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BiOS talks sampler

Because there is just too much going on to see it all: here is a small sampling of presentations heard at SPIE Photonics West 2016.

BiOS Symposium SPIE Photonics West


From the BiOS Symposium


Compact multiphoton microscopes in early detection of ovarian cancer

Jennifer Barton, University of Arizona, presented in a Gynecology session Saturday morning in the conference on Diagnosis and Treatment of Diseases in the Breast and Reproductive System on the work of her research team in using multiphoton microscopy systems to enable high-resolution, deep-tissue imaging of ovarian carcinomas (9689-131).

Barton demonstrated how the use of fiber-coupled femtosecond laser systems instead of Ti:sapphire lasers has aided in designing extremely compact 2- and 3-photon microscopy systems, which could be packaged easily in a handheld probe or a laparoscope. For such systems, lateral resolution of 1.1 μm was achieved for source excitation wavelength of 1150 nm.

The imaging results from normal and neoplastic tissue in the ovaries and the fallopian tube demonstrated their great potential for early diagnosis of ovarian cancer.

The presentation also highlighted interesting findings that indicate that the 3-photon excited fluorescence and third harmonic generation signal came strongly from lipids and connective tissue whereas the 2-photon excited fluorescence came mainly from collagen.


Real-time assessment of tumor margins

Optical contrast agents for determining tumor margins in tissue was the subject of an invited talk (9696-28) on Sunday morning​ by Eben Rosenthal of Stanford University and Jason Warram from the University of Alabama School of Medicine, on work performed when Rosenthal was at the University of Alabama Brimingham. The technique is a real-time measurement that provides clinicians with immediate feedback that could alter the management of patient disease.

In a feasibility study with mice to determine performance compared to pathology, luciferase imaging was used as the gold standard, by which the fluorescence imaging demonstrated an 85% sensitivity, compared to 54% sensitivity in pathology; both techniques exhibited the same specificity.

However, because the optical agents are disease-specific, there is an inherent limitation that would prevent fluorescence imaging from replacing pathology completely. Warram said he is confident that there is still "a great deal to learn away from the benchtop," and encouraged fellow researchers to have open dialogues with surgeons about what would be of most benefit to patients.


Probing environmental enteric dysfunction (EED) with light

An invited session Sunday morning on "'Virtual Biopsy of the Gut" -- a Bill & Melinda Gates Foundation-funded project -- in the Endoscopic Microscopy conference looked at optical biopsy techniques to investigate the underlying causes of and potential interventions for environmental enteric dysfunction (EED). EED is an inflammatory disease of small intestine wide-spread among young children in low-income countries.

The session, chaired by Alex Thompson of Imperial College London, featured four talks covering a range of topics relevant to and useful for better understanding of EED. All the talks focused on generating awareness and engagement from a wider biophotonics community for this cause.

Michael Hughes, Imperial College London, provided a horizon scan on potential applications of virtual biopsy techniques for monitoring EED (9691-53). He noted that the optical biopsy systems could be used as either research or point-of-care tool. He also highlighted considerations such as invasiveness, cost, expertise infrastructure, and system maintenance, as well as capabilities to measure structural changes, gut leakage and systemic and intestinal inflammatory conditions efficiently to bear in mind while using these techniques for EED.

Optical biopsy techniques such as advanced endoscopy (e.g., narrow-band imaging, capsule endoscopy etc.), endoscopic microscopy (e.g., high-resolution microendoscopy (HRME), probe-based confocal laser endomicroscopy (pCLE) etc.), optical coherence tomography, and spectroscopy were presented as potential key contenders.

Paul Kelly, Queen Mary University of London (9691-54), gave a narrative review on the current understanding on environmental enteropathy (EE) and how it is wide-spread amongst children in tropical and environmentally challenged countries.

He noted that a high percentage -- 45% -- of child mortality rates is associated with problems such as malnutrition and chronic inflammations established during infancy.

Sharing the experience from his extensive studies on EED in Africa, Paul highlighted various consequences of this syndrome, including micronutrient malabsorption, oral vaccine failure, and growth failure and stunting, and presented research results of in vivo imaging of gut leakage and epithelial damage using probe-based confocal laser endomicroscopy (pCLE) in 61 Zambian adults with EE.

