3D Extrusion Printing of Biphasic Anthropomorphic Brain Phantoms Mimicking MR Relaxation Times Based on Alginate-Agarose-Carrageenan Blends

Abstract

The availability of adapted phantoms mimicking different body parts is fundamental to establishing the stability and reliability of magnetic resonance imaging (MRI) methods. The primary purpose of such phantoms is the mimicking of physiologically relevant, contrast-creating relaxation times T 1 and T 2 . For the head, frequently examined by MRI, an anthropomorphic design of brain phantoms would imply the discrimination of gray matter and white matter (WM) within defined, spatially distributed compartments. Multichannel extrusion printing allows the layer-bylayer fabrication of multiple pastelike materials in a spatially defined manner with a predefined shape. In this study, the advantages of this method are used to fabricate biphasic brain phantoms mimicking MR relaxation times and anthropomorphic geometry. The printable ink was based on purely naturally derived polymers: alginate as a calcium-cross-linkable gelling agent, agarose, ιcarrageenan, and GdCl 3 in different concentrations (0−280 μmol kg −1 ) as the paramagnetic component. The suggested inks (e.g., 3Alg-1Agar-6Car) fulfilled the requirements of viscoelastic behavior and printability of large constructs (>150 mL). The microstructure and distribution of GdCl 3 were assessed by scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX). In closely monitored steps of technological development and characterization, from monophasic and biphasic samples as printable inks and cross-linked gels, we describe the construction of large-scale phantom models whose relaxation times were characterized and checked for stability over time.

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

“…11,37 Agarose-PVP gels are mechanically brittle and would require containers to preserve compartment shape. 38,39 These materials may also be liable to diffusive osmosis changes in parameters near compartmental interfaces due to ∼5 nm PVP gradient through ∼150 nm agarose pores (although not observed in this study). In contrast, agarose-CSB-PAG combinations provide mechanical stability, can be molded into permanent structures, and prevent micron-size vesicle 23 diffusion through ∼0.1 µm PAG5% pores at compartment interfaces.…”

“…Agarose‐PVP gels are mechanically brittle and would require containers to preserve compartment shape 38,39 . These materials may also be liable to diffusive osmosis changes in parameters near compartmental interfaces due to ∼5 nm PVP gradient through ∼150 nm agarose pores (although not observed in this study).…”

Toward Printing the Brain: A Microstructural Ground Truth Phantom for MRI

“…Attempts to create brain phantoms using 3D printing methods have been previously reported. However, those approaches used techniques that provide much lower printing resolutions, resulting in larger channel diameters that are more appropriate for mimicking muscle microstructure (e.g., Berry et al [30] and Bieniosek et al [31] ) or for multiphasic, anthropomorphic phantoms (e.g., Kilian et al [32] ). So far, high-resolution stereolithography methods, such as 2PP 3D printing, were considered unsuitable for the production of an MRI brain phantom, due to the challenges in scalability.…”

“…[ 31 ] ) or for multiphasic, anthropomorphic phantoms (e.g., Kilian et al. [ 32 ] ). So far, high‐resolution stereolithography methods, such as 2PP 3D printing, were considered unsuitable for the production of an MRI brain phantom, due to the challenges in scalability.…”

Diffusion‐Based 3D Bioprinting Strategies

“…[ 126 ] Another strategy to control diffusion is to employ diffusion barriers, such as a non‐diffusive material extruded from an additional cartridge, to prevent or reduce diffusion. Such barriers would enable concentration‐dependent properties, such as zonally defined mechanical, [ 127 ] conductive, [ 128 ] or paramagnetic [ 129 ] characteristics, to be maintained over time.…”