Malignant brain tumours have some of the highest death rates of any cancer type, and during surgery, doctors still rely on slow methods to try to find the borders between healthy and diseased tissue. A new kind of microscope could one day enable the same analysis in real time in the operating room.
“As you can imagine with the brain, doctors need to minimize the amount of tissue they remove because of the impact on the patient,” said Parsin Haji Reza, principal investigator and professor of systems design engineering at the University of Waterloo, in a press release.
At the same time, any missed cancer tissue leads to lower survival rates and worse outcomes for patients. That makes it especially important to be able to visualize the fine line that separates the tumour from healthy brain tissue.
During surgery, doctors are guided by pre-operative medical imaging like CT and MRI, but these methods only give the rough boundaries. Microscopic analysis is still needed, and the main way of doing this is to cut out a piece of tissue, and make frozen slices for staining with dyes to look at subcellular features. This only takes about 20 minutes to do, but the results are tricky to interpret because the slices can be distorted.
Until now, the final and most accurate way of knowing whether the tumour has been fully removed has been to send tissue samples for a laboratory test after the operation, because it takes up to two weeks to complete. The tissue samples are formalin-fixed and embedded in paraffin to get thin slices without distorting their shape before staining and analysis.
Now a research team from the University of Waterloo and the University of Alberta has developed a protocol to use a photoacoustic microscope to do this same analysis without staining. So far, the process has only been used on tissue slices, but the process is dye-free, contact-free, and nearly instantaneous. Their study was published in Scientific Reports.
The device is called a photoacoustic remote sensing (PARS) microscope. The microscope sends multi-coloured laser pulses into tissue. Different parts of the cell absorb the light differently, and as this happens the tissue heats up and expands, producing sound waves that are specific to properties of the tissue. Reading those waves with a second laser can show all the same details as traditional staining, but without the dyes. The resulting images allow healthy and cancerous tissue to be distinguished.
In the study, the tumour boundaries found using PARS on unstained tissue slices are a close match to the ones found using standard post-operative tissue staining. This is the first step in creating a way to image the boundaries in situ, without having to cut out a sample.
The microscope is capable of visualizing a greater than 1 mm tissue thickness without slicing. In future, the team hopes to refine the technology such that brain tissue won’t need to be removed to be analyzed.
Notably, compared to other photoacoustic technologies, PARS also doesn’t require any part of the microscope to come into direct contact with tissue to take a measurement. For brain surgery, this is an important practical feature that minimizes the chances of infection.
The team founded a spin-off company called illumiSonics to commercialize the technology, which they aim to put into operating rooms to analyze tissue samples by the end of the year. The ultimate goal is to establish the capability to image the uncut brain during surgery within the next three to five years. This will give the kind of immediate and microscopic guidance that will allow precise excision of tumour tissue, leaving healthy tissue intact.
Surgeons need every advantage they can get during cancer surgeries, and this real-time information has the potential to help more patients achieve remission.