Layered piezoelectric structures with arbitrary acoustic termination impedances.

Multilayer piezoelectric transducers and resonators are widely used for generating propagating and standing acoustic waves as well as for sensor devices. More recently, layered piezoelectric structures based on thin film technology became increasingly important for electromechanical filters used in mobile phones. As a consequence, analytical mathematical modeling of such structures is of high interest. In this paper, a general rigorous transfer matrix description for one-dimensional (1D) layered structures consisting of piezoelectric, visco-elastic, and dielectric layers of arbitrary number is introduced to characterize the electrical and mechanical behavior of a general piezoelectric transducer or resonator with two electrodes and arbitrary acoustic termination impedances (Rig-1D-model). This model is the most general 1D analytical description of layered piezoelectric structures available and can be used for the characterization of various composite transducer and resonant sensor applications. Considered in detail are layered structures with the technically important cases of only one electromechanically coupled mode, and the structure at one or both outer surfaces is in contact with semi-infinite media. For such devices, it is shown how the frequency dependence of the total electrical admittance and spatial dependence of the displacements can be calculated.

Broadband near-infrared hyperspectral single pixel imaging for chemical characterization.

We introduce a compressive sensing based approach for single pixel hyperspectral chemical imaging in a broad spectral range in the near-infrared. Fully integrated MEMS based Fabry-Pérot tunable filter spectrometers and a digital micro-mirror device were employed to achieve spectral and spatial resolution, respectively. The available spectral range from 1500 to 2200 nm covers molecular overtone vibrations enabling chemical identification. Hyperspectral images of different adhesives deposited on a textile were recorded revealing their chemical composition. Furthermore, spectrally resolved near-infrared images with compression rates up to 90% are presented. The approach of single pixel imaging illustrates a promising technology for the infrared spectral range superior to conventionally used costly focal plane arrays.

Primary calibration by reciprocity method of high-frequency acoustic-emission piezoelectric transducers.

Although acoustic-emission (AE) piezoelectric transducers have distinctive variations in sensitivity, depending on frequency, propagation medium, and coupling, the vast majority of AE research is conducted by utilizing uncalibrated AE transducers. As a consequence, most results obtained by different groups are not comparable among each other. In this work, primary calibration by the method of reciprocity is shown. Rayleigh and longitudinal wave calibration curves are presented for piezoelectric high-frequency broadband transducer, mounted on steel and aluminium, in the frequency range 300 kHz-4 MHz. Influences on primary calibration of AE transducers, namely, by coupling medium, contact pressure, and propagation medium, are investigated.

In vivo tear film thickness measurement and tear film dynamics visualization using spectral domain optical coherence tomography.

Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the tear film. Traditional methods used for the evaluation of tear film stability are invasive or show limited repeatability. Here we propose a new non-invasive fully automated approach to measure tear film thickness based on spectral domain optical coherence tomography and on an efficient delay estimator. Silicon wafer phantom were used to validate the thickness measurement. The technique was applied in vivo in healthy subjects. Series of tear film thickness maps were generated, allowing for the visualization of tear film dynamics. Our results show that the in vivo central tear film thickness measurements are precise and repeatable with a coefficient of variation of about 0.65% and that repeatable tear film dynamics can be observed. The presented approach could be used in clinical setting to study patients with dry eye disease and monitor their treatments.

Deep learning differentiates between healthy and diabetic mouse ears from optical coherence tomography angiography images.

We trained a deep learning algorithm to use skin optical coherence tomography (OCT) angiograms to differentiate between healthy and type 2 diabetic mice. OCT angiograms were acquired with a custom-built OCT system based on an akinetic swept laser at 1322 nm with a lateral resolution of ∼13 µm and using split-spectrum amplitude decorrelation. Our data set consisted of 24 stitched angiograms of the full ear, with a size of approximately 8.2 × 8.2 mm, evenly distributed between healthy and diabetic mice. The deep learning classification algorithm uses the ResNet v2 convolutional neural network architecture and was trained on small patches extracted from the full ear angiograms. For individual patches, we obtained a cross-validated accuracy of 0.925 and an area under the receiver operating characteristic curve (ROC AUC) of 0.974. Averaging over multiple patches extracted from each ear resulted in the correct classification of all 24 ears.

