In an interview with SPIE last fall, Rafael Yuste, professor of neuroscience at Columbia University and the "brains" behind the US government's BRAIN Initiative, stated, "One of the big challenges I see (in advancing the study of the human brain) is the need to image in 3D, and that calls for the reinvention of the microscope."
If the BiOS Hot Topics session at SPIE Photonics West 2017 is any indication, the research community is well on its way to meeting the challenge. Advances in microscopy dominated the rapid-fire Hot Topics presentations, detailing advances that could dramatically influence molecular research, drug development, and clinical diagnostics.
Alberto Diaspro of the Istituto Italiano di Tecnologia celebrated the evolution of the microscope in his talk, "The Extra Microscope." From the "microscopiums" and "telescopiums" of the 1600s to the nanoscale optical microscopes ("nanoscopy") of today, "with the microscope we can make visible what is invisible," Diaspro noted. "We are interested not only in the cell, but what is in the cell, the cell interactions. And this is what we can address with the microscope."
Toward this end, Richard Levenson a medical doctor and professor at the University of California, Davis Medical Center, described a novel technique that uses ultraviolet surface excitation for slide-free tissue microscopy. Dubbed "MUSE," it could have profound implications for global health, Levenson said.
"Pathology is still the gold standard for diagnosis and therapy guidance, and we still use ‘state of the art' equipment: a microscope and a slide," he said. "But the pathologist has to go through multiple steps, and it takes hours to go from a ‘lump' to a slide. With MUSE, we are proposing to get rid of all those steps and make it a three-minute process."
Based on intellectual property jointly developed at Lawrence Livermore National Lab and UC Davis, the MUSE microscope uses short-wavelength UV light that penetrates only microns-deep into tissue, eliminating the need for precision-cut, thin specimens. The physical setup is simple (the light source, for example, is a single UV LED) - so simple, in fact, that some people are adapting MUSE for use with cell phones. In addition, the single-wavelength, 280-nm LED can excite many fluorescent dyes simultaneously.
"We can also look at very large fields of view, such as a whole brain slice, because we don't have to make thin slices," Levenson said. "So it makes it a very convenient tool for neurophotonics, for looking at very large areas of the brain."
It also good for imaging the skin and surgical margins, plus a variety of other clinical and pre-clinical applications, he added.
"With MUSE, we see surfaces, not just cut sections," he said. "So we can see what things actually look like. We can see the structure and ‘color' (false color) of things more or less in their native format, vs. arbitrarily in sections. With MUSE you get a combination of electron microscopy and fluorescence."
Optical imaging tools
In his talk on "Biomedical Imaging and Spectroscopy with Scattered Light," Lev Perelman of Harvard University Beth Israel Deaconess Medical Center shared his group's research involving CLASS (confocal light absorption and scattering spectroscopic microscopy). This unique combination of confocal microscopy and light-scattering spectroscopy provide new insights into cell structures using the innate light-scattering spectra within each cell as the source of the contrast.
"There are approximately 1,000 different types of cells in the human body, but they are all built from the same set of building blocks: organelles, or membrane-bounded compartments inside the cells," Perelman said. "And different wavelengths of light can be used to look at how light is scattered by these organelles, without the need for any external markers."
His group has used this approach to study cancer progression in live esophageal cells and also to image organs, such as Barrett's esophagus, often a precursor to oral and pharyngeal cancers. "Using endoscopic multispectral scanning light-scattering imaging, it takes only one minute to scan the entire esophagus," he said.
Other talks during the two-hour Hot Topics session covered optical imaging tools and techniques, from noninvasive optical biopsies to cardiac optogenetics, next-generation optical coherence tomography (OCT), molecular transport in live cells, and optical topography. Here are some highlights:
Robert Alfano of the City College of New York/City University of New York and a pioneer in the development of optical biopsy techniques, provided an update on recent advances in this field. Among the notable findings from his lab at CCNY: that tryptophan is a key marker for aggressive cancer. "Cancer cells like to eat tryptophan," he said.
