Bioimaging funding stimulates harmonized research

Fulton Schools faculty members receive support from Chan Zuckerberg Initiative for multidisciplinary research

August 13, 2021

A portmanteau of science and dialogue, Scialog supports research and multidisciplinary collaboration allowing researchers to address scientific challenges of global significance. For three Arizona State University researchers, selection as grantees for Scialog: Advancing BioImaging will give them a unique opportunity to explore the next generation of imaging technologies in a three-year initiative designed to spark creativity and generate ideas for novel research projects.

Benjamin Bartelle, assistant biomedical engineering professor, and Barbara Smith, associate biomedical engineering professor, both in the Ira A. Fulton Schools of Engineering at ASU, and Douglas Shepherd, an assistant physics professor in The College of Liberal Arts and Sciences, were each selected to participate on one of 10 research teams bringing together physicists, biologists, bioengineers and medical imaging specialists to develop solutions in advanced bioimaging. Image courtesy of Pixabay Download Full Image

Each researcher will receive $50,000 in funding to support their team’s project. The Research Corporation for Science Advancement, Chan Zuckerberg Initiative, or CZI, and the Frederick Gardner Cottrell Foundation are funding a combined total of $1.15 million to support 23 awards across 10 research teams in this inaugural year.

“Imaging technologies play a critical role in CZI’s mission to support the science and technology that will make it possible to cure, prevent or manage all disease by the end of the century,” said Stephani Otte, science program officer for imaging at CZI. “We hope these teams of early-career researchers will advance the imaging field’s ability to observe and analyze biological processes and help build a much deeper mechanistic understanding of biological systems, identify potential points of intervention in disease and inform directive treatments.”

Converging to decode data

man's portrait

Benjamin Bartelle

The first virtual meeting of the Scialog: Advanced BioImaging series occurred in May, and it’s where Bartelle and collaborators Lu Wei of the California Institute of Technology and Ulugbek Kamilov of Washington University in St. Louis began discussions for their project, “Enabling Noninvasive Lipid Profiling with Intermodal Deep Learning.”

Lipids are a part of every cell and embedded in every tissue in the body. Lipid biomarkers can be found in everything from blood samples to tumors, but in most cases, it is unknown if they are the cause or the product of a disease.

The team will use magnetic resonance spectroscopy and Raman imaging, techniques that generate images with both spectral and spatial information, to detect lipids. They will use the Raman imaging, which is highly sensitive, to decode MR imaging, which can be used clinically, on the same field of view using an artificial intelligence algorithm called "deep learning.”

Bartelle says that the goal of his lab is to create new tools to resolve and manipulate neuroimmune signaling.

“Lipid signaling is one well-known form of inflammatory signaling that we can currently detect only by drawing blood and measuring from plasma,” Bartelle said. “I don’t just say ‘inflammatory signaling’ because our best understanding of that right now is that there are dozens of different kinds of inflammation that can’t be treated the same way.”

Circulating lipids like triglycerides can indicate inflammation or heart disease; but if diseased tissue is on the other side of the blood-brain barrier, it may be difficult to detect. A patient could also have some focal inflammatory signaling that a drop of blood would not locate.

This is where MRI comes into the picture.

“We can see almost everywhere in a human patient, and sometimes you can even pick up inflammation by seeing edema,” Bartelle said. “That’s a dead giveaway for something like a stroke, but that doesn’t give you any specifics on what is happening. You need something molecularly specific. It turns out MRI might be good for that, too.”

MRI is based on chemistry method nuclear magnetic resonance, which allows for information about atomic nuclei to be read out as a spectrum of molecular information. Combining the imaging of MRI with the molecular information from nuclear magnetic resonance is called magnetic resonance spectroscopic imaging, or MRSI.

“I was talking with Lu Wei about how her method, Raman spectroscopy, is actually really great at identifying all kinds of individual molecules from tissue, as long as you have a slice in a dish in front of your Raman microscope,” Bartelle said. “We wondered if there was a way to use Raman data to ‘decode’ MRSI data. Dr. Kamilov has a lot of experience building such decoders, so we approached him about working together.”

