Del Mar Photonics - Newsletter Fall 2010 - Newsletter Winter 2010

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Photonics West 2011: Presentations on photonics applications in mouse models research

Oxidative stress of photodynamic antimicrobial chemotherapy inhibits Candida albicans virulence

Paper 7887-10 of Conference 7887
Date: Saturday, 22 January 2011
Time: 12:00 PM ?12:20 PM

Author(s): Ilka T. Kato, Renato A. Prates, Instituto de Pesquisas Energéticas e Nucleares (Brazil); George P. Tegos, The Univ. of New Mexico (United States) and Massachusetts General Hospital (United States) and Harvard Medical School (United States); Michael R. Hamblin, Massachusetts General Hospital (United States) and Harvard Medical School (United States) and Massachusetts Institute of Technology (United States); Martha Simões Ribeiro, Instituto de Pesquisas Energéticas e Nucleares (Brazil)
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In this study, the virulence of Candida albicans submitted to sublethal photodynamic inactivation was evaluated. C. albicans were exposed to sublethal photodynamic challenge using methylene blue as photosensitizer, associated with a diode laser irradiation (?=660nm). The parameters of irradiation were selected in causing no reduction of viable cells as sublethal photodynamic challenge. The potential effects of PACT on virulence determinants of C. albicans were investigated by analysis of germ tube formation and in vivo pathogenicity assays using a mice model for systemic infection. The oxidative damage promoted by sublethal photodynamic inactivation inhibited virulence factors and reduced in vivo pathogenicity of C. albicans.

Efficacy of continuous wave and pulsed wave transcranial laser therapy (TLT) in the treatment of Alzheimer's disease (AD) in an amyloid precursor protein transgenic mouse (APP Tg) model

Paper 7887-19 of Conference 7887
Date: Saturday, 22 January 2011
Time: 5:00 PM ?5:20 PM

Author(s): Luis H. De Taboada, PhotoThera, Inc. (United States); Jin Yu, Salim El-Amouri, Medical Univ. of South Carolina (United States); Sebastiano Gattoni-Celli, Charleston VA Medical Ctr. (United States); Steven Richieri, Thomas McCarthy, PhotoThera, Inc. (United States); Jackson Streeter, Banyan Biomarkers, Inc. (United States); Mark S. Kindy, Medical Univ. of South Carolina (United States)
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Continuous Wave (CW) and Pulsed Wave (PW) TLT was tested for efficacy in a transgenic (Swedish/London) APP mouse model of AD. Administration of TLT was associated with a dose-dependent reduction in amyloid load and the numbers of Aß plaques. All TLT doses mitigated the behavioral deficits seen with advanced amyloid deposition and reduced the expression of inflammatory markers in the APP Tg mice. All TLT doses produced an increase in sAPP-a and a decrease in sAPP-ß levels consistent with inhibition of the ß-secretase activity. Oxygen consumption and ATP concentrations in the brains of APP Tg mice were significantly reduced compared to Wt mice, but essentially restored in the PW TLT treated APP mice. PW TLT induced a transient increase in c-fos protein expression, while Wt and APP Tg mice alone showed little to no c-fos activity. These studies suggest that TLT is a potential candidate for the treatment of AD.

Dual thermal ablation modality of solid tumors in a mouse model

Paper 7901-34 of Conference 7901
Date: Monday, 24 January 2011
Time: 2:20 PM ?2:40 PM

Author(s): Gal Shafirstein, Eduardo G. Moros, K. Barnes, Leah Hennings, Jessica Weber, Beata Przybyla, Robert Griffin, Univ. of Arkansas for Medical Sciences (United States)
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The objective of this work is to develop a new combination therapy consisting of cryoablation and conductive high-temperature ablation(C/HTA), for enhanced thermal ablation of solid tumors. The C/HTA probe was tested, in Balb/c mice bearing solid 4T1 tumors, in comparison to cryoablation and high temperature ablation, only. The C/HTA device induced larger ablation zones, in comparison to either modality alone. The relatively high thermal conductivity of ice, in comparison to water and native tissue, and the reduction in the intracellular pH of the treated margins are assumed to be the main causes for the improved C/HTA outcomes. Grant support: Winthrop Rockefeller Cancer-Institute, Fashion- Footwear Association of New York.

Non-invasive multimodal confocal imaging of squamous cell carcinoma in mice

Paper 7883A-18 of Conference 7883A
Date: Saturday, 22 January 2011
Time: 4:10 PM ?4:30 PM

Author(s): Anna N. Yaroslavsky, Univ. of Massachusetts Lowell (United States); Pawel A. Mroz M.D., Harvard Medical School (United States) and Massachusetts General Hospital (United States); Victor A. Neel, Massachusetts General Hospital (United States)
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We present reflectance and fluorescence confocal images acquired in vivo from squamous cell carcinomas (SCC) developed in SENCAR mice. 0.25 mg/ml aqueous MB was injected in anesthetized mice around cancerous areas. In vivo noninvasive imaging was performed using a multimodal confocal system. Reflectance images were acquired at 658 and 785 nm. Fluorescence images were excited at 658 nm and registered between 690 and 710 nm. Imaging results were compared to the respective H&E histopathology. Both reflectance and fluorescence images of SCC exhibited patterns close to those of human SCC and correlated well with histopathology.

Variations in the optical scattering properties of skin in murine animal models

Paper 7907-28 of Conference 7907
Date: Sunday, 23 January 2011
Time: 11:50 AM ?12:10 PM

Author(s): Katherine Calabro, Boston Univ. (United States); Allison Curtis, Jean-Rene Galarneau, Thomas Krucker, Novartis Institutes for Biomedical Research, Inc. (United States); Irving J. Bigio, Boston Univ. (United States)
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Direct and/or indirect measurement of mouse skin is common in the development of novel biomedical optics techniques. In this work we identify sources of experimental variation that may arise in these studies, indicating that care can be taken to avoid or compensate for their affects. Specifically, gender differences in skin thickness are found to cause differences in the reflectance and scattering coefficient value by up to a factor of two. Additionally, changes in the hair growth cycle are found to influence scattering strength due to changes in skin thickness, and also from melanin collection in hair follicles.

Study of photosensitizers pharmacokinetics in mouse tumor model by transillumination fluorescence imaging in vivo

Paper 7886-30 of Conference 7886
Date: Sunday, 23 January 2011
Time: 4:10 PM ?4:30 PM

Author(s): Marina V. Shirmanova, Irina V. Balalaeva, Marina A. Sirotkina, N.I. Lobachevsky State Univ. of Nizhni Novgorod (Russian Federation); Anna G. Orlova, Ilya V. Turchin, Institute of Applied Physics (Russian Federation); Elena V. Zagaynova, Nizhny Novgorod State Medical Academy (Russian Federation)
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This work demonstrates the possibility of investigation of pharmacokinetics of photosensitizers by means of fluorescence transillumination imaging in vivo. The experiments were performed on transplantable mouse cervical carcinoma using three drugs: photosens, alasens and fotoditazin. Animals were scanned by a single source (semiconductor laser) and detector (FMP) pair in transilluminative configuration. Based on fluorescence imaging, we evaluated in vivo the main pharmacokinetics parameters: maximum tumor-uptake, half-life in tumor, clearance. The results on kinetics of photosensitizers in tumor obtained in vivo agreed with data of standard methods ex vivo.

Del Mar Photonics - Newsletter Fall 2010 - Newsletter Winter 2010

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Comparison of fluorescence tomography of protease-activatable probes in mouse lung tumors with x-ray micro-CT

Paper 7892-32 of Conference 7892
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Xiaofeng Zhang, Cristian Badea, A. Paiman Ghafoori, David Kirsch, Yi Qi, G. Allan Johnson, Duke Univ. (United States)
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Fluorescence tomography provides a noninvasive means to probe the biochemistry within living animals with high sensitivity and specificity. Detection of proteases signifies key diseases in cancer research. In this in vivo animal study, we adopted a protease-mediated activatable fluorescent imaging probe, ProSense 750. The 3D distributions of the fluorescent probe in the living animals was reconstructed using free-space fluorescence diffuse optical tomography, and subsequently compared to anatomical images obtained using x-ray micro-CT. It was observed that activation of the imaging probe was not completely accordant to tumor size.

Laser injury and in-vivo multimodal imaging using a mouse model

Paper 7897-38 of Conference 7897
Date: Tuesday, 25 January 2011
Time: 4:00 PM ?4:20 PM

Author(s): Ginger M. Pocock, Air Force Research Lab. (United States); Adam Boretsky, Praveena Gupta, The Univ. of Texas Medical Branch (United States); Jeffrey W. Oliver, Air Force Research Lab. (United States); Massoud Motamedi, The Univ. of Texas Medical Branch (United States)
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A murine model was used to perform in vivo experiments of laser-induced thermal damage to the retina. The expression kinetics and protein localization of biomarkers after laser induced injury to the retina and skin would provide a better understanding of the laser exposure levels at which the tissue becomes "stressed" and may be useful to detect sub-threshold laser damage that may or may not manifest as a visible lesion. A Heidelberg Spectralis HRA with a spectral domain optical coherence tomographer (OCT) was used to obtain images of the fundus and obtain cross-sectional views of the retina. Subthreshold and threshold lesions were observed using the OCT, infrared (IR) reflectance, and autofluorescence imaging modalities to observe lesion appearance. Volumetric representations of the retina were created to visualize lesion localization of damage.

Development and validation of a combined photoacoustic micro-ultrasound system for in-vivo oxygen saturation estimation

Paper 7899-84 of Conference 7899
Date: Tuesday, 25 January 2011
Time: 5:30 PM ?5:45 PM

Author(s): Andrew Needles, Andrew Heinmiller, Pinhas Ephrat, David Bates, Corina Bilan-Tracey, Catherine Theodoropoulos, Desmond Hirson, Visualsonics Inc. (Canada); F. Stuart Foster, Sunnybrook Health Sciences Ctr. (Canada)
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Photoacoustic (PA) imaging can estimate the spatial distribution of oxygen saturation (SO2) in blood, and be co-registered with B-Mode images of the surrounding anatomy. This talk will focus on the development of a PA imaging mode on a commercially available array based micro-ultrasound (礥S) system that is capable of creating such images. Beamforming techniques, mode-interleaving, digital sampling and signal processing will be described, along with a new technique for in vivo validation of PA-SO2 estimation.

Imaging of hyaloid vessels in mouse embryonic eye with swept source optical coherence tomography

Paper 7885-6 of Conference 7885
Date: Saturday, 22 January 2011
Time: 9:30 AM ?9:45 AM

Author(s): Kirill V. Larin, Univ. of Houston (United States)
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Throughout much of embryonic development, the mammalian lens is surrounded by a hyaloid vascular system. This vasculature is considered vital for the maturation and growth of the lens. OCT is a 3D imaging modality, which has the capability of producing high resolution (~8祄) images with an imaging depth of up to 3 mm. We tested the capability of OCT to perform live 3D imaging of the hyaloid vasculature in the embryonic eye in utero. Our results suggest that OCT can be used to understand the development and progression of hyaloid vasculature in the vitreous region of the eye.

Cortical blood flow imaging of mouse stroke model by high-speed spectral OCT

Paper 7883E-109 of Conference 7883E
Date: Saturday, 22 January 2011
Time: 4:00 PM ?4:20 PM

Author(s): Ireneusz Grulkowski, Nicolaus Copernicus Univ. (Poland); Grzegorz Wilczynski, Nencki Institute of Experimental Biology (Poland); Danuta Bukowska, Maciej Szkulmowski, Nicolaus Copernicus Univ. (Poland); Jakub Wlodarczyk, Nencki Institute of Experimental Biology (Poland); Karol Karnowski, Daniel Ruminski, Andrzej A. Kowalczyk, Maciej Wojtkowski, Nicolaus Copernicus Univ. (Poland)
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We have developed and applied a high-speed spectral OCT system to image small animal brains. OCT imaging with high temporal and spatial resolution enabled cortical blood flow visualization. We imaged the brain vascular network of an anesthetized mouse stroke model. We demonstrated the impact of induced stroke on the brain vasculature. The preliminary studies have revealed local ischemia in the areas of the stroke.

In-utero imaging of mouse embryonic development with optical coherence tomography

Paper 7889-9 of Conference 7889
Date: Monday, 24 January 2011
Time: 11:00 AM ?11:15 AM

Author(s): Saba H. Syed, Univ. of Houston (United States); Irina V. Larina, Mary E. Dickinson, Baylor College of Medicine (United States); Kirill V. Larin, Univ. of Houston (United States)
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Embryonic imaging is the most important tool in understanding and investigating developmental diseases. Mouse embryos have long served as an ideal model for the study of mammalian embryonic developmental processes. OCT is a promising technique introduced recently to developmental biology. In this study we introduce OCT as a novel technique to image live mouse embryos from stage 12.5 through 17.5 days post-coitus (dpc). This study suggest that OCT can serve as a powerful tool to image mouse embryos with a resolution of ~8 祄 and can help in understanding abnormalities in developmental processes caused by mutations, or toxic drugs.

Visualization of mouse kidney perfusion with multispectral optoacoustic tomography (MSOT) at video rate

Paper 7899-39 of Conference 7899
Date: Monday, 24 January 2011
Time: 11:15 AM ?11:30 AM

Author(s): Andreas Buehler, Eva Herzog, Daniel Razansky, Vasilis Ntziachristos, Helmholtz Zentrum München GmbH (Germany)
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We report herein on a novel multi-spectral optoacoustic tomography (MSOT) system for deep tissue small animal imaging. The previously undocumented capacity of whole body optoacoustic tomography at video rate has been demonstrated by visualizing mouse kidney perfusion using Indocyanine Green in vivo.

Imaging necrosis in mouse models of muscular dystrophy with three-dimensional optical coherence tomography

Paper 7889-12 of Conference 7889
Date: Monday, 24 January 2011
Time: 11:45 AM ?12:00 PM

Author(s): Blake R. Klyen, Thea Shavlakadze, Miranda D. Grounds, David D. Sampson, The Univ. of Western Australia (Australia)
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We report the use of three-dimensional optical coherence tomography (3D-OCT) in conjunction with Evans blue dye, a marker for muscle fiber permeability, used to guide the 3D-OCT imaging. We apply this to imaging mouse skeletal muscle tissue from exercise-induced damage models of dystropathology in human muscular dystrophy. Images are presented that show the ability of 3D-OCT to identify lesions, regions of necrosis and inflammation, within large volumes of skeletal muscle tissue, and differentiate these from the surrounding intact muscle fibers. These results demonstrate that 3D-OCT is a suitable modality for small animal imaging studies of muscular dystrophy.

