Frits F. de Mul

University of Groningen, Groningen, Province of Groningen, Netherlands

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Publications (168)246.56 Total impact

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    ABSTRACT: Objective: Clinical acceptance of laser-Doppler perfusion monitoring (LDPM) of microcirculation suffers from lack of quantitatively reliable signal data, due to varying tissue constitution, temperature, hydration, etc. In this article, we show that a novel approach using physiological models for response upon provocations provides quantitatively and clinically relevant time constants.Methods: We investigated this for two provocation protocols: postocclusive reactive hyperemia (PORH) and iontophoresis shots, measured with LDPM on extremities. PORH experiments were performed on patients with peripheral arterial occlusive disease (PAOD) or diabetes mellitus (DM), and on healthy controls. Iontophoresis experiments were performed on pre-eclamptic patients and healthy controls. We developed two dynamical physical models, both based on two characteristic time constants: for PORH, an “arterial” and a “capillary” time constant and, for iontophoresis, a “diffusion” and a “decay” time constant.Results: For the different subject groups, we could extract time constants that could probably be related to physiological differences. For iontophoresis, a shot saturation constant was determined, with very different values for different groups and administered drugs.Conclusions: With these models, the dynamics of the provocations can be investigated and quantitative comparisons between experiments and subject groups become available. The models offer a quantifiable standard that is independent of the type of LDPM instrumentation.
    Microcirculation (New York, N.Y.: 1994) 09/2009; 16(7):559 - 571. · 2.37 Impact Factor
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    ABSTRACT: We report novel direct quantitative comparisons between 3D profiling measurements and simulations of human vocal fold vibrations. Until now, in human vocal folds research, only imaging in a horizontal plane was possible. However, for the investigation of several diseases, depth information is needed, especially when the two folds act differently, e.g. in the case of tumour growth. Recently, with our novel depth-kymographic laryngoscope, we obtained calibrated data about the horizontal and vertical positions of the visible surface of the vibrating vocal folds. In order to find relations with physical parameters such as elasticity and damping constants, we numerically simulated the horizontal and vertical positions and movements of the human vocal folds while vibrating and investigated the effect of varying several parameters on the characteristics of the phonation: the masses and their dimensions, the respective forces and pressures, and the details of the vocal tract compartments. Direct one-to-one comparison with measured 3D positions presents-for the first time-a direct means of validation of these calculations. This may start a new field in vocal folds research.
    Physics in Medicine and Biology 08/2009; 54(13):3955-77. · 2.70 Impact Factor
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    ABSTRACT: We designed and developed a laser line-triangulation endoscope compatible with any standard high-speed camera for a complete three-dimensional profiling of human vocal fold vibration dynamics. With this novel device we are able to measure absolute values of vertical and horizontal vibration amplitudes, length and width of vocal folds as well as the opening and closing velocities from a single in vivo measurement. We have studied, for the first time, the generation and propagation of mucosal waves by locating the position of its maximum vertical position and the propagation velocity. Precise knowledge about the absolute dimensions of human vocal folds and their vibration parameters has significant importance in clinical diagnosis and treatment as well as in fundamental research in voice. The new device can be used to investigate different kinds of pathological conditions including periodic or aperiodic vibrations. Consequently, the new device has significant importance in investigating vocal fold paralysis and in phonosurgical applications.
    Physics in Medicine and Biology 06/2008; 53(10):2667-75. · 2.70 Impact Factor
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    ABSTRACT: We report the design of a novel laser line-triangulation laryngoscope for the quantitative visualization of the three-dimensional movements of human vocal folds during phonation. This is the first successful in vivo recording of the three-dimensional movements of human vocal folds in absolute values. Triangulation images of the vocal folds are recorded at the rate of 4000 fps with a resolution of 256x256 pixels. A special image-processing algorithm is developed to precisely follow the subpixel movements of the laser line image. Vibration profiles in both horizontal and vertical directions are calibrated and measured in absolute SI units with a resolution of +/-50 microm. We also present a movie showing the vocal folds dynamics in vertical cross section.
    Journal of Biomedical Optics 01/2008; 13(6):064024. · 2.75 Impact Factor