The three researchers know enough about each other’s fields to harmonize their approaches while lending expertise in their respective specialties. Wei and Bartelle will collect MRSI and Raman data and translate the information to assist Kamilov in the decoding process.

Bartelle says that if they achieve their goal, they will have a computational tool that can take MRSI data and translate it into individual chemical species using an algorithm trained on Raman data.

“The end result would be something you could use on a patient to diagnose what kind of inflammation is going on, where it is and how best to treat it,” Bartelle said. “Think of it as a machine learning tool that can read things from MRSI that no human could. This could become a critical tool for determining a course of treatment for any brain disorder from migraine to stroke to neurodegeneration. We’ve never been able to see these things before so it’s hard to say just what will be the ultimate application.”

The innovative thinking and fusion of ideas and expertise are why Scialog convenes scientists to explore cutting-edge projects.

Two imaging systems, one novel solution

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Barbara Smith

Barbara Smith’s Scialog: Advancing BioImaging award is for a project named “Microendoscopy-Guided Diagnosis and Treatment of Early-Stage Ovarian Cancer.” It is a collaboration with Bryan Spring of Northeastern University and will draw on her research, which uses microendoscopy to diagnose and treat early-stage cancer.

Smith and Spring are currently developing independent microendoscopy systems. Their project will enable the integration of two imaging techniques to investigate early-stage ovarian cancer as it develops in the fallopian tubes.

“This vision to develop practical screening methods aims to save lives and reduce health care costs by mitigating the occurrence of advanced-stage disease,” Smith said. “Through this work, we aim to develop a clinically relevant imaging tool capable of scanning the entire fallopian tube to enable routine screenings for early-stage ovarian cancer detection.”

The project could result in an innovative approach to screen a large-volume area at a high resolution in the fallopian tubes.

“This enables, for the first time, synthesis of comprehensive, high-resolution volumetric renders of the fallopian tube to precisely locate neoplasms for immediate image-guided ablation, biopsy collection and follow-up surveillance,” Smith said. “It would be transformative for catching and treating premalignant lesions.”

The team’s proposed advance in bioimaging is driven by a critical need and represents a bold step forward that will enable clinical diagnostics for early-stage ovarian cancer.

“This collaboration formed by the Scialog grant will join labs that are distinctly suited to work together towards a critical scientific advance that has not otherwise been achieved,” says Smith.

New and better tools will always be a need in health care systems, allowing for better diagnosis and information on how to care for patients. The funding of these projects has the potential to fill gaps in modern medicine.

“With more awards than any Scialog to date, this initiative is off to a great start,” said Daniel Linzer, president and CEO of RCSA. “We’re grateful for funding partnerships that enable us to seed even more projects with the potential to transform an area of science.”

Erik Wirtanen

Web content comm administrator, Ira A. Fulton Schools of Engineering


Biology in motion: ASU professor awarded 2 Scialog Awards to fund research on advanced biological imaging

August 20, 2021

Douglas Shepherd, an assistant professor in Arizona State University’s Department of Physics, was recently awarded two Scialog Advanced Bioimaging awards that will fund two research projects using optics to visualize and quantify molecular biology in challenging settings.

Shepherd is among 10 multidisciplinary research teams selected as part of the first year of Scialog: Advancing BioImaging, a three-year initiative supported by the Research Corporation for Science Advancement, the Chan Zuckerberg Initiative and the Frederick Gardner Cottrell Foundation, that aims to accelerate the development of the next generation of imaging technologies. Douglas Shepherd, an assistant professor in Arizona State University’s Department of Physics, was recently awarded two Scialog Advanced Bioimaging awards that will fund two research projects using optics to visualize and quantify molecular biology in challenging settings. Download Full Image

“We are incredibly proud of Dr. Shepherd for being selected as a recipient of two Scialog Advanced Bioimaging awards,” said Patricia Rankin, chair of the Department of Physics in The College of Liberal Arts and Sciences. 

“The high impact work of the Shepherd Lab on developing and applying new bioimaging tools to understand biological regulation at the single-molecule level is a prime example of the innovation taking place within the Department of Physics and Center for Biological Physics. These well-deserved awards will enable Dr. Shepherd and his team to continue driving transformation and to innovate new ways to visualize biology in action.”

Two additional ASU faculty from the Ira A. Fulton Schools of Engineering, Barbara Smith and Benjamin Bartelle, were also selected as recipients of the award.

Shepherd’s first project, “4D molecular tracking using kilohertz framerate multimodal microscopy,” is funded by the Research Corporation for Science Advancement and will partner with Nick Galati, an assistant professor at Western Washington University in the Department of Biology and Shannon Quinn, an associate professor at the University of Georgia in the Department of Computer Science and the Department of Cellular Biology. 

The interdisciplinary team will work to develop and benchmark a multimodal microscopy approach that enables single particle tracking within motile cilia. Motile cilia, or moving microscopic vibrating organelles found on the surface of certain cells, are found in human lungs, the respiratory tract and the middle ear. Among other functions, they work to clear our airways of mucus and dirt, allowing us to breathe more easily. 

Motile cilia have been imaged before, however the dynamic processes that take place within them have only been investigated in artificially immobilized cilia — giving an incomplete understanding of a fundamental subcellular process that shapes human development. To give a more complete picture of motile cilia, the team will blend rapid quantitative phase imaging, fluorescence microscopy of individual cilia, and predictive particle tracking within the ciliary waveform.

“We might be able to understand how diseases actually change the physical motion of these microscopic hairlike structures in a way that nobody has ever understood before,” Shepherd said. “We need to be able to connect the fact that we see dysfunction to what is actually physically occurring on the cell. That is a current focus area in biomedical sciences, because as disease treatments become more targeted, we have to have finer and finer grain information available about exactly what's going on.”

His second project, “Wide-field, single-pixel fluorescence imaging with on-chip nanophotonics,” is funded by the Chan Zuckerberg Initiative and will partner with Lisa Poulikakos, an assistant professor at the University of California, San Diego in the Department of Mechanical and Aerospace Engineering. 

Poulikakos and Shepherd aim to develop a unique approach to aberration and scatter-resistant microscopy that circumvents the limitations of traditional optics. Traditional fluorescence imaging methods are unable to form sharp images past 0.1 mm into tissue samples, because tissue scatters and absorbs light as it travels through the sample. 

Researchers continue to create new methods to create sharp images as deep as a few millimeters into tissue samples. These scatter-resistant imaging methods are often significantly slower and require specialized lasers when compared to traditional methods, limiting their portability and adaptability. The team aims to simplify the experimental approach for scatter-resistant imaging by harnessing the power of a nanometer level fabrication and computational optics.

Using nanophotonics, the process of controlling light using materials patterned at the nanoscale, the team will create a lensless system that is capable of illuminating tissue samples using thousands of specifically designed patterns. The team will then design a computational framework that can decode a sharp image by extracting unique information from each pattern.

“Both of these awards center around interdisciplinary ideas on how to visualize and quantify molecular and cellular biology in unique and challenging situations where traditional approaches fail,” Shepherd said. “I am excited about the new collaborations established through Scialog and looking forward to exploring the boundaries with bioimaging with my fellow awardees."

In Shepherd’s Quantitative Imaging and Inference Lab, or QI2 Lab, he and his team of researchers are broadly interested in developing methods to study, understand and predict how cells make decisions during development. Five people in the QI2 Lab will contribute to the Scialog projects including one postdoctoral student, one professional research scientist and three graduate students.

The $50,000 award per project will support Shepherd’s research for one year. Depending on the outcome, he and his collaborators plan on applying for additional grants.

Emily Balli

Manager of marketing and communications, New College of Interdisciplinary Arts and Sciences