SWIFT magnetic resonance tool assures removal of nanoparticles from rewarmed samples.

A team funded in part by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and led by University of Minnesota (UMN) researchers has developed a new method for thawing frozen tissue that may enable long–term storage and subsequent viability of tissues and organs for transplantation. The method, called nanowarming, prevents tissue damage during the rapid thawing process that would precede a transplant.

The team’s study published in the journal Science Translational Medicine, demonstrated how a bath of solution with evenly distributed and magnetized iron–oxide nanoparticles can be heated with electromagnetic waves to quickly and non–destructively thaw larger volumes of solution and tissue than had previously been rewarmed. With additional development, the researchers hope the method can be applied to revolutionize and dramatically improve organ storage for transplants.

To make preserved–then–nanowarmed tissues usable, the iron–oxide first must be washed out of the sample. This key element in assuring tissue viability required a novel imaging technique to confirm elimination of nanoparticles. The research team included NIBIB–funded experts in biomedical imaging from the UMN’s Center for Magnetic Resonance Research, who adapted a non–invasive imaging technique, called SWIFT, to study samples following the rewarming process. SWIFT is based on magnetic resonance imaging (MRI).

Freezing tissue can currently be used for long–term storage only of small biomaterials samples. A method, called vitrification, cools the samples in solution to between –160 and –196 degrees Celsius so they are preserved in an ice–free, glass–like state. The larger the sample, however, the more prone it is to crystallization and fracture when rewarmed. To avoid this problem and to potentially store larger samples that could include heart vessels and transplantable portions of organs such as a kidney, liver, or lung, the researchers added iron oxide to the preservation solution. Further, the nanoparticles received silica coating, which had the effect of evenly dispersing them within the solution.

To rewarm samples without damaging tissue, the researchers used MRI equipment comprised of a copper coil that creates an alternating magnetic field in and around the sample. The electromagnetic waves created in the device had limited effect on tissue and cells but stimulated and heated the nanoparticles distributed throughout the sample. The heated nanoparticles, in turn, rewarmed the sample.

Researchers performed warming experiments with human skin cells, pig arteries, and pig heart–valve–flap tissues in volumes with solution up to 50 to 80 milliliters (about 10 to 16 teaspoons). They found that convection heat transfer, the gold–standard approach to rewarming smaller systems of about 1 milliliter, is not able to prevent crystallization or cracking damage in larger systems. Samples that they rewarmed in the coil system – where evenly distributed nanoparticles warmed tissue and cells in a fast and uniform way—successfully rewarmed without this damage. The nanowarming method can generate 100 degrees of heating per minute, which is significantly faster and more uniform than convection in the larger systems.

“Successful nanowarming of cryopreserved tissues requires that high concentrations of iron–oxide nanoparticles are uploaded and evenly distributed in the tissues prior to cooling, and washed out completely after thawing,” said co–author Michael Garwood, PhD, professor of radiology, University of Minnesota. “Prior to the development of SWIFT, no imaging technique had been capable of quantifying high concentrations of iron–oxide nanoparticles in tissues non–invasively.”