Indocyanine green enhanced near-infrared laser treatment of SCK tumors in a mouse model

Paper 7901-37 of Conference 7901
Date: Monday, 24 January 2011
Time: 3:45 PM ?4:00 PM

Author(s): Gal Shafirstein, Univ. of Arkansas for Medical Sciences (United States); Wolfgang Bäumler, Univ. Clinics Regensburg (Germany); Ran Friedman, K. Barnes, Leah Hennings, Jessica Weber, Robert Griffin, Univ. of Arkansas for Medical Sciences (United States)
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The objective of this study was to determine the efficacy of indocyanine green (ICG) dye in enhancing near infrared (NIR) laser ablation of tumors in a mouse model. Tumors were treated with 808-nm laser using 86 J/cm2 radiant exposures preceded by intravenous injection of 4 mg/kg body weight of ICG solution or sterile water. No skin damage was observed in the treated animals. Minor thermal damage and necrosis was observed histologically in the tumor post laser/water treatment and substantial intra-tumor damage was observed in tissue collected from tumors that were treated with laser/ICG.

Del Mar Photonics - Newsletter Fall 2010 - Newsletter Winter 2010

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Differential distribution of dopamine functionalized quantum rods in mouse

Paper 7909-43 of Conference 7909
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): A. Guardascione, Istituto di Cibernetica CNR (Italy); A. Ragusa, National Nanotechnology Lab. CNR (Italy); M. Rimoli, R. Russo, Univ. Federico II (Italy); Claudia Tortiglione, Angela Tino, Istituto di Cibernetica CNR (Italy)
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The conjugation of bioactive molecules to water soluble fluorescent semiconductors nanocrystals, opens new perspectives to the studies of drug distribution in target tissues and organs. The neurotransmitter dopamine (DA) is involved in a variety of signaling pathways and its altered levels have been found in different pathological conditions, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD). The possibility to modulate brain DA levels might hold great promise for therapeutic purposes. As free DA is not able to cross the blood-brain barrier DA based produg, such as galactosylated DA, GalDA, already proved to mediate DA diffusion across the BBB. With the aim to investigate the extent of their release/accumulation into target cells, we have recently produced fluorescent nanocrystals (Quantum Rods) conjugated to GalDA. Here, we characterize the pharmacodistribution of the functional abduct (GalDA-QRs) administered intravenously in mice. We present the selective distribution of GalDA-QRs one hour after injection and the relative amount detected ex vivo in different organs is discussed in the general frame of cell- and tissue specific interactions with nanoparticles, opening new perspectives in the design and feasibility to use inorganic nanoparticles for diagnosis and therapeutic purposes.

Imaging of the intact mouse cochlea by spectral-domain optical coherence tomography

Paper 7889-108 of Conference 7889
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Simon S. Gao, Rice Univ. (United States); Anping Xia, Stanford Univ. (United States); Tao Yuan, Patrick Raphael, Baylor College of Medicine (United States); Ryan L. Shelton, Brian E. Applegate, Texas A&M Univ. (United States); John S. Oghalai, Baylor College of Medicine (United States)
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Current medical imaging modalities do not provide high enough resolution to detect minor changes in the cochlea, the hearing organ. We sought to develop the technique of optical coherence tomography (OCT) to image the cochlea noninvasively. We used spectral domain OCT with a center wavelength of 950 nm and a bandwidth of ~100 nm. We found that the intracochlear soft tissue is visible through bone and that structural differences can be seen in the cochlea of newborn and adult mice. We conclude that spectral domain OCT is an effective technique for noninvasive imaging of the murine cochlea.

In-vivo cellular metabolism of mouse liver revealed by multiphoton microscopy

Paper 7903-62 of Conference 7903
Date: Tuesday, 25 January 2011
Time: 10:35 AM ?10:50 AM

Author(s): Chun-Chin Wang, Wei-Liang Chen, Zhi-Ru Lin, Feng-Chieh Li, Ara Ghazaryan, Hsuan-Shu Lee, Sung-Jan Lin, Chen-Yuan Dong, National Taiwan Univ. (Taiwan)
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We performed a novel method to observe the dynamics of the uptake, processing, and excretion of fluorescent probes in the hepatobiliary system of mice in vivo. A hepatic window was installed on the upper abdomen of mice to acquire time-lapse images. The high resolution images show sequential uptake and processing of fluorescent probes by hepatocytes and the subsequent excretion into bile canaliculi within 50 min. The kinetics of fluorescence intensities in hepatocytes and sinusoids were measured and analyzed in time series and spatial distribution. We demonstrated a promising technique to study intravital hepatic metabolism about normal and diseased mice.

Multimodality optical imaging of ovarian cancer in a post-menopausal mouse model

Paper 7890-32 of Conference 7890
Date: Tuesday, 25 January 2011
Time: 11:30 AM ?11:50 AM

Author(s): Jennifer M. Watson, Photini F. Rice, David L. Bently, Samuel L. Marion, The Univ. of Arizona (United States); Molly A. Brewer, Univ. of Connecticut Health Ctr. (United States); Patricia B. Hoyer, Jennifer K. Barton, The Univ. of Arizona (United States)
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Our goal is to use optical imaging to detect cancer development on the sub cellular scale. By determining the microscopic changes that precede ovarian cancer we hope to develop a minimally invasive screening test for high risk patients. A mouse ovarian cancer model has been developed by treating mice with 4-Vinylcyclohexene Diepoxide to induce ovarian failure and 7, 12-Dimethylbenz[a]anthracene (DMBA) to induce ovarian cancer. Using optical coherence tomography (OCT) and multiphoton microscopy (MPM) we have obtained co-registered en face images of twenty mouse ovaries ex vivo. Preliminary analysis indicates that OCT and MPM can visualize ovarian microstructure. During the next year we will be completing a long term survival study using post-menopausal mice that have been treated with DMBA to induce cancer and imaged in vivo at time points before and after treatment.

Fluorescence lifetime molecular tomography of a genetically expressed FRET construct in a mouse

Paper 7896-65 of Conference 7896
Date: Wednesday, 26 January 2011
Time: 9:50 AM ?10:10 AM

Author(s): James A. McGinty, Imperial College London (United Kingdom); Vadim Y. Soloviev, Univ. College London (United Kingdom); Daniel W. Stuckey, Khadija B. Tahir, Romain Laine, Imperial College London (United Kingdom); Dominic J. Wells, The Royal Veterinary College (United Kingdom); Jo V. Hajnal, Alessandro Sardini, Imperial College London (United Kingdom); Simon R. Arridge, Univ. College London (United Kingdom); Paul M. W. French, Imperial College London (United Kingdom)
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We demonstrate 3-D tomographic FLIM reconstruction of a genetically expressed FRET construct, including negative controls, in mice ex vivo. The FRET construct and controls were characterised in a time-resolved spectrofluorometer before being electroporated into the anterior tibialis of mice. Five days post-electroporation, at the peak of expression, the mice were sacrificed and imaged, acquiring both excitation and fluorescence signals using a wide-field time-gated imaging system with rotational scanning. The reconstructions, using a diffusion analogue of a back-projection algorithm, display a reduction in fluorescence lifetime and quantum yield for the FRET construct compared to the controls, clearly reporting the FRET interaction.
 

Del Mar Photonics - Newsletter Fall 2010 - Newsletter Winter 2010

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Optical microangiography provides in vivo 3D images of intracochlear microstructures and microvascular perfusion in mice

Paper 7883C-186 of Conference 7883C
Date: Saturday, 22 January 2011
Time: 1:10 PM ?1:30 PM

Author(s): Ruikang K. Wang, Hrebesh M. Subhash, Viviana Davila, Hai Sun, Anh T. Nguyen-Huynh, Alfred L. Nuttall, Oregon Health & Science Univ. (United States)
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Dynamic three-dimensional imaging of lung parenchyma by OCT in mice

Paper 7893-24 of Conference 7893
Date: Monday, 24 January 2011
Time: 8:20 AM ?8:40 AM

Author(s): Sven Meissner, Technische Univ. Dresden (Germany); Arata Tabuchi, St. Michael's Hospital (Canada); Michael Mertens, Charité Universitätsmedizin Berlin (Germany); Wolfgang M. Kübler, St. Michael's Hospital (Canada); Edmund Koch, Technische Univ. Dresden (Germany)
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We present a method for dynamic 3-D imaging of healthy and injured subpleural lung tissue in the ventilated mouse. We use triggered swept source OCT to image murine subpleural alveoli during the inspiratory phase. The acquired B-scans are combined off-line into one volume scan for each pressure level. The air fraction in healthy lungs and injured lungs is measured using 2-D OCT en-face images. Upon lung inspiration from 2 to 12 cmH2O ventilation pressure, the air fraction increases in healthy lungs by up to 11% and in injured lungs by 8%. This expansion correlates well with results of previous studies.

In-vivo optical measurement of activity-dependent fluorescence change in striatum using synaptophluorin mice

Paper 7883G-140 of Conference 7883G
Date: Monday, 24 January 2011
Time: 8:50 AM ?9:10 AM

Author(s): Sang Beom Jun, Guohong Cui, Xin Jin, Michael D. Pham, Christopher Thaler, Steven S. Vogel, National Institutes of Health (United States); Rui Costa, Instituto Gulbenkian de Ciência (Portugal); David M. Lovinger, National Institutes of Health (United States)
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A novel method is proposed to monitor neural activity in synaptophluorin transgenic mice using fiber optics and time-correlated single photon counting. Synaptophluorin is a pH-sensitive EGFP derivative that increases fluorescence upon exocytosis. The optic fibers and a microelectrode array were assembled and implanted into the dorsolateral striatum region of the mice. Anesthesia with isoflurane induced the decrease of photon emission/detection as well as the decreases of electrical neural activity. In behaving animals, fluorescence was transiently increased by an auditory stimulus. These findings indicate that we can use in vivo photometry to measure fluorescence changes that report physiological changes in brain.

In vivo longitudinal photoacoustic imaging of subcutaneous tumours in mice

Paper 7899-40 of Conference 7899
Date: Monday, 24 January 2011
Time: 11:30 AM ?11:45 AM

Author(s): Jan G. Laufer, Peter Johnson, Edward Z. Zhang, Barbara Pedley, Paul C. Beard, Univ. College London (United Kingdom)
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Photoacoustic tomography provides 3D images of superficial vascular networks with high spatial resolution, can be used to visualise the distribution of contrast agents, and is therefore suited to the study of the progression and treatment of human diseases in small animal models. In vivo photoacoustic images of subcutaneous tumours in mice were acquired over several days to monitor tumour growth and changes in the vasculature. Through multiwavelength imaging and spectral analysis, differences in the oxygenation distribution across the tumour were measured. The results suggest that photoacoustic imaging could play a role in the development of new antiangiogenic therapies.

Thermal ablation and/or spatially fractionated radiation (GRID) therapy for down-staging locally advanced breast cancer

Paper 7901-39 of Conference 7901
Date: Monday, 24 January 2011
Time: 4:20 PM ?4:35 PM

Author(s): Gal Shafirstein, Robert Griffin, K. Barnes, Jessica Weber, Sunil Sharma, Eduardo G. Moros, Univ. of Arkansas for Medical Sciences (United States)
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The purpose of this work was to test our hypothesis that thermal ablation and/or spatially fractionated radiation (GRID) therapy can be used for significant tumor cytoreduction of locally advanced tumors. Conductive interstitial thermal therapy and/or GRID radiotherapy were used to treat Balb/c mice bearing 4T1 tumors. A 2 to 4-fold reduction in tumor's growth was observed in the treated animals in comparison to the control animals. Our preliminary results showed that both GRID and CITT could be effective for significant tumor cytoreduction in 4T1 tumors implanted in Balb/c mice. Grant support: Winthrop Rockefeller Cancer-Institute, Fashion- Footwear Association of New York.

Non-invasive quantification of the metabolic rate of oxygen (MRO2) by photoacoustic microscopy: a hyperthermia study of the mouse ear

Paper 7899-22 of Conference 7899
Date: Sunday, 23 January 2011
Time: 4:00 PM ?4:15 PM

Author(s): Junjie Yao, Konstantin Maslov, Lihong V. Wang, Washington Univ. in St. Louis (United States)
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Many diseases, normal decay and physiological functions are closely related to alterations in the metabolic rate of oxygen (MRO2). In this study, we demonstrate that all the parameters for MRO2 quantification can be simultaneously obtained by optical-resolution photoacoustic microscopy (OR-PAM). MRO2 of the mouse ear under normothermia (31 ºC skin temperature) and controlled systematic hyperthermia (42 ºC skin temperature) was studied. As a result of hyperthermia, the MRO2 increased by 28.3 ?9.4%. The results show that OR-PAM, as a single noninvasive imaging modality, is intrinsically suitable for quantitative MRO2 measurement in microenvironments.

Implementing label-free microscopy and spectroscopy to study a new mouse model of non-alcoholic steatohepatitis

Paper 7903-91 of Conference 7903
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Iwan W. Schie, UC Davis Medical Ctr. (United States)
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Background: Most common nonalcoholic steatohepatitis (NASH) models in rodents are induced by feeding either diet containing high fat/high calorie (HFC) or methionine/choline deficient diet (MCD). The former caused overweight, NASH with mild insulin resistance; whereas the latter leads to weight loss, steatosis with no insulin resistance.Trans-10, cis-12 conjugated linoleic acid (CLA) is a positional and geometric isomer of linoleic acid found in partially hydrogenated vegetable oils. Controversial findings exit regarding its role in affecting lipid metabolism and fat deposition. The aim of the present study is to characterize steatosis influenced by CLA-rich diets using Raman spectroscopy and coherent anti-Stokes Raman scattering (CARS) microscopy.

Del Mar Photonics - Newsletter Fall 2010 - Newsletter Winter 2010

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Depth-resolved optical imaging of hemodynamic response within macro- and micro-circulatory beds in mouse brain

Paper 7898-36 of Conference 7898
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Yali Jia, Oregon Health & Science Univ. (United States); Jingyang Jiang, Oregon Health & Science Univ. (United States) and Tianjin Univ. (China); Zhongwei Zhi, Ruikang K. Wang, Oregon Health & Science Univ. (United States)
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We introduce a hemodynamic imaging system based on optical micro-angiography (OMAG) which is capable of resolving and quantifying 3D dynamic blood perfusion down to capillary level. By use of a hybrid scanning protocol, this system can measure the optical phase shifts caused by fast moving blood cells in macro-circulation and slow moving blood cells in micro-circulation. Here, the utility of OMAG was demonstrated by monitoring the hemodynamic response to a drug administration in mice. Our preliminary results show the potential of OMAG in studying neurovascular pathology and as well as in investigating efficacy of treatments.

