BiOS Hot Topics

New optical methods and tools to improve disease diagnostics and treatment and to provide new insights into the function of complex human organs like the brain were among the breakthroughs presented at the BiOS Hot Topics session during SPIE Photonics West in February.

The optical technologies and applications reported at BiOS this year and the commercial success of optical coherence tomography (OCT) are a reflection of how “we are all trying to help people,” according to SPIE Fellow R. Rox Anderson, BiOS symposium co-chair. “This symposium gets a little better, broader, and deeper every year,” he said.

One of eight Hot Topics speakers, SPIE Fellow Bruce Tromberg of Beckman Laser Institute (USA) described a multi-center clinical trial studying diffuse optics methods for assessing breast cancer chemotherapy – the first optics trial supported by the American College of Radiology.

“In breast cancer over the last 10-15 years, there has been tremendous growth in use of pre-surgical neoadjuvant chemotherapy for stage 2 to 4 tumors,” Tromberg explained. “There is a clinical need to predict the pathological response as early as possible.”

Tromberg’s group has been working with a combination of frequency-domain phase modulation and continuous-wave diffuse infrared spectroscopy for monitoring neoadjuvant chemotherapy.

Another talk covered developments in scanning-fiber endoscopy, which offers clinicians both an improved method of guided intervention and a higher resolution diagnostic capability, according to SPIE Member Eric Seibel of the University of Washington (USA).

Coherent fiber bundle technology is a mainstay for imaging very small ducts, but the resolution is only about 100 pixels across, Seibel explained. “Really, you are legally blind when you are using that scope,” he said, which is an issue with sophisticated procedures in small ducts.

Seibel’s group has focused on developing ultrathin widefield high-resolution endoscopy for imaging the bile duct for biopsy. “It is very important to get high-resolution images for this, and we had never seen these kinds of images before,” he said as he showed videos on a huge screen.

Gary Shambat, a member of Jelena Vuckovic’s group at Stanford University (USA) and a senior scientist at Adamant Technologies, told the audience about a nanoscale photonic probe. Built using semiconductor manufacturing methods, the device is enabling researchers to probe single cells for days at a time.

“We wanted to take an optical fiber and insert it into a single cell without too much damage” to measure nanocavity resonances in the cell, Shambat said. They attached the fiber with epoxy to a GaAs membrane and tested the nanoprobe on common cancer cells (PC3).

The process was “minimally cytotoxic” to the cells, with about 75% of the cells surviving. This means the probe could be used to measure long-term cell behavior; in early experiments, they observed cells containing the probe for eight days.

On the commercial side of biophotonics, Eric Swanson of OCT News paid tribute to innovative researchers, government support, and an “entrepreneurial spirit” for their role in making optical coherence tomography (OCT) the most successful biomedical optics product to date.

First introduced into ophthalmology clinics and, more recently, cardiology practices, OCT technology is the basis for more than 40 OCT companies worldwide today and is used in surgery, microscopy, the oral cavity, bronchoscopy, gastroenterology, dermatology, gynecology, neurology, and pathology, Swanson noted.

“Over the last decade, more than half a billion dollars has been invested by government agencies, and the ROI on that investment has been outstanding,” Swanson said.

“The clinical translation of OCT has been impactful scientifically, clinically, and economically,” he said.

Meanwhile, a decade of research has pushed photoacoustic computed tomography (CT) to the forefront of molecular-level imaging, according to SPIE Fellow Lihong Wang, a professor at Washington University, St. Louis (USA) and editor-in-chief of the Journal of Biomedical Optics.

Modern optical microscopy has resolution and diffraction limitations, Wang noted. But noninvasive functional photoacoustic CT has overcome this limit, offering deep penetration with optical contrast and ultrasonic resolution of 1 to 7 cm depth of penetration. The technology can be used in evaluating sentinel lymph nodes for breast-cancer staging.

Several “Hot Topics” presentations focused on how optical tools are helping to improve our understanding of neurological structures and processes.

Massachusetts General Hospital’s David Boas, editor-in-chief of the new SPIE journal Neurophotonics, discussed how advances in microscopy are providing new details about how oxygen is delivered and consumed in the brain and elsewhere in the body. But microvascular oxygenation is a very complicated process, he noted, and “We need methods to measure blood flow in the capillary networks.”

He and his collaborators are using multimodal microscopy to study microvascular blood flow and map oxygen throughout the vascular network. “What we found is that significant oxygen is extracted from the arterioles – in fact, 50% of oxygen being distributed is coming from the arterioles, and this is a new finding,” Boas said.

Paul Selvin and colleagues at the University of Illinois at Urbana-Champaign have developed quantum dots that provide super resolution imaging of AMPA receptors (AMPAR) and support structures at live neuronal synapses.

Using photo-activated localization super-resolution microscopy (PALM) and the PALM cycle to achieve 10-20 nm resolution, they have measured the exact distance between pre-synapse and post-synapse and observed the volume change of synapses. They did this by creating quantum dots (~8 nm) that can fit inside the synapse and big quantum dots (~20 nm) that can bind to them.

“We can get 3D fluorescence imaging with 10-20 nm resolution,” with photostable dots, Selvin said, to gather totally new information about synapse function.

As part of the European Union’s Human Brain Project’s efforts to build a whole-brain imaging infrastructure, Francesco Pavone and collaborators at the European Laboratory for Non-Linear Spectroscopy have combined two-photon correlative microscopy and light-sheet microscopy to enhance the ability to image the brain and its processes.

“Two-photon microscopy can only acquire superficial layers, so we correlate with confocal light sheet microscopy to reconstruct the entire brain and trace single processes,” Pavone said.

Biophotonics researchers and post-docs looking for a welcoming environment in which to begin their next project might want to consider Brazil, where SPIE is organizing a biophotonics conference in 2015.

“São Paulo accounts for about half of the science that occurs in Brazil and publishes more scientific articles than any country in Latin America,” according to Carlos H. de Brito Cruz, science director for the Foundation for the Support of Research in the State of São Paulo (FAPESP).

With a taxpayer-supported 2012 budget of about R$1.035 billion (about US $500 million), FAPESP offers grants ranging from $200,000 to $3 million for a broad spectrum of scientific research projects, including optics and photonics, Brito told an audience at SPIE Photonics West in February. There are currently 100 optics/photonics grants in process, he noted.

Two Brazilian researchers gave presentations on their FAPESP projects:

• A multimodal photonic platform that can be used to manipulate and acquire spatial- and time-resolved biochemical and biomechanical information from single live cells, developed by Carlos Lenz Cesar’s group at University of Campinas.

• A project under the direction of Helena Nader at University of Sao Paulo that is using biophotonics to better understand the mode of action of the anti-thrombotic drug Heparin.

SPIE member Cristina Kurachi of University of São Paulo is the local organizer of an SPIE biophotonics conference to be held 22-26 May 2015 in Rio de Janeiro. The new event will be collocated with a meeting of the International Photodynamic Association.

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