Dror Fixler

Bar Ilan University, Gan, Tel Aviv, Israel

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Publications (51)123.76 Total impact

  • [Show abstract] [Hide abstract]
    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. · 3.50 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; · 13.03 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.
    02/2014;
  • 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. · 2.75 Impact Factor
  • 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; · 13.03 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. · 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. · 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
  • 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. · 3.50 Impact Factor
  • 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. · 2.75 Impact Factor
  • 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 05/2013; · 3.86 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. · 1.70 Impact Factor
  • L Turgeman, D Fixler
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    ABSTRACT: In time correlated single photon counting (TCSPC) systems the maximum signal throughput is limited by the occurrence of pile-up and other effects. In many biological applications that exhibit high levels of fluorescence intensity (FI), pile-up related distortions yields serious distortions in the fluorescence lifetime (FLT) calculation as well as significant decrease in the signal to noise ratio (SNR). Recent developments that allow the use of high repetition rate light sources (in the range of 50 to 100 MHz) in fluorescence lifetime imaging (FLIM) experiments enable minimization of classical pile-up related distortions. However, modern TCSPC configurations that use high-repetition-rate excitation sources for FLIM, suffer from dead time related distortions that cause unpredictable distortions of the FI signal. In this work, the loss of SNR described by F-value as it is typically done in FLIM systems. This F-value describes the relation of the relative standard deviation in the estimated FLT to the relative standard deviation in FI measurements. Optimization of the F-value allows minimization of signal distortion, as well as shortening of the acquisition time for certain samples. We applied this method for Fluorescein and Erythrosine fluorescent solutions that have different FLT values (4 nsec and 140 psec respectively).
    IEEE transactions on bio-medical engineering 01/2013; · 2.15 Impact Factor
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    ABSTRACT: Recently in phototherapy the use of diodes and broadband light devices instead of lasers was suggested for economical and practical reasons. It has been argued that lasers are not superior to LEDs since they lose their coherence and polarization once they penetrate into biological tissues. However, the polarization point has never been experimentally proven. In this work, to the best of our knowledge, we have for the first time experimentally validated the conditions that affect the polarization state of light when laser illumination propagates through a biological tissue with and without flow. In our experiments we measured the polarization of light passing through phantoms as well as through uncooked turkey meat. The measurements were performed for varied integration time, thickness and flow rates. It was experimentally validated that the tissue thickness hardly influences the polarization in comparison to flow for a reduced scattering coefficient of 0.8 mm−1 while there is no flow. Furthermore, when the flow is perpendicular to the polarization plane its velocity highly affects the polarization. However, when the flow is parallel to the polarization plane there is almost no change in the propagating light's polarization state. Thus, one outcome of this work is that since the biological tissue is not static and contains many blood vessels and capillaries, the polarization of the laser may be lost when light penetrates the tissue.
    Optics and Lasers in Engineering 06/2012; 50(6):850–854. · 1.70 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the effect of extremely low frequency and weak magnetic fields (WMF) on cardiac myocyte Ca(2+) transients, and to explore the involvement of potassium channels under the WMF effect. In addition, we aimed to find a physical explanation for the effect of WMF on cardiac myocyte Ca(2+) transients. Indo-1 loaded cells, which were exposed to a WMF at 16 Hz and 40 nT, demonstrated a 75 ± 4% reduction in cytosolic Ca(2+) transients versus control. Treatment with the K(ATP) channel blocker, glibenclamide, followed by WMF at 16 Hz exposure, blocked the reduction in cytosolic calcium transients while treatment with pinacidil, a K(ATP) channel opener, or chromanol 293B, a selective potassium channel blocker of the delayed rectifier K(+) channels, did not inhibit the effect. Based on these finding and the ion cyclotron resonance frequency theory, we further investigated the effect of WMF by changing the direct current (DC) magnetic field (B(0) ). When operating different DC magnetic fields we showed that the WMF value changed correspondingly: for B(0)  = 44.5 µT, the effect was observed at 17.05 Hz; for B(0)  = 46.5 µT, the effect was observed at 18.15 Hz; and for B(0)  = 49 µT the effect was observed at 19.1 Hz. We can conclude that the effect of WMF on Ca(2+) transients depends on the DC magnetic field level. Bioelectromagnetics. © 2012 Wiley Periodicals, Inc.
