[Paper Review] Design and Characterisation of Tissue-Mimicking Gel Phantoms for Diffusion Kurtosis Imaging

Z.G. Portakal-Uçar, Sophie Shermer+4 more|arXiv (Cornell University)|Aug 30, 2016

MRI in cancer diagnosis3 citations

TL;DR

This study develops tissue-mimicking gel phantoms using agar, agarose, and PVA with added glass microspheres to enable accurate diffusion kurtosis imaging (DKI) for MRI quality assurance and protocol optimization. By tuning microsphere concentration, kurtosis values were increased from 0.05 to 0.523, closely matching in vivo tissue values, while maintaining stable diffusion and relaxation properties over six months at room temperature.

ABSTRACT

Purpose: The aim of this work was to create tissue-mimicking gel phantoms appropriate for diffusion kurtosis imaging (DKI) for quality assurance, protocol optimization and sequence development. Methods: A range of agar, agarose and polyvinyl alcohol phantoms with concentrations ranging from 1.0% to 3.5%, 0.5% to 3.0% and 10% to 20%, respectively, and up to 3 g of glass microspheres per 100 ml were created. Diffusion coefficients, excess kurtosis values and relaxation rates were experimentally determined. Results: The kurtosis values for the plain gels ranged from 0.05 with 95% confidence interval (CI) of $(0.029, 0.071)$ to $0.216(0.185, 0.246)$, well below the kurtosis values reported in the literature for various tissues. The addition of glass microspheres increased the kurtosis of the gels with values up to $0.523(0.465, 0.581)$ observed for gels with the highest concentration of microspheres. Repeat scans of some of the gels after more than six months of storage at room temperature indicate changes in the diffusion parameters of less than 10%. The addition of the glass microspheres reduces the apparent diffusion coefficients (ADCs) and increases the longitudinal and transverse relaxation rates but the values remain comparable to those for plain gels and tissue, with ADCs observed ranging from $818(585, 1053) imes 10^{-6}$ mm$^2$/s to $2257(2118, 2296) imes 10^{-6}$ mm$^2$/s, and R1 values ranging from $0.34(0.32, 0.35)$ 1/s to $0.51(0.50, 0.52)$ 1/s, and R2 values ranging from $9.69(9.34, 10.04)$ 1/s to $33.07(27.10, 39.04)$ 1/s. Conclusions: Glass microspheres can be used to effectively modify diffusion properties of gel phantoms and achieve a range of kurtosis values comparable to those reported for a variety of tissues.

Motivation & Objective

• To design tissue-mimicking gel phantoms suitable for diffusion kurtosis imaging (DKI) in MRI quality assurance and protocol development.
• To address the lack of phantoms with tunable non-Gaussian diffusion properties that match in vivo kurtosis values.
• To ensure long-term stability of phantom diffusion and relaxation parameters under ambient storage conditions.
• To characterize the impact of glass microspheres on diffusion coefficients, kurtosis, and relaxation rates (R1, R2) in gel matrices.
• To validate the phantoms' reproducibility and consistency across repeated scans over six months.

Proposed method

• Prepared agar, agarose, and polyvinyl alcohol (PVA) gels with concentrations ranging from 1.0% to 3.5%, 0.5% to 3.0%, and 10% to 20%, respectively.
• Incorporated glass microspheres (up to 3 g per 100 mL) into gels to increase microstructural heterogeneity and enhance kurtosis.
• Acquired multi-b-value diffusion-weighted MRI data on a 3T scanner to compute apparent diffusion coefficients (ADC), kurtosis (K), and relaxation rates (R1, R2).
• Performed repeated scans on stored phantoms after six months to assess long-term stability of diffusion and relaxation parameters.
• Used voxel-wise analysis to evaluate spatial homogeneity of diffusion and relaxation maps.
• Applied statistical analysis with 95% confidence intervals to quantify uncertainty in measured parameters.

Experimental results

Research questions

• RQ1 Can gel phantoms with tunable kurtosis be created using common gelling agents and glass microspheres to mimic in vivo tissue non-Gaussian diffusion?
• RQ2 How does the addition of glass microspheres affect the apparent diffusion coefficient (ADC), kurtosis, and relaxation rates (R1, R2) in agar, agarose, and PVA gels?
• RQ3 To what extent do the diffusion and relaxation properties of these phantoms remain stable over long-term storage at room temperature?
• RQ4 Can the phantoms maintain tissue-mimicking characteristics in terms of relaxation times and diffusion behavior across different gel types and microsphere concentrations?
• RQ5 How do the measured kurtosis values compare to those reported in human tissues, and can they be tuned to match clinical ranges?

Key findings

• Plain agar, agarose, and PVA gels exhibited low kurtosis values, ranging from 0.05 (95% CI: 0.029–0.071) to 0.216 (0.185–0.246), significantly below typical in vivo tissue values.
• Addition of glass microspheres increased kurtosis up to 0.523 (95% CI: 0.465–0.581), closely matching kurtosis values reported in various human tissues.
• Apparent diffusion coefficients (ADC) ranged from 818 (585–1053) × 10⁻⁶ mm²/s to 2257 (2118–2296) × 10⁻⁶ mm²/s, with values decreasing as microsphere concentration increased.
• Longitudinal relaxation rates (R1) ranged from 0.34 (0.32–0.35) /s to 0.51 (0.50–0.52) /s, and transverse relaxation rates (R2) from 9.69 (9.34–10.04) /s to 33.07 (27.10–39.04) /s, remaining within tissue-relevant ranges.
• Repeat scans after six months showed changes in diffusion parameters of less than 10%, indicating strong long-term stability of the phantoms.
• Spatial homogeneity analysis revealed standard deviations of diffusion and relaxation parameters at the few percent level, indicating good uniformity across the phantom volume.