title: Improving the homogeneity of tissue-mimicking cryogel phantoms for medical             imaging.
abstract: OBJECTIVE
  Tissue-mimicking phantoms can help in uncovering potential weaknesses in medical imaging systems. This work presents a new approach to developing phantoms for magnetic resonance elastography (MRE). Elastography requires sufficiently large and well-characterized phantoms to accurately validate motion estimation methods and to provide accurate stiffness measurements. Physically crosslinked polyvinyl alcohol hydrogels, prepared by the freeze-thaw technique, have been extensively used as MRE phantoms. However, the large cryogels developed by this technique usually exhibit variations in properties due to the low thermal conductivity of the polymeric solution. This leads to variations in freezing-thawing rates across the gels. Therefore, designing homogeneous large cryogels with tissue-mimicking mechanical properties poses a challenge to medical imaging researchers.
  
  
  METHODS
  Unlike conventional freeze-thaw techniques that use either sudden freezing or ramp freezing, the authors have developed a modified freeze-thaw process featuring a combination of multiple ramps and isotherms within a single freeze-thaw cycle. Aiming to develop brain-mimicking phantoms, they have blended three different water-soluble polymers (polyvinyl pyrrolidone, agarose, and polyacrylic acid) with polyvinyl alcohol and produced cryogels with a wide range of mechanical properties and swelling characteristics. The effect of the modified process on mechanical properties, swelling, and melting enthalpy of the produced gels has been investigated in this study.
  
  
  RESULTS
  It was demonstrated that imposing additional isotherms at the vicinity of phase change temperatures could effectively reduce the variations in properties within a typical large phantom (diameter vs height: 100 mm × 100 mm). While the conventional freeze-thaw process resulted in ∼16% variation in the enthalpy of fusion across the produced gels, the modified process reduced this variation to below 8%. The homogeneity in mechanical properties was also improved by over 50% compared to the conventional process. Upon comparing the mechanical properties of the gels with those of brain white matter, the authors have shown that a blend of polyvinyl alcohol and polyvinyl pyrrolidone can provide brain-mimicking properties, while leading to stable gels.
  
  
  CONCLUSIONS
  The modified freeze-thaw process enabled to minimize the temperature gradient within the large cryogel phantoms during the freeze-thaw cycle. The results of this study can help to fill the gaps in the scientific literature with regard to developing homogeneous phantoms for medical imaging. This work also provides a solid foundation for future studies in this field and could facilitate formulating new hydrogels to replicate the viscoelastic properties of soft tissues.
authors.affiliation: Bioengineering, Chemical and Paper Engineering Department, Miami University, Oxford, OH, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Minton
authors.forename: Amin
authors.initials: A
authors.lastname: Iravani
authors.forename: Azizeh-Mitra
authors.initials: AM
authors.lastname: Yousefi
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry; D059985:Cryogels / Q000737:chemistry; D054459:Elasticity Imaging Techniques / Q000295:instrumentation*; D055595:Mechanical Phenomena; D019047:Phantoms, Imaging; D011205:Povidone / Q000737:chemistry; D012685:Sepharose / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000180:Acrylic Resins; D059985:Cryogels; C006903:carbopol 940; D012685:Sepharose; D011205:Povidone