Automated segmentation of dermal fillers in OCT images of mice using convolutional neural networks.

We present a system for automatic determination of the intradermal volume of hydrogels based on optical coherence tomography (OCT) and deep learning. Volumetric image data was acquired using a custom-built OCT prototype that employs an akinetic swept laser at ~1310 nm with a bandwidth of 87 nm, providing an axial resolution of ~6.5 µm in tissue. Three-dimensional data sets of a 10 mm × 10 mm skin patch comprising the intradermal filler and the surrounding tissue were acquired. A convolutional neural network using a u-net-like architecture was trained from slices of 100 OCT volume data sets where the dermal filler volume was manually annotated. Using six-fold cross-validation, a mean accuracy of 0.9938 and a Jaccard similarity coefficient of 0.879 were achieved.

Magnetic field effects on particle beams and their implications for dose calculation in MR-guided particle therapy.

PURPOSE: To investigate and model effects of magnetic fields on proton and carbon ion beams for dose calculation. METHODS: In a first step, Monte Carlo simulations using Gate 7.1/Geant4.10.0.p03 were performed for proton and carbon ion beams in magnetic fields ranging from 0 to 3 T. Initial particle energies ranged from 60 to 250 MeV (protons) and 120 to 400 MeV/u (carbon ions), respectively. The resulting dose distributions were analyzed focusing on beam deflection, dose deformation, as well as the impact of material heterogeneities. In a second step, a numerical algorithm was developed to calculate the lateral beam position. Using the Runge-Kutta method, an iterative solution of the relativistic Lorentz equation, corrected for the changing particle energy during penetration, was performed. For comparison, a γ-index analysis was utilized, using a criteria of 2%/2 mm of the local maximum. RESULTS: A tilt in the dose distribution within the Bragg peak area was observed, leading to non-negligible dose distribution changes. The magnitude was found to depend on the magnetic field strength as well as on the initial beam energy. Comparison of the 3 T dose distribution with non-B field (nominal) dose distributions, resulted in a γmean (mean value of the γ distribution) of 0.6, with 14.4% of the values above 1 and γ1 % (1% of all points have an equal or higher γ value) of 1.8. The presented numerical algorithm calculated the lateral beam offset with maximum errors of less than 2% with calculation times of less than 5 µs. The impact of tissue interfaces on the proton dose distributions was found to be less than 2% for a dose voxel size of 1 × 1 × 1 mm3 . CONCLUSION: Non-negligible dose deformations at the Bragg peak area were identified for high initial energies and strong magnetic fields. A fast numerical algorithm based on the solution of the energy-corrected relativistic Lorentz equation was able to describe the beam path, taking into account the particle energy, magnetic field, and material.

Quantification accuracy of neuro-oncology PET data as a function of emission scan duration in PET/MR compared to PET/CT.

OBJECTIVES: To evaluate and compare the effect of reduced acquisition time, as a surrogate of injected activity, on the PET quantification accuracy in PET/CT and PET/MR imaging. METHODS: Twenty min 18F-FDG phantom measurements and 10min 18F-FET brain scans were acquired in a Biograph-True-Point-True-View PET/CT (n=8) and a Biograph mMR PET/MR (n=16). Listmode data were repeatedly split into frames of 1min to 10min length and reconstructed using two different reconstruction settings of a 3D-OSEM algorithm: with post-filtering ("OSEM"), and without post-filtering but with resolution recovery ("PSF"). Recovery coefficients (RCmax, RCA50) and standard uptake values (SUVmax, SUVA50) were evaluated. RESULTS: RCmax (phantom) and SUVmax (patients) increased significantly when reducing the frame duration. Significantly lower deviations were observed for RCA50 and SUVA50, respectively, making them more appropriate to compare PET studies at different number of counts. No statistical significant differences were observed when using post-filtering and reducing the frame time to 4min (RCA50, reference 20min, phantom) and to 3min (SUVA50, reference 10min, patients). CONCLUSIONS: For hybrid aminoacid brain imaging, frame duration (or injected activity) can potentially be reduced to 30% of the standard used in clinical routine without significant changes on the quantification accuracy of the PET images if adequate reconstruction settings and quantitative measures are used. Frame times below 4min in the NEMA phantom are not advisable to obtain quantitative and reproducible measures.