In addition, his research team has demonstrated three short-wave infrared optical windows that appear to offer advantages for optical biopsies: 1100-1350 nm, 1600-1870 nm, and 2100-2300 nm.
"Over the years, the 650-950 nm was mainly used to go into tissues via silicon detectors," Alfano said. "But with the advent of InGaAs and InSb CCD/CMOS detectors, we can now go into the infrared. In particular, 1700 nm allows you to go deep into tissue without scattering and with good absorption. So as long as you're not photon starved, you will get good images."
Emilia Entcheva, professor of biomedical engineering at George Washington University, walked the audience through her group's work in cardiac optogenetics, a new framework for the study of cardiac electrophysiology and arrhythmias. Their goal is to use optogenetic sensors and actuators to achieve high throughput, all-optical cardiac electrophysiology for applications in drug development (cardiotoxicity screen), drug discovery, and patient-specific therapies via the functional characterization of stem-cell derived heart microtissues.
Her group has developed OptoDyCE, a fully automated system for all-optical cardiac electrophysiology. The device is the first high-throughput cardiac optogenetic system that can do this, according to Entcheva, and it has the potential to process 600 independent multi-cellular tissue samples per hour and more than 10,000 compounds per day.
Zhongping Chen of the University of California, Irvine discussed advances in functional OCT, noting that 2016 was the 25th anniversary of OCT and 2017 is the 20th anniversary of Doppler OCT and OCT angiography. His talk focused primarily on OCT angiography and Doppler OCT. In addition to clinical applications, D-OCT is important for vascular mapping, neuron detection, and for studying neurovascular disease and respiratory cilia function, Chen noted.
"OCT has made a tremendous impact in clinical medicine, particularly ophthalmology," he said. "What is most exciting is that this technology has been translated to the clinic, where it has become the standard of care for studying microvasculature."
Other speakers included Enrico Gratton, also of UC-Irvine, whose work centers on new forms of fluctuation correlation spectroscopy and fluorescence diffusion tensor image analysis to map the diffusion of molecules, and Hideaki Koizumi of Hitachi, who said his dream is to develop a "mindscope" that could be used for diagnosing brain diseases such as depression and schizophrenia.
SPIE Britton Chance Biomedical Optics Award
The Hot Topics session on 28 January began with a talk by Christopher Contag, the founding director of a new biomedical research institute at Michigan State University and recipient of the 2017 SPIE Britton Chance Biomedical Optics Award.
Contag, a pioneer of in vivo optical imaging using bioluminescent reporters, reported on advances in imaging and microscopy technologies, including a tiny snap-together microscope.
Contag was named director of the new Institute for Quantitative Health Science and Engineering and chair of the Department of Biomedical Engineering in the College of Engineering at Michigan State in 2016. He leads an interdisciplinary team of researchers whose goals are to build tools to understand complex biological processes and develop new therapies for cancer and other diseases.
The SPIE Britton Chance Biomedical Optics Award recognizes Contag's invention of in vivo optical imaging using bioluminescent and fluorescent reporters and the work at his former lab at Stanford University that used biological sources of light to image key biological processes in living mammals.
For more information on the award, see the SPIE Professional article.
Sergio Fantini of Tufts University (USA) moderated the Hot Topics Session. Symposium chairs for BiOS are SPIE Fellows James Fujimoto of MIT and R. Rox Anderson of the Wellman Center, Massachusetts General Hospital, and Harvard Medical School (USA).
Photonics West 2017, 28 January through 2 February at the Moscone Center in San Francisco, CA (USA), encompassed more than 4700 presentations on light-based technologies across more than 95 conferences. It was also the venue for dozens of technical courses for professional development, the Prism Awards for Photonics Innovation, the SPIE Startup Challenge, a two-day job fair, two major exhibitions, and a diverse business program with more than 25 events.
SPIE Photonics West 2018 will run 27 January through 1 February at Moscone Center.