The Case Center for Imaging Research (CCIR) is housed in the Department of Radiology at Case Western Reserve University (CWRU) and University Hospitals – Cleveland Medical Center (UHCMC) in Cleveland, Ohio. The center specializes in using sophisticated imaging approaches to conduct medical and scientific research.
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The CCIR's distinct location inside the University Hospitals of Cleveland facilitates a collaborative environment that gathers researchers across multiple domains, including imaging, mathematics, chemistry, physics, biomedical engineering, and radiology, to contribute to medical science.
The Imaging Research Core is the CCIR’s functional arm at CWRU. Its central aim is to offer new imaging approaches to researchers across Northeast Ohio.
As a tenured professor in the CCIR, Professor Chris Flask uses magnetic resonance imaging (MRI) to investigate disease mechanisms, decipher results, determine the optimal approach, and, chiefly, identify each imaging method’s constraints. His research interests include the development of novel, rapid, and reproducible quantitative MRI approaches, including magnetic resonance fingerprinting techniques, and their use for various genetic conditions like cystic fibrosis, autosomal recessive and dominant polycystic kidney disease, and sickle cell disease.
In his research, Professor Flask works closely with radiologists and clinicians in the hospital, allowing this research to help numerous patients whose diagnoses and treatments will become more precise, comfortable, safer, and less expensive due to these advancements in imaging.
“We have experts from multiple fields bringing all their knowledge together to determine how to approach these medical problems from an imaging perspective, and answer questions in unique and profound ways,” said Prof. Flask. “Collaboration has become the gold standard in biomedical research because you can’t answer these questions alone. We’re looking at how we can work together and apply imaging techniques with the goal of helping patients.”
Using advanced technology from Bruker, Professor Flask and his team are reaching new horizons in MRI and imaging technology to develop novel approaches to utilizing preclinical animal studies and making their findings applicable to clinical settings.
Where the CCIR began
In 1999, the National Cancer Institute singled out medical imaging, particularly cellular and molecular imaging, as a key opportunity for treating cancer. With its robust imaging program in the School of Medicine and the Case School of Engineering, CWRU faculty members Jeffrey Duerk, PhD, Jonathan Lewin, MD, and David Wilson, PhD, imagined the development of the CCIR. The center’s construction started in 2001 following a $12 million commitment from the university for faculty startup, renovations, staff, and pilot funding.
Professor Flask, who was still a graduate student and conducting his own research, was given a principal role in coordinating the design and construction of the upcoming facility, which was finally launched in 2005.
“That’s also when I started working closely with Bruker on site planning enabling MRI experiments tailored to CCIR’s specific needs,” he notes. The relationships Professor Flask built in those early years became the basis of the CCIR’s collaborative nature, which continues today.
“Preclinical research was really exploding at the time,” he says. “My job was to help figure out how to get the lab built and make it operational. It was a blessing in many ways because I’ve sat down with almost every person at CWRU and University Hospitals – Cleveland Medical Center to ask for help, and that enabled me to establish relationships. Those interactions were the very beginning of the highly collaborative environment that we’ve built here in the CCIR, so we were able to hit the ground running and grow rapidly when the center opened.”
Uniting preclinical and clinical research
From the beginning, the CCIR team has believed that preclinical and clinical investigators from different disciplines working together can lead to a more holistic approach to solving complicated medical challenges.
Merging preclinical and clinical research speeds up the translation of scientific discoveries from the lab to real-world settings, enabling novel opportunities for enhancing patient care and medical advancements.
“We had a unique opportunity because the CCIR is part of the Department of Radiology at CWRU and University Hospitals,” Professor Flask says. “It’s not typical. Our approach is about bringing basic scientists and clinicians together and using imaging as a scientific hub. The people and the collaborations make the difference.”
The CCIR provides access to imaging technology and serves as a gateway to imaging approaches designed in-house by faculty, and opportunities to generate new imaging approaches that meet researchers' needs.
Current imaging use cases comprise imaging for detecting and visualizing disease, drug delivery, biodistribution, and pharmacokinetic modeling, gene expression imaging, imaging of cancer and early assessments of cancer therapies, cardiovascular imaging, metabolism, nanotechnology development, imaging physics, and hardware and software engineering.
“The CCIR really draws all of these diverse researchers to the table to enable a broader discussion on biomedical imaging applications,” Professor Flask explained. “We have 30-40 researchers here at any given moment, as well as a critical mass of expertise across multiple disciplines. Research is not for the faint of heart. Your grant funding is based on building a good team, and it requires the ability to dialogue. It comes down to people with the skills, but also the willingness. We want people who want to work together – and Bruker as a partner also fits that profile.”
Professor Flask and his team use lessons from preclinical studies carried out on animal models with Bruker tools to investigate disease mechanisms, treatments, and interventions. This can then help design clinical trials by providing fundamental information about how a certain treatment or method may work. Comparing preclinical data with pathological data, CCIR researchers can improve their understanding of the translational relevance of preclinical results to human diseases.
“I always need validation of what our imaging data is showing us, so we’re comparing our preclinical quantitative MRI results with what we’re seeing in pathology,” Professor Flask said. “We’re constantly asking researchers if they really know what they are measuring. The advantage of combining pre-clinical and clinical MRI methods is having the confidence to know exactly what the data is showing us by scanning both animals and patients and being able to compare those results. It’s an iterative process that has proven to be very successful.”
