Synchrotron-Based Tissue Imaging

With intensity a million times brighter than sunlight, a new synchrotron-based imaging technique offers high-resolution pictures of the molecular composition of tissues with unprecedented speed and quality. Carol Hirschmugl, a physicist at the University of Wisconsin-Milwaukee (UWM), led a team of researchers from UWM, the University of Illinois at Urbana-Champaign and the University of Illinois at Chicago to demonstrate these new capabilities.

Hirschmugl and UWM scientist Michael Nasse built a facility called Infrared Environmental Imaging (IRENI) to perform the technique at the Synchrotron Radiation Center (SRC) at the Madison campus of the University of Wisconsin. The technique provided by the facility employs multiple beams of synchrotron light to illuminate a state-of-the-art camera, instead of just one beam.

IRENI-generated images (right) are 100 times less pixelated than those from conventional infrared imaging (left). Using multiple beams from a synchrotron made the difference, providing enough light to obtain a detailed image of the sample. With this technique, the quality of the chemical images is now similar to that of optical microscopy. (Image: Carol Hirschmugl and Michael Nasse)

IRENI cuts the amount of time needed to image a sample from hours to minutes, while quadrupling the range of the sample size and producing high-resolution images of samples that do not have to be tagged or stained, as they would for imaging with an optical microscope.

“Since IRENI reveals the molecular composition of a tissue sample, you can choose to look at the distribution of functional groups, such as proteins, carbohydrates and lipids,: Hirschmugl said. The team reported that the technique provides both detailed structure and chemistry for each sample.

The technique could have broad applications not only in medicine, but also in pharmaceutical drug analysis, art conservation, forensics, biofuel production and advanced materials such as graphene, Hirschmugl said.

The work, which was described in a recent edition of Nature Methods, is a collaboration with the labs of Rohit Bhargava of the Urbana-Champaign campus of the University of Illinois and Virgilia Macias and André Kajdacsy-Balla of the Chicago campus. “It has taken three years to establish IRENI as a national user facility located at the SRC,” Nasse said. “It is the only facility of its kind worldwide.”

The unique features of the synchrotron make it a highly versatile light source in spectroscopy. Streams of speeding electrons emit continuous light across the entire electromagnetic spectrum so that researchers can access whatever wavelength is best absorbed for a particular purpose. The team focused on the mid-IR range to form graphic “fingerprints” of biochemically important molecules.

Using 12 beams of synchrotron light in this range allows researchers to collect thousands of these chemical fingerprints simultaneously, producing an image that is 100 times less pixelated than in conventional IR imaging.

“We did not realize until now the improvement in detail and quality that sampling at this pixel size would bring,” Bhargava said. “The quality of the chemical images is now quite similar to that of optical microscopy, and the approach presents exciting new possibilities.”

The team tested the technique on breast and prostate tissue samples to determine its capabilities for potential use in diagnostics for cancer and other diseases. It detected features that distinguished the epithelial cells, in which cancers begin, from the stromal cells, which are the type found in deeper tissues, with unprecedented detail.

Separating the two layers of cells is a “basement membrane” that prevents malignant cells from spreading from the epithelial cells into the stromal cells. Early-stage cancers are concentrated in the epithelial cells, but metastasis occurs when the basement membrane is breached. Using a prostate cancer sample, the team had encouraging results in locating spectra of the basement membrane, but more work needs to be done.

For more information, visit: www.uwm.edu