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  • 1. Abrahamsson, S.
    et al.
    Blom, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Agostinho, A.
    Jans, Daniel
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Jost, A.
    Müller, M.
    Nilsson, Linnea
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Bernhem, K.
    Lambert, T. J.
    Heintzmann, R.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Multifocus structured illumination microscopy for fast volumetric super-resolution imaging2017In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 8, no 9, p. 4135-4140, article id #294866Article in journal (Refereed)
    Abstract [en]

    We here report for the first time the synergistic implementation of structured illumination microscopy (SIM) and multifocus microscopy (MFM). This imaging modality is designed to alleviate the problem of insufficient volumetric acquisition speed in superresolution biological imaging. SIM is a wide-field super-resolution technique that allows imaging with visible light beyond the classical diffraction limit. Employing multifocus diffractive optics we obtain simultaneous wide-field 3D imaging capability in the SIM acquisition sequence, improving volumetric acquisition speed by an order of magnitude. Imaging performance is demonstrated on biological specimens.

  • 2.
    Chu, Liliang
    et al.
    KTH, School of Information and Communication Technology (ICT), Centres, Zhejiang-KTH Joint Research Center of Photonics, JORCEP.
    Wang, Shaowei
    KTH, School of Information and Communication Technology (ICT), Centres, Zhejiang-KTH Joint Research Center of Photonics, JORCEP.
    Li, Kanghui
    KTH, School of Information and Communication Technology (ICT), Centres, Zhejiang-KTH Joint Research Center of Photonics, JORCEP.
    Xi, Wang
    Zhao, Xinyuan
    Qian, Jun
    KTH, School of Information and Communication Technology (ICT), Centres, Zhejiang-KTH Joint Research Center of Photonics, JORCEP.
    Biocompatible near-infrared fluorescent nanoparticles for macro and microscopic in vivo functional bioimaging2014In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 5, no 11, p. 4076-4088Article in journal (Refereed)
    Abstract [en]

    Near-infrared (NIR) imaging technology has been widely used for biomedical research and applications, since it can achieve deep penetration in biological tissues due to less absorption and scattering of NIR light. In our research, polymer nanoparticles with NIR fluorophores doped were synthesized. The morphology, absorption/emission features and chemical stability of the fluorescent nanoparticles were characterized, separately. NIR fluorescent nanoparticles were then utilized as bright optical probes for macro in vivo imaging of mice, including sentinel lymph node (SLN) mapping, as well as distribution and excretion monitoring of nanoparticles in animal body. Furthermore, we applied the NIR fluorescent nanoparticles in in vivo microscopic bioimaging via a confocal microscope. Under the 635 nm-CW excitation, the blood vessel architecture in the ear and the brain of mice, which were administered with nanoparticles, was visualized very clearly. The imaging depth of our one-photon microscopy, which was assisted with NIR fluorescent nanoprobes, can reach as deep as 500 mu m. Our experiments show that NIR fluorescent nanoparticles have great potentials in various deep-tissue imaging applications.

  • 3. Li, Fang
    et al.
    Zhu, Huilin
    Gao, Qianqian
    Xu, Guixiong
    Li, Xinge
    Hu, Ziqiang
    He, Sailing
    KTH, School of Electrical Engineering (EES), Electromagnetic Engineering. S China Normal Univ, Peoples R China.
    Using functional near-infrared spectroscopy (fNIRS) to detect the prefrontal cortical responses to deception under different motivations2015In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 6, no 9, p. 3503-3514Article in journal (Refereed)
    Abstract [en]

    In this study, functional near-infrared spectroscopy (fNIRS) was adopted to investigate the prefrontal cortical responses to deception under different motivations. By using a feigned memory impairment paradigm, 19 healthy adults were asked to deceive under the two different motivations: to obtain rewards and to avoid punishments. Results indicated that when deceiving for obtaining rewards, there was greater neural activation in the right inferior frontal gyrus (IFG) than the control condition. When deceiving for avoiding punishments, there was greater activation in the right inferior frontal gyrus (IFG) and the left middle frontal gyrus (MFG) than the control condition. In addition, deceiving for avoiding punishments led to greater neural activation in the left MFG than when deceiving for obtaining rewards. Furthermore, the results showed a moderate hit rate in detecting deception under either motivation. These results demonstrated that deception with different motivations led to distinct responses in the prefrontal cortex. fNIRS could provide a useful technique for the detection of deception with strategy of feigning memory impairment under different motivations.

