Georg Schmitz

Ruhr-Universität Bochum, Bochum, North Rhine-Westphalia, Germany

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Publications (89)88.06 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We report an experimental finding of photoacoustic signal enhancement from finite sized DNA–gold nanoparticle networks. We synthesized DNA-functionalized hollow and solid gold nanospheres (AuNS) to form finite sized networks, which were characterized by means of optical extinction spectroscopy, dynamic light scattering, and scanning electron microscopy in transmission mode. It is shown that the signal amplification scales with network size for networks comprising either hollow or solid AuNS as well as networks consisting of both types of nanoparticles. The laser intensities applied in our multispectral setup (λ = 650 nm, 850 nm, 905 nm) were low enough to maintain the structural integrity of the networks. This reflects that the binding and recognition properties of the temperature-sensitive cross-linking DNA-molecules are retained.
    Materials Research Express. 10/2014; 1(4):045015.
  • Martin F Schiffner, Georg Schmitz
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    ABSTRACT: In pulse-echo ultrasound imaging (PEUI) of soft tissues, the scattered sound field is governed by spatial fluctuations of the two mechanical parameters compressibility and mass density. Spatial fluctuations in compressibility act as isotropic monopole radiators while spatial fluctuations in mass density act as anisotropic dipole radiators. Conventional strategies for linear image reconstruction in PEUI, e.g., delay-and-sum, minimum variance, and synthetic aperture focusing, exclusively account for monopole scattering. This neglect of the inhomogeneous mass density might be accompanied by a loss of diagnostically relevant information, e.g., the detection of tissue abnormalities. In this study, we formulate a linear inverse scattering problem to recover separate, space-resolved maps of the spatial fluctuations in both mechanical parameters from measurements of the scattered acoustic pressure. The physical model accounts for frequency-dependent absorption and dispersion in accordance with the time causal model. The computational costs are effectively reduced by the usage of the fast multipole algorithm. The concept is evaluated using simulated and experimentally obtained radio frequency data.
    The Journal of the Acoustical Society of America 04/2014; 135(4):2179. · 1.65 Impact Factor
  • Markus C Hesse, Georg Schmitz
    Biomedizinische Technik/Biomedical Engineering 09/2013; · 1.16 Impact Factor
  • Source
    Markus C Hesse, Leili Salehi, Georg Schmitz
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    ABSTRACT: In diagnostic ultrasound imaging, the image reconstruction quality is crucial for reliable diagnosis. Applying reconstruction algorithms based on the acoustic wave equation, the obtained image quality depends significantly on the physical material parameters accounted for in the equation. In this contribution, we extend a proposed iterative nonlinear one-parameter compressibility reconstruction algorithm by the additional reconstruction of the object's inhomogeneous mass density distribution. The improved iterative algorithm is able to reconstruct inhomogeneous maps of the object's compressibility and mass density simultaneously using only one conventional linear transducer array at a fixed location for wave transmission and detection. The derived approach is based on an acoustic wave equation including spatial compressibility and mass density variations, and utilizes the Kaczmarz method for iterative material parameter reconstruction. We validate our algorithm numerically for an unidirectional pulse-echo breast imaging application, and thus generate simulated measurements acquired from a numerical breast phantom with realistic compressibility and mass density values. Applying these measurements, we demonstrate with two reconstruction experiments the necessity to calculate the mass density in case of tissues with significant mass density inhomogeneities. When reconstructing spatial mass density variations, artefacts in the breast's compressibility image are reduced resulting in improved spatial resolution. Furthermore, the compressibility relative error magnitude within a diagnostically significant region of interest (ROI) decreases from 3.04% to 2.62%. Moreover, a second image showing the breast's inhomogeneous mass density distribution is given to provide additional diagnostic information. In the compressibility image, a spatial resolution moderately higher than the classical half-wavelength limit is observed.
