In the 2016 report “Convergence: The Future of Health”, leaders from Massachusetts Institute of Technology (MIT) and their colleagues detailed the imminent problems facing the healthcare sector. These include the rising cost of care and the growing disparity of care among groups of people. Despite the technological advancements of the digital age, medical researchers still cannot find solutions for the prevention, early diagnosis and effective treatment for some of the world’s most widespread illnesses.
The report suggests that the most effective way to solve these problems is for the larger scientific community to embrace the concept of Convergence in Healthcare — a cooperative approach to research in which members of different scientific, technology, engineering and math (STEM) disciplines work together in a way so immersive that it moves beyond collaboration. Convergence in Healthcare focuses on creating a research community to effectively synthesize collective knowledge to help researchers identify novel and innovative methods of solving the world’s most pressing human health problems.
To best illustrate the potential that Convergence in Healthcare has for radically changing modern medicine, the authors of “Convergence: The Future of Health” highlight four specific medical areas. Among these is medical imaging, a technique that radically changed the way physicians identified and treated disease in the 20th century. Though this area of medicine has advanced drastically over the last century, Convergence in Healthcare could take imaging even further to give physicians new tools for preventing, diagnosing and treating illnesses with greater accuracy and less invasiveness than ever before. Listed below are three recent advances demonstrating the power of the Convergence revolution through the way it is changing medical imaging of the human body.
The medical community currently detects the function and processes of the body at the cellular and molecular level primarily through antibody “staining,” in which fluorescent molecules bind themselves to specific targets on various tissues and cells. The fluorescence left behind identifies the markers that medical professionals intend to observe, which can then be viewed via microscopy. While useful, the approach is limited because too many stained markers within a sample overlap spectrally and spatially, making it difficult for researchers to effectively observe complex illnesses with many target markers such as cancer.
Convergence in Healthcare has yielded two types of techniques with significant potential for more effective molecular imaging. First, through the work of professionals with backgrounds in engineering, pathology and biology, researchers developed the multiplexed ion beam imaging (MIBI) technique, which tags antibodies with metals rather than fluorescence to identify target markers at the molecular level. Markers targeted with any of the more than 100 isotopically pure metals can then be identified and observed through ion mass spectrometry, giving researchers the ability to observe as many different molecules in a single patient sample.
The second Convergent technique for molecular imaging relies on the detection of and ability to locate different forms of RNA within a cell — information that allows researchers to establish levels of gene activity within that cell. Using gene activity data, researchers are able to assess which proteins the cell is synthesizing, giving them an advanced ability to catalogue gene expression and create a comprehensive view of how the body reacts to disease at the molecular level. The two main methods of this form of molecular imaging brought about by Convergence include multiplexed error-robust fluorescence in situ hybridization (MERFISH) and fluorescence in situ sequencing (FISSEQ).
Whole organ imaging
The traditional method of obtaining information about the molecular makeup and structure of whole human organs requires medical professionals to procure thin, sliced sections of the organ in question and observe these samples using light and fluorescent microscopy. While this method may yield useful data on molecular function within an organ, data on the organ’s three-dimensional structure is lost in the process, reducing much of the method’s effectiveness. This is especially true of organs such as the brain, which remains the least understood and most complex organ in the human body.
One Convergent approach aiming to solve this issue and produce a more comprehensive picture of the brain is called CLARITY, which produces a transparent, three-dimensional image of the whole brain. Karl Deisseroth, MD, PhD, along with Stanford University chemical engineers and neuroscientists, developed the technique which employs a hydrogel that binds to various molecules in the brain, including proteins and nucleic acids. Scientists form a polymer from the gel to keep the molecules in place, then dissolve the lipids and other opaque elements within the brain using detergents. The result is a transparent model of the brain that leaves the structure intact, but allows researchers to view the complex internal structures through chemical markers and light microscopy.
Whole body imaging
Through whole body imaging, medical professionals seek a thorough overview of the human body’s internal systems to identify the presence of disease at earlier stages. As each system of the body is complex in its own right, a Convergent approach to a macroscopic view of the human body could help doctors improve their ability to diagnose and treat illnesses during a timeframe that increases the likelihood of patient recovery.
One Convergent initiative in whole body imaging is Raman spectroscopy, an analytical process used in chemistry and material sciences, which illuminates a sample to measure the frequency and intensity of scattered radiations to reveal the characteristics of the molecules within the sample. A Convergence in Healthcare application to this process — and to whole body imaging — allowed scientists to test its ability in animal models to reflect molecular interactions across multiple events simultaneously, with acute sensitivity and high spatial resolution. Raman spectroscopy is now used to help guide surgeons through procedures, identify breast cancer tumors and create a comprehensive picture of the gastrointestinal tract.