New technology could make biopsies a thing of the past
High-speed 3D microscope can see real-time cellular detail in living
tissues to guide surgery, speed up tissue analyses, and improve treatments


Date:
March 28, 2022
Source:
Columbia University School of Engineering and Applied Science
Summary:
Researchers have developed a technology that could replace
conventional biopsies and histology with real-time imaging within
the living body.

MediSCAPE is a high-speed 3D microscope 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.



FULL STORY ==========================================================================
A Columbia Engineering team has developed a technology that could replace conventional biopsies and histology with real-time imaging within
the living body. Described in a new paper published today in Nature
Biomedical Engineering, MediSCAPE is a high-speed 3D microscope 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.


==========================================================================
For many medical procedures, particularly cancer surgery and screening,
it is common for doctors to take a biopsy, cutting out small pieces of
tissue to be able to take a closer look at them with a microscope. "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," says Elizabeth Hillman, professor of biomedical engineering
and radiology at Columbia University and senior author of the study.

Hillman's group dreamed of a bold alternative, wondering whether
they could capture images of the tissue while it is still within the
body. "Such a technology could give a doctor real-time feedback about
what type of tissue they are looking at without the long wait," she
explains. "This instant answer would let them make informed decisions
about how best to cut out a tumor and ensure there is none left behind." Another major benefit of the approach is that cutting tissue out, just
to figure out what it is, is a hard decision for doctors, especially
for precious tissues such as the brain, spinal cord, nerves, the eye,
and areas of the face.

This means that doctors can miss important areas of disease. "Because
we can image the living tissue, without cutting it out, we hope that
MediSCAPE will make those decisions a thing of the past," says Hillman.

Although some microscopes for surgical guidance are already available,
they only give doctors an image of a small, single 2D plane, making
it difficult to quickly survey larger areas of tissue and interpret
results. These microscopes also generally require a fluorescent dye to
be injected into the patient, which takes time and can limit their use
for certain patients.

Over the past decade, Hillman, who is also Herbert and Florence Irving Professor at Columbia's Zuckerman Mind Brain Behavior Institute, has
been developing new kinds of microscopes for neuroscience research
that can capture very fast 3D images of living samples like tiny worms,
fish, and flies to see how neurons throughout their brains and bodies
fire when they move. The team decided to test whether their technology,
termed SCAPE (for Swept Confocally Aligned Planar Excitation microscopy)
could see anything useful in tissues from other parts of the body.



==========================================================================
"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," says Kripa Patel, a recent PhD graduate
from the Hillman lab and lead author of the study. "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, 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." As she "roved around," Patel could even
stitch together the acquired volumes and turn the data into large 3D representations of the tissue that a pathologist could examine as if it
were a full box of histology slides.

"This was something I didn't expect -- that I could actually look at
structures in 3D from different angles," says collaborator Dr. Shana
Coley, a renal pathologist at Columbia University Medical Center who collaborated closely on the study. "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." The team
demonstrated the power of MediSCAPE for a wide range of applications,
from analysis of pancreatic cancer in a mouse, to Coley's interest in
non- destructive, rapid evaluation of human transplant organs such as
kidneys. Coley helped the team get fresh samples from human kidneys to
prove that MediSCAPE could see telltale signs of kidney disease that
matched well to conventional histology images.

The team also realized that by imaging tissues while they are alive
in the body, they could get even more information than from lifeless
excised biopsies.

They found that they could actually visualize blood flow through tissues,
and see the cellular-level effects of ischemia and reperfusion (cutting
off the blood supply to the kidney and then letting it flow back in).



========================================================================== "Understanding whether tissues are staying healthy and getting good
blood supply during surgical procedures is really important," says
Hillman. "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."
A critical final step for the team was to reduce the large format of
the standard SCAPE microscopes in Hillman's lab to something that would
fit into an operating room and could be used by a surgeon in the human
body. Post-doctoral fellow Wenxuan Liang worked with the team to develop
a smaller version of the system with a better form factor, and a sterile imaging cap. PhD candidate Malte Casper helped to acquire the team's
first demonstration of MediSCAPE in a living human, collecting images
of a range of tissues in and around the mouth.

These results included rapidly imaging while a volunteer literally licked
the end of the imaging probe, producing detailed 3D views of the papillae
of the tongue.

Eager to take this technology to the next level with a larger clinical
trial, the team is currently working on commercialization and FDA
approval. Hillman adds, "We are just so amazed to see what MediSCAPE
reveals every time we use it on a new tissue, and especially that we
barely ever even needed to add dyes or stains to see structures that pathologists can recognize." Hillman and her team hopes that MediSCAPE
will make standard histology a thing of the past, putting the power of real-time histology and decision making into the surgeon's hands.

Funding for this work was provided by the Columbia-Coulter Translational Research Partnership and the Coulter Foundation Early Career programme
to E.M.C.H; the National Institutes of Health BRAIN initiative grants U01NS09429, UF1NS108213 to E.M.C.H and U19NS104649 to Costa; NCI grant U01CA236554 to E.M.C.H. and Brenner; the National Science Foundation
NSF-GRFP DGE -- 1644869 to K.B.P., IGERT 0801530 to V.V. and CAREER CBET-0954796 to E.M.C.H.; the Simons Foundation Collaboration on
the Global Brain 542951 to E.M.C.H.; the Department of Defense MURI W911NF-12-1-0594 to E.M.C.H.; and the Kavli Institute for Brain Science
to E.M.C.H.

Intellectual property related to SCAPE microscopy is held by
Columbia University and is licensed to Leica Microsystems for certain applications. The authors of this study could benefit financially from commercial development of this technology.


========================================================================== Story Source: Materials provided by Columbia_University_School_of_Engineering_and_Applied Science. Original
written by Holly Evarts. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Kripa B. Patel, Wenxuan Liang, Malte J. Casper, Venkatakaushik
Voleti,
Wenze Li, Alexis J. Yagielski, Hanzhi T. Zhao, Citlali Perez
Campos, Grace Sooyeon Lee, Joyce M. Liu, Elizabeth Philipone,
Angela J. Yoon, Kenneth P. Olive, Shana M. Coley, Elizabeth
M. C. Hillman. High-speed light-sheet microscopy for the
in-situ acquisition of volumetric histological images of
living tissue. Nature Biomedical Engineering, 2022; DOI:
10.1038/s41551-022-00849-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220328112123.htm

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