Fabrizio Martelli

Medical Physics, Optics, Computational Physics

PhD
35.22

Publications

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    ABSTRACT: Diffuse correlation spectroscopy (DCS) is the technique of choice for non-invasive assessments of human bone blood flow. However, DCS classical algorithms are based on the fundamental assumption that the electric field of the light reaching the DCS photodetector is a zero-mean complex Gaussian variable. The non-validity of this hypothesis might produce inaccurate blood flow estimations. It is shown that for the human tibia, the "Gaussian hypothesis" holds for interoptode distances ≥20 mm. This lower boundary seems to depend on the type of investigated tissue.
    No preview · Article · Feb 2016 · Applied Optics
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    ABSTRACT: A mechanically switchable solid inhomogeneous phantom simulating localized absorption changes was developed and characterized. The homogeneous host phantom was made of epoxy resin with black toner and titanium dioxide particles added as absorbing and scattering components, respectively. A cylindrical rod, movable along a hole in the block and made of the same material, has a black polyvinyl chloride cylinder embedded in its center. By varying the volume and position of the black inclusion, absorption perturbations can be generated over a large range of magnitudes. The phantom has been characterized by various time-domain diffuse optics instruments in terms of absorption and scattering spectra, transmittance images, and reflectance contrast. Addressing a major application of the phantom for performance characterization for functional near-infrared spectroscopy of the brain, the contrast was measured in reflectance mode while black cylinders of volumes from ≈20 mm3 to ≈270 mm3 were moved in lateral and depth directions, respectively. The new type of solid inhomogeneous phantom is expected to become a useful tool for routine quality check of clinical instruments or implementation of industrial standards provided an experimental characterization of the phantom is performed in advance. © 2015 The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
    Full-text · Article · Dec 2015 · Journal of Biomedical Optics
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    ABSTRACT: In this work, we have tested the optimal estimation (OE) algorithm for the reconstruction of the optical properties of a two-layered liquid tissue phantom from time-resolved single-distance measurements. The OE allows a priori information, in particular on the range of variation of fit parameters, to be included. The purpose of the present investigations was to compare the performance of OE with the Levenberg-Marquardt method for a geometry and real experimental conditions typically used to reconstruct the optical properties of biological tissues such as muscle and brain. The absorption coefficient of the layers was varied in a range of values typical for biological tissues. The reconstructions performed demonstrate the substantial improvements achievable with the OE provided a priori information is available. We note the extreme reliability, robustness, and accuracy of the retrieved absorption coefficient of the second layer obtained with the OE that was found for up to six fit parameters, with an error in the retrieved values of less than 10%. A priori information on fit parameters and fixed forward model parameters clearly improves robustness and accuracy of the inversion procedure. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
    No preview · Article · Nov 2015 · Journal of Biomedical Optics
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    ABSTRACT: The in-vivo optical properties of the human head are investigated in the 600–1100 nm range on different subjects using continuous wave and time domain diffuse optical spectroscopy. The work was performed in collaboration with different research groups and the different techniques were applied to the same subject. Data analysis was carried out using homogeneous and layered models and final results were also confirmed by Monte Carlo simulations. The depth sensitivity of each technique was investigated and related to the probed region of the cerebral tissue. This work, based on different validated instruments, is a contribution to fill the existing gap between the present knowledge and the actual in-vivo values of the head optical properties.
    No preview · Article · Jun 2015 · Biomedical Optics Express
  • Tiziano Binzoni · Fabrizio Martelli
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    ABSTRACT: It is shown that an analytical noise-free implementation of Monte Carlo simulations [Appl. Opt.54, 2400 (2015).10.1364/AO.54.002400APOPAI1559-128X] for diffuse correlation spectroscopy (DCS) may be successfully used to check the ability of a given DCS model to generate a reliable estimator of tissue blood flow. As an example, four different DCS models often found in the scientific literature are tested on a simulated tissue (semi-infinite geometry) with a Maxwell-Boltzmann probability distribution function for red blood cell speed. It is shown that the random model is the best model for the chosen speed distribution but that (1) some inaccuracies in the DCS model in taking into account red blood cell concentration and (2) some inaccuracies, probably due to a low-order approximation of the DCS model, are still observed. The method can be easily generalized for other speed/flow probability distribution functions of the red blood cells.
