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Indiana CTSI-supported IU-Notre Dame Collaboration To Support New Imaging Service

Nina Welding • DATE: September 11, 2014

As imaging technology grows more sophisticated, scientists are increasingly able to pull back the curtain on processes which once remained hidden from the eye.

But as technology increases the ability to gather visual data on the body's "microenvironment," the ability to process that information — to understand what exactly you're seeing — doesn't always keep pace. To address this gap, Indiana University School of Medicine scientists have teamed up with computer scientists from the University of Notre Dame — with support from the Indiana Clinical and Translational Sciences Institute — to grapple with the results of this "Big Data."

Nadia Carlesso, M.D.,  associate professor in the Departments of Pediatrics and of Medical and Molecular Genetics at the IU School of Medicine, is the lead scientist on new intravital fluorescent microscopy (IVFM) methods to observe the effects of cancer — and cancer treatment — on the function of blood vessels in the bone marrow. Her team started out applying IVFM to her lab's primary research interest — conditions in the bone that give rise to leukemia — or, more specifically, to the role bone marrow endothelial cells play in the regulation of blood cell regeneration after injury.

The group is already offering the ability to provide similar analysis to other investigators across the IU School of Medicine as a “mini-core,” and continue to grow and develop the service. The collaboration with Notre Dame will take the project even further through creation of more general quantitative analytical and statistical tool to analyze large data-sets of 3D and 4D images.

“We’ve got a very reliable way to image the vasculature and record the flow of blood within the bone marrow capillaries of the calvarium,” said Dr. Carlesso, referring to the skull bones, which are pulled back in mouse models after sedation in order to allow the microscope to record blood flow in vivo. “Now our challenge is how to develop analytic tools that can really make sense of resulting large data sets.”

Her team’s work is supported in part by IU Center for Biological Microscopy (ICBM), whose powerful multi-photon microscope allows investigators to witness processes that cannot be viewed with less powerful, conventional microscopy. The use of injectable dyes and transgenic mice whose hematopoietic cells grow green allow the team to clearly see the complicated effect of disease on the vascular network. Interpretation of the visual data is the hard part.

Danny Z. Chen
Danny Z. Chen
Dr. Carlesso’s main collaborator on this “interpretation” is Danny Z. Chen, professor of computer science and engineering at Notre Dame. The director of the ICBM is Bruce Molitoris, M.D., professor of medicine at the IU School of Medicine. The scientific director of the center is Kenneth Dunn, professor of medicine and of biochemistry molecular biochemistry at the school.

“There is a lot of specialized software on the market, but it isn’t useful to us because it’s all been developed to look at the physiologically normal images,” Dr. Carlesso said. “When you start to look at disease conditions — transplantation, irradiation, chemotherapy, leukemia, inflammation — then the image becomes more complex and more difficult to define. The blood vessels relax and get damaged and a lot of liquid gets into the tissue. You need to develop new analytical tools so you're not getting [image] artifacts. Once you’re able to define what is real versus what is not, then you can quantitatively measure the size of the veins; the number of blood vessels, capillaries, or branch points; the average length of vessels per segment; the size of the segments — whatever you need for your experiment.”

The collaboration with Notre Dame received support from the Indiana CTSI after Dr. Carlesso sought assistance from the Indiana CTSI Project Development Team Program — specialized teams of experts that provide advice and support on clinical and translational research projects. Earlier this year, the project received a two-year $20,000 grant to fund a doctoral student devoted to the project at Notre Dame as well as the cost of transgenic mice and travel funds.
“We are really proud of the Indiana CTSI grant,” Dr. Carlesso said. “It’s been wonderful to be able to collaborate with Dr. Chen and his team on this project. We meet a few times a year, plus we Skype and email all the time. It’s really been very valuable.”

Ultimately, Dr. Carlesso aims to seek greater external funding for the project. She also aims to turn the IVFM into a full-fledged service core — a goal also supported by the Indiana CTSI through the Kelley School of Business-Indiana CTSI ATP Business Management Assistance Program. The program, which recently completed its sixth year, teams MBA students from the IU Kelley School of Business with facilities affiliated with the Indiana CTSI to provide business development expertise and recommendations.

On Aug. 19, Dr. Carlesso, Dr. Dunn, and several other colleagues heard the results of this analysis from these business students, who spent a total of over 100 hours analyzing the IVFM processes to provide recommendations on improving efficiency, service marketing and potential pricing structures. Hopefully, she said, the group will soon be able to offer its services not only to investigators at IU, but also across Purdue and Notre Dame.

"The possibilities are really great," she said. "This is a complex technology that no other institutions are providing as a service to the community of researchers because of its challenges and costs. We are very lucky to have the support of our institution in this endeavor."

Carlesso added that until recently this technology was only accessible to a handful of research groups in the country.

"Seeing is believing," she added. "There are now things that we would never be able to visualize, discover, or prove without this technology. It's cutting-edge and it can increase the impact of our researcher’s publications and grant applications; but most of all it can lead to new insights on the cell-cell interactions in the tumor microenvironment and allowing for drug screening toward the discovery of more effective therapies.”

Story by Kevin Fryling
Indiana CTSI Newsletter
September 9, 2014