Functional transcranial photoacoustic micro-imaging of mouse cerebrovascular cross-section and hemoglobin oxygenation changes during forepaw electrical stimulation

Paper 7899-106 of Conference 7899
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Lun-De Liao, You-Yin Chen, Chin-Teng Lin, Jyh-Yeong Chang, National Chiao Tung Univ. (Taiwan); Meng-Lin Li, National Tsing Hua Univ. (Taiwan)
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In this study, we report on using a 50-MHz functional photoacoustic microscopy (PAM) to transcranially image the cross-section and hemoglobin oxygenation (SO2) changes of single mouse cortical vessels in response to left forepaw electrical stimulation. Three difference levels of the cortical vessels (i.e., with different-sized diameters of 350, 120 and 55 um) on activated regions were marked to measure their functional cerebrovascular cross-section and SO2 changes as a function of time. The averaged vasodilatation observed at the three vessel levels was about 18%, 23% 34% upon stimulation, respectively. Moreover, its correlation with the electrical stimulation paradigm was also statistically analyzed.

Synthesis and characterization of CdHgTe/SiO2 nanoparticles for in-vivo study of their dynamic distribution in mouse model

Paper 7910-26 of Conference 7910
Date: Tuesday, 25 January 2011
Time: 9:30 AM ?9:50 AM

Author(s): Haiyan Chen, Sisi Cui, Yueqing Gu, China Pharmaceutical Univ. (China)
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In this study, CdHgTe/SiO2 core-shell nanoparticles were synthesized by coating of silylating reagent on the surface of CdHgTe QDs. The size change after coating a silica shell had been characterized by laser size analyzer. Photoluminescence studies showed that the silica shell resulted in a minor decline of fluorescence intensity and greatly increased photostability in phosphate-buffered saline buffers. Acute toxicity study indicated the obvious toxicity reduction of CdHgTe QDs after coating with silica shell. The dynamic bio-distribution of CdHgTe/SiO2 nanoparticles in living mouse was in vivo monitored by a NIR imaging system. Results indicated the liver-intestine metabolic pathway of these Nanoparticles.

Anti-transforming growth factor beta antibody combined with photodynamic therapy for renal cell carcinoma in mice

Paper 7900-2 of Conference 7900
Date: Monday, 24 January 2011
Time: 9:30 AM ?10:00 AM

Author(s): Michael R. Hamblin, Pawel A. Mroz M.D., Massachusetts General Hospital (United States)
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Photodynamic therapy (PDT) has been shown to be an effective locally ablative anti-cancer treatment that has the additional advantage of inducing tumor-directed immune response. We hypothesize that PDT combined with anti-TGF beta antibody that does not significantly affect the population of cytotoxic T lymphocytes (CTL) and, at the same time, has the potency to decrease the immunosuppressive effects of Treg mediated by TGF beta. This hypothesis was tested with aTGF-beta antibody combined with BPD-mediated PDT in a BALB/c renal cell carcinoma model.

Volumetric in-vivo imaging of intracochlear microstructures and microvascular perfusion in mice using high-speed spectral domain optical coherence tomography and ultra-high-sensitive optical micro-angiography

Paper 7889-102 of Conference 7889
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Hrebesh M. Subhash, Viviana Davila, Hai Sun, Anh T. Nguyen-Huynh, Alfred L. Nuttall, Ruikang K. Wang, Oregon Health & Science Univ. (United States)
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Studying the inner ear microstructures and microvascular dynamics is extremely important to understand the cochlear function and to further advance the diagnosis, prevention and treatment of many otologic disorders. There is considerable interest in developing new methods for in vivo imaging of the complex anatomy of the mammalian cochlea and the micro vascular perfusion within it for both clinical as well as fundamental studies. In this study, we explored the feasibility of high-speed spectral domain optical coherence tomography (SD-OCT) and ultra-high sensitive optical microangiography (UHS-OMAG) for volumetric in vivo imaging of intracochlear microstructures and microvascular perfusion in mice, respectively.

Label-free in-vivo optical micro-angiography imaging of cerebral capillary blood flow within meninges and cortex in mice with the skull left intact

Paper 7889-37 of Conference 7889
Date: Tuesday, 25 January 2011
Time: 11:00 AM ?11:15 AM

Author(s): Yali Jia, Ruikang K. Wang, Oregon Health & Science Univ. (United States)
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Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ~2 mm, with an unprecedented imaging sensitivity to the blood flow at ~4 祄/s. In this study, we demonstrate the utility of OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within meninges and cortex in mice with the cranium left intact. The results indicate that OMAG can be a valuable tool for the study of meningeal circulations

Low-coherence wavefront sensing for AO imaging in rodent eyes

Paper 7885-42 of Conference 7885
Date: Sunday, 23 January 2011
Time: 11:45 AM ?12:00 PM

Author(s): Robert D. Ferguson, Daniel X. Hammer, Mircea Mujat, Nicusor V. Iftimia, Niyom Lue, David P. Biss, Ankit H. Patel, Physical Sciences Inc. (United States); James D. Akula, Children's Hospital Boston (United States)
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Rodent models of human eye disease have significantly increased the demand for, and the value of, new in vivo animal eye imagers with cellular resolution. The small eye of the mouse has the potential to provide the best and brightest imaging of any mammal eye, with superior retinal image resolution. However, due to the poor optical quality of mouse eyes even high resolution imaging can't easily select layers for precision adaptive optics (AO) correction. We describe recent progress toward the develop and demonstration a new, compact multimodal AO imaging platform optimized for rodent imaging, and novel alternatives to SHWS including a low-coherence wavefront sensing (LCWS) techniques.

In-vivo particle image velocimetry of the blood flow using the confocal laser scanning microscope

Paper 7906A-24 of Conference 7906A
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Ho Lee, Wi-Han Kim, SungMin Choi, Cheol-Woo Park, Kyungpook National Univ. (Korea, Republic of)
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In the previous meeting (PhotonicWest 2010), we reported "the blood cell-based Particle Image Velocimetry (PIV)" in a micro-tube using the confocal microscope. In that study, we employed blood cells as tracing particles, while previous microscopy-assisted PIV required exogenous particles as the tracing particles. In this study, we are reporting the application of the "the blood cell-based PIV" for the measurements of blood stream in a live animal. We used video-rate CLSM to observe blood cells in a live mouse ear. The acquired images were used to perform PIV, thus providing the blood velocity profile in capillaries of live mouse ear.

Steroid-induced osteoporosis monitored by Raman spectroscopy

Paper 7883F-124 of Conference 7883F
Date: Saturday, 22 January 2011
Time: 9:20 AM ?9:40 AM

Author(s): Jason R. Maher, Masahiko Takahata, Hani A. Awad, Andrew J. Berger, Univ. of Rochester (United States)
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Glucocorticoids are frequently used to treat inflammatory disorders such as rheumatoid arthritis. Unfortunately, extended exposure to this steroid is the leading cause of physician-induced osteoporosis, leaving patients susceptible to fractures at rates of 30-50%. In this presentation, we report correlations between Raman spectra and biomechanical strength tests on bones of placebo- and glucocorticoid-treated mice. Both wild-type mice and a transgenic model of rheumatoid arthritis have been studied. A two-way ANOVA model reveals statistically significant spectral differences as influenced by glucocorticoid treatment and mouse type. In addition, we discuss strategies to extract key Raman parameters of bone through overlying soft tissue.

Potentialities of a new bimodal x-ray/fluorescence tomograph within a cyindrical geometry for preclinical studies

Paper 7892-18 of Conference 7892
Date: Saturday, 22 January 2011
Time: 4:40 PM ?5:00 PM

Author(s): Anne Koenig, Anne Planat-Chrétien, Jean-Guillaume Coutard, Lionel Hervé, Marco Brambilla, Commissariat à l'Énergie Atomique (France); Véronique Josserand, Jean-Luc Coll, Institut Albert Bonniot (France); Jean-Marc Dinten, Commissariat à l'Énergie Atomique (France)
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An instrument dedicated to the co-registration of optical and X-ray measurements, has been developed: specific acquisition protocol and reconstruction software have been developed for carrying out fluorescence diffuse optical tomography in a cylindrical geometry consistent with XCT. Actual animal geometry provided by the X-ray tomography is used to give animal boundaries to the diffuse optical tomography reconstruction algorithm. To evaluate performances of this new optical imaging system, experiments have been conducted on phantoms, mice with fluorescent capillaries, and finally on mice bearing tumours. The fluorescence reconstructions are shown to be geometrically consistent with X-ray ones.

High-resolution in-vivo targeted imaging of colorectal dysplasia with a LED-based confocal microendoscope

Paper 7893-5 of Conference 7893
Date: Sunday, 23 January 2011
Time: 9:30 AM ?9:50 AM

Author(s): Sakib F. Elahi, Sharon J. Miller, Thomas D. Wang M.D., Univ. of Michigan (United States)
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We demonstrate a LED-based, flexible, fibered microscope that is sufficiently small to pass through the instrument channel of a small animal endoscope for in vivo molecular imaging of the colonic mucosa of mice. The instrument delivers excitation light through a fiber-optic bundle with outer diameter 680 祄, and achieves 0.7 mW of power with a lateral resolution of 4 祄. Independently, FITC-labeled selective and control peptides are applied topically to the mucosa of transgenic mice that spontaneously develop distal colonic adenomas. Using the microendoscope, we found that targeted peptide preferentially binds to adenomas with three-fold greater affinity.

In-vivo small animal optical imaging enhanced with indocyanine green and saline

Paper 7892-38 of Conference 7892
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Ning Liu, Yuting Lin, Mitchell Hsing, Orhan Nalcioglu, Gultekin Gulsen, Univ. of California, Irvine (United States)
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We present a comparison of the in vivo mice optical images enhanced with ICG and saline separately. The multimodality imaging system used here combines frequency-domain optical techniques and MRI. 16 fibers (8 illuminations and 8 collections) radially arranged to obtain the transverse images of the mice revealing tumor. The acquisition time for one optical image was 16 seconds. Each dynamic measurement lasted for 50 minutes, with bolus injection at 5mins. The pharmacokinetics of ICG and saline at the same tumor location showed comparable signal level, but opposite curvature variation. The reconstructed tomograms showed enhancement at tumor location in both cases.

Systemic induction of heat shock protein 70 following tumor treatment by photodynamic therapy

Paper 7900-1 of Conference 7900
Date: Monday, 24 January 2011
Time: 9:00 AM ?9:30 AM

Author(s): Mladen Korbelik, Soroush Merchant, The BC Cancer Agency Research Ctr. (Canada)
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Photodynamic therapy (PDT) induces a strong upregulation of heat shock protein 70 (Hsp70) in treated tumor. We report that Hsp70 gene expression was increased following PDT in the tumor and liver of host mice. Recombinant Hsp70 protein administered to tumor-bearing mice accumulated in both the liver and tumor but the tumor:liver ratio was found to increase when the tumors were treated by PDT. Thus following PDT, Hsp70 is upregulated at distant systemic sites and sequestered to damaged tumor tissue to facilitate the disposal of dying cells and influence the development of antitumor immune response elicited by this therapy.

Monitoring early tumor response to drug therapy using optical tomography

Paper 7896-43 of Conference 7896
Date: Tuesday, 25 January 2011
Time: 9:10 AM ?9:30 AM

Author(s): Molly L. Flexman, Hyun-Keol Kim, Columbia Univ. (United States); Sonia L. Hernandez, Jianzhong Huang, Tessa Johung, Columbia Univ. Medical Ctr. (United States); Jong Hwan Lee, Fotios Vlachos, Columbia Univ. (United States); Darrell J. Yamashiro, Jessica J. Kandel, Columbia Univ. Medical Ctr. (United States); Andreas H. Hielscher, Columbia Univ. (United States)
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Anti-angiogenic drugs have shown promising results in cancer therapy but have also shown a large variability in effectiveness. We present a study that uses optical tomography to image mice implanted with two different kidney tumor models. We found that a Ewing sarcoma tumor model shows a statistically significant drop in blood volume within 5 days of treatment with bevacizumab, an FDA approved anti-angiogenic drug. Mice implanted with a neuroblastoma tumor model, known to not respond well to bevacizumab, do not show this drop in blood volume, suggesting that optical tomographic imaging may be used to monitor early treatment response.

Tumor hypoxia fluorescence imaging using 2-nitroimidazole bis-carboxylic acid indocyanine dye conjugate

Paper 7896-63 of Conference 7896
Date: Wednesday, 26 January 2011
Time: 9:10 AM ?9:30 AM

Author(s): Nrusingh C. Biswal, Christopher Pavlik, Michael B. Smith, Univ. of Connecticut (United States); Liisa T. Kuhn, Kevin P. Claffey, Univ. of Connecticut Health Ctr. (United States); Quing Zhu, Univ. of Connecticut (United States)
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We present the tumor-targeted hypoxia fluorescence imaging using a novel 2-nitroimidazole indocyanine dye conjugate. In-vivo tumor targeting in six mice demonstrated that a measured half-life of 2-nitroimidazole-indocyanine dye wash out was significantly longer (112?2.37 minutes) than that of unconjugated indocyanine dye alone (69.75?4.01 minutes). Fluorescence images of mice tumors showed a 2.6-fold contrast of dye uptake with hypoxic conjugate injection compared to that with unconjugated indocyanine dye injection. A fluorescence emission ratio of 2.5-fold was found between the tumor cells treated with the 2-nitroimidazole-indocyanine dye and incubated under hypoxia compared to the cells in normoxia condition.

Multisite and multidepth tumors localization enhancement after autofluorescence removal

Paper 7896-64 of Conference 7896
Date: Wednesday, 26 January 2011
Time: 9:30 AM ?9:50 AM

Author(s): Anne-Sophie Montcuquet, Fabrice P. Navarro, Lionel Hervé, Commissariat à l'Énergie Atomique (France); Jérôme I. Mars, Institut National Polytechnique de Grenoble (France); Jean-Marc Dinten, Commissariat à l'Énergie Atomique (France)
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Fluorescence imaging in diffusive media locates tumors tagged by injected fluorescent markers in NIR wavelengths. For deep embedded markers, natural autofluorescence of tissues comes to be a limiting factor to tumor detection and accurate FDOT reconstructions. A spectroscopic approach coupled with Non-negative Matrix Factorization source separation method is explored to discriminate fluorescence sources according to their fluorescence spectra and remove unwanted autofluorescence. We successfully removed autofluorescence from acquisitions on living mice with a single subcutaneous tumor or two capillary tubes inserted at different depths. Future experiments on mice with mutli-site and multi-depth tumors will be presented at BIOS 2011 symposium.