Rebecca Richards-Kortum, Rice University, gave an engaging talk (9691-55) on how using an affordable, compact, and HRME could eventually eliminate the need for taking excision biopsies during the screening of esophageal squamous cell neoplasia (ESCN).

Discussing the prevalence of esophageal cancer in developing countries, with highest risk areas in northern China, Richards-Kortum highlighted how traditional ESCN screening techniques such as Lugol's chromoendoscopy offer high sensitivity (>95%) but low specificity (<65%), leading to poor prognosis.

She presented results of using tablet-interfaced HRME to provide automated classification of the surface epithelium in an in vivo clinical study of 177 patients in U.S. and China, achieving very high sensitivity and specificity (95% and 91% respectively).

With such a statistically significant improvement in specificity, she noted that using HRME for ESCN screening, over half of the unnecessary biopsies could have been avoided.

The last talk for the session was presented by Michalina Gora, CNRS and Massachusetts General Hospital (9691-56), on swallowable tethered capsule endomicroscopy device for cellular level imaging of the small intestine.

Gora underscored the challenges related to engaging peristalsis and passing the capsule through the pylorus that were involved in extending the capsule -- originally developed for imaging the esophagus --for high-resolution screening of the small intestine.

She noted how the weight of the capsule plays a critical role in determining the time taken for it to pass through the pylorus (30 to 90 minutes). She presented circumferential imaging results of the entire intestine with 10 μm resolution even in presence of bile and discussed progress towards adapting the capsule design for safe and high resolution imaging of celiac and EED diseases safely in the pediatric population.


THz imaging to reduce follow-up surgery

To accommodate the growing momentum in the field of terahertz sensing and imaging, SPIE Photonics West inaugurated a dedicated session on the topic in the conference on Optical Interactions of Tissues and Cells. Tyler Bowman, University of Arkansas presented an invited paper (9706-1) Sunday afternoon on his group's research in improving and automating breast cancer margin detection from THz images of biological samples.

Current methods of evaluating cancer margins from resected tissue require time-consuming slicing, staining and analysis of samples by pathologists, a process which takes up to several weeks after the surgery; 20-40% of these samples return with positive margins.

Bowman presented THz imaging as a method to enable margin assessment during surgery. THz imaging has the benefits of being a low-power, non-ionizing imaging technique with inherent contrast between cancerous and non-cancerous tissue. By developing their image processing algorithms, they hope to create an automated process for determining cancer margins that would not require manual intervention or qualitative assessment.

Ultimately, it would obviate the need for patients to return for follow-up surgeries.


New approach to ionizing radiation dosimetry using HWG fibers

Arash Darafsheh, University of Pennsylvania, presented work (9702-36) Sunday afternoon on the development of a fiber-optic probe with promise to provide dosimetric value in the clinic.

The sub-mm probe is flexible, and can be placed either on the skin surface or in the natural cavities of the patient to measure radiation dose during treatments. These measurements can be compared to the theoretical values of the treatment plan in real time, and provide a new level of treatment verification.

While the idea of using an optical fiber as a dosimetric sensor for this application is not new, the approach used by Darafsheh and his group provides a novel solution to an inherent problem. Because most fibers have a dielectric material core, Cherenkov light is produced in the fiber when irradiated, contaminating the dosimetric signal.

Darafsheh concluded that using a silver-coated hollow waveguide fiber (HWG) with an air core and inserted phosphor scintillator tip provides dosimetric signal transmission, and minimizes the Cherenkov contamination, making the probe compatible for in vivo dosimetry.​


A $10 OCT system -- yes, it is possible!

A novel design and fabrication approach to build miniaturized OCT platforms for as low as US$10 was presented by Martin Leahy of the National University of Ireland, Galway (NUIG), Monday afternoon (9697-28).

Leahy noted how realizing the parallels between the optical units in a DVD pick-up drive and some core-components of an OCT system propelled his research team to take these easily-available, low-cost, mass-manufactured optical units and use them in building compact and low-cost OCT platforms.

