the mechanical stiffness of the liver. To mimic different stages of liver fibrosis, commercially available phantoms (Model 039, CIRS, Inc.) have been produced for clinical quality assurance and research purposes. The purpose of this study was to investigate the mechanical property variability of the phantoms in two lots of CIRS Model 039 phantoms. METHODS: Each lot consisted of phantoms of four stiffness types, and there were 8-10 phantoms of each type. Shear wave elastography measurements were conducted on each phantom at 10 different angles. Group velocity measurements and phase velocity curves were calculated for every SWE acquisition. Multilevel functional principal component analysis (MFPCA) was performed on phase velocity data, which decomposes each phase velocity curve into the sum of eigenfunctions of two levels. The variance of the component scores of levels 1 and 2 were used to represent inter-phantom and intra-phantom variability, respectively. The 95% confidence intervals of phase velocity in a phantom type were calculated to reflect curve variability. DISCUSSION: The standard deviations of the group velocity for phantoms of any type were less than 0.04 and 0.02 m/s for lots 1 and 2, respectively. For both lots, in every type, the phase velocity curves of most individual phantoms fall within the 95% confidence interval. CONCLUSION: MFPCA is an effective tool for analyzing the inter- and intra-phantom variability of phase velocity curves. Given the known variability of a fully tested lot, estimation of the variability of a new lot can be performed with a reduced number of phantoms tested.

Thermoacoustic range verification during pencil beam delivery of a clinical plan to an abdominal imaging phantom.

PURPOSE: The purpose of this phantom study is to demonstrate that thermoacoustic range verification could be performed clinically. Thermoacoustic emissions generated in an anatomical multimodality imaging phantom during delivery of a clinical plan are compared to simulated emissions to estimate range shifts compared to the treatment plan. METHODS: A single-field 12-layerproton pencil beam scanning (PBS)treatment plancreated in Pinnacle prescribing6 Gy/fractionwas delivered by a superconducting synchrocyclotron to a triple modality (CT, MRI, and US) abdominal imaging phantom.Data was acquired by four acoustic receivers rigidly affixed to a linear ultrasound array. Receivers 1-2 were located distal to the treatment volume, whereas 3-4 were lateral. Receivers' room coordinates were computed relative to the ultrasound image plane after co-registration to the planning CT volume. For each prescribed beamlet, a set of thermoacoustic emissions corresponding to varied beam energies were computed. Simulated emissions were compared to measured emissions to estimate shifts of the Bragg peak. RESULTS: Shifts were small for high-dose beamlets that stopped in soft tissue. Signals acquired by channels 1-2 yielded shifts of -0.2±0.7mm relative to Monte Carlo simulations for high dose spots (~40 cGy) in the second layer. Additionally, for beam energy ≥125 MeV, thermoacoustic emissions qualitatively tracked lateral motion of pristine beams in a layered gelatin phantom, and time shifts induced by changing phantom layers were self-consistent within nanoseconds. CONCLUSIONS: Acoustic receivers tuned to spectra of thermoacoustic emissions may enable range verification during proton therapy.