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Monthly Tip Sheet: Research Highlights from Biomedical Optics Express - August 2011

WASHINGTON, Aug. 17—The following highlights summarize key research published in the August issue of Biomedical Optics Express, the Optical Society’s (OSA) principal outlet for serving the biomedical optics community with rapid, open-access, peer-reviewed papers related to optics, photonics and imaging in the life sciences. The journal scope encompasses theoretical modeling and simulations, technology development, and biomedical studies and clinical applications.

In this issue:

  1. Near-infrared imaging system shows promise as future pancreatic cancer diagnostic tool
  2. Research team achieves first two-color STED microscopy of living cells
  3. Cellular laser microsurgery illuminates research in vertebrate biology


1. Near-infrared imaging system shows promise as future pancreatic cancer diagnostic tool

Near-infrared imaging system

A: Photograph of the OCT instrument and imaging probe; B,B’: Gross appearance and magnified OCT image of the malignant mucinous cystic neoplasmsm (MCN); C,C’: Gross appearance and magnified OCT image of the benign serous cystic adenoma (SCA). MCNs have large cavities, filled with a mucinous fluid that scatters light (see yellow arrow), while SCAs have a honeycomb structure of smaller cavities separated by a tiny septae (see red arrow). The SCA fluid is optically transparent and does not scatter light. OCT scale bar: 500 μm. Images courtesy of Dr. Nicusor Iftimia, Physical Sciences Inc. and Dr. William Brugge, Massachusetts General Hospital.

A team of researchers from four Boston-area institutions led by Nicusor Iftimia from Physical Sciences, Inc. has demonstrated for the first time that optical coherence tomography (OCT), a high resolution optical imaging  technique that works by bouncing near-infrared laser light off biological tissue, can reliably distinguish between pancreatic cysts that are low-risk and high-risk for becoming malignant. Other optical techniques often fail to provide images that are clear enough for doctors to differentiate between the two types.

To test the diagnostic potential of OCT imaging, researchers used the technique to examine surgically removed pancreatic tissue samples from patients with cystic lesions. By identifying unique features of the high-risk cysts that appeared in the OCT scans, the team developed a set of visual criteria to differentiate between high and low risk cysts. They then tested the criteria by comparing OCT diagnoses to those obtained by examining thin slices of the pancreatic tissue under a microscope. Their results, described in the August issue of the Optical Society’s (OSA) open-access journal Biomedical Optics Express, showed that OCT allowed clinicians to reliably differentiate between low-risk and high-risk cysts with a success rate close to that achieved by microscope-assisted examinations of slices of the same samples.

Future studies by the research team will focus on improving imaging resolution to further differentiate between solid lesions and autoimmune pancreatitis, and test this technology in vivo. They recently received FDA approval for testing this technology in human patients by using an OCT probe small enough to be inserted into the pancreas through a biopsy needle, which will be guided into suspect masses in the pancreas by endoscopic ultrasound imaging. A pilot clinical study is planned to start within the next couple of months. If in vivo data will prove reliable differentiation between the two types of cysts, a study in a larger number of patients will be planned, contingent on NIH funding and FDA approval.

Paper: "Differentiation of pancreatic cysts with optical coherence tomography (OCT) imaging: an ex-vivo pilot study," Biomedical Optics Express, Iftimia et al., Vol. 2, Issue 8, pp. 2372-2382.

2. Research team achieves first two-color STED microscopy of living cells

first two-color STED microscopy of living cells

Live cell two-color STED time series of HEK293 cells labeled with EGF-CLIPf-ATTO647N (magenta) and EGFR-SNAPf-Chromeo494 (green). Data has been normalized to correct for bleaching. The shown images have been cropped from the original raw data. Scale bar = 1 μm. Pellett et al., Biomed. Opt. Express 2, 2364-2371 (2011).