  • 4. Liu, Jing
    et al.
    Wu, Ruitao
    Li, Nana
    Zhang, Xin
    Zhan, Qiuqiang
    He, Sailing
    KTH, School of Electrical Engineering (EES), Electromagnetic Engineering. Zhejiang University, China.
    Deep, high contrast microscopic cell imaging using three-photon luminescence of beta-(NaYF4:Er3+/NaYF4) nanoprobe excited by 1480-nm CW laser of only 1.5-mW2015In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 6, no 5, p. 1857-1866Article in journal (Refereed)
    Abstract [en]

    It is challenging to achieve deep microscopic imaging for the strong scattering in biotissue. An efficient three-photon luminescence can effectively increase the penetration depth. Here we report that beta-NaYF4: Er3+/NaYF4 UCNPs were excited by a 1480-nm CW-laser and emitted 543/653-nm light through a three-photon process. With the merit of the hexagonal crystal phase, sub-milliwatt laser power was utilized to excite the UCNP-probed cells to minimize the heating effect. The polymer-coated UCNPs were shown to be harmless to cells. The deep, high contrast in vitro microscopic imaging was implemented through an artificial phantom. Imaging depth of 800 mu m was achieved using only 1.5 mW excitation and a 0.7 NA objective. The green/red emission intensities ratio after penetrating the phantom was studied, indicating that longer emission wavelength is preferred for deep multiphoton microscopy. The proposed and demonstrated beta-UCNPs would have great potential in three-photon microscopy. (C) 2015 Optical Society of America

  • 5.
    Pollnau, Markus
    et al.
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics. University of Twente, Netherlands.
    Hammer, M.
    Dongre, C.
    Hoekstra, H. J. W. M.
    Combined microfluidic-optical DNA analysis with single-base-pair sizing capability2016In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 7, no 12, p. 5201-5207, article id 275075Article in journal (Refereed)
    Abstract [en]

    DNA sequencing by microchip capillary electrophoresis (CE) enables cheap, highspeed analysis of low reagent volumes. One of its potential applications is the identification of genomic deletions or insertions associated with genetic illnesses. Detecting single base-pair insertions or deletions from DNA fragments in the diagnostically relevant size range of 150−1000 base-pairs requires a variance of σ2 < 10−3. In a microfluidic chip post-processed by femtosecond-laser writing of an optical waveguide we CE-separated 12 blue-labeled and 23 red-labeled DNA fragments in size. Each set was excited by either of two lasers powermodulated at different frequencies, their fluorescence detected by a photomultiplier, and blue and red signals distinguished by Fourier analysis. We tested different calibration strategies. Choice of the fluorescent label as well as the applied fit function strongly influence the obtained variance, whereas fluctuations between two consecutive experiments are less detrimental in a laboratory environment. We demonstrate a variance of σ2 ≈4 × 10−4, lower than required for the detection of single base-pair insertion or deletion in an optofluidic chip.

  • 6.
    Shaker, Kian
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Jakob C.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Quantitative predictions in small-animal X-ray fluorescence tomography2019In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 10, no 8, p. 3773-3788, article id 364926Article in journal (Refereed)
    Abstract [en]

    X-ray fluorescence (XRF) tomography from nanoparticles (NPs) shows promise for high-spatial-resolution molecular imaging in small-animals. Quantitative reconstruction algorithms aim to reconstruct the true distribution of NPs inside the small-animal, but so far there has been no feasible way to predict signal levels or evaluate the accuracy of reconstructions in realistic scenarios. Here we present a GPU-based computational model for small-animal XRF tomography. The unique combination of a highly accelerated Monte Carlo tool combined with an accurate small-animal phantom allows unprecedented realistic full-body simulations. We use this model to simulate our experimental system to evaluate the quantitative performance and accuracy of our reconstruction algorithms on large-scale organs as well as mm-sized tumors. Furthermore, we predict the detection limits for sub-mm tumors at realistic NP concentrations. The computational model will be a valuable tool for optimizing next-generation experimental arrangements and reconstruction algorithms.

  • 7. Wen, Xuanyuan
    et al.
    Wang, Baoju
    Wu, Ruitao
    Li, Nana
    He, Sailing
    KTH, School of Electrical Engineering (EES), Electromagnetic Engineering. South China Normal University, China.
    Zhan, Qiuqiang
    Designed Er3+-singly doped NaYF4 with double excitation bands for simultaneous deep macroscopic and microscopic upconverting bioimaging2016In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 7, no 6, p. 2174-2185Article in journal (Refereed)
    Abstract [en]

    Simultaneous deep macroscopic imaging and microscopic imaging is in urgent demand, but is challenging to achieve experimentally due to the lack of proper fluorescent probes. Herein, we have designed and successfully synthesized simplex Er3+-doped upconversion nanoparticles (UCNPs) with double excitation bands for simultaneous deep macroscopic and microscopic imaging. The material structure and the excitation wavelength of Er3+-singly doped UCNPs were further optimized to enhance the upconversion emission efficiency. After optimization, we found that NaYF4:30% Er3+@NaYF4:2% Er3+ could simultaneously achieve efficient two-photon excitation (2PE) macroscopic tissue imaging and three-photon excitation (3PE) deep microscopic when excited by 808 nm continuous wave (CW) and 1480 nm CW lasers, respectively. In vitro cell imaging and in vivo imaging have also been implemented to demonstrate the feasibility and potential of the proposed simplex Er3+-doped UCNPs as bioprobe.