    Physics in Medicine and Biology 08/2013; 58(17):6163-6178. · 2.70 Impact Factor
  • Leili Salehi, Georg Schmitz
    IEEE Ultrasound Symposium; 07/2013
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    ABSTRACT: The effect of variations in microbubble shell composition on microbubble resonance frequency is revealed through experiment. These variations are achieved by altering the mole fraction and molecular weight of functionalized polyethylene glycol (PEG) in the microbubble phospholipid monolayer shell and measuring the microbubble resonance frequency. The resonance frequency is measured via a chirp pulse and identified as the frequency at which the pressure amplitude loss of the ultrasound wave is the greatest as a result of passing through a population of microbubbles. For the shell compositions used herein, we find that PEG molecular weight has little to no influence on resonance frequency at an overall PEG mole fraction (0.01) corresponding to a mushroom regime and influences the resonance frequency markedly at overall PEG mole fractions (0.050-0.100) corresponding to a brush regime. Specifically, the measured resonance frequency was found to be 8.4, 4.9, 3.3 and 1.4 MHz at PEG molecular weights of 1000, 2000, 3000 and 5000 g/mol, respectively, at an overall PEG mole fraction of 0.075. At an overall PEG mole fraction of just 0.01, on the other hand, resonance frequency exhibited no systematic variation, with values ranging from 5.7 to 4.9 MHz. Experimental results were analyzed using the Sarkar bubble dynamics model. With the dilatational viscosity held constant (10(-8) N·s/m) and the elastic modulus used as a fitting parameter, model fits to the pressure amplitude loss data resulted in elastic modulus values of 2.2, 2.4, 1.6 and 1.8 N/m for PEG molecular weights of 1000, 2000, 3000 and 5000 g/mol, respectively, at an overall PEG mole fraction of 0.010 and 4.2, 1.4, 0.5 and 0.0 N/m, respectively, at an overall PEG mole fraction of 0.075. These results are consistent with theory, which predicts that the elastic modulus is constant in the mushroom regime and decreases with PEG molecular weight to the inverse 3/5 power in the brush regime. Additionally, these results are consistent with inertial cavitation studies, which revealed that increasing PEG molecular weight has little to no effect on inethe rtial cavitation threshold in the mushroom regime, but that increasing PEG molecular weight decreases inertial cavitation markedly in the brush regime. We conclude that the design and synthesis of microbubbles with a prescribed resonance frequency is attainable by tuning PEG composition and molecular weight.
    Ultrasound in medicine & biology 05/2013; · 2.46 Impact Factor
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    ABSTRACT: The detection of microbubble contrast agents with ultrasound imaging techniques is the subject of ongoing research. Commonly, the nonlinear response of the agent is employed for detection. The performance of these techniques is, however, affected by nonlinear sound propagation. As an alternative, the change in echo response resulting from microbubble destruction can be employed to detect the agent. In this work, we propose a novel criterion for microbubble destruction detection that allows the rejection of tissue at a defined significance level even for highly echogenic structures in the presence of nonlinear propagation. Most clinical systems provide the hardware requirements for acquisitions consisting of multiple pulses transmitted at the same position, as used in Doppler imaging. Therefore, we develop a processing strategy that distinguishes contrast agent from other stationary or moving structures using these sequences. The proposed criterion is based on the variance of the phase shift of consecutive echoes in the sequence, which, in addition to tissue rejection, permits the distinction of motion from agent disruption. Phantom experiments are conducted to show the validity of the criterion and demonstrate the performance of the new method for contrast detection. Each detection series consists of 20 identical pulses at 9.5 MHz (4.7 MPa peak negative pressure) transmitted at a pulse repetition frequency of 5 kHz. The sequence is applied to phantoms under varied motion and flow conditions. As a first step toward molecular imaging, the technique is applied to microbubbles targeted to vascular endothelial growth factor receptor 2 (VEGFR2) in vitro. The results show a uniform rejection of the background signal while maintaining a contrast enhancement by more than 40 dB. The area under the receiver operating characteristics (ROC) curve is used as the performance metric for the separation of contrast agent and tissue signals, and values larger than 97% demonstrate that an excellent separation was achieved.
