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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Columbia University Researchers Say New High-Speed 3D Microscope Could Replace Traditional Biopsy, with Implications for Surgical Pathology

Columbia University’s MediSCAPE enables 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 City have developed a high-speed 3D microscope for diagnosis of cancers and other diseases that they say could eventually replace traditional biopsy and histology “with real-time imaging within the living body.”

The technology is designed to enable in situ 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 needing to remove tissues and wait for pathology results,” according to a Columbia University news story.

The research team, led by Columbia University professor of biomedical engineering and radiology Elizabeth Hillman, PhD, described the technology in a paper published in Nature Biomedical Engineering, titled, “High-Speed Light-Sheet Microscopy for the In-Situ Acquisition of Volumetric Histological Images of Living Tissue.”

“The way that biopsy samples are processed hasn’t changed in 100 years, they are cut out, fixed, embedded, sliced, stained with dyes, positioned on a glass slide, and viewed by a pathologist using a simple microscope. This is why it can take days to hear news back about your diagnosis after a biopsy,” said Hillman in the Columbia news story.

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

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

Shana M. Coley, MD, PhD
“This was something I didn’t expect—that I could actually look at structures in 3D from different angles,” said nephropathologist and study co-author Shana M. Coley, MD, PhD (above), Director, Transplant Translational Research and Multiplex Imaging Center at Arkana Laboratories, in the Columbia news story. At the time of the Columbia study, Coley was an assistant professor at Columbia University and a renal pathologist at the 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 derive from the sample, the better for delivering more effective patient care,” she added. (Photo copyright: Arkana Laboratories.)

How MediSCAPE Works

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

The MediSCAPE microscope thus captures 2D slices which are rapidly 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 fresh mouse kidney, and we were stunned to see gorgeous structures that looked a lot like what you get with standard histology,” said optical systems engineer and the study’s lead author, Kripa Patel, PhD, in the Columbia news story. “Most importantly, we didn’t add any dyes to the mouse—everything we saw was natural fluorescence in the tissue that is usually too weak to see.

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

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

“Understanding whether tissues are staying healthy and getting good blood supply during surgical procedures is really important,” she said in the Columbia news story. “We also realized that if we don’t have to remove (and kill) tissues to look at them, we can find many more uses for MediSCAPE, even to answer simple questions such as ‘what tissue is this?’ 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 with tissues directly.”

Clinical Trials and FDA Clearance

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

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

“They will initially seek permission to use it for tumor screening and guidance during operations—a lower and easier class of approval—but ultimately, they hope to be allowed to use it for diagnosis,” Liang wrote.

Charles Evans, PhD, research information manager at Cancer Research UK, told I News, “Using surgical biopsies to confirm a cancer diagnosis can be time-consuming and distressing for patients. And ensuring all the cancerous tissue is removed during surgery can be very challenging unaided.”

He added, “more work will be needed to apply this technique in a device that’s practical for clinicians and to demonstrate whether it can bring benefits for people with cancer, but we look forward to seeing the next steps.” 

Will the Light Microscope be Replaced?

In recent years, research teams at various institutions have been developing technologies designed to enhance or even replace the traditional light microscope used daily by anatomic pathologists across the globe.

And digital scanning algorithms for creating whole-slide images (WSIs) that can be analyzed by pathologists on computer screens are gaining in popularity as well.

Such developments may spark a revolution in surgical pathology and could signal the beginning of the end of the light microscope era.

Surgical pathologists should expect to see a steady flow of technologically advanced systems for tissue analysis to be submitted to the FDA for pre-market review and clearance for use in clinical settings. The light microscope may not disappear overnight, but there are a growing number of companies actively developing different technologies they believe can diagnose either or both tissue and digital images of pathology slides with accuracy comparable to 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 the In-Situ Acquisition of Volumetric Histological Images of Living Tissue

SCAPE Microscopy

UC Davis Researchers Develop Microscope That Uses Ultraviolet Light for Diagnosis, Eliminates 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 Near Future