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3248 Fluorescence-Guided Neurosurgery with 5-Aminolevulinic-Acid and Second-Window-Indocyanine-Green: A murine model and investigation into suitable cell lines.
- Steve Cho, John Y.K. Lee, Saad Sheikh
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 105
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OBJECTIVES/SPECIFIC AIMS: This study aims to understand the utility of 5-ALA and SWIG in detecting areas of neoplasm in a murine model of GBM. Primary outcome is the distribution of the two dyes in comparison to the true tumor extent; the sensitivity, specificity, PPV, and NPV of both dyes will be calculated. The secondary outcome is the suitability of existing cell-lines used for GBM research for studies in fluorescence-guided surgery. METHODS/STUDY POPULATION: Two cell lines are used for this research: U87, derived from human GBM; and GL261, derived from rodent stem cells. U87 are implanted intracranially into 6-week old athymic, nude, female mice, while GL261 are implanted intracranially into 10-week old female C57BL/6 mice. The mice are weighed every 3 days to monitor health and bioluminescence imaging is performed between 7-10 days after implantation to confirm tumor implantation and monitor tumor growth. The mice are sacrificed between 10-21 days after implantation. 5mg/kg of intravenous ICG is administered 24-hours prior to harvest and 250mg/kg of intraperitoneal 5-ALA is administered 3-hours prior to harvest. Once the mice are sacrificed, their brains are quickly harvested and placed in cold formalin. Using a high-resolution Odyssey CLx scanner, near-infrared fluorescence from ICG is captured in coronal cross sections of the brains through the tumor. Similarly, 5-ALA fluorescence is imaged using a 405nm LED excitation source and 610-690nm bandpass filter. Afterwards, slices of the brain are stained with H&E, which serves as the gold-standard of the extent of tumor. Images from ICG, 5-ALA, and H&E can then be compared using ImageJ to compare the extent of tumor to the distribution of the dyes. RESULTS/ANTICIPATED RESULTS: In separate, previous studies in humans, both 5-ALA and SWIG have demonstrated utility in detecting residual neoplasm in HGG resections. In general, 5-ALA is more specific for areas of neoplasm, while SWIG is more sensitive. Thus, I anticipate that in this study, SWIG will show a greater distribution than 5-ALA, with SWIG distributing to areas beyond the tumor and 5-ALA distributing within, but not completely covering, the tumor. SWIG’s sensitivity and NPV for detecting tumor should be >90%, while its specificity and PPV may be closer to 50%. For 5-ALA, specificity and PPV should be close to 80-90%, but its sensitivity and NPV may be <50%. In terms of cell-line, preliminary results suggest that U87 cells are not suitable for research involving 5-ALA. We suspect that this is partly due to the limited infiltrative nature of U87 cells; in fact, the cells form a spherical mass, imitating metastases rather than true HGGs. The U87 masses do not have significant vascularity, which likely limits the amount of 5-ALA that can distribute to inside the tumor. DISCUSSION/SIGNIFICANCE OF IMPACT: 5-ALA is currently the only FDA-approved agent for fluorescence-guided neurosurgery. However, it has multiple limitations, which ultimately results in its low sensitivity and NPV. Our novel technique, which has demonstrated much higher sensitivity at the cost of specificity, offers an alternative that may help surgeons better achieve total resections in the operating room. These two agents have not been compared directly in humans or mice. Thus, this experiment sets up an important precedent, on which a human clinical trial comparing the two agents’ effects on resection rates and patient outcome can be performed. Ultimately, this work will lay the foundation for future research into fluorescence-guided neurosurgery, both in the visible and NIR spectrum.
The science of EChO
- Giovanna Tinetti, James Y-K. Cho, Caitlin A. Griffith, Olivier Grasset, Lee Grenfell, Tristan Guillot, Tommi T. Koskinen, Julianne I. Moses, David Pinfield, Jonathan Tennyson, Marcell Tessenyi, Robin Wordsworth, Alan Aylward, Roy van Boekel, Angioletta Coradini, Therese Encrenaz, Ignas Snellen, Maria R. Zapatero-Osorio, Jeroen Bouwman, Vincent Coudé du Foresto, Mercedes Lopez-Morales, Ingo Mueller-Wodarg, Enric Pallé, Franck Selsis, Alessandro Sozzetti, Jean-Philippe Beaulieu, Thomas Henning, Michael Meyer, Giuseppina Micela, Ignasi Ribas, Daphne Stam, Mark Swain, Oliver Krause, Marc Ollivier, Emanuele Pace, Bruce Swinyard, Peter A.R. Ade, Nick Achilleos, Alberto Adriani, Craig B. Agnor, Cristina Afonso, Carlos Allende Prieto, Gaspar Bakos, Robert J. Barber, Michael Barlow, Peter Bernath, Bruno Bézard, Pascal Bordé, Linda R. Brown, Arnaud Cassan, Céline Cavarroc, Angela Ciaravella, Charles Cockell, Athéna Coustenis, Camilla Danielski, Leen Decin, Remco De Kok, Olivier Demangeon, Pieter Deroo, Peter Doel, Pierre Drossart, Leigh N. Fletcher, Matteo Focardi, Francois Forget, Steve Fossey, Pascal Fouqué, James Frith, Marina Galand, Patrick Gaulme, Jonay I. González Hernández, Davide Grassi, Matt J. Griffin, Ulrich Grözinger, Manuel Guedel, Pactrick Guio, Olivier Hainaut, Robert Hargreaves, Peter H. Hauschildt, Kevin Heng, David Heyrovsky, Ricardo Hueso, Pat Irwin, Lisa Kaltenegger, Patrick Kervella, David Kipping, Geza Kovacs, Antonino La Barbera, Helmut Lammer, Emmanuel Lellouch, Giuseppe Leto, Mercedes Lopez Morales, Miguel A. Lopez Valverde, Manuel Lopez-Puertas, Christophe Lovi, Antonio Maggio, Jean-Pierre Maillard, Jesus Maldonado Prado, Jean-Baptiste Marquette, Francisco J. Martin-Torres, Pierre Maxted, Steve Miller, Sergio Molinari, David Montes, Amaya Moro-Martin, Olivier Mousis, Napoléon Nguyen Tuong, Richard Nelson, Glenn S. Orton, Eric Pantin, Enzo Pascale, Stefano Pezzuto, Ennio Poretti, Raman Prinja, Loredana Prisinzano, Jean-Michel Réess, Ansgar Reiners, Benjamin Samuel, Jorge Sanz Forcada, Dimitar Sasselov, Giorgio Savini, Bruno Sicardy, Alan Smith, Lars Stixrude, Giovanni Strazzulla, Gautam Vasisht, Sandrine Vinatier, Serena Viti, Ingo Waldmann, Glenn J. White, Thomas Widemann, Roger Yelle, Yuk Yung, Sergey Yurchenko
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- Journal:
- Proceedings of the International Astronomical Union / Volume 6 / Issue S276 / October 2010
- Published online by Cambridge University Press:
- 10 November 2011, pp. 359-370
- Print publication:
- October 2010
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The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are?