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    ABSTRACT: Laser Doppler flux signals show temporal fluctuations caused by physiological phenomena like heartbeat, respiration, and local variation of vascular tonus, vasomotion. This study investigates the influence of fiber arrangement, equipment and two probe locations on the variations in laser Doppler flux signals in five frequency bands in the absence of provocations. Two probes with detecting optical fibers at several distances from the illuminating source were used, as well as instruments from two manufacturers. The results show that normalization of the filtered flux signals with the mean flux leads to an enormous decrease of the influence of fiber distance. The difference between instruments is small after normalization. Some influence of probe location remains after normalization. Development of a standard method for normalization of the variations in laser Doppler signals is recommended.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2007; 2007:4076-9.
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    ABSTRACT: We present a physical model to describe iontophoresis time recordings. The model is a combination of monodimensional material diffusion and decay, probably due to transport by blood flow. It has four adjustable parameters, the diffusion coefficient, the decay constant, the height of the response, and the shot saturation constant, a parameter representing the relative importance of subsequent shots (in case of saturation). We test the model with measurements of blood perfusion in the capillary bed of the fingers of women who recently had preeclampsia and in women with a history of normal pregnancy. From the fits to the measurements, we conclude that the model provides a useful physical description of the iontophoresis process.
    Journal of Biomedical Optics 01/2007; 12(1):014032. · 2.75 Impact Factor
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    ABSTRACT: An integrated optoelectronic probe with small dimensions, for direct-contact laser Doppler blood flow monitoring has been realized. A vertical cavity surface emitting laser (VCSEL), and a chip with photodetectors and all necessary electronics are integrated in a miniature probe head connected to a laptop computer. The computer sound processor is utilized for acquisition and digital signal processing of the incoming Doppler signal. In this paper, the design of the laser Doppler perfusion monitor is described and its performance is evaluated. We demonstrate our perfusion monitor to be less sensitive to subject motion than a commercial fiber-optic device. For medium and high perfusion levels, the performance of our integrated probe is comparable to the fiberoptic flowmeter containing a normal edge-emitting laser diode. For very low perfusion levels, the signal-to-noise ratio of the fiber-optic device is higher. This difference can mainly be attributed to the shorter coherence length of the VCSEL compared with the edge-emitting laser diode.
    IEEE Transactions on Biomedical Engineering 11/2006; 53(10):2067-74. · 2.35 Impact Factor
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    ABSTRACT: The position and broadening of the Raman band associated with the phosphate symmetric stretching vibration in hydroxyapatite are simulated using a simple inter- and intra-ionic potential. The results are compared with experimental values. This comparison was made as a function of the incorporation of carbonate ions in the lattice for a number of substitution models. The line width of the phosphate symmetric stretching vibration is shown both theoretically and experimentally to be dependent on the carbonate content. Good agreement between calculations and experiment is obtained. The results of the calculations offer some support to the suggestions in the literature that the dielectric constant has to be considered as a function of the distance in the lattice, increasing beyond the first environmental layer.
    Journal of Raman Spectroscopy 04/2005; 19(1):13 - 21. · 2.68 Impact Factor
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    ABSTRACT: To facilitate the quantitative analysis of post-occlusive reactive hyperaemia (PORH), measured with laser-Doppler perfusion monitoring (LDPM) on extremities, we present a flow model for the dynamics of the perfusion of the tissue during PORH, based on three parameters: two time constants (tau1 and tau2) and the ratio of the maximum flux and the resting flux. With these three constants quantitative comparisons between experiments will be possible and, therefore, we propose to adopt this approach as future standard. For this reason, we also developed a computer program to perform the fit of the model to measured data.
    IEEE Transactions on Biomedical Engineering 03/2005; 52(2):184-90. · 2.35 Impact Factor
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    ABSTRACT: We present photoacoustic images of tumor neovascularization obtained over a 10-day period after subcutaneous inoculation of pancreatic tumor cells in a rat. The images were obtained from ultrasound generated by absorption in hemoglobin of short laser pulses at a wavelength of 1064 nm. The ultrasound signals were measured in reflection mode using a single scanning piezodetector, and images were reconstructed with a weighted delay-and-sum algorithm. Three-dimensional data visualize the development and quantify the extent of individual blood vessels around the growing tumor, blood concentration changes inside the tumor and growth in depth of the neovascularized region.
    Optics Express 02/2005; 13(1):89-95. · 3.55 Impact Factor
