Benlloch Baviera, Jose María
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- PublicationCharacterization of Viscoelastic Media Combining Ultrasound and Magnetic-Force Induced Vibrations on an Embedded Soft Magnetic Sphere(Institute of Electrical and Electronics Engineers, 2021-12) Cebrecos Ruiz, Alejandro; Jiménez González, Noé; Tarazona Tárrega, Rafael; Company, Miguel; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; GENERALITAT VALENCIANA; AGENCIA ESTATAL DE INVESTIGACION; UNIVERSIDAD POLITECNICA DE VALENCIA; Agència Valenciana de la Innovació[EN] We report a method to locally assess the complex shear modulus of a viscoelastic medium. The proposed approach is based on the application of a magnetic force to a millimeter-sized steel sphere embedded in the medium and the subsequent monitoring of its dynamical response. A coil is used to create a magnetic field inducing the displacement of the sphere located inside a gelatin phantom. Then, a phased-array system using 3 MHz ultrasound probe operating in pulse-echo mode is used to track the displacement of the sphere. Experiments were conducted on several samples and repeated as a function of phantom temperature. The dynamic response of the sphere measured experimentally is in good agreement with Kelvin¿Voigt theory. Since the magnetic force is not affected by weak diamagnetic media, our proposal results in an accurate estimation of the force acting on the inclusion. Consequently, the estimated viscoelastic parameters show excellent robustness and the elastic modulus agrees with the measurements using a quasi-static indentation method, obtaining errors below 10% in the whole temperature range. The use of the macroscopic inclusion limits the direct application of this method in a biomedical context, but it provides a robust estimation of the elastic modulus that can be used for material characterization in industrial applications.
- PublicationTranscranial acoustic holograms for arbitrary fields generation using focused ultrasound into the brain(Acoustical Society of America, 2019-09-06) Jiménez-Gambín, Sergio; Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; Generalitat Valenciana; European Regional Development Fund; Agència Valenciana de la Innovació[EN] We present 3D printed holographic lenses that correct the aberrations of the skull and, simultaneously, produce arbitrary ultrasonic fields with the geometry of brain structures. Using experimental techniques on a human skull phantom (HSP), a multiple-point focusing lens is designed to focus at both human hippocampi at once; a beam following an arbitrary curved trajectory, i.e., a self-bending beam; and a holographic plate producing a broad focus that overlaps with the left hippocampus (LH). Skull and LH geometries and acoustic properties are obtained from CT-scans and MRI, respectively. Time-reversal (TR) method is used to obtain the magnitude and phase of the back-propagated field from the target shape towards the lens surface. The holographic lenses are designed assuming each pixel of the lens vibrates as a Fabry-Pérot resonator. The resulting lenses are 3D printed using SLA techniques. The three studied cases show similar results in simulation and experiment with and without the HSP: for the bi-focal beam, the reconstructed field accurately matches the target foci; for the curved trajectory beam, the target acoustic image is reconstructed by the designed holographic lens; for the broad focus beam, results present the same qualitative performance providing a similar overall covering of the LH. The reported holographic lenses can be used to control the spatial features of ultrasonic beams inside the skull in an unprecedented manner using single-element ultrasonic sources.
- PublicationAcoustic Holograms for Bilateral Blood-Brain Barrier Opening in a Mouse Model(Institute of Electrical and Electronics Engineers, 2022-04) Jiménez-Gambín, Sergio; Jiménez González, Noé; Pouliopoulos, Antonios N.; Benlloch Baviera, Jose María; Konofagou, Elisa E.; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; GENERALITAT VALENCIANA; AGENCIA ESTATAL DE INVESTIGACION; AGENCIA VALENCIANA DE LA INNOVACION; National Institutes of Health, EEUU; Agència Valenciana de la Innovació[EN] Transcranial focused ultrasound (FUS) in conjunction with circulating microbubbles injection is the sole non-invasive technique that temporally and locally opens the blood-brain barrier (BBB), allowing targeted drug delivery into the central nervous system (CNS). However, single-element FUS technologies do not allow the simultaneous targeting of several brain structures with high-resolution, and multi-element devices are required to compensate the aberrations introduced by the skull. In this work, we present the first preclinical application of acoustic holograms to perform a bilateral BBB opening in two mirrored regions in mice. The system consisted of a single-element focused transducer working at 1.68 MHz, coupled to a 3D-printed acoustic hologram designed to produce two symmetric foci in anesthetized mice in vivo and, simultaneously, compensate the aberrations of the wavefront caused by the skull bones. T1-weighed MR images showed gadolinium extravasation at two symmetric quasi-spherical focal spots. By encoding time-reversed fields, holograms are capable of focusing acoustic energy with a resolution near the diffraction limit at multiple spots inside the skull of small preclinical animals. This work demonstrates the feasibility of hologram-assisted BBB opening for low-cost and highly-localized targeted drug delivery in the CNS in symmetric regions of separate hemispheres.
- PublicationHolograms to Focus Arbitrary Ultrasonic Fields through the Skull(American Physical Society, 2019-07-10) Jiménez-Gambín, Sergio; Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; Generalitat Valenciana; Agència Valenciana de la Innovació; Ministerio de Economía y Competitividad[EN] We report 3D-printed acoustic holographic lenses for the formation of ultrasonic fields of complex spatial distribution inside the skull. Using holographic lenses, we experimentally, numerically and theoretically produce acoustic beams whose spatial distribution matches target structures of the central nervous system. In particular, we produce three types of targets of increasing complexity. First, a set of points are selected at the center of both right and left human hippocampi. Experiments using a skull phantom and 3D printed acoustic holographic lenses show that the corresponding bi-focal lens simultaneously focuses acoustic energy at the target foci, with good agreement between theory and simulations. Second, an arbitrary curve is set as the target inside the skull phantom. Using time-reversal methods the holographic beam bends following the target path, in a similar way as self-bending beams do in free space. Finally, the right human hippocampus is selected as a target volume. The focus of the corresponding holographic lens overlaps with the target volume in excellent agreement between theory in free-media, and experiments and simulations including the skull phantom. The precise control of focused ultrasound into the central nervous system is mainly limited due to the strong phase aberrations produced by refraction and attenuation of the skull. Using the present method, the ultrasonic beam can be focused not only at a single point but overlapping one or various target structures simultaneously using low-cost 3D-printed acoustic holographic lens. The results open new paths to spread incoming biomedical ultrasound applications including blood-brain barrier opening and neuromodulation.
- PublicationBeamforming for large-area scan and improved SNR in array-based photoacoustic microscopy(Elsevier, 2021) Cebrecos Ruiz, Alejandro; García Garrigós, Juan José; Descals, A.; Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; European Social Fund; Generalitat Valenciana; Agencia Estatal de Investigación; European Regional Development Fund; Universitat Politècnica de València; Agència Valenciana de la Innovació[EN] Beamforming enhances the performance of array-based photoacoustic microscopy (PAM) systems for large-area scan. In this study, we quantify the imaging performance of a large field-of-view optical-resolution photoacoustic-microscopy system using an phased-array detector. The system combines a low-cost pulsed-laser diode with a 128-element linear ultrasound probe. Signal-to-noise ratio (SNR) and generalized contrast-to-noise ratio (gCNR) are quantified using the phased-array detector and applying three beamforming strategies: a no-beamforming method equivalent to a single-element flat transducer, a fixed focus beamforming method that mimics a single-element focused transducer, and a dynamic focus beamforming using a delay-and-sum (DAS) algorithm. The imaging capabilities of the system are demonstrated generating high-resolution images of tissue-mimicking phantoms containing sub-millimetre ink tubes and an ex vivo rabbit¿s ear. The results show that dynamic focus DAS beamforming increases and homogenizes SNR along 1-cm2 images, reaching values up to 15 dB compared to an unfocused detector and up to 30 dB compared to out-of-focus regions of the fixed focus configuration. Moreover, the obtained values of gCNR using the DAS beamformer indicate an excellent target visibility, both on phantoms and ex vivo. This strategy makes it possible to scan larger surfaces compared to standard configurations using single-element detectors, paving the way for advanced array-based PAM systems.
- PublicationGenerating Bessel beams with broad depth-of-field by using phase-only acoustic holograms(Nature Publishing Group, 2019-12-27) Jiménez-Gambín, Sergio; Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; Generalitat Valenciana; Agència Valenciana de la Innovació; Ministerio de Economía y Competitividad[EN] We report zero-th and high-order acoustic Bessel beams with broad depth-of-field generated using acoustic holograms. While the transverse field distribution of Bessel beams generated using traditional passive methods is correctly described by a Bessel function, these methods present a common drawback: the axial distribution of the field is not constant, as required for ideal Bessel beams. In this work, we experimentally, numerically and theoretically report acoustic truncated Bessel beams of flat-intensity along their axis in the ultrasound regime using phase-only holograms. In particular, the beams present a uniform field distribution showing an elongated focal length of about 40 wavelengths, while the transverse width of the beam remains smaller than 0.7 wavelengths. The proposed acoustic holograms were compared with 3D-printed fraxicons, a blazed version of axicons. The performance of both phase-only holograms and fraxicons is studied and we found that both lenses produce Bessel beams in a wide range of frequencies. In addition, high-order Bessel beam were generated. We report first order Bessel beams that show a clear phase dislocation along their axis and a vortex with single topological charge. The proposed method may have potential applications in ultrasonic imaging, biomedical ultrasound and particle manipulation applications using passive lenses.
- PublicationA new elastographic technique using acoustic vortices(IEEE, 2020-09-11) Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; Generalitat Valenciana; Agencia Estatal de Investigación; European Regional Development Fund; Agència Valenciana de la Innovació[EN] We present a novel method of elastography based on acoustic vortices to transfer angular momentum to tissue in addition to linear momentum. Focused vortex beams can push and twist tissue, and the rotation direction of the applied torque can be dynamically controlled by the modulation of the topological charge of the vortex. The technique results in a robust excitation of shear waves with quasi-omnidirectional radiation pattern and arbitrary waveform, which may have a great impact in imaging performance for elastography.
- PublicationMagnetic force induced vibration on a ferromagnetic sphere for viscoelastic media characterization(Acoustical Society of America, 2019-09-06) Cebrecos Ruiz, Alejandro; Company, Miguel; Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; Generalitat Valenciana; Ministerio de Economía y Competitividad[EN] A new method that combines transient magnetic forces with ultrasonic imaging and allows the local experimental characterization of the complex shear modulus of a viscoelastic medium is presented. By measuring the dynamics of a ferromagnetic inclusion under the application of a magnetic force, the viscoelastic properties of the medium are extracted. The system is composed of a coil, which creates a magnetic field that induces displacement on a ferromagnetic particle located inside a test phantom, and an ultrasound transducer operating in pulsed-echo mode, utilized to track the displacement of the particle with spatial resolution of several um. Experiments were conducted embedding a ferromagnetic sphere on test phantoms with different compositions and at different temperatures. The obtained results are in good agreement with the theoretical estimation of the dynamical response of a sphere and show robustness on the estimation of the viscoelastic parameters. Moreover, temperature dependent results show asymptotic elasticity values which are physically consistent for soft-solid media.
- PublicationFirst in-vivo Demonstration of Bilateral Blood-Brain Barrier Opening Using Acoustic Holograms in Mice(IEEE, 2020-09-11) Jiménez-Gambín, Sergio; Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Pouliopoulos, Antonios N.; Konofagou, Elisa E.; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; Generalitat Valenciana; Agencia Estatal de Investigación; European Regional Development Fund; National Institutes of Health, EEUU; Agència Valenciana de la Innovació; National Institute for Health Research, Reino Unido[EN] Focused ultrasound (FUS) with microbubbles allows for non-invasive targeted drug delivery into the central nervous system (CNS) by temporally and locally disrupting the bloodbrain barrier (BBB). However, current FUS technologies are not able to simultaneously target several brain structures. In this work, we open the BBB in two regions in a murine brain using a single-element transducer with a coupled 3D-printed holographic lens, which is designed to simultaneously create two symmetric foci in anesthetized mice in vivo. The proposed approach shows many advantages: (1) simple and low-cost; (2) correction of aberrations due to skull and water cone; and (3) multiple BBB opening (BBBO) locations with only one sonication, becoming a time- and cost-effective therapeutic system for neurological diseases. For the in-vivo experiment, contrast-enhanced, T1- weighted MRI scan was conducted following BBBO, showing gadolinium extravasation at two symmetric focal spots. The two BBBO regions were separated by 3.0 +- 0.7 mm (n=5 mice) compared to 5.3 mm in full-wave simulations. This work shows the capability of bifocal ultrasound generation in separate animals using a unique uCT scan. A bilateral BBBO was achieved with a single sonication using a holographic lens in mice, thus improving the efficiency and defining a new approach for several neurodegenerative diseases targeting symmetric brain structures, e.g. hippocampus, putamen or caudate. This study demonstrates the feasibility of hologram-assisted BBBO for targeted drug delivery in the CNS in symmetric regions in separate hemispheres.
- PublicationNumerical Study of Acoustic Holograms for Deep-Brain Targeting through the Temporal Bone Window(Elsevier, 2022-05) Andrés, Diana; Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; GENERALITAT VALENCIANA; AGENCIA ESTATAL DE INVESTIGACION; Agència Valenciana de la Innovació; Ministerio de Ciencia, Innovación y Universidades[EN] Acoustic holograms can encode complex wavefronts to compensate the aberrations of a therapeutical ultrasound beam propagating through heterogeneous tissues such as the skull, and simultaneously, they can generate diffraction-limited acoustic images, that is, arbitrary shaped focal spots. In this work, we numerically study the performance of acoustic holograms focusing at the thalamic nuclei when the source is located at the temporal bone window. The temporal window is the thinnest area of the lateral skull and it is mainly hairless, so it is a desirable area through which to transmit ultrasonic waves to the deep brain. However, in targeting from this area the bilateral thalamic nuclei are not aligned with the elongated focal spots of conventional focused transducers, and in addition, skull aberrations can distort the focal spot. We found that by using patient-specific holographic lenses coupled to a single-element 650-kHz-frequency 65-mm-aperture source, the focal spot can be sharply adapted to the thalamic nuclei in a bilateral way while skull aberrations are mitigated. Furthermore, the performance of these holograms was studied under misalignment errors between the source and the skull, concluding that for misalignments up to 5°, acoustic images are correctly restored. This work paves the way to designing clinical applications of transcranial ultrasound such as blood¿brain barrier opening for drug delivery or deep-brain neuromodulation using this low-cost and personalized technology, presenting desirable aspects for long-term treatments because the patient's head does not need to be shaved completely and skull heating is low.