Laser technique detects and colour-codes cancer tumours

The microscopy technique - called nonlinear interferometric vibrational imaging (NIVI) - can produce colour-coded images of tissue, outlining clear tumour boundaries, with more than 99 per cent confidence in less than five minutes.

In addition to taking a day or more for results, current diagnostic methods are subjective, based on visual interpretations of cell shape and structure. A small sample of suspect tissue is taken from a patient and a stain is added to make certain features of the cells easier to see. A pathologist looks at the sample under a microscope to see if the cells look unusual, often consulting other pathologists to confirm a diagnosis.

‘But the diagnosis is made based on very subjective interpretation - how the cells are laid out, the structure and the morphology,’ said Prof Stephen Boppart, who is affiliated with the university’s Beckman Institute for Advanced Science and Technology.

Rather than focus on cell and tissue structure, NIVI assesses and constructs images based on the molecular composition of the cells. Normal cells have high concentrations of lipids but cancerous cells produce more protein. By identifying cells with abnormally high protein concentrations the researchers could accurately differentiate between tumours and healthy tissue.

Molecules in the cells can be identified because they each have a unique vibrational state. When the resonance of that vibration is enhanced, it produces a signal that can be used to identify cells with high concentrations of a specific molecule.

The NIVI technique uses two beams of light to excite molecules in a tissue sample. One of NIVI’s two beams of light acts as a reference, so that combining that beam with the signal produced by the excited sample cancels out background noise and isolates the molecular signal. Statistical analysis of the resulting spectrum produces a colour-coded image at each point in the tissue: blue for normal cells, red for cancer.

Another advantage of the NIVI technique is more exact mapping of tumour boundaries, a murky area for many pathologists. The margin of uncertainty in visual diagnosis can be a wide area of tissue as pathologists struggle to discern where a tumour ends and normal tissue begins. The red-blue colour coding shows an uncertain boundary zone of about 100 microns - merely a cell or two.

‘Sometimes it’s very hard to tell visually whether a cell is normal or abnormal,’ Boppart said. ‘But molecularly, there are fairly clear signatures.’

The researchers are working to improve and broaden the application of their technique. By tuning the frequency of the laser beams, they could test for other types of molecules. They are working to make it faster, for real-time imaging, and exploring new laser sources to make NIVI more compact or even portable. They also are developing new light delivery systems, such as catheters, probes or needles that can test tissue without removing samples.