Using Raman spectroscopy to study the onset of labor

Paper 7890-45 of Conference 7890
Date: Tuesday, 25 January 2011
Time: 4:50 PM ?5:10 PM

Author(s): Elizabeth Vargis, Nathan Webb, B. C. Paria, Jeff Reese, Kelly Bennett, Vanderbilt Univ. (United States); Ayman Al-Hendy, Meharry Medical College (United States); Anita Mahadevan-Jansen, Vanderbilt Univ. (United States)
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Preterm labor is the second leading cause of neonatal mortality and can lead to a number of complications for the mother and her child. Having a tool to predict preterm labor could lead to an increased amount of births that come to term. While there are few ways to predict preterm labor with fetal fibronectin screening and cervical length measurements, over half of all preterm births are not diagnosed and do not fall into any high-risk category. This study seeks to predict the onset of labor by using Raman spectroscopy to detect changes in the cervix during pregnancy. Raman spectra were acquired from the cervix of non-gravid and gravid mice and humans, all of whom delivered at full term. We believe significant changes will occur in the Raman spectra obtained during the course of pregnancy. Preliminary results show that there are differences based on cycling status alone, in both mice and humans. Furthermore, there are significant changes that occur during pregnancy. This study will determine if Raman spectroscopy can be used to predict when labor will occur, most likely due to the effect of cervical softening and changes in hormonal levels on the spectra. Any algorithm that can be developed to predict when a woman will enter labor will greatly benefit the outcome for pregnant women and their children.

 

Del Mar Photonics - Newsletter Fall 2010 - Newsletter Winter 2010

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Kinetics of gold nanorod distribution in mouse tissues after intravenous injection monitored with optoacoustic tomography

Paper 7899-157 of Conference 7899
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Richard Su, Anton Liopo, Hans-Peter F. Brecht, Sergey A. Ermilov, Alexander A. Oraevsky, TomoWave Labs., Inc. (United States)
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A three dimensional laser optoacoustic imaging system analyzed the kinetics of gold nanorod (GNR) distribution after being intravenously injected into live mice. Animals were scanned prior to GNR injection and then periodically up to one week post-injection. Because GNR were stabilized with a toxic material, cetyltrimethylammonium bromide, we purified GNR for in vivo use by centrifugation, filtration, and pegylation and verified in MTT assays. Higher levels of GNR were found in liver macrophages after 48 hours and decreased after seven days. GNR injected in mice were found in the periphery within hours before settling into certain organs after a day.

Folate receptor targeted Type-1 photosensitizer bioconjugates for tumor visualization and phototherapy

Paper 7886-12 of Conference 7886
Date: Saturday, 22 January 2011
Time: 3:30 PM ?3:50 PM

Author(s): Raghavan Rajagopalan, Amruta R. Poreddy, Nicole Putnam, Amolkumar Karwa, Rick M. Fitch, Karen P. Galen, Maureen Nichols, Lori Chinen, Arti Naik, Carolyn Sympson, Richard B. Dorshow, Covidien (United States)
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Folate receptors are over expressed in many types of cancers, including, ovarian, breast, and cervical. In our continuing efforts toward the development of targeted Type 1 phototherapeutic agents, an azide-based Type 1 photosensitizer, a fluorophore, and a dual diagnostic-therapeutic probe consisting of the fluorophore and the photosensitizer units were prepared and independently conjugated to two vectors that target folate receptors. The results of in vitro binding and cell viability assays using KB ovarian cancer cells, and in vivo studies using the nude mouse xenograft model demonstrating selective uptake and tumor destruction will be presented.

Simultaneous multimodality optical and MR imaging of tumor micro-environment within implanted window chambers

Paper 7902-14 of Conference 7902
Date: Saturday, 22 January 2011
Time: 4:15 PM ?4:35 PM

Author(s): Mir Farrokh Shayegan Salek, College of Optical Sciences, The Univ. of Arizona (United States); Dominique Jennings, Harvard-Massachusetts Institute of Technology (United States); Tzu-Yu Wu, Arthur F. Gmitro, The Univ. of Arizona (United States)
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A modular platform capable of doing optical microscopy inside an MRI instrument is developed. This is done by relaying the optical image to outside of the MR bore. Our device enables simultaneous optical and MR imaging of the same tissue and thus creates the ideal situation for doing comparative or complementary studies using these two modalities. Initial experiments have been done using GFP labeled tumor cells implanted in mouse dorsal skin fold window chamber. Overall system design and results of preliminary vascular permeability studies will be presented.

High-speed dynamic laser speckle imaging of changes of microcirculation in vivo

Paper 7898-11 of Conference 7898
Date: Sunday, 23 January 2011
Time: 9:50 AM ?10:10 AM

Author(s): Jia Qin, Lin An, Ruikang K. Wang, Oregon Health & Science Univ. (United States)
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In this study, we will present our novel observations when a high speed laser speckle imaging method is used to image the microcirculation within tissue beds. Based on these new observations, we demonstrate the relative changes of dynamic microvascular blood flow through occluding the main blood vessels and then reperfusion in the mouse ear flap. The promising results show that the high speed LSI can give useful information as to transient and dynamic microcirculation during occlusion and reperfusion.

Smart velocity ranging quantifiable optical micro-angiography

Paper 7898-18 of Conference 7898
Date: Sunday, 23 January 2011
Time: 2:20 PM ?2:40 PM

Author(s): Zhongwei Zhi, Yali Jia, Lin An, Ruikang K. Wang, Oregon Health & Science Univ. (United States)
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In this study, we introduce a new type of OMAG called Quantifiable Optical Microangiography (QOMAG) which is capable of performing quantitative flow imaging with smart velocity ranging. The feasibility of QOMAG for quantitative flow imaging is evaluated using a well defined flow in a glass capillary. Further, in vivo studies were executed on cerebral blood flow of mouse model with the cranium left intact. Multi-range detailed blood flow velocity distribution within intracranial dura mater and cortex can be given by QOMAG simultaneously.

In vivo skin microscopy

Paper 7893-4 of Conference 7893
Date: Monday, 24 January 2011
Time: 3:00 PM ?3:20 PM

Author(s): Wibool Piyawattanametha, National Electronics and Computer Technology Ctr. (Thailand); Hyejun Ra, Emilio Gonzalez-Gonzalez, Stanford Univ. School of Medicine (United States); Michael J. Mandella, National Electronics and Computer Technology Ctr. (Thailand); Gordon S. Kino, Stanford Univ. School of Medicine (United States); Olav D. Solgaard, National Electronics and Computer Technology Ctr. (Thailand); Devin Leake, Dharmacon, Inc. (United States); Thomas D. Wang M.D., Univ. of Michigan (United States); Roger L. Kaspar, TransDerm, Inc. (United States); Anthony Oro, Christopher H. Contag, Stanford Univ. School of Medicine (United States)
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We demonstrate a Dual-Axes Confocal (DAC) fluorescence microscopy and obtain in vivo skin images in mouse models and humans. The DAC microscope delivers an excitation wavelength of 785 nm with a maximum laser output of 2.5 mW at the surface mucosa. Confocal images can then be collected at a scan rate of 5 frames/second. The transverse and axial resolutions are 5 祄 and 7 祄, respectively.

In vivo skin microscopy

Paper 7930-4 of Conference 7930
Date: Monday, 24 January 2011
Time: 3:00 PM ?3:20 PM

Author(s): Wibool Piyawattanametha, National Electronics and Computer Technology Ctr. (Thailand); Hyejun Ra, Emilio Gonzalez-Gonzalez, Stanford Univ. School of Medicine (United States); Michael J. Mandella, National Electronics and Computer Technology Ctr. (Thailand); Gordon S. Kino, Stanford Univ. School of Medicine (United States); Olav D. Solgaard, National Electronics and Computer Technology Ctr. (Thailand); Devin Leake, Dharmacon, Inc. (United States); Thomas D. Wang M.D., Univ. of Michigan (United States); Roger L. Kaspar, TransDerm, Inc. (United States); Anthony Oro, Christopher H. Contag, Stanford Univ. School of Medicine (United States)
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We demonstrate a Dual-Axes Confocal (DAC) fluorescence microscopy and obtain in vivo skin images in mouse models and humans. The DAC microscope delivers an excitation wavelength of 785 nm with a maximum laser output of 2.5 mW at the surface mucosa. Confocal images can then be collected at a scan rate of 5 frames/second. The transverse and axial resolutions are 5 祄 and 7 祄, respectively.

A combined photoacoustic, pulse echo ultrasound and optical coherence tomography endoscopy

Paper 7899-158 of Conference 7899
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Yi Yang, Tianheng Wang, Patrick D. Kumavor, Univ. of Connecticut (United States); Xiang Li, Qifa Zhou, The Univ. of Southern California (United States); Quing Zhu, Univ. of Connecticut (United States)
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We have developed a novel prototype combined photoacoustic, pulse-echo ultrasound and OCT endoscopy. The endoscopy consists of a ball lensed OCT probe, a right-angle multimode fiber for delivering the laser beam for PAT, and a high frequency ultrasound transducer of 35 MHz center frequency. Mouse ear and pig ovary were imaged ex vivo to demonstrate the capability of this new combined endoscopy. Simultaneously acquired microvascular and high resolution anatomy images at subsurface and deeper tissue range demonstrate the synergy of the combined endoscopy over each modality alone.

Tracking Au nanoring delivery into biotissue with optical coherence tomography

Paper 7889-114 of Conference 7889
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Cheng-Kuang Lee, Hung-Yu Tseng, Chia-Yun Lee, Han-Yi Chou, Shou-Yen Wu, Ting-Ta Chi, Kai-Min Yang, Jyh-Yang Wang, Yean-Woei Kiang, Chih-Chung Yang, National Taiwan Univ. (Taiwan); Meng-Tsan Tsai, Chang Gung Univ. (Taiwan)
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The resonant and non-resonant Au nanorings (NRIs) are delivered into mouse liver samples for tracking their diffusion in the samples through continual optical coherence tomography (OCT) scanning for one hour. With resonant Au NRIs, the average A-mode scan profiles of OCT scanning at different delay times clearly demonstrate the extension of strong backscattering depth with time. The calculation of speckle variance among successive OCT scanning images, which can be used to represent the local transport speed of Au NRIs, leads to the illustrations of downward propagation and spreading of major Au NRI motion spot with time.

In-vivo cancer therapy monitoring with diffuse optical techniques

Paper 7896-41 of Conference 7896
Date: Tuesday, 25 January 2011
Time: 8:30 AM ?8:50 AM

Author(s): Regine Choe, Saurav Pathak, So Hyun Chung, Univ. of Pennsylvania (United States); Turgut Durduran, ICFO - Instituto de Ciencias Fotónicas (Spain); Han Y. Ban, David R. Busch, Tiffany Averna, Erin M. Buckley, Meeri N. Kim, Univ. of Pennsylvania (United States); Angela DeMichele, Carolyn Mies, Mark A. Rosen, Mitchell D. Schnall, The Univ. of Pennsylvania Health System (United States); Arjun G. Yodh, Univ. of Pennsylvania (United States)
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There is a great interest in detecting early metabolic changes which may precede morphological changes. To this end, we measured blood flow, oxy- and deoxy-hemoglobin concentrations of cancer using a hybrid frequency-domain diffuse optical and correlation spectroscopy instrument to track therapy. The results of monitoring neoadjuvant chemotherapy of breast cancer patients in correlation to histopathological response will be presented. In addition, the effects of radiation therapy in human head and neck patients, and molecular therapy on a xenograft mouse model of head and neck cancer will be presented.

Fluorescence lifetime optical projection tomography

Paper 7904-19 of Conference 7904
Date: Tuesday, 25 January 2011
Time: 4:50 PM ?5:10 PM

Author(s): James A. McGinty, Imperial College London (United Kingdom); Daniel W. Stuckey, Imperial College Healthcare NHS Trust (United Kingdom); Gao Sun, Harriet B. Taylor, Guy A. Rutter, Imperial College London (United Kingdom); Alessandro Sardini, Imperial College Healthcare NHS Trust (United Kingdom); Jonathan R. Lamb, Imperial College London (United Kingdom); Gordon W. Stamp, The Royal Marsden NHS Foundation Trust (United Kingdom); Margaret J. Dallman, Paul M. W. French, Imperial College London (United Kingdom)
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Having extended optical projection tomography (OPT) to 3-D fluorescence lifetime tomography (tomoFLIM), we present a detailed characterisation of an intensity-based and time-resolved OPT system that we have optimised in terms of spatial resolution, signal-to-noise and total acquisition time. This system has been applied to cm scale volumetric imaging of chick embryos, mouse pancreas (to measure the islet volume in excised murine pancreata) and human tissue resections (for 3-D histology without the need for serial sectioning). We have also developed a higher magnification system implementing modulation transfer function-dependent filters for imaging zebrafish expressing fluorescent protein labels.

Ultra-high-sensitive optical micro-angiography reveals dynamic changes of depth-resolved microcirculations within skeletal muscles

Paper 7898-2 of Conference 7898
Date: Saturday, 22 January 2011
Time: 1:30 PM ?2:00 PM

Author(s): Yali Jia, Ruikang K. Wang, Oregon Health & Science Univ. (United States)
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In this study, we demonstrate the utility of OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within skeletal muscles in mice. By use of the mouse model of hind-limb ischemia, we show OMAG can yield the chronic assessment of time-dependent changes in muscle perfusion and perfusion reserve along tissue depth. These findings indicate that OMAG can represent a sensitive and consistent technique to effectively study pharmacologic therapies aimed at promoting the growth and development of collateral vessels.

Validation of method for enhanced production of red-shifted bioluminescent photons in vivo

Paper 7902-33 of Conference 7902
Date: Sunday, 23 January 2011
Time: 4:00 PM ?4:20 PM

Author(s): Joe Dragavon, Samantha Blazquez, Chelsea Samson, Spencer Shorte, Institut Pasteur (France)
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Bioluminescence imaging is a technique that allows for the non-invasive observation of biological events in intact living organisms, ranging from single cells to small rodents. In animal models, the constant presence of hemoglobin leads to a further decrease in detectable photons. We have developed and validated a technique that is able to red-shift the bioluminescent photons to the optical region of >650nm, a region of minimal absorbance by hemoglobin. We show this novel technique yields a substantial increase in the number of red photons for in vitro and in vivo conditions, both in isolated single cells and intact living mice

Bioconjugated ICG-micellar nanocapsules as translational fluorescent agents for in-vivo optical molecular imaging

Paper 7910-25 of Conference 7910
Date: Tuesday, 25 January 2011
Time: 9:10 AM ?9:30 AM

Author(s): Yong-Ping Chen, The Johns Hopkins Univ. (United States); Kyle L. Davis, North Carolina State Univ. (United States); Michelle Garner, Tulane Univ. (United States); Xingde Li, The Johns Hopkins Univ. (United States)
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To enable bioconjugation for tumor targeting and molecular imaging, the (PEO)-OH terminals on the corona of the ICG-micelles are pre-activated and then conjugated with antibodies. Recently in vivo fluorescence imaging of tumor-bearing mice with bioconjugated ICG-micelles has demonstrated strong enhancement in molecular specificity when comparing with nonconjugated ICG-micelles or free ICG. The bio-functionalized ICG-nanocapsules hold strong promise for translating optical molecular imaging to in vivo clinical practice.