Accelerating novel treatments for rare diseases
Professor Flask’s work includes some of the most complex conditions in contemporary medicine, such as cystic fibrosis and polycystic kidney disease.1,2,3,4,5 Of particular note, his recent work with Dr. Katherine Dell, MD, a pediatric nephrologist at CWRU and the Cleveland Clinic, has shown promise in delivering a basis for the application of quantitative MRI methods to stage and monitor progression in children and young adults with autosomal recessive polycystic kidney disease (ARPKD).
The team is especially excited as ARPKD is a genetic condition linked to considerable mortality and morbidity in babies and young children, and there are currently no disease-specific treatment options available for patients.
“It’s one of my proudest moments, because our imaging work will likely directly enable some of the first clinical trials for kids with ARPKD,” Professor Flask explains. “It’s a disease that not many people know about because it’s rare, but it’s also quite lethal. Approximately one third of the kids with ARPKD don’t make it out of the neonate phase. Of the kids that do survive, another 50 percent have significant and sometimes life-threatening clinical issues by 15 years of age.”
It is also an example of Professor Flask and the CCIR team’s strong motivation to make a positive societal impact. This kind of collaborative work has significant potential for creating meaningful change to enhance patients' lives.
“My personal experience as a father of a child with a chronic disease, who spent considerable time in a hospital undergoing tests and treatment, has profoundly impacted my research,” he explains. “It’s beyond just diagnosing a child with a disease. It’s determining the status of the disease, how well the child is responding to therapy and the physiological effects. We want to make medicine better, more rigorous, and more objective to help patients.”
Working with Bruker
The CCIR has both the 7.0 T and 9.4 T Bruker BioSpec preclinical MRI tools, which were selected to aid the team with their most complex use cases. Developed for the growing market of preclinical imaging and molecular MRI, the innovative modular concept of the Bruker BioSpec facilitates small animal MRI applications in life science, biomedical, and preclinical studies.
“Bruker provides us with state-of-the-art instrumentation. In my mind, there is no real competitor,” Professor Flask explains. “It’s a very stable system, which is important because we are conducting some very challenging MRI experiments. We push the preclinical scanners very hard as our goal is to have imaging data on a mouse model in 10 seconds, not every hour or two, so we can see the dynamics of the physiology and organ-based function. Most of the other preclinical MRI systems on the market cannot meet these technical demands.”
Next steps
Building on these accomplishments, Professor Flask and his colleagues intend to expand the collaborative environment of CCIR to encompass multimodal imaging approaches, such as positron emission tomography (PET) and PET-MRI, which can lead to even more comprehensive research. Part of this plan includes adding PET to the center’s human MRI system, which would enable large animal and human studies to be conducted.
“We have enough of a critical mass of people to show that this preclinical and clinical partnership really does work,” Professor Flask said. “We want more people to understand how it all fits, so the integration becomes even bigger. We’re bringing the same approach to multimodal imaging because these techniques are very complementary and have much more potential. For example, you can take some of our quantitative MRI methods and MR fingerprinting methods that provide information on tissue composition and function, and then couple it with PET imaging capabilities to provide complementary mechanistic and molecular information. That’s where our program is headed.”
By integrating data from different imaging approaches, investigators and professionals can build a more complete picture, improving their ability to diagnose, analyze, and interpret complex phenomena. That expansion includes further collaborative opportunities, alongside research on other conditions.
“By taking the successful model that we’ve already established and expanding into a multimodal platform, we’re adding knowledge as well as bringing more people on board. It also enables us to tackle other diseases like Alzheimer’s with neurotransmitter assessments, brain architecture and connectivity. It’s a whole new area with great potential to help patients that I’m excited about seeing grow significantly in the next few years.”
References and further reading
- Dasenbrook, E.C. et al. (2013). Normalized T1 magnetic resonance imaging for assessment of regional lung function in adult cystic fibrosis patients - a Cross-Sectional study, PLoS ONE, 8(9), p. e73286. https://doi.org/10.1371/journal.pone.0073286.
- Donnola, S.B. et al. (2015). Preliminary comparison of normalized T1 and non-contrast perfusion MRI assessments of regional lung disease in cystic fibrosis patients, Journal of Cystic Fibrosis, 16(2), pp. 283–290. https://doi.org/10.1016/j.jcf.2015.11.009.
- McBennett, K. et al. (2021). Magnetic resonance imaging of cystic fibrosis: Multi-organ imaging in the age of CFTR modulator therapies, Journal of Cystic Fibrosis, 21(2), pp. e148–e157. https://doi.org/10.1016/j.jcf.2021.11.006.
- MacAskill, C.J. et al. (2020). Multi-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and initial patient results, Pediatric Research, 89(1), pp. 157–162. https://doi.org/10.1038/s41390-020-0883-9.
- MacAskill, C.J. et al. (2021). Rapid B1-Insensitive MR fingerprinting for quantitative kidney imaging, Radiology, 300(2), pp. 380–387. https://doi.org/10.1148/radiol.2021202302.
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