    Bioelectromagnetics 04/2012; · 1.86 Impact Factor
  • Source
    Lior Turgeman, Dror Fixler
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    ABSTRACT: Recent developments in the field of single molecule orientation imaging have led us to devise a simple framework for analyzing fluorescence intensity fluctuations in single molecule polarization sensitive experiments. Based on the new framework, rotational dynamics of individual molecules are quantified, in this paper, from the short time behavior of the time averaged fluorescence intensity fluctuation trajectories. The suggested model can be applied in single molecule fluorescence fluctuations experiments to extract accurate expectation values of photon counts during very short integration time in which rotational diffusion is likely not to be averaged out.
    Optics Express 04/2012; 20(8):9276-83. · 3.53 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 03/2012; · 3.86 Impact Factor
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    ABSTRACT: The ability to quantitatively and non-invasively detect nanoparticles has important implications on their development as an in-vivo cancer diagnostic tool. The Diffusion Reflection (DR) method is a simple, non-invasive imaging technique which has been proven useful for the investigation of tissue's optical parameters. In this study, Monte Carlo (MC) simulations, tissue-like phantom experiments and in-vivo measurements of the reflected light intensity from tumor bearing mice are presented. Following intravenous injection of antibody conjugated poly (ethylene glycol)-coated (PEGylated) gold nanorods (GNR) to tumor-bearing mice, accumulation of GNR in the tumor was clearly detected by the DR profile of the tumor. The ability of DR measurements to quantitate in-vivo the concentration of the GNR in the tumor was demonstrated and validated with Flame Atomic Absorption spectroscopy results. With GNR as absorbing contrast agents, DR has important potential applications in the image guided therapy of superficial tumors such as head and neck cancer, breast cancer and melanoma.
    Journal of Biophotonics 03/2012; 5(3):263-73. · 3.86 Impact Factor
  • Dror Fixler, Zeev Zalevsky
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    ABSTRACT: Recently in phototherapy the use of diodes and broadband light devices instead of lasers was suggested for economical and practical reasons. It has been argued that lasers have no preference over diodes since they lose their coherency and polarization once penetrating into biological tissues. In this talk we have for the first time experimentally validated the conditions that affect the polarization state of light when laser illumination is propagated through a biological tissue with and without a flow. In additional we will present physical modeling showing that illuminating a flow in a medium with linear polarized light can be highly correlated to the direction and rate of the flow through that medium.
    Proc SPIE 02/2012;
  • Lior Turgeman, Dror Fixler
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    ABSTRACT: A general framework to include fluctuations in the single molecule fluorescence intensity (FI) signal due to random changes in molecule dipole orientation was introduced at Optics Express (21, 2007). By assuming continuous changes in dipole orientation described by Brownian rotational diffusion, this research derives the probability density function (PDF) equation of FI fluctuations. Solution of the proposed equation for several limiting cases and different correlation times yields the short time behavior of FI fluctuations. Monte Carlo simulations results, in accordance with those found in theory will be presented during our talk.
    Proc SPIE 02/2012;

Publication Stats

183 Citations
123.76 Total Impact Points

Institutions

  • 1997–2014
    • Bar Ilan University
      • • Institute of Nanotechnology and Advanced Materials (BINA)
      • • Faculty of Engineering
      • • Department of Mathematics
      • • Department of Physics
      Gan, Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
      Tell Afif, Tel Aviv, Israel
  • 2013
    • Tel Aviv University
      • Department of Biomedical Engineering
      Tel Aviv, Tel Aviv, Israel