Conical scan pattern for enhanced visualization of the human cornea using polarization-sensitive OCT.

Conventional imaging of the human cornea with optical coherence tomography (OCT) relies on telecentric scanning optics with sampling beams that are parallel to the optical axis of the eye. Because of the shape of the cornea, the beams have in some areas considerable inclination to the corneal surface which is accompanied by low signal intensities in these areas and thus an inhomogeneous appearance of corneal structures. In addition, alterations in the polarization state of the probing light depend on the angle between the imaging beam and the birefringent axis of the sample. Therefore, changes in the polarization state observed with polarization-sensitive (PS-) OCT originate mainly from the shape of the cornea. In order to minimize the effects of the corneal shape on intensity and polarization-sensitive based data, we developed a conical scanning optics design. This design provides imaging beams that are essentially orthogonal to the corneal surface. Thus, high signal intensity throughout the entire imaged volume is obtained and the influence of the corneal shape on polarization-sensitive data is greatly reduced. We demonstrate the benefit of the concept by comparing PS-OCT imaging results of the human cornea in healthy volunteers using both scanning schemes.

Super-resolved thickness maps of thin film phantoms and in vivo visualization of tear film lipid layer using OCT.

In optical coherence tomography (OCT), the axial resolution is directly linked to the coherence length of the employed light source. It is currently unclear if OCT allows measuring thicknesses below its axial resolution value. To investigate spectral-domain OCT imaging in the super-resolution regime, we derived a signal model and compared it with the experiment. Several island thin film samples of known refractive indices and thicknesses in the range 46 - 163 nm were fabricated and imaged. Reference thickness measurements were performed using a commercial atomic force microscope. In vivo measurements of the tear film were performed in 4 healthy subjects. Our results show that quantitative super-resolved thickness measurement can be performed using OCT. In addition, we report repeatable tear film lipid layer visualization. Our results provide a novel interpretation of the OCT axial resolution limit and open a perspective to deeper extraction of the information hidden in the coherence volume.

Can a commercial diagnostic ultrasound device accelerate thrombolysis? An in vitro skull model.

BACKGROUND AND PURPOSE: Recently, 3 clinical trials revealed encouraging results in recanalization and clinical outcome in acute stroke patients when 2-MHz transcranial Doppler monitoring was applied. This study investigated whether a 1.8-MHz commercial diagnostic ultrasound device has the potential to facilitate thrombolysis using an in vitro stroke model. METHODS: Duplex-Doppler, continuous wave-Doppler, and pulsed wave (PW)-Doppler were compared on their impact on recombinant tissue plasminogen activator (rtPA)-mediated thrombolysis. Blood clots were transtemporally sonicated in a human stroke model. Furthermore, ultrasound attenuation of 5 temporal bones of different thickness was determined. RESULTS: In comparison, only PW-Doppler accelerated rtPA-mediated thrombolysis significantly. Without temporal bone, PW-Doppler plus rtPA showed a significant enhancement in relative clot weight loss of 23.7% when compared with clots treated with rtPA only (33.9+/-5.5% versus 27.4+/-5.2%; P<0.0005). Ultrasound attenuation measurements revealed decreases of the output intensity of 86.8% (8.8 dB) up to 99.2% (21.2 dB), depending on temporal bone thickness (1.91 to 5.01 mm). CONCLUSIONS: Without temporal bone, PW-Doppler significantly enhanced thrombolysis. However, because of a high attenuation of ultrasound by temporal bone, no thrombolytic effect was observed in our in vitro model, although Doppler imaging through the same temporal bone was still possible.

A new immobilisation method to arrange particles in a gel matrix by ultrasound standing waves.

