Dror Fixler

Bar Ilan University, Gan, Tel Aviv, Israel

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Publications (58)137.21 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper introduces a theoretical and practical model for reconstructing the scattering properties of a participating media. Our theory is based on a robust generalization of the Gerchberg-Saxton (G-S) algorithm. At the end of this algorithm the reduced scattering coefficient μ's of a given substance, can be estimated from the standard deviation (STD) of the retrieved phase of the remitted light. We use the theory to compute the phase's STD that directly correlated to the optical properties for different types of milk components, and we derive a novel appearance model for milk parameterized by the lactose and protein contents. Our results show that we are able to detect the possibility of lactose and milk proteins' quantitative signature by the G-S optical tool, en route to the design of a novel milk-content-monitoring tool. Sketch of the experimental setup for light intensity measurements and reduced scattering coefficient reconstruction. The samples were prepared from various milk components: whey protein, sodium casienate and lactose, at different concentrations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Journal of Biophotonics 04/2015; 9999(9999). DOI:10.1002/jbio.201400144 · 3.86 Impact Factor
  • Journal of Biophotonics 04/2015; 9999. DOI:10.1002/jbio.201400136 · 3.86 Impact Factor
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    ABSTRACT: Several approaches for optimization of fluorescence lifetime imaging microscopy (FLIM) system have been recently suggested. This paper discusses the influences of photons losses on the optimization of FLIM systems based time-correlated single photon counting (TCSPC) technique, considering the limitations associated with detecting the required amount of photons by the system. The fluorescence intensity (FI) and fluorescence lifetime (FLT) were measured in different operating regimes of the imaging system. The relation between parameters such as excitation power, detector gain, laser repetition rate, is also analyzed. Based on data acquisition limitations of typical TCSPC systems, we discuss the considerations for choosing the correct system parameters, which would most influence the accuracy of FLIM experiments. A simple scheme for optimization of FLIM systems for different types of fluorescent samples is finally suggested. - See more at: http://eurekaselect.com/128060#sthash.1W1q4fyI.dpuf
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    ABSTRACT: Determining the physical penetration depth of nanoparticles (NPs) into tissues is a challenge that many researchers have been facing in recent years. This paper presents a new noninvasive method for detecting NPs in tissue using an optical iterative technique based on the Gerchberg-Saxton (G-S) algorithm. At the end of this algorithm the reduced scattering coefficient (µs'), of a given substance, can be estimated from the standard deviation (STD) of the retrieved phase of the remitted light. Presented in this paper are the results of a tissue simulation which indicate a linear ratio between the STD and the scattering components. A linear ratio was also observed in the tissue-like phantoms and in ex vivo experiments with and without NPs (Gold nanorods and nano Methylene Blue). The proposed technique is the first step towards determining the physical penetration depth of NPs.
    Biomedical Optics Express 11/2014; 5(11):3871-3881. DOI:10.1364/BOE.5.003871 · 3.50 Impact Factor
  • Dror Fixler, Tsviya Nayhoz, Krishanu Ray
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    ABSTRACT: In this paper we report the optical properties of fluorescein-conjugated gold nanoparticles (GNPs) in solid phantoms using diffusion reflection (DR) and fluorescence lifetime imaging microscopy (FLIM). The GNPs attached with fluorescein in solution were studied by fluorescence correlation spectroscopy. The intensity decays were recorded to reveal the fluorescence lifetime of fluorescein while in the near-field vicinity of the GNPs. The DR method was used to explore the solid phantoms containing GNPs, indicating the light propagation from the surface of solid phantoms. The resulting DR slopes of the reflected intensity showed the higher the GNP concentration, the bigger the slope. Fluorescence intensity, lifetime, and anisotropy images of solid phantoms were investigated by FLIM. The exploration of optical properties and molecular imaging combined with DR and FLIM methods is a new approach that has not been established until now. The combined DR-FLIM technique is expected to provide discrimination based on unique spectroscopic fingerprints of GNPs that could be utilized for cell imaging. This paper includes a combined study with a variety of methods, which may lead to multimodal imaging for surfaces (by FLIM) and deep penetration (up to cm by the DR) together.
