A team led by a Northwestern
University biomedical engineer has developed a new optical technique that
holds promise for minimally invasive screening methods for the early diagnosis
of cancer.
The researchers have shown for the first time that nanoscale changes are present
in cells extremely early on in carcinogenesis. Their technique, partial-wave
spectroscopy (PWS), can detect subtle abnormal changes in human colon cancer
cells even when those same cells appear normal using conventional microscopy.
The study is published online by the Proceedings of the National Academy of
Sciences.
A simple yet sensitive method, PWS quantifies the statistical properties of
cell nanoscale architecture by using the signal generated by light waves striking
the cell.
PWS can provide information not only about individual cells, but it also can
look inside the cell and see the cell's fundamental "building blocks,"
such as proteins, nucleosomes and intracellular membranes, and detect changes
to this cell nanoarchitecture. Conventional microscopy cannot do this, and other
techniques that can (to some degree) are expensive and complex.
"Imagine a cell as a house and the cell's fundamental building blocks
as bricks," said Vadim Backman, professor of biomedical engineering at
Northwestern's McCormick School of Engineering and Applied Science.
"Our technique can see not only the sizes of the house's bricks but the
details of those bricks. And it can show when those bricks are in trouble even
when the house looks normal. Conventional microscopy can see the individual
houses but not the bricks that make up the house. That's a significant difference,"
said Backman, who led the research.
Backman and his colleagues studied both human colon cancer cell lines and cells
from a colon cancer animal model. In both cases, the PWS technique showed that
an increase in the disorder of cells on the nanoscale parallels genetic events
in the early stages of carcinogenesis.
"We have to look at cell morphology at the nanoscale," said Backman.
"Cells are not just a bag of molecules -- the nanoarchitecture can control
many cellular processes and activities."
The team studied three variants of malignant human cells, each exhibiting a
different degree of aggressive behavior. (In all three, the malignancy resulted
from genetic alteration.)
Using PWS, the researchers were able to distinguish each cell line. They found
architectural disorder in all three but of varying degrees; the most aggressively
malignant cell line showed the most intracellular disorder. When viewed using
microscopy, all three cell lines looked normal, and each was indistinguishable
from the others. The same trend was found in the researchers' study of cells
from an animal model.
"If the PWS screening technique for colon cancer is validated by appropriate
clinical trials, there is the potential for preventing many thousands of cancer
deaths each year," said Allen Taflove, professor of electrical engineering
and computer science at Northwestern. He collaborated with Backman in conducting
computer simulations of how light interacts with the complex structure of a
cell and is an author of the paper.
In addition to cancer research, PWS could find use in biomechanics (to study
the nanoscale architecture of polymers, materials or tissue), tissue engineering
and stem cell research.
"Anywhere you use microscopy you could use PWS and get more information,"
said Backman. "PWS can work with virtually anything, and it can detect
features as small as 20 nanometers."
Authors of the PNAS paper from Backman's research group are lead author and
graduate student Hariharan Subramanian; research associate Prabhakar Pradhan,
a theoretical physicist who predicted that PWS should work; and Yang Liu, a
former graduate student and now an assistant professor at the University of
Pittsburgh who performed the first experiments to demonstrate PWS.
Other authors are Ilker Capoglu, Xu Li, Jeremy Rogers and Alexander Heifetz,
from Northwestern University; and Dhananjay Kunte and Hemant Roy, M.D., from
NorthShore University HealthSystem (formerly Evanston Northwestern Healthcare).
The PNAS paper is titled "Optical Methodology for Detecting Histologically
Unapparent Nanoscale Consequences of Genetic Alterations in Biological Cells."
Posted December 12th, 2008
