MIT Research News' Journal
 
[Most Recent Entries] [Calendar View]

Monday, July 20th, 2020

    Time Event
    10:59a
    Exhaled biomarkers can reveal lung disease

    Using specialized nanoparticles, MIT engineers have developed a way to monitor pneumonia or other lung diseases by analyzing the breath exhaled by the patient.

    In a study of mice, the researchers showed that they could use this system to monitor bacterial pneumonia, as well as a genetic disorder of the lungs called alpha-1 antitrypsin deficiency.

    “We envision that this technology would allow you to inhale a sensor and then breathe out a volatile gas in about 10 minutes that reports on the status of your lungs and whether the medicines you are taking are working,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT.

    More safety testing would be needed before this approach could be used in humans, but in the mouse study, no signs of toxicity in the lungs were observed.

    Bhatia, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science, is the senior author of the paper, which appears today in Nature Nanotechnology. The first author of the paper is MIT senior postdoc Leslie Chan. Other authors are MIT graduate student Melodi Anahtar, MIT Lincoln Laboratory technical staff member Ta-Hsuan Ong, MIT technical assistant Kelsey Hern, and Lincoln Laboratory associate group leader Roderick Kunz.

    Monitoring the breath

    For several years, Bhatia’s lab has been working on nanoparticle sensors that can be used as “synthetic biomarkers.” These markers are peptides that are not naturally produced by the body but are released from nanoparticles when they encounter proteins called proteases.

    The peptides coating the nanoparticles can be customized so that they are cleaved by different proteases that are linked to a variety of diseases. If a peptide is cleaved from the nanoparticle by proteases in the patient’s body, it is later excreted in the urine, where it can be detected with a strip of paper similar to a pregnancy test. Bhatia has developed this type of urine test for pneumonia, ovarian cancer, lung cancer, and other diseases. 

    More recently, she turned her attention to developing biomarkers that could be detected in the breath rather than the urine. This would allow test results to be obtained more rapidly, and it also avoids the potential difficulty of having to acquire a urine sample from patients who might be dehydrated, Bhatia says.

    She and her team realized that by chemically modifying the peptides attached to the synthetic nanoparticles, they could enable the particles to release gases called hydrofluoroamines that could be exhaled in the breath. The researchers attached volatile molecules to the end of the peptides in such a way that when proteases cleave the peptides, they are released into the air as a gas.

    Working with Kunz and Ong at Lincoln Laboratory, Bhatia and her team devised a method for detecting the gas from the breath using mass spectrometry. The researchers then tested the sensors in mouse models of two diseases — bacterial pneumonia caused by Pseudomonas aeruginosa, and alpha-1 antitrypsin deficiency. During both of these diseases, activated immune cells produce a protease called neutrophil elastase, which causes inflammation.

    For both of these diseases, the researchers showed that they could detect neutrophil elastase activity within about 10 minutes. In these studies, the researchers used nanoparticles that were injected intratracheally, but they are also working on a version that could be inhaled with a device similar to the inhalers used to treat asthma.

    Smart detection

    The researchers also demonstrated that they could use their sensors to monitor the effectiveness of drug treatment for both pneumonia and alpha-1 antitrypsin deficiency. Bhatia’s lab is now working on designing new devices for detecting the exhaled sensors that could make them easier to use, potentially even allowing patients to use them at home.

    “Right now we’re using mass spectrometry as a detector, but in the next generation we’ve been thinking about whether we can make a smart mirror, where you breathe on the mirror, or make something that would work like a car breathalyzer,” Bhatia says.

    Her lab is also working on sensors that could detect more than one type of protease at a time. Such sensors could be designed to reveal the presence of proteases associated with specific pathogens, including perhaps the SARS-CoV-2 virus.

    The research was funded by a Global Health Innovation Partnership grant from the Bill and Melinda Gates Foundation; Massachusetts General Hospital; the Ragon Institute of MGH, MIT, and Harvard; Janssen Research and Development; and the Kathy and Curt Marble Cancer Research Fund.

    2:50p
    Better simulation meshes well for design software (and more)

    The digital age has spurred the rise of entire industries aimed at simulating our world and the objects in it. Simulation is what helps movies have realistic effects, automakers test cars virtually, and scientists analyze geophysical data.

    To simulate physical systems in 3D, researchers often program computers to divide objects into sets of smaller elements, a procedure known as “meshing.” Most meshing approaches tile 2D objects with patterns of triangles or quadrilaterals (quads), and tile 3D objects with patterns of triangular pyramids (tetrahedra) or bent cubes (hexahedra, or “hexes”).

    While much progress has been made in the fields of computational geometry and geometry processing, scientists surprisingly still don’t fully understand the math of stacking together cubes when they are allowed to bend or stretch a bit. Many questions remain about the patterns that can be formed by gluing cube-shaped elements together, which relates to an area of math called topology.

