The technique of staining histopathology slides has been a basic part of the craft for many decades, but researchers from Beckman Institute, Christie Clinic in Urbana, and the University of Illinois at Chicago have reported using a stain-free method called Spatial Light Interference Microscopy (SLIM) to image slides as well, or even better than with staining.
Some details from the press release:
Popescu said that the SLIM’s interferometric (which measures phase differences in the light path) capability is what makes it work with a great sensitivity, down to the molecular scale. And that capability is why SLIM can be so valuable for greatly improving the chances of early detection and treatment of cancer.
“What that means is that only a small number of molecules arranged in a certain way are enough to give us the optical signal that something is going to happen here,” he said. “Ideally, we would like to detect cancer at the single-cell level. So, can we find a cell that looks abnormal and do everything so much earlier where the process is still reversible. We know that the disease starts at the nanoscale, at the molecular level, and we think we have the proper tool to catch these early events.”
Staining is commonly used for biological tissue to provide contrast in light microscopes and spotlight features such as tumors. The SLIM method is not only label-free but can gather empirical data on morphological, or structural, tissue information for automated screening at the nanoscale, providing objective evaluations of data on structures such as tumor margins that can be difficult for pathologists to assess.
“We think that the most important advantage of SLIM is that it provides quantitative, objective information,” Popescu said. “Right now, in the clinic, the diagnosis is subjective; it’s a human that does it. There are studies showing that two pathologists agree on a diagnosis only four out of five times.
Here’s from the study abstract in Journal of Biomedical Optics:
The gold standard in histopathology relies on manual investigation of stained tissue biopsies. A sensitive and quantitative method for in situ tissue specimen inspection is highly desirable, as it would allow early disease diagnosis and automatic screening. Here we demonstrate that quantitative phase imaging of entire unstained biopsies has the potential to fulfill this requirement. Our data indicates that the refractive index distribution of histopathology slides, which contains information about the molecular scale organization of tissue, reveals prostate tumors and breast calcifications. These optical maps report on subtle, nanoscale morphological properties of tissues and cells that cannot be recovered by common stains, including hematoxylin and eosin. We found that cancer progression significantly alters the tissue organization, as exhibited by consistently higher refractive index variance in prostate tumors versus normal regions. Furthermore, using the quantitative phase information, we obtained the spatially resolved scattering mean free path and anisotropy factor g for entire biopsies and demonstrated their direct correlation with tumor presence. In essence, our results show that the tissue refractive index reports on the nanoscale tissue architecture and, in principle, can be used as an intrinsic marker for cancer diagnosis.
Abstract in Journal of Biomedical Optics: Tissue refractive index as marker of disease