    No preview · Article · Jun 2015 · Applied Optics
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    ABSTRACT: We present a proof of concept prototype of a time-domain diffuse optics probe exploiting a fast Silicon PhotoMultiplier (SiPM), featuring a timing resolution better than 80 ps, a fast tail with just 90 ps decay time-constant and a wide active area of 1 mm<sup>2</sup>. The detector is hosted into the probe and used in direct contact with the sample under investigation, thus providing high harvesting efficiency by exploiting the whole SiPM numerical aperture and also reducing complexity by avoiding the use of cumbersome fiber bundles. Our tests also demonstrate high accuracy and linearity in retrieving the optical properties and suitable contrast and depth sensitivity for detecting localized inhomogeneities. In addition to a strong improvement in both instrumentation cost and size with respect to legacy solutions, the setup performances are comparable to those of state-of-the-art time-domain instrumentation, thus opening a new way to compact, low-cost and high-performance time-resolved devices for diffuse optical imaging and spectroscopy.
    No preview · Article · Jun 2015 · Optics Express
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    ABSTRACT: Light is a powerful tool to non-invasively probe highly scattering media for clinical applications ranging from oncology to neurology, but also for molecular imaging, and quality assessment of food, wood and pharmaceuticals. Here we show that, for a paradigmatic case of diffuse optical imaging, ideal yet realistic time-domain systems yield more than 2-fold higher depth penetration and many decades higher contrast as compared to ideal continuous-wave systems, by adopting a dense source-detector distribution with picosecond time-gating. Towards this aim, we demonstrate the first building block made of a source-detector pair directly embedded into the probe based on a pulsed Vertical-Cavity Surface-Emitting Laser (VCSEL) to allow parallelization for dense coverage, a Silicon Photomultiplier (SiPM) to maximize light harvesting, and a Single-Photon Avalanche Diode (SPAD) to demonstrate the time-gating capability on the basic SiPM element. This paves the way to a dramatic advancement in terms of increased performances, new high impact applications, and availability of devices with orders of magnitude reduction in size and cost for widespread use, including quantitative wearable imaging.
    No preview · Article · May 2015 · Biomedical Optics Express
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    ABSTRACT: The classical reciprocity relation of radiative transfer fails for two points placed in regions having different indices of refraction. A modified reciprocity relation that involves the relative refractive index between the two points considered was previously derived for the continuous wave (cw) radiative transfer equation and for the cw diffusion equation (DE) [J. Opt. Soc. Am. A14, 486 (1997)10.1364/JOSAA.14.000486JOAOD61084-7529]. In this paper, we extend these findings to the time-dependent DE and we discuss some implications to diffuse optical tomography.
    Full-text · Article · Apr 2015 · Journal of the Optical Society of America A
  • Tiziano Binzoni · Fabrizio Martelli
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    ABSTRACT: Classical Monte Carlo (MC) simulations for laser-Doppler flowmetry (LDF) often necessitate too long computation times and specialized hardware. This is particularly true for LDF at large interoptode spacing with low absorption coefficients and large anisotropic factors representing real biological tissues. For this reason, a random numbers free "analytical" implementation of the classical MC (MC<sub>an</sub>) is proposed. The MC<sub>an</sub> approach allows to obtain noise exempt LDF spectra in a short time and with a simple personal laptop. The proposed MC<sub>an</sub> holds for a diffusive regime of light propagation and it is practically implemented for a semi-infinite geometry. Its validity is demonstrated by comparisons with the classical MC.
    No preview · Article · Mar 2015 · Applied Optics
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    ABSTRACT: Application of light spectroscopy based techniques for the detection of cancers have emerged as a promising approach for tumor diagnostics. In-vivo or freshly excised samples are normally used for point spectroscopic studies. However, ethical issues related to in-vivo studies, rapid decay of surgically excised tissues and sample availability puts a limitation on in-vivo and in-vitro studies. There has been a few studies reported on the application of formalin fixed samples with good discrimination capability. Usually formalin fixation is performed to prevent degradation of tissues after surgical resection. Fixing tissues in formalin prevents cell death by forming cross-linkages with proteins. Previous investigations have revealed that washing tissues fixed in formalin using phosphate buffered saline is known to reduce the effects of formalin during spectroscopic measurements. But this could not be the case with reflectance measurements. Hemoglobin is a principal absorbing medium in biological tissues in the visible range. Formalin fixation causes hemoglobin to seep out from red blood cells. Also, there could be alterations in the refractive index of tissues when fixed in formalin. In this study, we propose to investigate the changes in tissue optical properties between freshly excised and formalin fixed brain tissues. The results indicate a complete change in the spectral profile in the visible range where hemoglobin has its maximum absorption peaks. The characteristic bands of oxy-hemoglobin at 540, 580 nm and deoxy-hemoglobin at 555 nm disappear in the case of samples fixed in formalin. In addition, an increased spectral intensity was observed for the wavelengths greater than 650 nm where scattering
    No preview · Conference Paper · Feb 2015
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    ABSTRACT: The adoption of a short source-detector distance, combined with a time-resolved acquisition, can be advantageous in diffuse optical imaging due to the stricter spatial localization of the probing photons, provided that the strong burst of early photons is suppressed using a time-gated detection scheme. We propose a model for predicting the effect of the time-gated measurement system using a time-variant operator built on the system response acquired at different gate delays. The discrete representation of the system operator, termed Spread Matrix, can be analyzed to identify the bottlenecks of the detection system with respect to the physical problem under study. Measurements performed on tissue phantoms, using a time-gated single-photon avalanche diode and an interfiber distance of 2 mm, demonstrate that inhomogeneities down to 3 cm can be detected only if the decay constant of the detector is lower than 100 ps, while the transient opening of the gate has a less critical impact.
    No preview · Article · Feb 2015 · Journal of Physics D Applied Physics
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    ABSTRACT: We propose a simple and reliable solid phantom for mimicking realistic localized absorption changes within a diffusive medium. The phantom is based on a solid matrix holding a movable black inclusion embedded in a rod. Translating the rod parallel to the phantom surface, the inhomogeneity can be positioned beneath the source-detector pair (perturbed case) or far from it (unperturbed case). Examples of time-resolved transmittance measurements and time-resolved reflectance scans are shown to demonstrate the properties and the versatility of the phantom.
    No preview · Article · Jan 2015
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    ABSTRACT: We propose a simple and reliable solid phantom for mimicking localized absorption changes within a diffusive medium. The phantom is based on the Equivalence Relation stating that any realistic absorption inhomogeneity can be mimicked by a totally absorbing sphere of adequate volume. Applying this concept, we constructed a solid phantom holding a movable black inclusion to be positioned beneath the source-detector pair (perturbed case) or far from it (unperturbed case). Different absorption perturbations can be mimicked by changing the volume and the position of the black object both in transmittance and reflectance configuration. Time-resolved measurements of transmittance images and a lateral reflectance scan are presented.
    No preview · Article · Jan 2015
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    ABSTRACT: Diffuse Optics is growing in terms of applications ranging from e.g. oximetry, to mammography, molecular imaging, quality assessment of food and pharmaceuticals, wood optics, physics of random media. Time-domain (TD) approaches, although appealing in terms of quantitation and depth sensibility, are presently limited to large fiber-based systems, with limited number of source-detector pairs. We present a miniaturized TD source-detector probe embedding integrated laser sources and single-photon detectors. Some electronics are still external (e.g. power supply, pulse generators, timing electronics), yet full integration on-board using already proven technologies is feasible. The novel devices were successfully validated on heterogeneous phantoms showing performances comparable to large state-of-the-Art TD rack-based systems. With an investigation based on simulations we provide numerical evidence that the possibility to stack many TD compact source-detector pairs in a dense, null source-detector distance arrangement could yield on the brain cortex about 1 decade higher contrast as compared to a continuous wave (CW) approach. Further, a 3-fold increase in the maximum depth (down to 6 cm) is estimated, opening accessibility to new organs such as the lung or the heart. Finally, these new technologies show the way towards compact and wearable TD probes with orders of magnitude reduction in size and cost, for a widespread use of TD devices in real life.
    No preview · Conference Paper · Jan 2015
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    ABSTRACT: The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging.
    Full-text · Article · Aug 2014 · Journal of Biomedical Optics
  • Tiziano Binzoni · Fabrizio Martelli
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    ABSTRACT: Analytical models, describing laser Doppler flowmetry and its derived applications, are based on fundamental assumptions of photon scattering angles. It is shown by means of Monte Carlo simulations that, even in the case these assumptions are correct, the presence of a specific source–detector configuration may bias the shape of the probability density functions describing scattering angle behavior. It is found that these biased shapes are generated by selective filtering of photons induced by a particular source–detector configuration. In some specific cases, this phenomenon might invalidate laser Doppler analytical models.
    No preview · Article · Jul 2014 · Applied Optics
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    ABSTRACT: We present the experimental implementation and validation of a phantom for diffuse optical imaging based on totally absorbing objects for which, in the previous paper [J. Biomed. Opt. 18(6), 066014, (2013)], we have provided the basic theory. Totally absorbing objects have been manufactured as black polyvinyl chloride (PVC) cylinders and the phantom is a water dilution of intralipid-20% as the diffusive medium and India ink as the absorber, filled into a black scattering cell made of PVC. By means of time-domain measurements and of Monte Carlo simulations, we have shown the reliability, the accuracy, and the robustness of such a phantom in mimicking typical absorbing perturbations of diffuse optical imaging. In particular, we show that such a phantom can be used to generate any absorption perturbation by changing the volume and position of the totally absorbing inclusion. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.
    Full-text · Article · Jul 2014 · Journal of Biomedical Optics
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    ABSTRACT: A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.
    Full-text · Article · Jun 2014 · Biomedical Optics Express
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    ABSTRACT: In this paper, after a critical review of the literature, we present two forward solvers and a new methodology for description of photon migration in the presence of totally absorbing inclusions embedded in diffusive media in both time and CW domains. The first forward solver is a heuristic approach based on a higher order perturbation theory applied to the diffusion equation (DE) [denoted eighth-order perturbation theory (EOPT)]. The second forward solver [denoted eighth-order perturbation theory with the equivalence relation (EOPTER) ] is obtained by combining the EOPT solver with the adoption of the equivalence relation (ER) [J. Biomed. Opt.18, 066014 (2013)]. These forward solvers can possibly overcome some evident limitations of previous approaches like the theory behind the so-called banana-shape regions or exact analytical solutions of the DE in the presence of highly or totally absorbing inclusions. We also propose the ER to reformulate the problem of a totally absorbing inclusion in terms of another inclusion having a finite absorption contrast and a re-scaled volume. For instance, we have shown how this approach can indeed be used to simulate black inclusions with the Born approximation. By means of comparisons with the results of Monte Carlo simulations, we have shown that the EOPTER solver can model totally absorbing inclusions with an error smaller than about 10%, whereas the EOPT solver shows an error smaller than about 20%, showing a performance largely better than that observed with solvers proposed previously.
    Full-text · Article · Mar 2014 · Journal of the Optical Society of America A
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    Rosario Esposito · Fabrizio Martelli · Sergio De Nicola
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    ABSTRACT: We have developed a theoretical model for photon migration through scattering media in the presence of an absorbing inhomogeneity. A closed-form solution for the average diffuse intensity has been obtained through an iterative approximation scheme of the steady-state diffusion equation. The model describes absorbing defects in a wide range of values. Comparisons with the results of Monte Carlo simulations show that the error of the model is lower than 3% for size inclusion lower than 4 mm and absorption contrast up to the threshold value of the "black defect." The proposed model provides a tractable mathematical basis for diffuse optical and photoacoustic tomographic reconstruction techniques.
    Full-text · Article · Feb 2014 · Optics Letters

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