Imaging sub-nanomolar concentrations through more than five centimeters of tissue with time-domain diffuse fluorescence tomography

Paper 7896-66 of Conference 7896
Date: Wednesday, 26 January 2011
Time: 10:40 AM ?11:00 AM

Author(s): Frederic Leblond, Fadi El-Ghussein, Brian W. Pogue, Dartmouth College (United States); Kenneth M. Tichauer, Dartmouth College (Canada); Robert W. Holt, Dartmouth College (United States)
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Photodetection based on time-correlated single-photon counting technology is used to demonstrate that diffuse fluorescence tomography can detect fluorophores in transmission through more than five centimeters in tissue-simulating phantoms, and that this can be achieved for sub-nanomolar concentrations with dyes commonly used for in vivo pre-clinical biological studies. Our results demonstrate that an unprecedented level of sensitivity can be achieved with time-domain fluorescence tomography allowing this technology to be used for applications involving animals larger than mice as well as applications where limited contrast is available.

Quantitative in-vivo lifetime imaging using a time-domain platform with a supercontinuum tunable laser for extended spectral coverage

Paper 7910-54 of Conference 7910
Date: Wednesday, 26 January 2011
Time: 1:50 PM ?2:10 PM

Author(s): Niculae Mincu, Dao Chao Huang, Marilyse Piche, Guobin Ma, Advanced Research Technologies Inc. (Canada)
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The continuously expanding number of fluorescent probes developed for molecular imaging in vivo requires new instruments, more flexible and with higher quantification power. Responding to those requirements we propose a new instrument: it combines the sensitivity of time correlated single photon detection with the extended spectral coverage of a pulsed supercontinuum laser in a sensitive and flexible time-domain platform for in vivo molecular imaging in small animals. The performance of the system is demonstrated on a case study, using NEO-STEM-PMSR50-PEG fluorescent nanoprobes and sequential imaging of CD-1 nude mice.

Nanoscale nuclear architecture for cancer diagnosis by spatial-domain low-coherence quantitative phase microscopy

Paper 7907-3 of Conference 7907
Date: Saturday, 22 January 2011
Time: 9:10 AM ?9:30 AM

Author(s): Pin Wang, Rajan K. Bista, David Y. Lo, Walid E. Khalbuss, Wei Qiu, Kevin D. Staton, Lin Zhang, Univ. of Pittsburgh (United States); Teresa A. Brentnall M.D., Univ. of Washington (United States); Randall E. Brand M.D., Yang Liu, Univ. of Pittsburgh (United States)
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Alterations in nuclear architecture are the hallmark diagnostic characteristic of cancer cells. In this work, we show that the nuclear architectural characteristics quantified by spatial-domain low-coherence quantitative phase microscopy (SL-QPM), is more sensitive for the identification of cancer cells than conventional cytopathology. We demonstrated the importance of nuclear architectural characteristics in both an animal model of intestinal carcinogenesis - APC/Min mouse model and human cytology specimens with colorectal and pancreatic cancers by identifying cancer from cytologically non-cancerous appearing cells. The determination of nanoscale nuclear architecture using this simple and practical optical instrument is a significant advance towards cancer diagnosis.

Long-term, time-lapse, multimodal microscopy for tracking cell dynamics in live tissue

Paper 7902-4 of Conference 7902
Date: Saturday, 22 January 2011
Time: 9:30 AM ?9:50 AM

Author(s): Benedikt W. Graf, Eric J. Chaney, Maria Carmen Valero Quiros, Marina Marjanovic, Marni D. Boppart, Stephen A. Boppart M.D., Univ. of Illinois at Urbana-Champaign (United States)
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High speed intravital microscopy has emerged as an essential tool for studying cellular dynamics in live tissue. However the timescales that tissue can be continuously observed is limited to several hours. We present methods for observing long term cellular dynamics in live tissue based on three-dimensional registration of time-lapse intravital microscopy images. These methods are applied for in vivo tracking of bone-marrow derived GFP-labeled stem cells in mouse skin following bone marrow transplants from GFP donors into wildtype hosts. This enables tracking of these cells after local cutaneous injury, and for investigating the role of skin stem cells in wound healing.

Monitoring human melanocytic cell responses to piperine using multispectral imaging

Paper 7883A-8 of Conference 7883A
Date: Saturday, 22 January 2011
Time: 10:50 AM ?11:10 AM

Author(s): Ravikant Samatham, Kevin G. Phillips, Julia Sonka, Philippe Thuillier, Amala Soumyanath, Steven L. Jacques, Oregon Health & Science Univ. (United States)
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Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We find a direct link between increased absorption due to melanin in multispectral imaging and increased melanocyte proliferation and dendritic spread revealed by standard bright field microscopy.

Wide-field in-vivo spectral and fluorescence imaging microscopy of microvessel blood supply and oxygenation

Paper 7902-7 of Conference 7902
Date: Saturday, 22 January 2011
Time: 11:45 AM ?12:05 PM

Author(s): Jennifer Lee, Mamta Wankhede, Brian S. Sorg, Univ. of Florida (United States)
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The ability to measure microvessel function in laboratory animals can be useful for development of vascular targeting drugs. Blood supply time gives information related to microvessel morphology and hemoglobin saturation gives information on microvessel oxygen transport. These parameters together may yield much information since theoretically microvessel morphology can influence microvessel oxygenation in some tissues; however, these measurements have not yet been combined. In this study, we report the combination of blood supply time and hemoglobin saturation imaging of microvessels in tumors using widefield fluorescence and spectral imaging, respectively. The correlation between the measurements in a mouse mammary tumor is analyzed.

Size- and structure-dependent toxicity of silica particulates

Paper 7909-9 of Conference 7909
Date: Saturday, 22 January 2011
Time: 1:55 PM ?2:05 PM

Author(s): Sanshiro Hanada, Kenichi Miyaoi, Akiyoshi Hoshino, Kenji Yamamoto M.D., International Medical Ctr. of Japan (Japan)
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Nano- and micro-particulates firmly attach with the surface of various biological systems. In some chronic pulmonary disease such as asbestosis and silicosis, causative particulates will induce chronic inflammatory disorder, followed by poor prognosis diseases. We assessed cytotoxicity of the various kinds of silica particles, including amorphous and crystal silica, in mouse alveolar macrophage culture. Their cytotoxicity depends on particle size and is related with inflammation response. By contrast, production of TGF-beta, which is fibrosis maker, by addition of crystal silica was much higher than that of amorphous silica. We conclude that differences of silica particulate affect cytotoxicity and immune response.

Fully parallel adaptive finite element simulation using the simplified spherical harmonics approximations for frequency domain fluorescence molecular imaging

Paper 7892-14 of Conference 7892
Date: Saturday, 22 January 2011
Time: 2:40 PM ?3:00 PM

Author(s): Yujie Lu, Banghe Zhu, The Univ. of Texas Health Science Ctr. at Houston (United States); Haiou Shen, Virginia Polytechnic Institute and State Univ. (United States); John C. Rasmussen, The Univ. of Texas Health Science Ctr. at Houston (United States); Ge Wang, Virginia Polytechnic Institute and State Univ. (United States); Eva M. Sevick-Muraca, The Univ. of Texas Health Science Ctr. at Houston (United States)
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In frequency-domain fluorescence molecular imaging, diffusion approximation theory has been extensively applied. However, high-order photon migration models need to be further investigated. In this paper, a frequency-domain parallel adaptive finite element solver is developed with the simplified spherical harmonics (SPN) approximations. The validation results show that high-order SPN can effectively correct the modeling errors of diffusion equation especially when the tissues have high absorption characteristics and/or when high modulation frequency measurements are used. Furthermore, the parallel adaptive mesh evolution strategy improves the modeling precision and the simulation speed on a realistic digital mouse phantom.

Localized surface plasmon properties of Au nanorings and their diffusion in biotissue

Paper 7909-15 of Conference 7909
Date: Saturday, 22 January 2011
Time: 5:05 PM ?5:25 PM

Author(s): Cheng-Kuang Lee, Shou-Yen Wu, Hung-Yu Tseng, Ting-Ta Chi, Kai-Min Yang, Jyh-Yang Wang, National Taiwan Univ. (Taiwan); Meng-Tsan Tsai, Chang Gung Univ. (Taiwan); Yean-Woei Kiang, Chih-Chung Yang, National Taiwan Univ. (Taiwan)
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Aqueous solutions of Au nanorings (NRs) with different localized surface plasmon resonance (LSPR) wavelengths are prepared. The resonant and non-resonant Au NRs are delivered into mouse liver samples for tracking Au NR diffusion through OCT scanning. With resonant Au NRs, the average A-mode scan profiles of OCT scanning at different delay times demonstrate the extension of strong backscattering depth. The calculation of speckle variance among successive OCT scanning images, which can be used to represent the local transport speed of Au NRs, leads to the illustrations of downward propagation and spreading of major Au NR motion spot with time.

Endoscopic detection of murine colonic dysplasia using a novel fluorescently labeled peptide

Paper 7893-2 of Conference 7893
Date: Sunday, 23 January 2011
Time: 8:30 AM ?8:50 AM

Author(s): Sharon J. Miller, Bishnu Joshi, Adam Gaustad, Eric R. Fearon, Thomas D. Wang M.D., Univ. of Michigan (United States)
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Current screening endoscopy does not detect all pre-malignant (dysplastic) colorectal mucosa, thus requiring the development of more sensitive, targeted techniques to improve detection. The presented work utilized phage display to identify a novel peptide binder to colorectal dysplasia in a CPC;Apc mouse model. A wide-field, small animal endoscope capable of fluorescence excitation (450-475 nm) identified polyps via white light and also collected fluorescence images (510 nm barrier filter) of peptide binding. The peptide bound ~2-fold greater to the colonic adenomas when compared to the control. We have imaged fluorescence-labeled peptide binding in vivo that is specific towards distal colonic adenomas.

Optical-resolution photoacoustic microscopy of ischemic stroke

Paper 7899-5 of Conference 7899
Date: Sunday, 23 January 2011
Time: 9:15 AM ?9:30 AM

Author(s): Song Hu, Konstantin Maslov, Washington Univ. in St. Louis (United States); Ernie Gonzales, Jin-Moo Lee, Washington Univ. School of Medicine (United States); Lihong V. Wang, Washington Univ. in St. Louis (United States)
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A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy (OR-PAM) to study ischemic stroke in a middle cerebral artery (MCA) occlusion mouse model. OR-PAM observed that within core regions of the stroke, the average hemoglobin oxygen saturation (sO2) within arteries/arterioles and veins drop ~20% and ~45%, respectively, during the MCA occlusion. After reperfusion, the vessel sO2 in the core region recovered back to normal values. Vasodilation was also observed during MCA occlusion and after MCA reperfusion.

Comparison of microwave and iron-oxide nanoparticle hyperthermia radiosensitization in murine breast tumors

Paper 7901-13 of Conference 7901
Date: Sunday, 23 January 2011
Time: 2:40 PM ?3:00 PM

Author(s): Andrew J. Giustini, Dartmouth Medical School (United States) and Dartmouth College (United States); Alicia A. Petryk, Dartmouth College (United States); P. Jack Hoopes, Dartmouth Medical School (United States)
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Hyperthermia is an effective radiosensitizer and has the potential to be used in clinical cancer therapy if it can be directed specifically to tumors. Iron oxide nanoparticles (IONP) excited by alternating magnetic fields have been shown to be an effective way to specifically heat tumors in vivo. We have demonstrated that the combination of IONP hyperthermia with ionizing radiation delays the growth of mouse breast tumors by more than double the delay achieved by either modality alone. We have also compared this combined IONP / radiation therapy to the combination of ionization radiation with microwave-induced hyperthermia.

Integrated photoacoustic and fluorescence confocal microscopy

Paper 7899-21 of Conference 7899
Date: Sunday, 23 January 2011
Time: 3:45 PM ?4:00 PM

Author(s): Yu Wang, Konstantin Maslov, Chulhong Kim, Song Hu, Lihong V. Wang, Washington Univ. in St. Louis (United States)
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Optical-resolution photoacoustic microscopy has demonstrated utility in imaging and characterizing microvasculature networks in vivo. This work presents a novel imaging system that integrates optical-resolution photoacoustic microscopy and fluorescence confocal microscopy for simultaneous photoacoustic and fluorescence imaging. The integrated system can acquire intrinsically registered photoacoustic and fluorescence images in a single scan. The micrometer resolution allows imaging of blood vessels down to the capillary level. Capable of providing microscopic imaging of both optical absorption and fluorescence contrasts, the system demonstrates in vivo imaging of oxygen saturation and oxygen partial pressure in mouse ears.

Development of a real-time photoacoustic microscope

Paper 7899-26 of Conference 7899
Date: Sunday, 23 January 2011
Time: 5:00 PM ?5:15 PM

Author(s): Lidai Wang, Junjie Yao, Li Li, Konstantin Maslov, Lihong V. Wang, Washington Univ. in St. Louis (United States)
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We present the development of a photoacoustic imaging system which has real-time imaging capability with optical resolution. The imaging system is capable of acquiring up to 40 photoacoustic frames per second depending on scanning range. Focused laser beams provide a lateral resolution of less than five microns. To demonstrate real-time imaging and high resolution, micron-sized carbon particle flow, whole blood flow in silicone tubing, and single red blood cell flow in a capillary vessel in a mouse ear were imaged in real time, which demonstrated the capability to image dynamic processes in vivo.

All fiber, 1064-nm time-lens source for coherent anti-Stokes Raman scattering and stimulated Raman scattering microscopy

Paper 7903-29 of Conference 7903
Date: Monday, 24 January 2011
Time: 10:41 AM ?11:01 AM

Author(s): Ke Wang, Cornell Univ. (United States); Christian W. Freudiger, Brian G. Saar, Harvard Univ. (United States); Jennifer Lee, Cornell Univ. (United States); Sunney X. Xie, Harvard Univ. (United States); Chris Xu, Cornell Univ. (United States)
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We use the time-lens concept to demonstrate a new scheme for synchronization of two pulsed light sources for biological imaging. An all fiber, 1064 nm time-lens source is synchronized to a picosecond solid-state Ti: Saphire mode-locked laser by using the mode-locked laser pulses as the clock. We demonstrate the application of this synchronized source for CARS and SRS imaging by imaging mouse tissues. Synchronized two wavelength pulsed source is a major technical difficulty for CARS and SRS imaging. The time-lens source demonstrated here may provide an all fiber, user friendly alternative for future SRS imaging.