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    ABSTRACT: A double-ring sensor was applied in photoacoustic tomographic imaging of artificial blood vessels as well as blood vessels in a rabbit ear. The peak-to-peak time (tau(pp)) of the laser (1064 nm) induced pressure transient was used to estimate the axial vessel diameter. Comparison with the actual vessel diameter showed that the diameter could be approximated by 2ctau(pp), with c the speed of sound in blood. Using this relation, the lateral diameter could also precisely be determined. In vivo imaging and monitoring of changes in vessel diameters was feasible. Finally, acoustic time traces were recorded while flushing a vessel in the rabbit ear with saline, which proved that the main contribution to the laser-induced pressure transient is caused by blood inside the vessel and that the vessel wall gives only a minor contribution.
    Physics in Medicine and Biology 11/2004; 49(20):4745-56. · 2.70 Impact Factor
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    ABSTRACT: The effects of fiber coupling and fiber length on photocurrent fluctuations are studied when the light of a laser diode transmitted to and from a dynamic turbid medium by a step-index multimode fiber is studied. When the laser light is coupled asymmetrically, filling only the higher-order modes, the photocurrent fluctuations are suppressed significantly when fiber lengths of as much as 16 m are added between the laser and the medium. Addition of as much as 16 m of detection fiber, or any fiber in the case of symmetric light coupling, leads to much less or no suppression of the photocurrent fluctuations.
    Applied Optics 05/2004; 43(10):2059-65. · 1.69 Impact Factor
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    ABSTRACT: The ability to correctly visualize the architectural arrangement of microvasculature is valuable to many diverse fields in medicine. In this study, we applied photoacoustics (PA) to obtain high-resolution images of submillimeter blood vessels. Short laser pulses are used to generate ultrasound from superficial blood vessels in several animal models. From these ultrasound waves the interior of blood vessels can be reconstructed. We present results from a novel approach based on the PA principle that allows specific in vivo visualization of dermal blood vessels without the use of contrast agents or ionizing radiation. We show PA images of externalized blood vessels and demonstrate in vivo PA imaging of vasculature through layers of skin varying in thickness.
    Lasers in Surgery and Medicine 02/2004; 35(5):354-62. · 2.46 Impact Factor
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    ABSTRACT: A photoacoustic double-ring sensor, featuring a narrow angular aperture, is developed for laser-induced photoacoustic imaging of blood vessels. An integrated optical fiber enables reflection-mode detection of ultrasonic waves. By using the cross-correlation between the signals detected by the two rings, the angular aperture of the sensor is reduced by a factor of 1.9, from 1.5 to 0.8 deg. Consequently, photoacoustic images could be obtained in a manner analogous to the ultrasound B-scan mode. Next, the cross section of artificial blood vessels is visualized by reconstruction of the absorbed energy distribution. Finally, in vivo imaging and the subsequent reconstruction of the absorbed energy distribution is demonstrated for superficial blood vessels in the human wrist.
    Journal of Biomedical Optics 01/2004; 9(6):1327-35. · 2.75 Impact Factor
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    ABSTRACT: This paper describes the simultaneous use of two, noninvasive, near-infrared techniques near-infrared spectroscopy (NIRS) and a continuous wave NIR laser Doppler flow system (LDF) to measure changes in the blood oxygenation, blood concentration and blood flow velocity in the brain. A piglet was used as animal model. A controlled change in the arterial CO2 pressure (PaCO2) was applied for achieving changes in the listed cerebrovascular parameters. The time courses of blood concentration parameters (NIRS) and RMS blood flow velocity (LDF) were found to correspond closely with those of carotid blood flow and arterial carbon dioxide pressure (PaCO2). This result shows the additional value of LDF when combined with NIRS, preferably in one instrument. Development of pulsed LDF for regional blood flow measurement is indicated.
    Physiological Measurement 12/2003; 24(4):N35-40. · 1.50 Impact Factor
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    ABSTRACT: The visualization of the brain vascular system could be of great importance for studying its functionality and for diagnosing possible disorders. In this paper we report the use of photoacoustics for imaging brain perfusion on Albino rats in vivo and post mortem. The measurements on the animals were direct on the skin surface. The blood perfusion on skull cartilage was imaged and 2D slices were constructed by using a beamforming algorithm. From the images representation the Interactive Data Language (IDL, Research System Inc.) was used. We also investigated the possibility of using the Evans Blue dye as a substitute of blood for imaging brain structures in vitro. The breakdown of the dye under pulsed laser irradiation was studied and the energy under which this effect occurs was calculated for the wavelength of 532 nm.
    Archives of Physiology and Biochemistry 11/2003; 111(4):389-97.
