C.V. Raman’s (unceasing) effect, 85 years on

On a mild Kolkata winter day in 1928, an Indian physicist called Chandrasekhara Venkata Raman and a colleague found that when a beam of light strikes a liquid, a small part of the light is scattered into a different colour. The scattering changes with the type of liquid.

For this seminal discovery, Raman—who was confident enough to book a ticket to Sweden before the announcement—got the Nobel Prize in 1930, the only Indian scientist to be so awarded. Raman scattering, as the effect is called, is used today to identify minerals, monitor manufacturing processes and detect diseases.

Raman’s enduring legacy is in evidence on the cover of the latest Science Translational Medicine, a prestigious journal. On Thursday, a team of scientists from Harvard University and the University of Michigan revealed a sophisticated new technique that uses mild lasers to create a colour-coded map of cancerous cells in the brain, holding out hope of more accurate surgery on deadly tumours.

Neurosurgeon Daniel Orringer and his colleagues use a greatly amped version of the Raman effect. Stimulated Raman Scattering (SRS) microscopy, as the method is called, was tested on mice and proven possible on brain tissue removed from a human patient with glioblastoma multiforme (GM), a particularly deadly variety of brain tumour.

Such tumours cannot be cured. After diagnosis, patients with GM live, on average, 18 months. The only hope is to excise the tumour, but the big problem for surgeons is the lack of clearly defined margins between healthy brain tissue and tumors.

The SRS technique, which is not yet refined enough to be used in operating rooms, appears better than the current method—a kind of staining—of diagnosing brain tumours. Both seem to be as accurate, but SRS microscopy can be done in real-time and, eventually, should not require removal of brain tissue.

“The neurosurgeons on our team have always been frustrated at the difficulty of differentiating tumour from normal brain during surgery,” Orringer told me in an interview. Last year, a paper published by his team in the Journal of Neurosurgery reported that in 75% of all brain-tumour operations, cancerous tissue that could safely be removed is left behind because surgeons, who must visually look for clues, such as colour and texture, would rather not take the chance.

In images released by the team, a tumour appears blue and healthy cells green, allowing surgeons, for the first time, to see the borders of tumours.

Tumours and normal brain tissue are chemically different. Tumours tend to be high in protein and low in lipids. Healthy brain tissue has generally equal quantities of both.

SRS relies on the interaction of light with cellular tissue, creating varying signals from the chemical bonds of fats and proteins. Every type of human cell, whether protein, lipid or DNA, has its own Raman signature, the key to creating colour-coded images. Orringer said the high-resolution SRS images reveal another difference between cancerous and healthy brain tissue. Cancer cells are often tightly packed together, whereas cells in most regions of the normal brain rarely touch.

Since spontaneous Raman scattering—of the type identified by the Nobel laureate—has a very weak signal, the research team amplified it by more than 10,000 times. The powerful signal allows for 30 multi-colour images every second, the rate needed for real-time live-action videos.

The team will now collect SRS images from specimens of human brain tumours. If this is successful, the researchers plan to develop a hand-held probe—no larger than a toothbrush—that can be used on patients. This would be a major advance because today tissue must be removed from the brain and examined under a microscope.

The development of the new technology is also a good example of how promising laboratory work should be taken to market. The SRS microscopy tool was developed and tested by a multidisciplinary team of scientists, including pathologists, chemists and neurosurgeons. A start-up, floated by co-author Xiaoliang Sunney Xie—a Harvard chemistry professor who has been pursuing applications of SRS for about 15 years—and his group, is working on an inexpensive laser and collaborating with another company to reduce the size of the image-taking probe.

“Technology developments never end,” said Orringer. The current iteration of SRS is being enhanced to make it sharper and swifter. If Raman’s original discovery was a Model-T, you could roughly term the new tool a late model Lamborghini.

Underlying every related development, though, is the principle of physics that Raman discovered 85 years ago in Kolkata on that February day, celebrated every year as National Science Day in India. “The great discoveries of C.V. Raman are at the core of SRS microscopy,” said Orringer. “Without his work, SRS microscopy would not be possible.”

Samar Halarnkar is a Bangalore-based journalist. This is a fortnightly column that explores the cutting edge of science and technology. Comments are welcome at frontiermail@livemint.com. To read Samar Halarnkar’s previous columns, go to www.livemint.com/frontiermail