Developing targeted fluorescent contrast agents for in-vivo micropathology guided resection of medulloblastoma

Paper 7910-12 of Conference 7910
Date: Monday, 24 January 2011
Time: 2:10 PM ?2:30 PM

Author(s): Danni Wang, Stony Brook Univ. (United States); Frank V. Cochran, Henry Haeberle, Christopher H. Contag, Stanford Univ. School of Medicine (United States); Jonathan T. C. Liu, Stanford Univ. (United States)
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The outcomes of brain tumor patients correlate with the degree of surgical resection. However, cautious resection is necessary to avoid neurological damage, especially in pediatric patients. Real-time image guidance will allow for improved resection in a larger proportion of patients, while reducing the debilitating effects of over-aggressive resections. We are developing in vivo microscopes and targeted contrast agents for guiding brain tumor resection. With the aid of a mouse model that spontaneously develops medulloblastoma, we are validating the use of both a monoclonal antibody as well as targeted bacteriophage as fluorescent contrast agents for the specific delineation of brain tumor margins in conjunction with real-time in vivo micropathology.

Silver nanoplates for enhanced photo-acoustic imaging and therapy of pancreatic cancer

Paper 7910-20 of Conference 7910
Date: Monday, 24 January 2011
Time: 5:00 PM ?5:20 PM

Author(s): Kimberly A. Homan, Michael Souza, Ryan Truby, Yun-Sheng Chen, Geoffrey P. Luke, Stanislav Y. Emelianov, The Univ. of Texas at Austin (United States)
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Approaches to cancer treatment are multipronged where several methods are employed simultaneously to eradicate all of the cancerous tissue. Silver nanoplates can aid in this multiplexed approach by carrying chemotherapeutic drugs, targeting cancer cells, and acting as photothermal agents for cancer. Additionally, the large absorption cross section of the nanoplates makes them excellent photoacoustic imaging contrast agents. Their ability to enhance photoacoustic imaging in vivo in a mouse model of pancreatic cancer was demonstrated. Overall, silver nanoplates represent a largely unexplored nanosystem for cancer imaging and treatment and we demonstrate their potential for multifunctional imaging and treatment of pancreatic cancer.


Blind spectral unmixing identifies the molecular signatures of absorbers in multispectral optoacoustic tomography

Paper 7899-123 of Conference 7899
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Nikolaos C. Deliolanis, Juergen Glatz, Andreas Buehler, Daniel Razansky, Vasilis Ntziachristos, Helmholtz Zentrum München GmbH (Germany)
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Deep tissue molecular imaging of contrast agents at realistic concentrations with photoacoustic (or optoacoustic) tomography remains a challenge. Detection of optical absorption contrast agents (nanoparticles, fluorochromes etc.) has been demonstrated by utilizing multispectral measurements, however spectral unmixing heavily depends on the accurate knowledge of the spectral profile of the absorbers. It becomes more challenging when considering that reconstruction algorithms might not be quantitative and also that the spectral absorption profile is convolved with the unknown illumination spectrum. We propose a blind spectral unmixing method that recovers both the spatial distribution of the contrast agents and their absorption spectrum and demonstrate it in whole body mouse imaging.

Development of a stigmatic imaging mass spectrometer using laser desorption/ionization

Paper 7902-74 of Conference 7902
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Kunio Awazu, Osaka Univ. (Japan) and Univ. of Fukui (Japan) and Japan Science and Technology Agency (Japan); Hisanao Hazama, Hirofumi Nagao, Hidetoshi Yoshimura, Jun Aoki, Osaka Univ. (Japan) and Japan Science and Technology Agency (Japan); Kenichi Fujii, Osaka Institute of Technology (Japan) and Japan Science and Technology Agency (Japan); Toshio Tashima, Japan Science and Technology Agency (Japan); Katsuyoshi Masuda, Suntory Institute for Bioorganic Research (Japan) and Japan Science and Technology Agency (Japan); Michisato Toyoda, Osaka Univ. (Japan) and Japan Science and Technology Agency (Japan); Yasuhide Naito, Graduate School for the Creation of New Photonics Industries (Japan) and Japan Science and Technology Agency (Japan)
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We are developing a stigmatic imaging mass spectrometer which consists of a laser desorption/ionization ion source and a multi-turn time-of-flight mass spectrometer (MULTUM-IMG) for measuring multiple biomolecules simultaneously with a high spatial resolution and short measurement time. As the result, ion images were obtained with spatial resolution of 3-4 um and maintained after ten circulations in the multi-turn circuit of MULTUM-IMG. Ion images of dyes from a stained mouse brain section were successfully obtained. The measurement time required for observing whole part of a hippocampus was 13 minutes and reduced to less than 1/10 of conventional imaging mass spectrometry.

 

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Effect of low-power laser irradiation on macrophage phagocytic capacity

Paper 7900-16 of Conference 7900
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Wei Chen, Feifan Zhou, Da Xing, Sheng Song, South China Normal Univ. (China); Wei R. Chen, Univ. of Central Oklahoma (United States) and South China Normal Univ. (China)
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Phagocytosis plays a pivotal role in host innate immunity. Low-power laser irradiation (LPLI) has been found to produce photobiological effects with evidence of interference with immunological functions. The effects of LPLI on the immune response have not been extensively characterized. In this study, we focused our attention on the effects of LPLI on the phagocytic activity of macrophages by using flow cytometry (FCM). The results showed that LPLI led to an increase in phagocytosis on both mouse peritoneal macrophages and the murine macrophage-like cell line RAW264.7.Our results indicated that LPLI with appropriate dosage can enhance the phagocytosis of macrophage

Longitudinal optical-resolution photoacoustic microscopy of tumor neovascularization

Paper 7899-104 of Conference 7899
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Song Hu, Rebecca Sohn, Andrea C. Santeford, Konstantin Maslov, Jeffrey M. Arbeit, Lihong V. Wang, Washington Univ. in St. Louis (United States)
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Neovascularization is essential for tumor growth and metastasis; however, existing technologies have difficulty in label-free chronic imaging of tumor microvascular elaboration. We applied longitudinal optical-resolution photoacoustic microscopy (OR-PAM) for noninvasive determination of vascular elaboration and microcirculatory dynamics of different human cancer xenografts grown in mouse ears. OR-PAM determined changes in functional neovascularization during tumor growth and VEGF signaling inhibition. Ex-vivo tissue analysis co-registered tumor biological responses (tumor cell perfusion, proliferation, apoptosis, microvessel density, and hypoxia) with regional functional neovascular data acquired by OR-PAM. Combinatorial biological and OR-PAM analysis will facilitate novel drug design and scheduling for more effective antineoplastic therapies.

PER-PACT system for simultaneous imaging of acoustic properties with photoacoustic imaging of tumors in small animals

Paper 7899-130 of Conference 7899
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Jithin Jose, Rene G. Willemink, Johan C. G. van Hespen, Univ. Twente (Netherlands); Johan W. Van Neck, Timo L. M. Ten Hagen, Univ. Medisch Ctr. Rotterdam, Erasmus MC (Netherlands); Wiendelt Steenbergen, Univ. Twente (Netherlands); Ton G. van Leeuwen, Univ. Twente (Netherlands) and Univ. van Amsterdam (Netherlands); Srirang Manohar, Univ. Twente (Netherlands)
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we present a system which allows simultaneous imaging of optical absorption properties and acoustic transmission properties of an object in a two-dimensional slice using a carefully positioned 'Passive' element in a photoacoustic imager. The passive element is placed at the far-end of the sample and it acts as an ultrasound source. The generated ultrasound interacts with the sample and can be measured using the same ultrasound detector as used for photoacoustic measurements.We will present detailed description of our system, effect of spatial distribution of SOS in photoacoustic imaging, followed by an iterative reconstruction algorithm which compensates for the SOS inhomogeneities in the imaging area. We have validated the method using appropriate phantoms and on a living mouse which has tumor implanted on the lower abdomen. The obtained images are quantitative in terms of the shape, size, location, and acoustic properties of the examined heterogeneities.

Multi-target photoacoustic molecular imaging of cardiovascular inflammatory biomarkers using bioconjugated gold nanorods

Paper 7899-57 of Conference 7899
Date: Tuesday, 25 January 2011
Time: 8:15 AM ?8:30 AM

Author(s): Seunghan Ha, Sakya Tripathy, Linda L. Lavery, Andrew Carson, Univ. of Pittsburgh Medical Ctr. (United States) and Univ. of Pittsburgh (United States); Ashish Agarwal, Nicholas A. Kotov, Univ. of Michigan (United States); Flordeliza S. Villanueva, Kang Kim, Univ. of Pittsburgh Medical Ctr. (United States) and Univ. of Pittsburgh (United States)
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Multiple cardiovascular inflammatory biomarkers were simultaneously imaged in vivo. A mouse model based on the vascular endothelium injury by a photochemical reaction of Rose Bengal dye to green light was used. Goldnanorods (GNR) (800nm) conjugated to ICAM-1 antibody and E-selectin antibody conjugated GNR (715nm) were injected. Photoacoustic intensity measured by a commercial ultrasound probe synchronized to a pulsed laser (10mJ/cm^2) at 715nm or 800nm clearly identified the upregulations of targeted biomarkers. Histopathology of the harvested tissues confirmed inflammation. The feasibility of simultaneous targeting and monitoring of inflammation responses in cardiovascular system using a commercial ultrasound has been demonstrated in vivo.

In vivo photoacoustic detection, magnetic enrichment and photothermal purging of circulating cancer stem cells targeted by nanoparticles

Paper 7899-58 of Conference 7899
Date: Tuesday, 25 January 2011
Time: 8:30 AM ?8:45 AM

Author(s): Ekaterina I. Galanzha, Univ. of Arkansas for Medical Sciences (United States); Jin-Woo Kim, Univ. of Arkansas (United States); Lyuba Varticovski M.D., National Cancer Institute (United States)
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Circulating cancer stem cells represent a rare, therapy-resistant subset of circulating tumor cells (CTCs) that hypothetically initiate metastasis. This study pioneered clinically-relevant multicolor high-speed photoacoustic flow cytometry for in vivo detection, enrichment, and eradication of cancer stem cells in peripheral blood circulation. As demonstrated in a breast-tumor-bearing mouse model, our platform is capable real-time enumeration and molecular characterization of circulating cancer stem cells during tumor progression with an unprecedented sensitivity threshold at one tumor cell among a billion normal blood cells. These preclinical studies may provide a new, advanced theranostic strategy to improve early diagnosis and therapy of metastatic tumors.

Ultra-high-resolution and ultra-high-sensitive optical micro-angiography based on supercontinuum light source

Paper 7889-40 of Conference 7889
Date: Tuesday, 25 January 2011
Time: 11:45 AM ?12:00 PM

Author(s): Zhongwei Zhi, Lin An, Jia Qin, Ruikang K. Wang, Oregon Health & Science Univ. (United States)
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We demonstrate for the first time an ultrahigh resolution and ultrahigh sensitive optical micro-angiography (UHS-OMAG) system that is realized by a supercontinuum light source and an ultrafast CMOS camera. The broad band light source with a central wavelength at ~800nm, emitted from the supercontinuum light source, provides a ~2祄 coherence gate for the system. With the fast CMOS camera employed in the spectrometer operating at ~70 kHz line rate, we demonstrate that the detailed blood vessel networks, including capillaries, buried within the tissue bed can be visualized. We present the results obtained from the human finger nail fold and the mouse ear flap. The excellent system imaging performance shows a great potential of our system in the future biological imaging application.

Multimodal optical coherence/photo-acoustic tomography of skin

Paper 7889-41 of Conference 7889
Date: Tuesday, 25 January 2011
Time: 1:30 PM ?1:45 PM

Author(s): Aneesh P. Alex, Cardiff Univ. (United Kingdom); Edward Z. Zhang, Univ. College London (United Kingdom); Boris Pova瀉y, Medizinische Univ. Wien (Austria); Jan G. Laufer, Univ. College London (United Kingdom); Bernd Hofer, Medizinische Univ. Wien (Austria); Carl Glittenberg M.D., Ludwig Boltzmann Institut (Austria); Boris Hermann, Medizinische Univ. Wien (Austria); Paul C. Beard, Univ. College London (United Kingdom); Wolfgang Drexler, Medizinische Univ. Wien (Austria)
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A novel non-invasive in vivo multimodal optical coherence tomography (OCT)/photoacoustic tomography (PAT) imaging system capable of obtaining structural and functional information simultaneously has been demonstrated in skin. A 1060 nm OCT system acquiring 47k depth-scans/s with ~7 祄 axial and ~ 20 祄 transverse resolutions has been incorporated into a backward-mode PA system. For PAT, the excitation wavelength was set to 670 nm and a focused laser beam at 1550 nm was used as the sensor interrogation beam. OCT and PAT images were obtained sequentially from a hairless mouse and the co-registered images were combined to form the final 3D image.

Diagnosing lung cancer using coherent anti-Stokes Raman scattering microscopy

Paper 7890-41 of Conference 7890
Date: Tuesday, 25 January 2011
Time: 3:30 PM ?3:50 PM

Author(s): Liang Gao, Rice Univ. (United States) and Methodist Hospital Research Institute (United States); Fuhai Li, Jiong Xing, Methodist Hospital Research Institute (United States); Michael J. Thrall, The Methodist Hospital (United States); Yaliang Yang, Zhiyong Wang, Pengfei Luo, Methodist Hospital Research Institute (United States); Kelvin K. Wong, Methodist Hospital Research Institute (United States) and The Methodist Hospital (United States); Hong Zhao, Methodist Hospital Research Institute (United States); Stephen T. C. Wong, Methodist Hospital Research Institute (United States) and The Methodist Hospital (United States) and Rice Univ. (United States)
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Lung carcinoma is the most prevalent type of cancer in the world, and it is responsible for more deaths than other types of cancer. Early detection of lung cancer can dramatically increase the survival rate. We investigated the feasibility of developing coherent anti-Stokes Raman scattering (CARS) microscopy into an early detection strategy for lung cancer using mouse models. CARS images from normal lung tissues and different subtypes of cancer lesions showed good correlation with their corresponding histological staining with regard to pathologically prevalent features, supporting the idea of applying CARS in vivo for label-free and minimally-invasive differential diagnostic applications.

Multiphoton fluorescence lifetime imaging of cleared tissue

Paper 7903-84 of Conference 7903
Date: Tuesday, 25 January 2011
Time: 5:50 PM ?6:05 PM

Author(s): Michael J. Levene, Sam Vesuna, Sonia Parra, Thomas H. Chia, Yale Univ. (United States)
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Optical clearing of fixed tissue enables multiphoton microscopy (MPM) of intrinsic fluorescence to depths of >2 mm in tissue. Large MPM image stacks of BABB cleared tissue offer great opportunity for advancing optical biopsy techniques and 3D histology through the development of 'virtual organs' that are compatible with traditional histological sample preparations, potentially easing its acceptance by the medical community. However, intrinsic sources of fluorescence in tissues often display broad excitation and emission spectra, complicating the ability to achieve molecular contrast. We present MPM-FLIM images of intrinsic fluorescence from mouse organs and human prostate biopsy samples cleared with BABB.

