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Capitalizing on Opportunities in Medical Imaging
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Capitalizing on Opportunities in Medical Imaging



Researchers in the Biomedical Imaging Laboratory are developing innovative technologies across disease areas.

It’s been a banner year for David Wilson, the Robert J. Herbold Professor of Biomedical Engineering at Case Western Reserve University, and his colleagues in the Biomedical Imaging Laboratory. So far in 2018, Wilson has obtained five grants totaling more than $5 million for his work on computational biomedical imaging and microscopy.

"My success hinges on the great ability at Case to work with collaborators. So many different opportunities present themselves just by walking the halls here," says Wilson. "There are some biomedical engineering departments that are relatively isolated from medical schools and hospitals. Our proximity to the School of Medicine and world-renowned hospitals makes us unique."

Partnering with clinicians and biomedical researchers, Wilson and his team have created computational tools for image segmentation, registration and quantitative analysis. They also conduct work in 3-D visualization, machine learning and imaging physics. One of their greatest successes is development of a cryo-imaging system that serially sections and images the block face of a frozen specimen, providing ultra-high resolution RGB and fluorescence volumes. The system, which is now being commercialized by the startup company BioInVision, allows preclinical researchers to view unparalleled levels of detail – down to an individual cell.

This year’s grants will allow the Biomedical Imaging Laboratory to advance projects in three different disease areas – cardiovascular, cancer and ophthalmological conditions – as well as a new 3-D microscopy technique. "Some bioengineers focus on one disease. I’ve opted to focus on the technology – the software and instrumentation side," says Wilson. "As a result, I’m not married to one application versus another. Instead, I look for opportunities."

Opportunities certainly abound for the Biomedical Imaging Laboratory.

Developments in Cardiovascular Imaging

Wilson is the principal investigator on two new grants in the cardiovascular field. The first, an R01 award from the National Institutes of Health (NIH), focuses on computer-assisted coronary artery stent intervention planning. The team utilizes optical coherence tomography (OCT) during catheterization. "You insert the catheter, with the imaging device on the tip, through the vasculature to obtain microscopic images inside the coronary arteries," says Wilson. "There is no way you can do this from outside the body with this kind of resolution."

Wilson and students in his lab have developed methods for identifying the types of atherosclerotic plaque in blood vessels using deep learning techniques. "Recently, we have focused on calcified plaque because cardiologists cannot readily apply stents if there is a lot of calcium," says Wilson. The technology created by the Biomedical Imaging Laboratory will allow clinicians to locate calcifications and decide where to place stents or adopt a plaque modification approach.

"With this grant, we’re going to be doing a lot of biomechanical experiments and imaging," says Wilson. "We have a great team aimed at trying to understand how best to deploy stents in the presence of calcifications." Among those working with Wilson is Hiram Bezerra, associate professor of medicine in the Case Western Reserve University School of Medicine.

Wilson’s second award related to cardiovascular research is an NIH Small Business Innovation Research (SBIR) grant with BioInVision, where he serves as chief technology officer. The team will use computed tomography (CT) perfusion imaging, parameter estimation and deep learning to examine blood flow in the myocardium, a procedure that has traditionally been done with positron emission tomography (PET) or single proton emission computed technology (SPECT) nuclear imaging.

There are several advantages to using CT, says Wilson. It’s more readily available and allows clinicians to do CT angiography to examine the blood vessels. "By adding our CT technology, clinicians can look at the blood vessels to see if there’s stenosis and also see if there is blood flowing into a specific region of tissue," he says.

Opportunities in Ophthalmology

Two years ago, Wilson moved into the ophthalmology space. This year, he was awarded at R21 grant from the NIH to analyze cornea endothelial images using machine learning and determine if the technology can be used to help predict keratoplasty failure. "Corneas are one of the most common tissue implants. If they fail, it’s a great expense and increases the chance of blindness in patients," says Wilson. "So the idea is to look at these images and use machine learning to better predict which corneas are at risk and need greater care."

On this project, Wilson is teaming with the Cornea Image Analysis Reading Center (CIARC) at Case Western Reserve University and University Hospitals Cleveland Medical Center. "The CIARC is the premier center in the world for analyzing these images, so it’s a perfect match," he says.

Wilson has a second ophthalmology project with Faruk Orge, a pediatric ophthalmologist at University Hospitals, as well as assistant professor of pediatrics and associate professor of ophthalmology at the Case Western Reserve University School of Medicine. Using a 3D microscopic ultrasound system developed by Orge to image the front part of the eye, they will study the ciliary body (responsible for most of the eye’s fluid production) and the drainage system. "This is a great new way to study glaucoma, and we think it could actually lead to image-guided treatment of glaucoma," says Wilson. This project was recently funded by the Case-Coulter Translational Research Partnership (CCTRP).

Studying Metastatic Cancer

A fourth award, related to the patented cryo-imaging system developed by the Biomedical Imaging Laboratory, offers potential in the oncology field. The NIH SBIR Phase II grant with BioInVision will focus on a cancer imaging and therapy analysis platform.

With cryo-imaging, preclinical researchers can take a tissue sample – even an entire mouse – and freeze it in liquid nitrogen. Then, the sample is placed under a cryo-microtome, where there is repeated sectioning and imaging of the block face of tissue. With extremely thin sectioning (thinner than a human hair) researchers can obtain very high resolution imaging of large tissues. "We can do color imaging as well as fluorescent imaging," says Wilson. "So if someone has labeled stem cells or cancer cells with a fluorescent marker, then we can image all the cells." Wilson’s team has created images where they’ve counted more than 500,000 cells in a mouse.

The new SBIR Phase II award will use cryo-imaging to study metastatic cancer. "We are developing software for better analysis of cancer therapeutics and imaging," says Wilson. "And we are developing new applications for things like immunotherapy in mice."

Advances in Microscopy

The final project has significant potential. The idea is to create a new technique for 3D microscopy with ultraviolet surface excitation (3D-MUSE).

A few months ago, Wilson saw Richard Levenson, a pathologist at the UC Davis Medical Center, give a talk to the Case Western Reserve Biomedical Engineering Department on the MUSE microscope he helped create. "When he spoke, the lightbulbs went off in my head and we teamed up," says Wilson. "With 3D MUSE, we are combining our cryo-sectioning machine with his new microscopy technique to get cellular resolution and sensitivity that we really didn’t have before. We are building a new system that can easily create terabyte histology of samples."

No matter the project, Wilson says success is all about the collaborators – and timing. "Some of these things are serendipitous," he admits. "You just talk to people, and there’s the opportunity for a new invention or project." Wilson hopes more new ideas are on the horizon for the Biomedical Imaging Laboratory.