    09/2014; 1(9):900-905. DOI:10.1021/ph500214m
  • Source
    Lior Turgeman, Dror Fixler
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    ABSTRACT: Recent developments in the field of fluorescence lifetime imaging microscopy (FLIM) techniques allow the use of high repetition rate light sources in live cell experiments. For light sources with a repetition rate of 20-100 MHz, the time-correlated single photon counting (TCSPC) FLIM systems suffer serious dead time related distortions, known as "inter-pulse pile-up". The objective of this paper is to present a new method to quantify the level of signal distortion in TCSPC FLIM experiments, in order to determine the most efficient laser repetition rate for different FLT ranges. Optimization of the F -value, which is the relation between the relative standard deviation (RSD) in the measured FLT to the RSD in the measured fluorescence intensity (FI), allows quantification of the level of FI signal distortion, as well as determination of the correct FLT of the measurement. It is shown that by using a very high repetition rate (80 MHz) for samples characterized by high real FLT's (4-5 ns), virtual short FLT components are added to the FLT histogram while a F -value that is higher than 1 is obtained. For samples characterized with short real FLT's, virtual long FLT components are added to the FLT histogram with the lower repetition rate (20-50 MHz), while by using a higher repetition rate (80 MHz) the "inter-pulse pile-up" is eliminated as the F -value is close to 1. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
    Journal of Biophotonics 06/2014; 7(6). DOI:10.1002/jbio.201300018 · 3.86 Impact Factor
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    ABSTRACT: In this study we report the use of gold nanorods (GNRs) as absorption contrast agents in the diffusion reflection (DR) method for the in vivo detection of atherosclerotic injury. The early detection and characterization of atherosclerotic vascular disease (ASVD) is considered to be one of the greatest medical challenges today. We show that macrophage cells, which are major components of unstable active atherosclerotic plaques, uptake gold nanoparticles (GNPs), resulting in a change in the optical properties of tissue-like phantoms and a unique DR profile. In vivo DR measurements of rats that underwent injury of the carotid artery showed a clear difference between the DR profiles of the injured compared with healthy arteries. The results suggest that DR measurements following GNRs administration represent a potential novel method for the early detection of atherosclerotic vascular disease.
    Nano Letters 04/2014; 14(5). DOI:10.1021/nl500573d · 13.03 Impact Factor
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    ABSTRACT: Intraoperative detection of residual disease in oral cancer may reduce the high rate of recurrences. The aim of the present study was to evaluate the detection sensitivity of diffusion reflection (DR) measurements of bioconjugated gold nanorods (GNRs) to cancerous sites in a rat model of oral squamous cell carcinoma. We used hyperspectral spectroscopy and DR measurements of GNRs bioconjugated to slide specimens of rat tongues where squamous carcinoma was induced by 4NQO (4-nitroquinoline-N-oxide). Wistar-derived male rats were used: 6 were sacrificed at wk 32 to 37 following 4NQO administration (experimental rats), as were 2 control rats at wk 32 and 36. The detection results were compared with histopathology: 19 sites of cancerous changes were identified microscopically (11 invasive cancer and 8 carcinoma in situ [CIS]). The GNRs attached selectively to areas of carcinomatous changes with an intensity exceeding 17 intensity units at 780 nm (overall specificity, 97%; overall sensitivity, 87%) when the hyperspectral spectroscopy system was used. The resulting DR slopes of the reflected intensity showed an increase of >80% in areas of invasive cancer and an increase of >30% in the CIS sites. The resulting intensity units of the hyperspectral spectroscopy system in the invasive cancer significantly exceed those of the CIS (t test, p = .0002; Mann-Whitney, p = .0024). The results demonstrate a great potential of the direct DR scanning as a new and simple tool for detecting residual disease intraoperatively.
    Journal of dental research 04/2014; 93(6). DOI:10.1177/0022034514529973 · 4.14 Impact Factor
  • Dror Fixler
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    ABSTRACT: In fluorescence fluctuation polarization sensitive experiments, the limitations associated with detecting the rotational timescale are usually eliminated by applying fluorescence correlation spectroscopy analysis. A new method to extract the rotational correlation time of molecule in fluorescence fluctuation polarization sensitive measurements is suggested in our talk. This new method is advantageous in cases where the rotational correlation time of the fluorescent molecule is much lower than the temporal resolution of the system, or in cases where the rotational correlation time is not observed by standard autocorrelation analysis methods such as fluorescence correlation spectroscopy (FCS) or rotational correlation functions analysis.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2014; DOI:10.1117/12.2036490 · 0.20 Impact Factor
  • Hamootal Duadi, Idit Feder, Dror Fixler
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    ABSTRACT: Most methods for measuring light-tissue interaction focus on volume reflectance, while very few measure light transmission. In a previous work, we suggested investigating the influence of blood vessel diameter on photons exiting the tissue at all exit angles to receive the full scattering profile. By this method, we have shown that there is a central angle, i.e., the isobaric point, independent of blood vessel diameter. The vessel diameter changes the effective reduced scattering coefficient. However, both the scattering profile and the value of the isobaric point strongly depend on optical properties and the exact geometry of the tissue. In this study, we investigate the dependency of the isobaric point on tissue diameter and scattering coefficient in both two-dimensional and three-dimensional simulations. We show that the value of this point linearly depends on tissue diameter. The findings of this work solve the dilemma of whether to measure transmission or reflection since the isobaric point reduces by half the total amount of exiting photons. Furthermore, the full scattering profile is sensitive to changes in the scattering properties, but a single isobaric point to these changes is expected. If this point is not found, it is a diagnostic indication of an unexpected change in the tissue.
