MediSCAPE, a high-speed 3D microscope developed by Columbia Engineers, can see cellular details in living tissue in real time to guide surgeries, speed up tissue analysis, and improve treatments. A Columbia Engineering team has developed technology that could replace traditional biopsies and histology with real-time imaging in the living body. Described in a new article published today (March 28, 2022) in Nature Biomedical EngineeringMediSCAPE is a high-speed 3D microscope capable of capturing images of tissue structures that could help surgeons navigate tumors and their borders without having to remove tissue and wait for pathological results. In many medical procedures, particularly cancer surgery and checkups, it is common for doctors to take a biopsy and cut out small pieces of tissue for a closer look with a microscope. “The way biopsy samples are processed hasn’t changed in 100 years, they are excised, fixed, embedded, sliced, stained with dyes, positioned on a slide and viewed by a pathologist with a simple microscope. Because of this, it can be days before you get any news about your diagnosis after a biopsy,” says Elizabeth Hillman, professor of biomedical engineering and radiology at the[{” attribute=””>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