In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life.
The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole.
EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates.
A Three Dimensional Self-folding Package (SFP) for Electronics
- David Gracias, Jeong-Hyun Cho, Steve Hu
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- Journal:
- MRS Online Proceedings Library Archive / Volume 1249 / 2010
- Published online by Cambridge University Press:
- 01 February 2011, 1249-F09-07
- Print publication:
- 2010
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We describe the concept of a 3D self-folding package (SFP) for sensors and electronic devices. The strategy is based on a self-assembly strategy wherein 2D panels interconnected with hinges spontaneously fold-up when they are released from the substrate; self-folding can be triggered by temperature or selected chemicals. The strategy enables packaging of devices in porous polyhedral geometries that can either be untethered or substrate-bound. Self-folding can enable packaging of devices in small 3D form factors and may enable efficient cooling due to porosity. The utilization of this self-folding platform to enable 3D packaging of cantilever sensors and magnetic field sensitive strain gauges is summarized.
Effects of feeding level and water temperature on growth, nutrient and energy utilization and waste outputs of rainbow trout (Oncorhynchus mykiss)
- Paula A. Azevedo, C. Young Cho, Steve Leeson, Dominique P. Bureau
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- Journal:
- Aquatic Living Resources / Volume 11 / Issue 4 / July 1998
- Published online by Cambridge University Press:
- 15 July 1998, pp. 227-238
- Print publication:
- July 1998
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A study was carried out to determine the effect of feeding level and water temperature on growth and feed efficiency, nutrient and energy utilization and waste outputs of rainbow trout. A practical diet was fed to near-satiation to groups of fish reared at 6, 9, 12 and 15 °C. At each temperature, the feed intake of other groups of fish was restricted to about 85 % or 70 % of the amount of feed consumed in the previous week by the fish fed to near-satiation. Total feed intakes over 12 weeks were, on average, 76 % and 65 % of total feed intake of the near-satiety group for R1 and R2, respectively. Reducing the feed allocation resulted in significantly (P < 0.05) lower weight gains compared to feeding to near-satiation regardless of the rearing temperature. Feeding level and water temperature had no significant (P < 0.05) effect on feed efficiency, carcass composition or efficiencies of digestible nitrogen and digestible energy retention. Increasing temperature resulted in an increase in the apparent digestibility of dietary dry matter, nitrogen and energy (P < 0.05). The increase in digestibility of dry matter and nitrogen with increasing temperature resulted in higher estimated total solid and solid nitrogen waste outputs per kg fish produced (P < 0.05) at lower water temperatures. Estimated dissolved nitrogen and phosphorus waste outputs (g/kg fish produced) were not affected by the feeding level or water temperature. A highly significant (P < 0.01) linear relationship was observed between metabolizable energy (ME) intake above basal metabolism and recovered energy. The efficiency of ME utilization for growth (Kpf) was 0.61 and this coefficient was not affected by feed intake or water temperature. Protein and lipid were deposited in a constant ratio (1 kJ protein gain: 1.4 kJ lipid gain) regardless of ME intake or water temperature.
Spectroscopie Studies of Confined Molecules Under Shear
- Iwao Soga, Ali Dhinojwala, Yoon-Kyoung Cho, Steve Granick
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- Journal:
- MRS Online Proceedings Library Archive / Volume 464 / 1996
- Published online by Cambridge University Press:
- 10 February 2011, 89
- Print publication:
- 1996
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We introduce two new techniques with the sensitivity to measure spectroscopie properties of confined molecules under shear. One concerns rheo-optics of fluids in micron-sized gaps. The experimental approach consists in applying periodic shear motion to fluid films confined between parallel plates separated by controllable film thickness from 0.1 to 100 micrometers. A key aspect is the concurrent ability to perform spectroscopie experiments (infrared or dielectric spectroscopy, or x-ray or neutron spectroscopy) of these fluids during flow.
The second technique consists in flow field experiments of polymer adsorption and orientation. The experimental approach is to produce one-directional shear, at rates up to 104 sec−1, past adsorbed polymer layers of thickness less than 0.01 micrometers. The selective augmentation of vibrational modes oriented preferentially along the chain backbone is then used to probe chain orientation in the direction of flow in a laminar flow field.