Two-photon fluorescence vascular imaging with a new fluorene-RGD peptide conjugate

Paper 7910-41 of Conference 7910
Date: Wednesday, 26 January 2011
Time: 8:20 AM ?8:40 AM

Author(s): Kevin D. Belfield, Alma R. Morales, Univ. of Central Florida (United States); Takeo Urakami, Junko Sawada, Sanford-Burnham Medical Research Institute (United States); Ciceron O. Yanez, Univ. of Central Florida (United States); Masanobu Komatsu, Sanford-Burnham Medical Research Institute (United States)
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Multiphoton fluorescence microscopy is a powerful tool in the study of living cells, and features of microvasculature. In the present study, a 2PFM interactive image-analysis method was utilized to evaluate the efficiency of a new 2PA conjugate which was designed to target avß3 integrin. The linear and nonlinear photophysical properties of this RGD peptide fluorescent conjugate were carefully measured. This conjugate was injected into the tail vein of a male C5BL/6 mouse that had been implanted subcutaneously with Lewis Lung Carcinoma cells. The excised tumors consisting of ~ 1 cm3 in volume were whole-mounted and imaged by 2PFM. Ex vivo 2PFM revealed the structure of functional vessels deep within the tumor mass.

Refractive index reconstruction of biological samples from multimodal phase microscopy

Paper 7904-25 of Conference 7904
Date: Wednesday, 26 January 2011
Time: 9:40 AM ?10:00 AM

Author(s): Heidy Sierra, Dana H. Brooks, Charles A. DiMarzio, Northeastern Univ. (United States)
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Extraction of quantitative information is important to better understand cellular activity in biological preparations. In particular the optical refractive index can be used to analyze the results of cellular processes. Phase microscopy modalities are widely used to image unstained biological samples. Here we present a constrained boundary iterative method to reconstruct the spatial distribution of refractive index combining information from two phase microscopy techniques. Simulations have confirmed the reliability of the proposed method. Experiments with measurements from mouse embryos at several development stages show that the proposed approach can reconstruct the distribution of the refractive index of these samples.

Dynamic in-vivo visualization of anastomosis between a prevascularized implantable tissue construct and host circulation

Paper 7897-50 of Conference 7897
Date: Wednesday, 26 January 2011
Time: 11:20 AM ?11:40 AM

Author(s): Sean White, Christopher Hughes, Bernard Choi, Steven C. George M.D., Univ. of California, Irvine (United States)
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The thickness of implantable engineered tissue is restricted by the relatively short diffusion path length of oxygen. One method for overcoming this limitation, termed prevascularization, entails the in vitro formation a vascular network within an engineered tissue construct capable of anastomosing with the host circulation following implantation. We utilized mouse dorsal window chambers to facilitate dynamic imaging of prevascularized tissue implants using laser speckle imaging, multispectral imaging, and multiphoton microscopy. This permits in vivo dynamic visualization and quantification of anastomosis and implant perfusion, and may be used to enhance the design of thick tissue engineered constructs and mechanisms of anastomosis.

Aberration correction in harmonic generation microscopy

Paper 7931-16 of Conference 7931
Date: Thursday, 27 January 2011
Time: 2:45 PM ?3:10 PM

Author(s): Alexander Jesacher, Innsbruck Medical Univ. (Austria); Anisha Thayil, Tomoko Watanabe, Tony Wilson, Shankar Srinivas, Martin J. Booth, Univ. of Oxford (United Kingdom)
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In harmonic generation microscopy, the sample is scanned with a focused short-pulsed laser beam and the second and/or third harmonic signal which is generated by the specimen is collected. Although the wavelength of the scanning beam can be in the near infrared, which implies a large penetration depth and low scattering, aberrations introduced by imperfect optics and specimen inhomogenity can have a large effect on image brightness, contrast and resolution. We show how aberrations in a harmonic generation microscope can be measured and corrected using modal wavefront sensing and a deformable mirror, which is integrated into the optical path of the microscope. We present results obtained from short- and long-term imaging of live mouse embryos.

Adaptive optics two photon scanning laser fluorescence microscopy

Paper 7931-17 of Conference 7931
Date: Thursday, 27 January 2011
Time: 3:40 PM ?4:05 PM

Author(s): Yaopeng Zhou, GE Healthcare (United States); Thomas Bifano, Boston Univ. (United States); Charles Lin, Wellman Ctr. for Photomedicine (United States)
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Two-photon scanning laser fluorescence microscopy provides a powerful tool for deep tissue imaging. However, optical aberrations from illumination beam path limit the peak power delivered to the imaging planes at samples. We have developed an AO system relying on a MEMS Deformable Mirror to compensate the optical aberrations in a two-photon scanning laser fluorescence microscope. The AO system utilized a Zernike polynomial based stochastic parallel gradient descent algorithm to optimize the DM shape for wavefront correction. The developed microscope is applied for subsurface imaging of mouse bone marrow.

Adaptive optics confocal fluorescence microscopy with direct wavefront sensing for brain tissue imaging

Paper 7931-21 of Conference 7931
Date: Thursday, 27 January 2011
Time: 5:10 PM ?5:25 PM

Author(s): Xiaodong Tao, Bautista R. Fernandez, Univ. of California, Santa Cruz (United States); Diana C. Chen, Lawrence Livermore National Lab. (United States); Oscar A. Azucena, Min Fu, Yi Zuo, Joel Kubby, Univ. of California, Santa Cruz (United States)
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Recently, there has been a growing interest in deep tissue imaging for the study of neurons. Unfortunately, because of the inhomogeneous refractive index of the tissue, the aberrations degrades the resolution and brightness of the final image. In this paper, we describe a confocal fluorescence microscope with adaptive optics which can correct aberrations based on direct wavefront measurements using a point source reference beacon and a Shack-Hartmann Wavefront Sensor (SHWS). The mouse brain tissues with different thicknesses are tested. After correction, the near diffraction limited image is achieved. The Strehl ratio increased by 70% after correction for the tissue with the thickness of 100祄.

Non-invasive in-vivo micro-Raman spectroscopy of a murine skin tumor model reveals cancer-specific spectral biomarkers

Paper 7883A-4 of Conference 7883A
Date: Saturday, 22 January 2011
Time: 9:00 AM ?9:20 AM

Author(s): Hequn Wang, Naiyan Huang, Jianhua Zhao, The BC Cancer Agency Research Ctr. (Canada); Harvey Lui M.D., The Univ. of British Columbia (Canada); Mladen Korbelik, Haishan Zeng, The BC Cancer Agency Research Ctr. (Canada)
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We developed a micro-Raman spectrometer system for differentiating tumor lesions from normal skin using an in vivo animal model. A study of 494 Raman spectra from 24 mice revealed different spectral patterns at different depths and between normal and tumor bearing skin sites. A peak at 899 cm-1 (possibly from proline or fatty acids) and one with higher intensity in the 1325 - 1330 cm-1 range (assigned to nucleic acids) were correlated with the presence of tumors and could potentially be used as biomarkers for skin cancer detection. Spectral diagnosis achieved diagnostic sensitivity of 95.8% and specificity of 93.8%.

Evaluation of the use of antibody conjugated plasmonic nanoparticles for brain tumor delineation

Paper 7883E-100 of Conference 7883E
Date: Saturday, 22 January 2011
Time: 10:40 AM ?11:00 AM

Author(s): Kevin C. Seekell, Christy Wilson, Gerald Grant, Adam P. Wax, Duke Univ. (United States)
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Complete resection of a pediatric brain tumor is a major factor in the survival rates of patients following surgery. Therefore, delineation of the brain tumor is an essential tool in helping the surgeon to remove the entire tumor while retaining normal tissues. In this study, the use of immunolabled plasmonic gold nanoparticles as intraoperative contrast agents for tumor delineation was tested. A modified microscope was designed to separately image bioluminescence and nanorod scattering from brain slices of nude mice. Both delineation methods identified the same areas on the samples with high specificity. Immunolabeled gold nanoparticles are effective for tumor delineation.

Size and surface chemistry of Au nanoparticles determine doxorubicin cytotoxicity

Paper 7909-51 of Conference 7909
Date: Saturday, 22 January 2011
Time: 11:20 AM ?11:40 AM

Author(s): Jay L. Nadeau, Hicham Chibli, Xuan Zhang, McGill Univ. (Canada)
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Several formulations of gold-doxorubicin conjugates (Au-Dox) have been reported. However, the effects of particle size, lability of the conjugating bond, and specific targeting have not been fully explored. In this work we compare the relative cytotoxicity of 5 nm vs. 2 nm Au-Dox, and explore the effects of polyethylene glycol (PEG) and specific cell-targeting sequences on toxicity in B16 melanoma cells and in mice. We find that Au-Dox does not show increased cytotoxicity over Dox alone unless the particles are small enough to enter the nucleus. Surprisingly, cleavable bonds do not increase effectiveness, with even stably-bonded Au-Dox showing maximum cytotoxicity in less than one hour. Preliminary studies on molecular mechanisms of action implicate reactive oxygen species formation leading to apoptosis as the primary cause of cell destruction, with Dox-resistant cancer cells showing reduced resistance to Au-Dox. These results have important implications for the development of Au nanoparticle-based anticancer agents.

Photobiomodulatory effects of He-Ne laser on excision wounds

Paper 7887-16 of Conference 7887
Date: Saturday, 22 January 2011
Time: 4:00 PM ?4:20 PM

Author(s): Vijendra Prabhu, Satish B. S. Rao, Manipal Univ. (India); Pramod Kumar, ; Lakshmi Rao, Manipal University (India); Krishna K. Mahato, Manipal Univ. (India)
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The present study was aimed to investigate the promotive effect of LLLT on excision wounds in Swiss albino mice using optical fiber probe based light device. Excision wounds were illuminated with single exposure of various laser doses except controls. Further, optimal dose of 2 J/cm2 was applied to excision wounds at different post-wounding treatment schedules. Progression of wound contraction, mean wound healing time and biochemical estimations from wound ground tissue were assessed. Granulation tissues were stained with Hematoxylin-Eosin staining and analyzed. Results demonstrated optimum tissue regeneration at 2 J/cm2 dose, applied immediately after the wounding as compared to controls.

Dual-drug MRI-FMT for quantification of binding affinity in vivo

Paper 7892-21 of Conference 7892
Date: Saturday, 22 January 2011
Time: 5:40 PM ?6:00 PM

Author(s): Scott C. Davis, Kimberley S. Samkoe, Julia A. O'hara, Kristian J. Sexton, Keith D. Paulsen, Brian W. Pogue, Dartmouth College (United States)
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This study examines specific binding of a receptor-targeted imaging agent in brain tumors using simultaneous MR-guided fluorescence molecular tomography (FMT) of two optical probes. Glioma cells which over-express epidermal growth factor receptor (EGFR) were grown in the brains of nude mice. Imaging began with the co-injection of two NIR fluorescence probes with different emission spectra; one probe targeted to EGFR and the other a negative control. Animals were imaged using an MRI-FMT system with spectrometer-based detectors. Spectrally unmixed signals were used to recover images of fluorescence yield of both drugs, facilitating the quantification of specific binding of the EGFR-targeted probe.

Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model

Paper 7901-12 of Conference 7901
Date: Sunday, 23 January 2011
Time: 2:20 PM ?2:40 PM

Author(s): Felix Rodriguez, Sr., Horacio Rivera Lamela, Sr., Vincent B. Cunningham, Univ. Carlos III de Madrid (Spain)
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We discuss in this article the implementation of a laser-tissue interaction and bioheat-transfer 2-D finite-element model for Photothermal Therapy (PTT) assisted with Gold Nanorods. We have selected Gold Nanorods as absorbing nanostructures in order to improve the efficiency of using compact diode lasers because of their high opto-thermal conversion efficiency at NIR spectra. The goal is to model the distribution of the optical energy among the tissue including the skin absorption effects and the tissue thermal response, with and without the presence of Nanorods. The heat generation due to the optical energy absorption and the thermal propagation will be computationally modeled and optimized. The model has been evaluated and compared with experimental ex-vivo data in fresh chicken muscle samples and in-vivo murine model. Finally, we will study the PTT in tumors by using the CT-26 human cancer cell-line to induce the corresponding xenografts in the animal's back of these BALB/c mice.

How does temperature affect the function of tissue macrophages?

Paper 7901-16 of Conference 7901
Date: Sunday, 23 January 2011
Time: 4:30 PM ?4:45 PM

Author(s): Chen-Ting Lee, Roswell Park Cancer Institute (United States)
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Macrophages sound a danger signal following injury or infection and become activated to release pro-inflammatory cytokines. Usually, tissue macrophages are exposed to an elevated temperature during inflammation. However, whether macrophages respond to temperature change to modulate their function is not clear. Here we studied thermal effects on macrophage functions from LPS-challenged mice at early or late activation stages which are representative of the initiation and resolution phases of inflammation. Our data suggest that in the initiation phase, thermal stress acts as a stimulus to enhance macrophage functions. However, for previously activated macrophages, thermal stress provides a negative signal that suppresses their cytokine production. These results increase our understanding of the role of elevated tissue temperature on modulation specific functions of macrophages. They also provide additional rationale for the use of hyperthermia in the treatment of chronic inflammation.

A hybrid approach combining microCT and fluorescence tomography: imaging workflow and system of coordinate registration

Paper 7892-41 of Conference 7892
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Robert Holt, Fadi El-Ghussein, Dartmouth College (United States); Kenneth M. Tichauer, Lawson Health Research Institute (Canada); Frederic Leblond, Brian W. Pogue, Dartmouth College (United States)
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A fluorescence imaging system was designed to interface with a microCT device. We focus on refining the workflow for meshing and the co-registration of the two systems. The former is performed by projection imaging in the microCT, reconstructing a volume, segmenting using image processing software, and meshing using NIRFAST. Co-registration is performed by exploiting the geometry of the fluorescence system. We determine the location of the geometrical center of a subject, which can be used to derive a translation between instruments. The co-registration will be validated by imaging a synthetic mouse phantom, as well as actual mice with implanted fluorophore concentrations.

Combination of optical imaging with NIR fluorophore and sonogram in breast cancer diagnosis

Paper 7886-45 of Conference 7886
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Kuo-Chih Liao, Tsung-Hsien Yen, Gi-Da Lee, Yu-Hsiang Chou, National Chung Hsing Univ. (Taiwan)
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The project will evaluate the potential of the combination imaging tools (optical imaging with near infrared fluorophore, SIDAG, and sonogram) for non-invasive, low facility requirement and low cost breast cancer diagnosis. The average value of optical and echo signals from normal tissue, benign lesion xenografts (extracellular membrane extract from the EHS mouse sarcoma) and malignant tumor xenografts (MCF-7 cell) developed in nude mice will be recorded and mapped for the following procedures: 1. Average threshold value of contrasts among the normal tissue, benign lesion xenograft and malignant tumor xenograft (screening). 2. Size and boundary of tumor tissue (staging of cancer). 3. Size and boundary of tumor tissue before and after chemotherapy (evaluation of treatment).

