Columbia University researchers say new high-speed 3D microscope could replace traditional biopsy, with implications for surgical pathology


Columbia University’s MediSCAPE allows surgeons to examine tissue structures in vivo, and a large-scale clinical trial is planned for later this year

Scientists at Columbia University in New York have developed a high-speed 3D microscope for diagnosing cancers and other diseases that they believe could eventually replace traditional biopsy and histology “with a real-time imaging in the living body”.

The technology is designed to allow on the spot tissue analysis. Known as MediSCAPE, the microscope is “capable of capturing images of tissue structures that could guide surgeons to navigate tumors and their boundaries without the need to remove tissue and wait for pathology results”, according to a Columbia University report.

The research team, led by Columbia University professor of biomedical engineering and radiology, Elizabeth Hillman, PhD, described the technology in an article published in Nature Biomedical Engineeringtitled “High-speed light sheet microscopy for the in situ acquisition of volumetric histological images of living tissue”.

“The way biopsy specimens are processed has not changed for 100 years, they are cut, fixed, embedded, sliced, stained with dyes, positioned on a glass slide and viewed by a pathologist using ‘a simple microscope. That’s why it can take days to hear news of your diagnosis after a biopsy,” Hillman said in the Columbia report.

“Our 3D microscope overcomes many of the limitations of previous approaches to enable visualization of cellular structures in living body tissues. This could give a doctor real-time information about the type of tissue they are examining without a long wait,” she added. I News.

Hillman’s team previously used the technology – initially dubbed SCAPE for “Swept Confocally Aligned Planar Excitation” microscopy – to capture 3D images of neurological activity in live samples of worms, fish and flies. In their recent study, the researchers tested the technology with human kidney tissue, the tongue of a human volunteer, and a mouse with pancreatic cancer.

“It was something I didn’t expect – that I could actually look at 3D structures from different angles,” said nephropathologist and co-author of the study Shana M. Coley, MD, Ph.D. (above), Director, Transplant Translational Research and Multiplex Imaging Center at Arkana Laboratories, in the Columbia report. At the time of the Columbia study, Coley was an assistant professor at Columbia University and a renal pathologist at Columbia University Medical Center. “We found many examples where we would not have been able to identify a structure from a 2D section on a histology slide, but in 3D we could clearly see its shape. In renal pathology in particular, where we routinely work with very limited amounts of tissue, the more information we can glean from the sample, the better it is to provide more effective patient care,” she added. . (Photo copyright: Arkana Laboratories.)

How MediSCAPE works

Unlike traditional 3D microscopes that use a laser to scan tiny dots of a tissue sample and then stitch those dots together into a 3D image, the MediSCAPE 3D microscope “illuminates tissue with a sheet of light – a plane formed by a beam laser that is focused in a special way,” I News reported.

The MediSCAPE microscope thus captures 2D slices that are quickly stacked into 3D images at a rate of more than 10 volumes per second, according to I News.

“One of the first tissues we looked at was a fresh mouse kidney, and we were amazed to see beautiful structures that looked very similar to what you get with standard histology,” the systems engineer said. optics and lead author of the study, Kripa Patel, PhD, in the Columbia report. “Most importantly, we didn’t add any dye to the mouse – all we saw was natural fluorescence in the tissue that is usually too faint to see.

“Our microscope is so efficient that we could see these faint signals well,” she continued, “even though we were also imaging entire 3D volumes at speeds fast enough to walk through in real time, scanning different areas of the tissue like if we were holding a flashlight.

A big advantage of the technology, Hillman noted, is the ability to scan living tissue in the body.

“It’s really important to understand if tissues stay healthy and get a good blood supply during surgeries,” she said in the Columbia report. “We also realized that while we don’t need to remove (and kill) tissue to examine it, we can find many other uses for MediSCAPE, even to answer simple questions like ‘what tissue is it from? is it? or to navigate around precious nerves. Both of these applications are really important for robotic and laparoscopic surgeries, where surgeons are more limited in their ability to identify and interact directly with tissue.

Clinical trials and FDA clearance

Early versions of SCAPE microscopes were too large for practical use by surgeons, so postdoctoral researcher Wenxuan Liang, PhD, co-author of the study, helped the team develop a smaller version that would fit would fit into an operating room.

Later this year, the researchers plan to launch a large-scale clinical trial, I News reported. Columbia scientists are hoping to get clearance from the US Food and Drug Administration (FDA) to develop a commercial version of the microscope.

“They will initially seek permission to use it for tumor screening and counseling during operations – a lower, easier class of approval – but eventually they hope to be allowed to use it for diagnosis,” said Liang writes.

Charles Evans, PhD, head of research information at Cancer Research UK, said I News, “Using surgical biopsies to confirm a diagnosis of cancer can be time-consuming and distressing for patients. And ensuring that all cancerous tissue is removed during surgery can be very difficult without help.

He added: “Further work will be needed to translate this technique into a practical device for clinicians and to demonstrate whether it can provide benefits for people with cancer, but we look forward to seeing the next steps.

Will the optical microscope be replaced?

In recent years, research teams from various institutions have developed technologies designed to improve, or even replace, the traditional optical microscope used daily by pathologists around the world.

And digital scanning algorithms for creating whole-slide images (WSI) that can be analyzed by pathologists on computer screens are also growing in popularity.

Such developments could spark a revolution in surgical pathology and could mark the beginning of the end of the era of the optical microscope.

Surgical pathologists should expect to see a steady stream of technologically advanced systems for tissue analysis to be submitted to the FDA for premarket review and clearance for clinical use. The optical microscope may not disappear overnight, but a growing number of companies are actively developing different technologies that they claim can diagnose tissue and digital images of pathology slides with an accuracy comparable to that of a pathologist.

Stephen beale

Related information:

New technology could make biopsies a thing of the past

Cancer care: 3D microscope that could replace tumor biopsies is ‘as revolutionary as ultrasound’

High-speed light sheet microscopy for in situ acquisition of volumetric histological images of living tissue

SCAPE microscopy

UC Davis researchers develop a microscope that uses ultraviolet light for diagnosis, eliminating the need for traditional histology slide preparation

Attention all surgical pathologists: Algorithms for automated primary diagnosis of digital pathology images likely to gain regulatory clearance in the near future

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