Neurophotonics hits its stride at BiOS

Following in the footsteps of the popular BiOS Hot Topics sessions, the first-ever neurophotonics plenary session at Photonics West this year featured 10 rapid-fire presentations covering the broad spectrum of neurophotonics R&D currently taking place worldwide.

"There is a strong focus on developing the technologies to dramatically impact our understanding of how the brain works," said David Boas, who moderated the session and is editor-in-chief of SPIE's Neurophotonics journal.

One of the initial challenges has been to find new ways to measure tens of thousands of neurons simultaneously. This requires taking an interdisciplinary approach to technology development that brings together neuroscientists, engineers, physicists, and clinical researchers. It also prompted SPIE to add a technology application track on the brain this year.

"SPIE recognized the need to bring together all the different groups in this field to get an overview of the many neurophotonics activities going on," Boas said.

The neurophotonics plenary session showcased the diversity of these research efforts, from genetically encoded indicators of neuronal activity to 3-photon microscopy for deep brain imaging, chemical sectioning for high throughput brain imaging, and mapping functional connections in the brain.

"We need to step back and think about all of these important methods and the larger picture," said Rafael Yuste, professor of neuroscience at Columbia University and a pioneer in the development of optical methods for brain research. His presentation covered novel neurotechnologies and their impact on science, medicine, and society.

"Why don't we already understand the brain?" Yuste asked. "People say it's just too complicated, but I believe the reason ... is that we don't have the right method yet. We do have methods that allow us to see entire activity of the brain, but not enough resolution of a single neuron. We need to be able to record from inside the neuron and capture every single spike in every neuron in brain circuits."

Yuste moderated the session with Boas.

Here are highlights from other plenary talks:

Genetically encoded indicators of neuronal activity

Robert Campbell

Francesco Pavone

Valentina Emiliani

Peter So

Taking a cue from Nobel Laureate Roger Tsien, a pioneer in the field of engineering proteins for neuroscience, Canadian researchers at the University of Alberta are working to develop new kinds of protein indicators to study neuronal activity, noted the university's Robert Campbell.

While early calcium indicators were synthetic tools, the Campbell Lab is working on genetically encoded proteins, taking a fluorescent protein and turning it into a calcium indicator, "a proxy for neuronal activity," Campbell said. Most recently, they have developed FlicR1, a new type of red fluorescent voltage indicator that can be used to image spontaneous activity in neurons. "We are very optimistic about this new indicator," he said.

Optical detection of spatial-temporal correlations in whole brain activity

Studying these types of correlations is "very important because morphology and functionality in the brain are tightly correlated to each other," said Francesco Pavone of Università degli Studi di Firenze in Italy.

His group is taking a multi-modality approach in mouse models to study brain rehabilitation following a stroke. They are using light-sheet microscopy to look at vasculature remodeling, two-photon imaging to study structural plastics, and wide-field meso-scale imaging to evaluate functional plasticity. "We would like to study at all brain levels the map of all activated cells," Pavone said.

Two-photon optogenetics with millisecond temporal precision and cellular resolution

"Do we have the technology to develop multi-cell, multiplane optogenetics with millisecond temporal resolution and single cell precision?" asked Valentina Emiliani, director of the Neurophotonics Laboratory at University Paris Descartes. Her lab is working with computer-generated holography, spatial light modulators (SLMs), and endoscopy to control the activity of a single neuronal cell.

"We have been able to achieve very robust photostimulation of a cell while the mice were freely moving, with nice spatial resolution," she said.

Monitoring synaptic activity across the full dendritic arbor

Peter So, professor of mechanical and biological engineering at Massachusetts Institute of Technology, described his group's work using 3D holographic excitation for targeted scanning as a way to study and map synaptic locations in the brain. "Neurons generate responses from many synaptic inputs, and we found that there are over 10,000 synaptic locations we would like to look at in parallel and map using synaptic coordinates to map activity," he said.

Chris Xu

Shaoqun Zeng

Adam Bauer

Maria Angela Franceschini

Edmund Talley

Three-photon microscopy for deep brain imaging

"Three-photon has vastly improved the signal-to-background ratio for deep imaging in non-sparsely labeled brain," said Cornell University's Chris Xu. By combining a long wavelength (1300-1700 nm, the optimum spectral windows for deep imaging) with high excitation, Xu said researchers are making new inroads into deep imaging of brain tissue. Three-photon microscopy is also valuable for structural imaging and for imaging brain activity "in an entire mouse cortical column," Xu added.

Mapping functional connections in the mouse brain for understanding and treating disease

Mapping brain function is typically performed using task-based approaches to relate brain topography to function, noted Adam Bauer of Washington University School of Medicine. "But we want to be able to help patients who are incapable of performing tasks, such as infants and those with impairments," he said.

For this reason, the lab has developed the functional connectivity optical intrinsic signal (fcOIS) imaging system to study mouse models of Alzheimer's, functional connectivity following focal ischemia, and to map cell-specific connectivity in awake mice.

Clinical neuro-monitoring with NIRS-DCS

Maria Angela Franceschini of the Athinoula A. Martinos Center for Biomedical Imaging described her group's work developing MetaOX, a tissue oxygen consumption monitor. The instrument has been tested in neonatal intensive care units to monitor hypoxic ischemic injury and therapeutic hypothermia.

It uses frequency-domain near infrared spectroscopy to acquire quantitative measurements of hemoglobin concentration and oxygenation and diffuse correlation spectroscopy to create an index of blood flow. The device is also being evaluated in Africa to study the effects of malnutrition on brain development, and in Uganda to study hydrocephalus outcomes in newborns.

Chemical sectioning for high throughput ex-vivo brain imaging

Shaoqun Zeng of the Wuhan National Lab for Optoelectronics in China outlined his group's work using chemical sectioning for high-throughput fluorescence imaging of a whole mouse brain at synaptic resolution. The goal is to systematically and automatically obtain a complete morphology of individual neurons.

Opportunities and priorities in neurophotonics: perspectives from the NIH

Edmund Talley of the US National Institutes of Health shared his experiences with the US BRAIN Initiative, which is slated to receive more than $430 million in the 2017 federal budget, plus $1.6 billion in dedicated funds through 2026 via the 21st Century Cures Act passed in December 2016.

"There is some very serious investment in neurotechnologies to understand how the mind works, and there is bipartisan political support," Talley said. "Multiple federal agencies are funding this."

Photonics West 2017, 28 January through 2 February at the Moscone Center, 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.