Evaluation of laser photobiomodulation in repair of cutaneous wounds in rats infected of staphylococcus aureus

Paper 7887-32 of Conference 7887
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Nicole Ribeiro Santos, Priscila C. Oliveira, Jean Nunes dos Santos, Antônio L. Barbosa Pinheiro, Univ. Federal da Bahia (Brazil)
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This work has as objective evaluates through a histological study the action of the laser in cutaneous wounds infected by Staphylococus aureus. Sixty mice will be used (Wistar), being accomplished in the back of each animal a wound of 1cm2, the animals will be divided in four groups: group control, group laser ?680nm; group Laser ?790nm; group Laser ?680nm + ?790nm (7 and 14 days; 10, 20 and 30J/cm2 . It is concluded that lasertehrapy resulted in a better repair in the groups with 20 e 30J/cm2 and ?680 and ?790nm laser light.

In-vivo validation of high-frequency ultrasound-guided fluorescence tomography system to improve delivery of photodynamic therapy

Paper 7886-37 of Conference 7886
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Akshat Paliwal, The Cleveland Clinic (United States); Sason Torosean, Josiah D. Gruber, Julia A. O'Hara, Brian W. Pogue, Dartmouth College (United States); Tayyaba Hasan, Massachusetts General Hospital (United States); Edward V. Maytin, The Cleveland Clinic (United States)
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PDT for skin cancer is sometimes only partially effective, due to inadequate levels of the fluorescent drug (PPIX) and its heterogeneous distribution. To image the PPIX distribution within tissue, we developed a fluorescence tomography system (FTS) that combines fluorescence detection array with high frequency ultrasound transducer. Validation experiments were performed in vivo using A431 tumor-bearing mice were treated with 5-aminolevulinic acid to induce production of PPIX. FTS reconstructions were compared with histology and data from bulk tumor slices imaged using ex vivo fluorescence scanner. Our data demonstrate the feasibility of using the FTS for subsurface imaging of PPIX in vivo.

Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies

Paper 7886-44 of Conference 7886
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Valeriy A. Privalov, Alexander V. Lappa, Elmir N. Bigbov, Chelyabinsk State Univ. (Russian Federation)
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A PDT experiment on 118 inbred white mice with transplanted Ehrlich's adenocarcinoma is performed to reveal mechanisms of necrosis formation. There were used a chlorine type photosensitizer "Radachlorine", and 662 nm wavelength diode laser. Histological investigations were conducted in different follow-up periods, they included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that one of the main mechanisms of tumor necrosis development after PDT is the hypoxic damage of tumor, provided by disturbances of microcirculatory bed. Four stages of necrosis formation are specified and described in the work.

Single-particle imaging by two-photon microscopy in vivo

Paper 7903-100 of Conference 7903
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Lisa Krapf, Univ. zu Lübeck (Germany); Jelena Dimitrijevic, Univ. Hamburg (Germany); Anna Schüth, Univ. zu Lübeck (Germany); Tobias Vossmeyer, Univ. Hamburg (Germany); Andreas Gebert, Univ. zu Lübeck (Germany); Horst Weller, Univ. Hamburg (Germany); Gereon Hüttmann, Univ. zu Lübeck (Germany)
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Due to the excellent penetration of NIR light in biological tissue, two-photon excitation laser scanning microscopy is an ideal tool to study morphology and dynamic processes in living tissue. Here, this technique is employed to investigate the interaction of nanoparticles with cells of the small intestine. As tracking of single nanoparticles is hampered by a mostly strong tissue autofluorescence, highly luminescent nanoparticles are required. We here show that semiconductor nanocrystals possess a sufficient cross section for two-photon excitation and that single nanocrystals can be detected. This approach was successfully used for studying in vivo particle uptake by the small intestinal mucosa of mice.

Transport-theory based multispectral imaging with PDE-constrained optimization

Paper 7896-91 of Conference 7896
Date: Sunday, 23 January 2011
Time: 5:30 PM

Author(s): Hyun-Keol Kim, Molly L. Flexman, Michael Khalil, Andreas H. Hielscher, Columbia Univ. (United States)
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We present a transport-theory-based PDE-constrained multispectral method for direct imaging of the spatial distributions of chromophores concentrations in biological tissue. The method solves the forward problem and the inverse problem in an all-at-once manner in the framework of a reduced Hessian sequential quadratic programming method. To illustrate the code's performance, we present numerical and experimental/clinical studies involving tumor bearing mice and diabetes feet. It is shown that the PDE-constrained multispectral method accelerates the reconstruction process by up to 15 times compared to unconstrained reconstruction algorithms and provides more accurate results as compared to the so-called two-step approach to multi-wavelength imaging.

Distribution of quantum dots after intraperitoneal administration, with reference to area-specific distribution in the brain

Paper 7909-38 of Conference 7909
Date: Monday, 24 January 2011
Time: 8:30 AM ?9:00 AM

Author(s): Shinji Fushiki M.D., Kyoko Itoh M.D., Shingo Kato, Takeshi Yaoi, Masafumi Umekage, Takenori Tozawa, Kyoto Prefectural Univ. of Medicine (Japan); Yutaka Yoshikawa, Hiroyuki Yasui, Kyoto Pharmaceutical Univ. (Japan); Akiyoshi Hoshino, Noriyoshi Manabe, Kenji Yamamoto M.D., International Medical Ctr. of Japan (Japan)
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The brain is a challenging organ for drug delivery due to the presence of the blood brain barrier. Here, we evaluated the tissue distribution of bioconjugated quantum dots(QDs), i.e., captopril-conjugated QDs (QDs-cap) following intraperitoneal injection into mice, employing ICP-MS and confocal microscopy coupled with spectrometric analysis. We demonstrated that intraperitoneally administered QDs-cap were delivered via systemic blood circulation into visceral organs at 6 hours after injection. Although QDs-cap were located predominantly inside the blood vessels in liver, kidney and brain, but a few were distributed in the parenchyma, especially noteworthy in the brain.

Quantification of optical absorption coefficients from acoustic spectra with photoacoustic tomography

Paper 7899-31 of Conference 7899
Date: Monday, 24 January 2011
Time: 8:45 AM ?9:00 AM

Author(s): Zijian Guo, Song Hu, Christopher P. Favazza, Washington Univ. in St. Louis (United States); Todd N. Erpelding, Ladislav Jankovic, Philips Research North America (United States); Lihong V. Wang, Washington Univ. in St. Louis (United States)
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Optical absorption is closely associated with many physiologically important parameters, such as the concentration and oxygen saturation of hemoglobin, and it can be used to quantify the concentrations of non-fluorescent molecules. We introduce a method to quantify the absolute optical absorption based upon the acoustic spectra of photoacoustic (PA) signals. This method has been implemented on various PA systems, including optical-resolution PA microscopy, acoustic-resolution PA microscopy, and reconstruction based PA array systems. We quantified the optical absorption coefficients of copper chloride samples at various wavelengths. We also quantified the oxygen saturation of hemoglobin in live mice.

Imaging the small animal cardiovascular system in real-time with multispectral optoacoustic tomography

Paper 7899-38 of Conference 7899
Date: Monday, 24 January 2011
Time: 11:00 AM ?11:15 AM

Author(s): Adrian Taruttis, Eva Herzog, Daniel Razansky, Vasilis Ntziachristos, Helmholtz Zentrum München GmbH (Germany)
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Multispectral Optoacoustic Tomography (MSOT) is an emerging technique for high resolution macroscopic imaging with optical and molecular contrast. We present cardiovascular imaging results from a multi-element real-time MSOT system recently developed for studies on small animals. Anatomical features relevant to cardiovascular disease, such as the carotid arteries, the aorta and the heart, are imaged in mice. The system's fast acquisition time, in tens of microseconds, allows images free of motion artifacts from heartbeat and respiration. Additionally, we present in-vivo detection of indocyanine green and gold nanorods at high spatial and temporal resolution, paving the way for molecular imaging applications.

Study on the modulation of cellular activity through the integration of gold nanostructured and laser therapy

Paper 7900-14 of Conference 7900
Date: Monday, 24 January 2011
Time: 4:50 PM ?5:10 PM

Author(s): Emiliano de Oliveira Barreto, Fabíola de Almeida Brito, Rafael V. Santos, Eduardo J. S. Fonseca, Jandir M. Hickmann M.D., Univ. Federal de Alagoas (Brazil)
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Gold nanoparticles (NPAu) have been attracting growing interest over the last decade because of their unique optical properties and biocompatibility for use in diagnosis, treatment, and as delivery vectors for biologic or pharmacologic agents. The low power laser irradiation (LPLI) is a non-invasive procedure that promotes a beneficial effect in several biological events. However, the effects of LPLI on cells exposed to gold nanoparticle (NPAu) are poorly understood. This study was undertaken to evaluate the effects of LPLI on proliferative response of the cells loaded with gold nanoparticles in vitro. For this, lymphocytes isolated of the lymph from naive mice were incubated overnight with NPAu and exposed to LPLI (10 mW) with variable treatment time. After 4 h the cell morphology and viability were evaluated by optical microscopy and MTT assay, respectively. We will present these evaluations for the lymphocytes incubated with and without (control group) NPAu.

Sensing and enumerating rare circulating cells with diffuse light

Paper 7902-79 of Conference 7902
Date: Monday, 24 January 2011
Time: 5:30 PM

Author(s): Eric W. Zettergren, Mark J. Niedre, Northeastern Univ. (United States)
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The goal of this research is to develop a method for enumerating rare circulating cells in-vivo with diffuse light allowing interrogation of larger blood vessels and blood volumes than currently possible. Our initial instrument is capable of detecting and counting single, calibrated cell-simulating fluorescent mircospheres when passed through a limb-mimicking flow phantom with similar optical properties, size and flow rates as the limb of a mouse. Characterization with Vybrant-DiD labeled cells was also performed. Future work includes testing of the instrument using circulating, fluorescently labeled T-Lymphocyte cells in mice in-vivo.

Gold nanoparticles for theranostic

Paper 7910-23 of Conference 7910
Date: Tuesday, 25 January 2011
Time: 8:30 AM ?8:50 AM

Author(s): Marina A. Sirotkina, Vadim V. Elagin, Marina V. Shirmanova, Nizhny Novgorod State Medical Academy (Russian Federation); Pavel D. Agrba, Institute of Applied Physics (Russian Federation); Victor A. Nadtochenko, N.N. Semenov Institute of Chemical Physics (Russian Federation); Elena V. Zagaynova, Nizhny Novgorod State Medical Academy (Russian Federation)
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In the present study we used bifunctional gold nanoparticles which are optimal for optical coherence tomography (OCT) diagnostics and laser heating. Gold nanoparticles were injected intravenously. The study was performed on CBA mice bearing cervical carcinoma. Noninvasive control of nanoparticle accumulation in tumor was carried out by the OCT device. Laser treatment was performed in 5 hours after nanoparticle injection. The tumor temperature was controlled to be 45癈. Histopathology and electron microscopy studies were conducted to observe the cell death in tumor. The anti-tumor impact of hyperthermia is confirmed by inhibition of tumor growth and induced apoptotic death of tumor cells.

Label-free 3D optical imaging of microcirculation within sentinel lymph node in vivo

Paper 7889-35 of Conference 7889
Date: Tuesday, 25 January 2011
Time: 10:30 AM ?10:45 AM

Author(s): Yeongri Jung, Zhongwei Zhi, Ruikang K. Wang, Oregon Health & Science Univ. (United States)
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Sentinel lymph node (SLN) is the first lymph node to drain wastes originated from cancerous tissue. There is a need for an in vivo imaging method that can image the intact SLN in order to further our understanding of its normal as well as abnormal functions. We report the use of ultrahigh sensitive optical microangiography (UHS-OMAG) to image functional microvascular and lymphatic vessel networks that innervate the intact lymph node in mice in vivo. The promising results show a potential role of UHS-OMAG in the future understanding and diagnosis of the SLN involvement in cancer development.

Imaging tumor specific peptide-targeting using spectral-domain optical coherence tomography

Paper 7890-31 of Conference 7890
Date: Tuesday, 25 January 2011
Time: 11:10 AM ?11:30 AM

Author(s): Ping Yu, Lixin Ma, Univ. of Missouri-Columbia (United States)
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We report imaging studies on tumor specific peptide-targeting in mice using a newly developed spectral-domain optical coherence tomography (SD-OCT). The system used two central wavelengths and an electro-optic modulation in the reference is used to get full-range deep imaging inside tumor. The optical probes were based on Bombesin (BBN). The SD-OCT imaging can identify normal tissue and tumor tissue through the difference in scattering coefficient, and trace the BBN probes in a severely compromised immunodeficient mouse model bearing human PC-3 prostate tumor xenografts. Our results demonstrated that SD-OCT is a potential tool for pre-clinical and clinical early cancer detection.

Application of near-infrared fluorescence imaging to monitor changes in HER2 expression after therapeutic intervention

Paper 7910-35 of Conference 7910
Date: Tuesday, 25 January 2011
Time: 5:00 PM ?5:20 PM

Author(s): Victor V. Chernomordik, Moinuddin Hassan, Rafal Zielinski, Amir H. Gandjbakhche, Jacek Capala, National Institutes of Health (United States)
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A method to quantify the overexpression of HER2 receptor in the tumor is suggested. Quantitative in vivo NIR optical imaging of xenografts mice with subcutaneous HER2-positive tumors was performed. Fluorescence images were obtained at several time points after intravenous injection of the dye to investigate binding kinetics. Compartmental ligands-receptor model was used to estimate HER2 expression from data, obtained with HER2-specific contrast agent, and monitor treatment with 17-DMAG. Initial slope, characterizing the temporal dependence of the fluorescence intensity, detected in the tumor, linearly depends on the HER2 expression, measured ex vivo by an ELISA assay for the same tumor.

Biodegradable NIR gold nanoclusters: photo-acoustic imaging and in-vivo clearance

Paper 7910-46 of Conference 7910
Date: Wednesday, 26 January 2011
Time: 10:40 AM ?11:00 AM

Author(s): Justina O. Tam, Avinash Murthy, Soon Joon Yoon, Stanislav Emelianov, Keith P. Johnston, The Univ. of Texas at Austin (United States); Konstantin V. Sokolov, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
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Plasmonic nanoparticles have shown strong potential as NIR imaging and therapeutic agents. However, a major roadblock to clinical translation is their non-biodegradability, and thus potential for long term in vivo systemic toxicity. Here, we investigate in vivo clearance of gold nanoclusters, which are assemblies of sub-5nm gold spheres into sub-100nm clusters mediated by a biodegradable polymer. Nanocluster degradation in Balb/c mice was measured using neutron activation analysis (NAA) and dark-field reflectance (DR) imaging at 1 day, 1 week, and 1 month after tail vein injection. Results showed degradation after 1 month and excretion of gold into feces and urine.
 

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