Together with the experts from Compact Imaging, a California-based start-up and their industry collaborator, Leahy's research group at NUIG developed a prototype multiple reference OCT (MR-OCT) system that uses voice coil extracted from the DVD player pickup unit and partial mirror in the reference arm of a conventional time-domain OCT system to provide A-scans at several depths simultaneously.

Once fully integrated, the miniaturized mobile-compatible sensors will be about the size of a quarter and would aim to address high volume applications in areas such as mobile based personal health monitoring, biometric security, ophthalmology, and more.


Bringing light and sound to cancer

Michal Tomaszewski, University of Cambridge, (9708-49) on Monday afternoon presented innovative developments in the field of multiSpectral optoacoustic tomography (MSOT) that elevate the optical contrast along macro- and microscale while still maintaining excellent spatiotemporal resolution.

Tomaszewski discussed vascularization and hypoxia as important prognostic factors for various types of cancers and demonstrated how varying respired oxygen content can provide insight into tumor oxygen transport and consumption.

He presented results of a longitudinal study using MSOT to measure changes in blood oxygenation of subcutaneous tumors in mice by combining baseline and kinetic changes. The results revealed the capabilities of MSOT to monitor the alterations in tissue microarchitecture as the tumor progresses, as well as successfully distinguishing between different stages of cancer.


See-through wearable bandage provides a window into tissue oxygenation

Motivated by the desire to help wounded soldiers, the smart wearable bandage developed by Zongxi Li and colleagues at Massachusetts General Hospital provides a non-invasive and real-time solution for two-dimensional optical mapping of tissue oxygenation in skin (9715-26).

Li described Tuesday morning how the transparent bandage uses a technique called phosphorescence quenching to enable pO2 and oxygen consumption visualization under ambient light. Such a bandage would light up oxygen with a simple color change for easy and dynamic monitoring of the progression of inflammation and wounds.

Applications of this oxygenation-sensitive smart bandage include dynamic monitoring of tissue ischemia, skin grafts, and would healing - which could eventually lead to improved success rates of surgeries following severe injuries or burns.


Offline reflection correction improves hyperspectral image contrast

One of the challenges in fluorescence imaging is separating the useful fluorescence signal from background and reflected excitation light. Siri Luthman, a researcher in the Vision Lab at the University of Cambridge, is working with colleagues to develop new techniques to overcome this hurdle (9711-23).

Luthman described on Tuesday morning work toward a low-cost approach that utilizes solid-state hyperspectral imaging sensors, which are both cheap and compact, in small animal imaging studies.

A multi-wavelength LED was used to excite four fluorescent contrast agents sensitive to 610nm, 647nm, 700nm and 750nm light. Luthman performed offline reflectance removal methods prior to constrained least squares spectral unmixing to improve image contrast.

The method included both a brute force aspect, as well as hybrid linear analysis, a statistical method that subtracts background variance.

The method was validated to increase detection sensitivity in both phantom experiments, and in vivo. Luthman is currently looking into applying similar techniques to imaging situations with higher fluorescent backgrounds to determine performance limits of the system.


Towards quantitative optoacoustic imaging in living subjects

New techniques for in vivo imaging require both technical and biological validation. Sarah Bohndiek and her research group at the University of Cambridge are seeking to do just that for multispectral optoacoustic tomography.

On Tuesday afternoon, Bohndiek presented the research of former lab member and postdoc Frederic Brochu, who developed a light fluence correction for reconstructed images (9708-80).

The fluence correction successfully established a linear correlation between pixel intensity and absorption coefficient, and reduced the impact of spectral coloring, in phantom experiments. After organ-level segmentation, a priori knowledge was used with a finite element approach, carried out on a GPU, in order to correct light fluence.

To illustrate the concept in living subjects, Bohndiek showed a mouse liver mapped to oxygenated and deoxygenated areas after applying spectral unmixing and fluence correction. The corrected images exhibited qualitative improvement for deep-tissue visualization. Bohndiek and her research group continue to work towards developing quantifiable optoacoustic imaging in vivo.


All photos © SPIE, the international society for optics and photonics, except where noted. Contact for images or permissions.

Contributors: Jacqueline Andreozzi, Khushi Vyas

SPIE Photonics West

13-18 February 2016
San Francisco, California, USA


Event news: SPIE Photonics West 2016

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