    IEEE transactions on ultrasonics, ferroelectrics, and frequency control 05/2013; 60(5):909-23. · 1.80 Impact Factor
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    ABSTRACT: The effect of modifying the shell composition of a population of microbubbles on their size demonstrated through experiment. Specifically, these variations include altering both the mole fraction and molecular weight of functionalized polymer, polyethylene glycol (PEG) in the microbubble phospholipid monolayer shell (1-15mol% PEG, and 1000-5000g/mole, respectively). The size distribution is measured with an unbiased image segmentation program written in MATLAB which identifies and sizes bubbles from micrographs. For a population of microbubbles with a shell composition of 5mol% PEG2000, the mean diameter is 1.42μm with a variance of 0.244μm. For the remainder of the shell compositions studied herein, we find that the size distributions do not show a statistically significant correlation to either PEG molecular weight or mole fraction. All the measured distributions are nearly Gaussian in shape and have a monomodal peak.
    Ultrasonics 04/2013; · 2.03 Impact Factor
  • M F Schiffner, T Jansen, G Schmitz
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    ABSTRACT: In this contribution we refined our previously introduced concept for pulse-echo ultrasound imaging based on compressed sensing (CS). Our goal was to reduce the number of sequential wave emissions per image and thus acquisition time, without diminishing image quality. Using measurement data obtained from a wire phantom (A) and a multi-tissue phantom (B), we evaluated our concept in comparison to B-mode, synthetic aperture focussing, delay-and-sum (DAS) beamforming, and filtered backpropagation (FBP). Emitting only a single plane wave, our CS approach yielded the best results for the sparse phantom A in terms of sidelobe reduction and lateral -6 dBwidths. For the non-sparse phantom B, CS yielded a higher contrast than DAS and FBP when a single plane wave was emitted and a curvelet or wavelet transform was used for sparse representation. The contrast was comparable to SA and B-mode.
    Biomedizinische Technik/Biomedical Engineering 08/2012; · 1.16 Impact Factor
  • T Jansen, M F Schiffner, G Schmitz
    Biomedizinische Technik/Biomedical Engineering 08/2012; · 1.16 Impact Factor
  • Biomedizinische Technik/Biomedical Engineering 08/2012; · 1.16 Impact Factor
  • M F Beckmann, L Girke, G Schmitz
    Biomedizinische Technik/Biomedical Engineering 08/2012; · 1.16 Impact Factor
  • Biomedizinische Technik/Biomedical Engineering 08/2012; · 1.16 Impact Factor
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    ABSTRACT: Photoacoustic (PA) imaging attracts a great deal of attention as an innovative modality for longitudinal, non-invasive, functional and molecular imaging in oncology. Gold nanoparticles (AuNPs) are identified as superior, NIR-absorbing PA contrast agents for biomedical applications. Until now, no systematic comparison of the optical extinction and PA efficiency of water-soluble AuNPs of various geometries and small sizes has been performed.Here spherical AuNPs with core diameters of 1.0, 1.4 and 11.2 nm, nanorods with longitudinal/transversal elongation of 38/9 and 44/12 nm and hollow nanospheres with outer/inner diameters of 33/19, 57/30, 68/45 and 85/56 nm were synthesized. The diode laser set-up with excitations at 650, 808, 850 and 905 nm allowed us to correlate the molar PA signal intensity with the molar extinction of the respective AuNPs. Deviations were explained by differences in heat transfer from the particle to the medium and, for larger particles, by the scattering of light. The molar PA intensity of 1.0 nm AuNPs was comparable to the commonly used organic dye methylene blue, and rapidly increased with the lateral size of AuNPs.