Researchers are able to achieve extremely high-resolution microscopy through a process known as stimulated emission depletion (STED) microscopy. This cutting-edge imaging system has pushed the performance of microscopes significantly past the classical limit, enabling them to image features that are even smaller than the wavelength of light used to study them. They are able to achieve this extreme vision by using a single-color fluorescent dye that absorbs and releases energy, revealing cells and cellular components (such as proteins) in unprecedented detail.

Current applications of STED microscopy have been limited to single color imaging of living cells and multicolor imaging in "fixed" or preserved cells. However, to study active processes, such as protein interactions, a two-color STED imaging technique is needed in living cells. This was achieved for the first time by a team of researchers from Yale University, as reported in the August issue of the Optical Society’s (OSA) open-access journal Biomedical Optics Express. The key to their success was in overcoming the challenges in labeling target proteins in living cells with dyes optimal for two-color STED microscopy. By incorporating fusion proteins, the researchers were able to improve the targeting between the protein and the dye, effectively bridging the gap. This allowed the researchers to achieve resolutions of 78 nanometers and 82 nanometers for 22 sequential two-color scans of two proteins—epidermal growth factor and epidermal growth factor receptor—in living cells.

The researchers expect that using this and other novel approaches will expand live cell STED microscopy to three and more colors, enabling 3-D imaging.

Paper: "Two-color STED microscopy in living cells," Biomedical Optics Express, Pellett et al., Volume 2, Issue 8, pp. 2364-2371.

3. Cellular laser microsurgery illuminates research in vertebrate biology

Using an ultrafast femtosecond laser, researchers at Tufts University in Medford, Mass., were able to label, draw patterns on, and remove individual melanocytes cells from a species of frog tadpole (Xenopus) without damaging surrounding cells and tissues. Melanocytes are the cells responsible for skin pigment; they also are descendants of a specific type of stem cell that has regenerative potential and other characteristics similar to some cancer cells.

By precisely marking and ablating these cells, the researchers were able to track how melanocytes migrated and regenerated within a live organism. The researchers hope this technique will enable new avenues of research in wound repair, regenerative medicine, and cancer studies. The new method could also be used to study how certain organisms respond to spinal cord damage and how they are able to regenerate portions of their spinal cords.

According to the researchers, femtosecond lasers have already become important tools in biological studies because of the ability to affect highly localized tissues. The laser in their research, described in the August issue of the Optical Society’s (OSA) open access journal Biomedical Optics Express, operated at a wavelength of 800 nm, which more readily affected melanocytes while protecting surrounding tissues. This highly selective characteristic enabled the study of cells both on the surface of the skin and in deeper tissue.

Paper: "Patterned femtosecond-laser ablation of Xenopus Laevis melanocytes for studies of cell migration, wound repair, and developmental processes," Mondia et al., Biomedical Optics Express, Volume 2, Issue 8, pp. 2383-2391.

EDITOR’S NOTE: For images or interviews with authors of the papers listed above, please contact Angela Stark, astark@osa.org or 202.416.1443. To get the monthly Biomedical Optics Express tip sheet, email astark@osa.org or follow @OpticalSociety on Twitter.

About Biomedical Optics Express
Biomedical Optics Express is OSA’s principal outlet for serving the biomedical optics community with rapid, open-access, peer-reviewed papers related to optics, photonics and imaging in the life sciences. The journal scope encompasses theoretical modeling and simulations, technology development, and biomedical studies and clinical applications. It is published by the Optical Society and edited by Joseph A. Izatt of Duke University. Biomedical Optics Express is an open-access journal and is available at no cost to readers online at http://www.OpticsInfoBase.org/BOE.

About OSA
Uniting more than 106,000 professionals from 134 countries, the Optical Society (OSA) brings together the global optics community through its programs and initiatives. Since 1916 OSA has worked to advance the common interests of the field, providing educational resources to the scientists, engineers and business leaders who work in the field by promoting the science of light and the advanced technologies made possible by optics and photonics. OSA publications, events, technical groups and programs foster optics knowledge and scientific collaboration among all those with an interest in optics and photonics. For more information, visit www.osa.org.

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