    New work out of MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) aims to explore several of these questions. Researchers have published a series of papers that address shortcomings of existing meshing tools by seeking out mathematical structure in the problem. In collaboration with scientists at the University of Bern and the University of Texas at Austin, their work shows how areas of math like algebraic geometry, topology, and differential geometry could improve physical simulations used in computer-aided design (CAD), architecture, gaming, and other sectors.

    “Simulation tools that are being deployed ‘in the wild’ don’t always fail gracefully,” says MIT Associate Professor Justin Solomon, senior author on the three new meshing-related papers. “If one thing is wrong with the mesh, the simulation might not agree with real-world physics, and you might have to throw the whole thing out.” 

    In one paper, a team led by MIT undergraduate Zoë Marschner developed an algorithm to repair issues that can often trip up existing approaches for hex meshing, specifically.

    For example, some meshes contain elements that are partially inside-out or that self-intersect in ways that can’t be detected from their outer surfaces. The team’s algorithm works in iterations to repair those meshes in a way that untangles any such inversions while remaining faithful to the original shape.

    “Thorny unsolved topology problems show up all over the hex-meshing universe,” says Marschner. “Until we figure them out, our algorithms will often fail in subtle ways.”

    Marschner’s algorithm uses a technique called “sum-of-squares (SOS) relaxation” to pinpoint exactly where hex elements are inverted (which researchers describe as being “invalid”). It then moves the vertices of the hex element so that the hex is valid at the point where it was previously most invalid. The algorithm repeats this procedure to repair the hex.

    In addition to being published at this week’s Symposium on Geometry Processing, Marschner’s work earned her MIT’s 2020 Anna Pogosyants UROP Award.

    A second paper spearheaded by PhD student Paul Zhang improves meshing by incorporating curves, edges, and other features that provide important cues for the human visual system and pattern recognition algorithms. 

    It can be difficult for computers to find these features reliably, let alone incorporate them into meshes. By using an existing construction called an “octahedral frame field” that is traditionally used for meshing 3D volumes, Zhang and his team have been able to develop 2D surface meshes without depending on unreliable methods that try to trace out features ahead of time. 

    Zhang says that they’ve shown that these so-called “feature-aligned” constructions automatically create visually accurate quad meshes, which are widely used in computer graphics and virtual reality applications.

    “As the goal of meshing is to simultaneously simplify the object and maintain accuracy to the original domain, this tool enables a new standard in feature-aligned quad meshing,” says Zhang. 

    A third paper led by PhD student David Palmer links Zhang and Marschner’s work, advancing the theory of octahedral fields and showing how better math provides serious practical improvement for hex meshing. 

    In physics and geometry, velocities and flows are represented as “vector fields,” which attach an arrow to every point in a region of space. In 3D, these fields can twist, knot around, and cross each other in remarkably complicated ways. Further complicating matters, Palmer’s research studies the structure of “frame fields,” in which more than one arrow appears at each point.

    Palmer’s work gives new insight into the ways frames can be described and uses them to design methods for placing frames in 3D space. Building off of existing work, his methods produce smooth, stable fields that can guide the design of high-quality meshes.

    Solomon says that his team aims to eventually characterize all the ways that octahedral frames twist and knot around each other to create structures in space. 

    “This is a cool area of computational geometry where theory has a real impact on the quality of simulation tools,” says Solomon. 

    Palmer cites organizations like Sandia National Labs that conduct complicated physical simulations involving phenomena like nonlinear elasticity and object deformation. He says that, even today, engineering teams often build or repair hex meshes almost completely by hand. 

    “Existing software for automatic meshing often fails to produce a complete mesh, even if the frame field guidance ensures that the mesh pieces that are there look good,” Palmer says. “Our approach helps complete the picture.”

    Marschner’s paper was co-written by Solomon, Zhang, and Palmer. Zhang’s paper was co-written by Solomon, Josh Vekhter, and Etienne Vouga at the University of Texas at Austin, Professor David Bommes of the University of Bern in Germany, and CSAIL postdoc Edward Chien. Palmer’s paper was co-written by Solomon and Bommes. Zhang and Palmer’s papers will be presented at the SIGGRAPH computer graphics conference later this month.

    The projects were supported, in part, by Adobe Systems, the U.S. Air Force Office of Scientific Research, the U.S. Army Research Office, the U.S. Department of Energy, the Fannie and John Hertz Foundation, MathWorks, the MIT-IBM Watson AI Laboratory, the National Science Foundation, the Skoltech-MIT Next Generation program, and the Toyota-CSAIL Joint Research Center.

    << Previous Day 2020/07/20
    [Calendar]
    Next Day >>

MIT Research News   About LJ.Rossia.org