    Nanotechnology 05/2012; 23(22):225707. · 3.84 Impact Factor
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    ABSTRACT: Photoacoustic imaging (PAI) combines high ultrasound resolution with optical contrast. Laser-generated ultrasound is potentially beneficial for cancer detection, blood oxygenation imaging, and molecular imaging. PAI is generally performed using solid state Nd:YAG lasers in combination with optical parametric oscillators. An alternative approach uses laser diodes with higher pulse repetition rates but lower power. Thus, improvement in signal-to-noise ratio (SNR) is a key step towards applying laser diodes in PAI. To receive equivalent image quality using laser diodes as with Nd:YAG lasers, the lower power must be compensated by averaging, which can be enhanced through coded excitation. In principle, perfect binary sequences such as orthogonal Golay codes can be used for this purpose when acquiring data at multiple wavelengths. On the other hand it was shown for a single wavelength that sidelobes can remain invisible even if imperfect sequences are used. Moreover, SNR can be further improved by using an imperfect sequence compared to Golay codes. Here, we show that pseudorandom sequences are a good choice for multispectral photoacoustic coded excitation (MSPACE). Pseudorandom sequences based upon maximal length shift register sequences (m-sequences) are introduced and analyzed for the purpose of use in MSPACE. Their gain in SNR exceeds that of orthogonal Golay codes for finite code lengths. Artefacts are introduced, but may remain invisible depending on SNR and code length.
    Proc SPIE 02/2012;
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    ABSTRACT: Ultrasound is one of the workhorses in clinical cancer diagnosis. In particular, it is routinely used to characterize lesions in liver, urogenital tract, head and neck and soft tissues. During the last years image quality steadily improved, which, among others, can be attributed to the development of harmonic image analysis. Microbubbles were introduced as intravascular contrast agents and can be detected with superb sensitivity and specificity using contrast specific imaging modes. By aid of these unspecific contrast agents tissues can be characterised regarding their vascularity. Antibodies, peptides and other targeting moieties were bound to microbubbles to target sites of angiogenesis and inflammation intending to get more disease-specific information. Indeed, many preclinical studies proved the high potential of targeted ultrasound imaging to better characterize tumors and to more sensitively monitor therapy response. Recently, first targeted microbubbles had been developed that meet the pharmacological demands of a clinical contrast agent. This review articles gives an overview on the history and current status of targeted ultrasound imaging of cancer. Different imaging concepts and contrast agent designs are introduced ranging from the use of experimental nanodroplets to agents undergoing clinical evaluation. Although it is clear that targeted ultrasound imaging works reliably, its broad acceptance is hindered by the user dependency of ultrasound imaging in general. Automated 3D-scanning techniques-like being used for breast diagnosis - and novel 3D transducers will help to make this fascinating method clinical reality.
    Current pharmaceutical design 01/2012; 18(15):2184-99. · 4.41 Impact Factor
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    ABSTRACT: Ferroelectric, piezoelectric thin film material and processes are gaining more and more importance for innovative devices that are focusing on miniaturization, high performance and integration. A piezoelectric thin film MEMs platform has been developed that enables miniaturized ultrasound transducers that operate in the frequency range of >50 kHz up to >10 MHz. The thin film ultrasound transducers show a high quality and reliability. With this technology platform ultrasound transducers have been developed that operate at 60–90 kHz and show a coverage >25 m at a low operating voltage of 12 V. The same technology platform has been used to realize ultrasound transducer arrays operating at 3–10 MHz. Ultrasound images have been demonstrated with these piezoelectric thin film transducer arrays.
    Integrated Ferroelectrics 01/2012; 134(1):25-36. · 0.38 Impact Factor
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    ABSTRACT: The destruction threshold of ultrasound contrast agents is an important parameter for safety and applications in targeted drug delivery. Since this threshold is a function of the chemical composition of lipid-shelled microbubbles, adjustment of this composition may allow tuning of the destruction threshold. To attain this goal, this study presents a framework for the analysis of the destruction threshold. A method for the theoretical determination of this threshold is presented. Theoretical results are subsequently validated by experiments, yielding a linear dependence between shell viscosity and elasticity and DSPE-PEG2000 concentration.