    Journal of Biomedical Optics 02/2014; 19(2):26007. DOI:10.1117/1.JBO.19.2.026007 · 2.75 Impact Factor
  • Dror Fixler
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    ABSTRACT: The ability to quantitatively and noninvasively detect nanoparticles in vivo has important implications on their development as optical sensors for medical diagnostics. We suggest a new method for cancer detection based on diffusion reflection (DR) measurements of gold nanorods (GNR). In our talk, the ability to extract optical properties of phantoms and their GNR concentrations from DR measurements will demonstrate. We will report, for the first time, GNR detection through upper tissue-like phantom layers, as well as the detection of a tumor presented as highly concentrated GNR placed deep within a phantom.
    Proceedings of SPIE - The International Society for Optical Engineering 01/2014; DOI:10.1117/12.2036487 · 0.20 Impact Factor
  • Zeev Zalevsky, Dror Fixler
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    ABSTRACT: We present a novel concept involving optical properties of gold-nanorods. When the gold-nanorods are located in a tumor the reflected light has low degree of polarization at two specific reflected wavelengths.
    Imaging Systems and Applications; 01/2014
  • Dror Fixler, Zeev Zalevsky
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    ABSTRACT: This paper presents a novel concept involving sensing the back-reflected and absorbed light at two polarization states and at several wavelengths from gold-nanorods (GNRs). While the GNRs are flowing in the bloodstream the reflected light has a high degree of polarization and only one resonance wavelength. When the GNRs are located in a tumor the reflected light has a low degree of polarization and two resonance wavelengths are detected. Such characteristics can assist in detecting a tumor in passive targeting and without labeling it.
    Nano Letters 11/2013; 13(12). DOI:10.1021/nl403927c · 13.03 Impact Factor
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    ABSTRACT: Most methods for measuring light-tissue interactions focus on the volume reflectance while very few measure the transmission. We investigate both diffusion reflection and diffuse transmission at all exit angles to receive the full scattering profile. We also investigate the influence of blood vessel diameter on the scattering profile of a circular tissue. The photon propagation path at a wavelength of 850 nm is calculated from the absorption and scattering constants via Monte Carlo simulation. Several simulations are performed where a different vessel diameter and location were chosen but the blood volume was kept constant. The fraction of photons exiting the tissue at several central angles is presented for each vessel diameter. The main result is that there is a central angle that below which the photon transmission decreased for lower vessel diameters while above this angle the opposite occurred. We find this central angle to be 135 deg for a two-dimensional 10-mm diameter circular tissue cross-section containing blood vessels. These findings can be useful for monitoring blood perfusion and oxygen delivery in the ear lobe and pinched tissues.
    Journal of Biomedical Optics 11/2013; 18(11):111408. DOI:10.1117/1.JBO.18.11.111408 · 2.75 Impact Factor
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    ABSTRACT: An optical lensless configuration for a remote noncontact measuring of mechanical contractions of a vast number of cardiac myocytes is proposed. All the myocytes were taken from rats, and the measurements were done in an in vitro mode. The optical method is based on temporal analysis of secondary reflected speckle patterns generated in lensless microscope configuration. The processing involves analyzing the movement and the change in the statistics of the secondary speckle patterns that are created on top of the cell culture when it is illuminated by a spot of laser beam. The main advantage of the proposed system is the ability to measure many cells simultaneously (∼1000 cells) and to extract the statistical data of their movement at once. The presented experimental results also include investigation of the effect of isoproteranol on cell contraction process.
    Journal of Biomedical Optics 10/2013; 18(10):101310. DOI:10.1117/1.JBO.18.10.101310 · 2.75 Impact Factor
  • Dror Fixler, Lior Turgeman
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    ABSTRACT: In order to maximize the signal-to-noise ratio for a given temporal-resolution of typical photon counting single-molecule polarization-sensitive system, this talk suggests examining the rate of convergence and the variance of the time-averaged measured fluorescence intensity.
    Imaging Systems and Applications; 06/2013
  • Dror Fixler, Rinat Ankri
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    ABSTRACT: The ability to quantitatively and noninvasively detect nanoparticles nearby the skin surface has important implications on their development as an in vivo cancer diagnostic tool. The diffusion reflection (DR) method is a simple, noninvasive imaging technique which has been proven useful for the investigation of the optical parameters of the tissue. A new method is presented for the measurements of gold nanorod (GNR) concentration in tissue-like phantoms, based on DR measurement and intense light absorption of GNR. Monte Carlo simulations and tissue-like phantom measurements of the reflected light intensity are presented. The ability to extract optical properties of phantoms and their GNR concentrations from DR measurements is demonstrated, followed by a discussion about the best mathematical model for light propagation in tissues, based on the diffusion theory.
    Journal of Biomedical Optics 06/2013; 18(6):61226. DOI:10.1117/1.JBO.18.6.061226 · 2.75 Impact Factor
  • Source
    Lior Turgeman, Dror Fixler
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    ABSTRACT: In fluorescence fluctuation polarization sensitive experiments, the limitations associated with detecting the rotational timescale are usually eliminated by applying fluorescence correlation spectroscopy analysis. In this paper, the variance of the time-averaged fluorescence intensity extracted from the second moment of the measured fluorescence intensity is analyzed in the short time limit, before fluctuations resulting from rotational diffusion average out. Since rotational correlation times of fluorescence molecules are typically much lower than the temporal resolution of the system, independently of the time bins used, averaging over an ensemble of time-averaged trajectories was performed in order to construct the time-averaged intensity distribution, thus improving the signal-to-noise ratio. Rotational correlation times of fluorescein molecules in different viscosities of the medium within the range of the anti-bunching time (1-10 ns) were then extracted using this method.
    Biomedical Optics Express 06/2013; 4(6):868-84. DOI:10.1364/BOE.4.000868 · 3.50 Impact Factor
  • Dror Fixler, Zeev Zalevsky
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    ABSTRACT: Many biological systems involve flow of various types of liquids. Estimation of the rate and direction of the flow is highly important for a large number of bio-medical related applications. The working point discussed in this paper involves a medium with a relatively low scattering coefficient such that the polarized light going through it is not depolarized, but rather modifies its polarization state instead. An experimental validation is presented, which shows that illuminating flow in a medium with linear polarized light, and measuring the change in polarization state at the output of the medium, can correlate highly with the direction and flow rate through that medium. By inspecting the spatial shape change in the spot of light, and the change of polarization state in relation to different integration times as well, the direction and flow rate can be fully extracted.
    Optics and Lasers in Engineering 02/2013; 51(2):91–95. DOI:10.1016/j.optlaseng.2012.09.007 · 1.70 Impact Factor
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    ABSTRACT: Spatial diffusion reflection (DR) measurements of gold nanorods (GNR) were recently suggested as a simple and highly sensitive non-invasive and non-ionizing method for real-time cancer detection. In this paper we demonstrate that wavelength dependent DR measurements enable the spectral red-shift observation of highly concentrated GNR. By conjugating targeting moieties to the GNR, large density of GNR can specifically home onto cancer cells. The inter-particle plasmon resonance pattern of the highly concentrated GNR leads to an extension and a red-shift (Δλ) in the absorption spectrum of the concentrated GNR. Dark-field microscopy was used in order to measure the expected Δλ in different GNR concentrations in vitro. Double-wavelength DR measurements of tissue-like phantoms and tumor bearing mice containing different GNR concentrations are presented. We show that the DR profile of the highly concentrated GNR directly correlate with the spectral extension and red-shift. This presented work suggests that wavelength dependent DR method can serve as a promising tool for real-time superficial tumor detection. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
    Journal of Biophotonics 02/2013; 6(2). DOI:10.1002/jbio.201200016 · 3.86 Impact Factor

Publication Stats

276 Citations
137.21 Total Impact Points

Institutions

  • 1997–2015
    • Bar Ilan University
      • • Institute of Nanotechnology and Advanced Materials (BINA)
      • • Department of Mathematics
      • • Department of Physics
      Gan, Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
      Tell Afif, Tel Aviv, Israel