  • 8. Zhao, Yuxiang
    et al.
    Zhan, Qiuqiang
    Liu, Jing
    He, Sailing
    KTH, School of Electrical Engineering (EES), Electromagnetic Engineering. South China Normal University (SCNU), China .
    Optically investigating Nd3+-Yb3+ cascade sensitized upconversion nanoparticles for high resolution, rapid scanning, deep and damage-free bio-imaging2015In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 6, no 3, p. 838-848Article in journal (Refereed)
    Abstract [en]

    The rapid development of upconversion nanoparticles (UCNPs) has been facing with a great challenge: intense emission, fast scanning, and deep imaging require high-power light irradiation with minimized heating effect (the intrinsic 975-nm excitation of Yb3+-sensitized UCNPs have overheating problem). By shifting the excitation peak from 975 nm to 795 nm, Nd3+-Yb3+ cascade sensitized upconversion nanoparticles (Nd-UCNPs) with minimized heating effect were reported as the new generation UCNPs. For the first time, within two optically modeled applications in vitro and in vivo, the damage outcomes under long time high power laser excitation were solidly calculated, complementing the damage-free study of Nd-UCNPs. The higher resolution (20% improvement) and five times faster scanning microscopy were successfully performed using Nd-UCNPs under safety laser power level. The computational results showed the Nd3+-Yb3+ energy transfer efficiency would not compromise the deep imaging ability, and the red (650-nm) emission is worth to be enhanced for deep tissue imaging. (C) 2015 Optical Society of America.

  • 9. Zhu, Huilin
    et al.
    Fan, Yuebo
    Guo, Huan
    Huang, Dan
    He, Sailing
    KTH, School of Electrical Engineering (EES), Electromagnetic Engineering. KTH, School of Information and Communication Technology (ICT), Centres, Zhejiang-KTH Joint Research Center of Photonics, JORCEP.
    Reduced interhemispheric functional connectivity of children with autism spectrum disorder: evidence from functional near infrared spectroscopy studies2014In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 5, no 4, p. 1262-1274Article in journal (Refereed)
    Abstract [en]

    Autism spectrum disorder (ASD) is a neuro-developmental disorder, which has been associated with atypical neural synchronization. In this study, functional near infrared spectroscopy (fNIRS) was used to study the differences in functional connectivity in bilateral inferior frontal cortices (IFC) and bilateral temporal cortices (TC) between ASD and typically developing (TD) children between 8 and 11 years of age. As the first report of fNIRS study on the resting state functional connectivity (RSFC) in children with ASD, ten children with ASD and ten TD children were recruited in this study for 8 minute resting state measurement. Compared to TD children, children with ASD showed reduced interhemispheric connectivity in TC. Children with ASD also showed significantly lower local connectivity in bilateral temporal cortices. In contrast to TD children, children with ASD did not show typical patterns of symmetry in functional connectivity in temporal cortex. These results support the feasibility of using the fNIRS method to assess atypical functional connectivity of cortical responses of ASD and its potential application in diagnosis.

  • 10. Zhu, Huilin
    et al.
    Li, Jun
    Fan, Yuebo
    Li, Xinge
    Huang, Dan
    He, Sailing
    KTH, School of Electrical Engineering (EES), Electromagnetic Engineering.
    Atypical prefrontal cortical responses to joint/non-joint attention in children with autism spectrum disorder (ASD): A functional near-infrared spectroscopy study2015In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 6, no 3, p. 690-701Article in journal (Refereed)
    Abstract [en]

    Autism spectrum disorder (ASD) is a neuro-developmental disorder, characterized by impairments in one's capacity for joint attention. In this study, functional near-infrared spectroscopy (fNIRS) was applied to study the differences in activation and functional connectivity in the prefrontal cortex between children with autism spectrum disorder (ASD) and typically developing (TD) children. 21 ASD and 20 TD children were recruited to perform joint and non-joint attention tasks. Compared with TD children, children with ASD showed reduced activation and atypical functional connectivity pattern in the prefrontal cortex during joint attention. The atypical development of left prefrontal cortex might play an important role in social cognition defects of children with ASD.

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