    Acoustical Imaging. 01/2012;
  • L. Salehi, G. Schmitz
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    ABSTRACT: Nonlinear ultrasound diffraction tomography reconstructs material parameters of a medium from transmitted and scattered sound waves taking into account multiple scattering, which is important in the presence of strongly scattering media like in breast tissue or the abdominal wall. Most nonlinear approaches propose algorithms to reconstruct the spatially varying speed of sound (SoS), which is equivalent to a spatially varying compressibility under the assumption of constant mass density. Here, we present an extension of a nonlinear reconstruction algorithm based on the Kaczmarz method to reconstruct both, density and compressibility simultaneously. We investigate errors arising from neglecting realistic density changes and demonstrate the improvements that can be introduced in the estimation of speed of sound by applying the proposed method.
    Ultrasonics Symposium (IUS), 2012 IEEE International; 01/2012
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    ABSTRACT: This paper discusses various interactions between ultrasound, phospholipid monolayer-coated gas bubbles, phospholipid bilayer vesicles, and cells. The paper begins with a review of microbubble physics models, developed to describe microbubble dynamic behavior in the presence of ultrasound, and follows this with a discussion of how such models can be used to predict inertial cavitation profiles. Predicted sensitivities of inertial cavitation to changes in the values of membrane properties, including surface tension, surface dilatational viscosity, and area expansion modulus, indicate that area expansion modulus exerts the greatest relative influence on inertial cavitation. Accordingly, the theoretical dependence of area expansion modulus on chemical composition - in particular, poly (ethylene glyclol) (PEG) - is reviewed, and predictions of inertial cavitation for different PEG molecular weights and compositions are compared with experiment. Noteworthy is the predicted dependence, or lack thereof, of inertial cavitation on PEG molecular weight and mole fraction. Specifically, inertial cavitation is predicted to be independent of PEG molecular weight and mole fraction in the so-called mushroom regime. In the "brush" regime, however, inertial cavitation is predicted to increase with PEG mole fraction but to decrease (to the inverse 3/5 power) with PEG molecular weight. While excellent agreement between experiment and theory can be achieved, it is shown that the calculated inertial cavitation profiles depend strongly on the criterion used to predict inertial cavitation. This is followed by a discussion of nesting microbubbles inside the aqueous core of microcapsules and how this significantly increases the inertial cavitation threshold. Nesting thus offers a means for avoiding unwanted inertial cavitation and cell death during imaging and other applications such as sonoporation. A review of putative sonoporation mechanisms is then presented, including those involving microbubbles to deliver cargo into a cell, and those - not necessarily involving microubbles - to release cargo from a phospholipid vesicle (or reverse sonoporation). It is shown that the rate of (reverse) sonoporation from liposomes correlates with phospholipid bilayer phase behavior, liquid-disordered phases giving appreciably faster release than liquid-ordered phases. Moreover, liquid-disordered phases exhibit evidence of two release mechanisms, which are described well mathematically by enhanced diffusion (possibly via dilation of membrane phospholipids) and irreversible membrane disruption, whereas liquid-ordered phases are described by a single mechanism, which has yet to be positively identified. The ability to tune release kinetics with bilayer composition makes reverse sonoporation of phospholipid vesicles a promising methodology for controlled drug delivery. Moreover, nesting of microbubbles inside vesicles constitutes a truly "theranostic" vehicle, one that can be used for both long-lasting, safe imaging and for controlled drug delivery.
    Theranostics 01/2012; 2(12):1140-59. · 7.81 Impact Factor

Publication Stats

218 Citations
88.06 Total Impact Points

Institutions

  • 2005–2014
    • Ruhr-Universität Bochum
      • Fakultät für Elektrotechnik und Informationstechnik
      Bochum, North Rhine-Westphalia, Germany
  • 2009
    • Drexel University
      • Department of Chemical and Biological Engineering
      Philadelphia, PA, United States
  • 2007
    • Philips
      • Philips Research
      Eindhoven, North Brabant, Netherlands