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    ABSTRACT: Teaching physics to first-year university students (in the USA: junior/senior level) is often hampered by their lack of skills in the underlying mathematics, and that in turn may block their understanding of the physics and their ability to solve problems. Examples are vector algebra, differential expressions and multi-dimensional integrations, and the Gauss and Ampère laws learnt in electromagnetism courses. To enhance those skills in a quick and efficient way we have developed 'Integrating Mathematics in University Physics', in which students are provided with a selection of problems (exercises) that explicitly deal with the relation between physics and mathematics. The project is based on computer-assisted instruction (CAI), and available via the Internet (http://tnweb.tn.utwente.nl/onderwijs/; or http://www.utwente.nl/; search or click to: CONECT). Normally, in CAI a predefined student-guiding sequence for problem solving is used (systematic problem solving). For self-learning this approach was found to be far too rigid. Therefore, we developed the 'adventurous problem solving' (APS) method. In this new approach, the student has to find the solution by developing his own problem-solving strategy in an interactive way. The assessment of mathematical answers to physical questions is performed using a background link with an algebraic symbolic language interpreter. This manuscript concentrates on the subject of APS.
    European Journal of Physics 10/2003; 25(1):51. · 0.64 Impact Factor
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    ABSTRACT: To investigate the feasibility of instrument-independent perfusion units for laser Doppler flowmetry, a comparison was performed of two commercial fiberoptic laser Doppler perfusion monitors measuring the same flux situation for two different types of probes. In vivo measurements were performed on the cortex of pig's kidney, with an ultrasonic arterial flow meter as reference. The flow was mainly varied by internal arterial constriction using a balloon catheter. For each probe, instruments are compared in terms of the ratio of laser Doppler flux and arterial flow. For a given probe, the flux-to-flow ratios of the two instruments show a linear mutual relationship for a wide variety of arterial flows and laser Doppler fluxes. In vitro measurements were performed on an aqueous suspension of polystyrene microspheres. For the probe with interfiber distance 500 microm the ratio of the in vivo fluxes appears to agree within 16% to the value found in vitro, while for the 250-microm probe a difference of 28% was found. For a wide range of fluxes, the in vivo flux values of one instrument can be translated into flux values for the other instrument, in spite of the instrumental differences. This enables the user to render experimental results independent of the specific instrument, thus facilitating multi-center studies.
    Microvascular Research 10/2003; 66(2):83-90. · 2.93 Impact Factor
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    ABSTRACT: We utilized a CMOS (Complementary Metal Oxide Semiconductor) video-camera for fast flow imaging with use of the laser-Doppler technique. A single sensor is used for both observation of the area of interest and measurements of the interference signal caused by dynamic light scattering from moving particles inside scattering objects. Particularly we demonstrate the possibility to image the distribution of the moving read blood cell concentration. This is a first step towards laser Doppler imaging without scanning parts, leading to a much faster imaging procedure compared to existing mechanical laser Doppler perfusion imagers.
    Proc SPIE 09/2003;
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    ABSTRACT: In laser Doppler flowmetry (LDF) deep perfusion measurements can be realized by using a large separation between the fibers used for illumination and detection. In order to achieve a sufficient signal-to-noise ratio, the power of the laser light can be increased, but only to the limit indicated by the safety regulations. In this paper, pulsed laser Doppler flowmetry (pLDF) is presented as a manner to increase the SNR without exceeding the safety limits. The method is based on the principle that light is needed only when the signal is being sampled. The setup is presented, and we will show results that indicate that equivalent results are obtained for a pulsed and continuous wave setup (cwLDF), however with a much smaller tissue exposure. Furthermore, the limits encountered in realizing a pulsed system will be discussed.
    Proc SPIE 07/2003;

Publication Stats

2k Citations
246.56 Total Impact Points

Institutions

  • 1990–2009
    • University of Groningen
      • • Department of Biomedical Engineering
      • • Centre for Biomedical Technology
      • • Department of Obstetrics and Gynaecology
      Groningen, Province of Groningen, Netherlands
  • 1984–2006
    • Universiteit Twente
      • Faculty of Science and Technology (TNW)
      Enschede, Overijssel, Netherlands
  • 2003
    • Abbott Laboratories
      • Abbott Laboratories
      North Chicago, IL, United States
  • 1999
    • Philips
      Eindhoven, North Brabant, Netherlands
  • 1988–1992
    • Universitair Medisch Centrum Groningen
      Groningen, Groningen, Netherlands
  • 1986
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom