Diagnostic imaging techniques have been around in health care clinics for decades, helping researchers to improve the life of millions. But imaging has now entered a new phase with mass spectrometry.
The technology, more formally known as imaging mass spectrometry (IMS), produces high-resolution images that show the localization of metabolites, proteins and drugs within tissue sections, allowing assessment of chemical changes at the cellular level.
While the first use of ionization methods to discover isotopes dates back to 1913, the technology accelerated in the early 1990s with the emergence of higher-resolution scanners, cheaper computing and advances in big data analytics that help analyze the vast amounts digitized mass spectral information produced.
Some 100 leading researchers in tissue IMS from academia and industry came together for a daylong conference at the Yale School of Public Health on October 19 to discuss advances and challenges in the field. This technology is particularly applicable to cancer research and drug discovery and development.
A pioneer in high-resolution imaging, Richard Caprioli, professor of chemistry and director of the Mass Spectrometry Research Center, Vanderbilt University School of Medicine, said that IMS is bridging the chasm between the science lab and the clinic. A pathologist can now mark a spot on an image, and through IMS can examine it at the molecular level. Or, cellular abnormalities can be revealed through the mass spec that are not detectable through other types of imaging technology.
IMS is being used to diagnose inflammatory bowel disease, to determine whether the underlying condition is Crohn’s disease, indeterminate or ulcerative colitis. In certain melanomas it is difficult to differentiate benign from malignant cells, but with IMS, it is clear cut. “This brings a new dimension to pathology,” said Caprioli to the gathering in Winslow Auditorium.
Caprioli’s group is developing a technique to merge images from various types of imaging platforms, such as an MRI, PET and mass spec, into one three-dimensional image. Similar to how high-resolution satellite imaging combines low-resolution black-and-white images with high-resolution color imaging, they fuse the images pixel by pixel and use predictive computing to fill in the gaps. Each type of scan has its strengths and weaknesses. This process captures the strengths from multiple sources and allows pathologists an even more comprehensive picture of tissue abnormalities on the molecular level.
“We spend more than $10 million a day on drug discovery,” said Richard Goodwin, another speaker and principal scientist in the Department of Drug Safety and Metabolism at AstraZeneca. Mass spectrometry, he adds, is a cost-effective technology that is used to study a drug’s concentration and distribution in tissue.
This brings a new dimension to pathology.
Richard Caprioli
Stephen Castellino, senior fellow and head of U.S. Ex Vivo Imaging at GlaxoSmithKline (GSK), said that the technology is allowing for a more holistic approach to drug discovery. “Before we looked at organs as boxes.” Now they focus on where a drug is interacting and how it behaves. One application of IMS at GSK is in testing means of drug delivery, i.e. oral aspiration, inhalation or injection to understand a drug’s ability to reach its target. “This picture of molecular histology is where biology meets chemistry,” he said.
Kirill A. Veselkov’s group at the Department of Surgery and Cancer at Imperial College London, is developing an open-source software and data platform that is applicable to multiple oncological types, such as colorectoral and breast cancer. The tool uses statistical machine learning techniques to allow operators to apply simple filters to data. His work in translational data analysis aims to bring clinically useful information into the clinic.
The YSPH Department of Environmental Health Sciences (EHS) is building its capacity for mass spectrometry, imaging and metabolomics research. The department recently created two labs dedicated to metabolomics research. Both use mass spectrometry to study the mechanisms of cellular responses to environmental stress. Current studies are looking at colon cancer, asthma, early-life exposures in pregnancy, and chemical exposures from artificial turf fields and hydraulic fracturing.
“It is critical to have dialogue from around the world in order to inform the members of Yale Cancer Center, Yale community and universities in New England about this state-of-the-art technology and the capabilities of our Metabolomics Center here at YSPH,” said Vasilis Vasiliou, professor and chair of EHS. He co-chaired the symposium with Assistant Professor Caroline Johnson. “Metabolomics and tissue imaging mass spectrometry are essential technologies and the Yale School of Public health is fully harnessing their enormous potential.”
Other speakers included Kevin L. Schey, professor of biochemistry and ophthalmology and visual sciences at Vanderbilt University School of Medicine, who uses IMS to study diseases of the aging eye, such as glaucoma, macular degeneration and cataracts; Per Andrén, an associate professor at Uppsala University in Sweden, who uses the technology to study neurotransmitters and Parkinson’s disease; Robert Michael Angelo, an assistant professor and pathologist at the Stanford University School of Medicine, who is developing new methods and new machinery to image biopsies; and Sheerin K. Shahidi-Latham, head of the Metabolomics and Imaging Mass Spectrometry, Drug Metabolism and Pharmacokinetics Department at Genentech, who sees the technology playing a role in a clinical trials and merging with metabolomics soon.
The event was co-sponsored by the Yale Cancer Center with funding from the Waters Corporation, Genentech and the Distilled Spirits Council.