Ultrasonic forces may be used to manipulate particles in suspension. For example, a standing wave ultrasound (US) field applied to a suspension moves the particles toward areas of minimal acoustic pressure, where they are orderly retained creating a predictable heterogeneous distribution. This principle of ultrasonic retention of particles or cells has been applied in numerous biotechnological applications, such as mammalian cell filtering and red blood cell sedimentation. Here, a new US-based cell immobilisation technique is described that allows manipulation and positioning of cells/particles within various nontoxic gel matrices before polymerisation. Specifically, gel immobilisation was used to directly demonstrate that the viability of yeast cells arranged by an US standing wave is maintained up to 4 days after treatment. The versatility of this immobilisation method was validated using a wide range of acoustic devices. Finally, the potential biotechnological advantages of this US-controlled particle positioning method combined with gel immobilisation/encapsulation technology are discussed.

Blood flow velocity vector field reconstruction from dual-beam bidirectional Doppler OCT measurements in retinal veins.

In this paper, we demonstrate the possibility to reconstruct the actual blood flow velocity vector field in retinal microvessels from dual-beam bidirectional Doppler optical coherence tomography measurements. First, for a better understanding of measured phase patterns, several flow situations were simulated on the basis of the known dual beam measurement geometry. We were able to extract the vector field parameters that determine the measured phase pattern, allowing for the development of an algorithm to reconstruct the velocity vector field from measured phase data. In a next step, measurements were performed at a straight vessel section and at a venous convergence; the obtained phase data were evaluated by means of the new approach. For the straight vessel section, the reconstructed flow velocity vector field yielded a parabolic flow. For the venous convergence, however, the reconstructed vector field deviated from a parabolic profile, but was in very good accordance with the simulated vector field for the given vessel geometry. The proposed algorithm allows predictions of the velocity vector field. Moreover, the algorithm is also sensitive to directional changes of the flow velocity as small as <1°, thereby offering insight in the flow characteristics of the non-Newtonian fluid blood in microvessels.

Ultrasound affects distribution of plasminogen and tissue-type plasminogen activator in whole blood clots in vitro.

Ultrasound of 2 MHz frequency and 1.2 W/cm(2) acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% +/-6.9% which is significantly higher (p<0.0001) than in the group of clots treated with rt-PA only (19.9% +/-4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 +/-2513 ng/ml vs. 2364 +/-725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p<0.0001), and broadened the zone of lysis from 8.9 +/-2.6 microm to 21.2 +/-7.2 microm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.

2MHz ultrasound enhances t-PA-mediated thrombolysis: comparison of continuous versus pulsed ultrasound and standing versus travelling acoustic waves.

In addition to fibrinolytic enzymes, ultrasound has the potential to enhance thrombolysis. High frequency ultrasound has the advantage that a combination of diagnostic and therapeutic ultrasound with only one device is possible. Therefore, we investigated the optimal high frequency (2 MHz) ultrasound field characteristics and application mode in vitro. Continuous ultrasound significantly enhanced rt-PA mediated thrombolysis: in a travelling wave field thrombolysis was augmented by 49.0 +/- 14.7% and in a standing wave field by 34.8 +/- 7.3%. In an intermittent application mode (1Hz, 10Hz, 100Hz, 1kHz) most efficient results were obtained for both wave fields using 1 Hz (46.4 +/- 10.7% and 39.1 +/- 6.6%, respectively). Referring to a possible in vivo application our in vitro data suggests that an intermittent application of a 2 MHz high frequency ultrasound using a travelling wave field would be the most potent application for lysing blood clots.

Comparison of fluidized bed and ultrasonic cell-retention systems for high cell density mammalian cell culture.

Economically viable biopharmaceutical production is to a high degree dependent on high product yields and stable fermentation systems that are easy to handle. In the current study we have compared two different fermentation systems for the production of recombinant protein from CHO cells. Both systems are fully scaleable and can be used for industrial high cell density bioprocesses. As a model cell line we have used a recombinant CHO cell line producing the enzyme arylsulfatase B (ASB). CHO cells were cultivated as adherent cell culture attached on Cytoline macroporous microcarrier (Amersham Biosciences, Sweden) using a Cytopilot Mini fluidized bed bioreactor (FBR, Vogelbusch-Amersham Biosciences, Austria) and as suspension culture using a stirred tank bioreactor equipped with a BioSep ultrasonic resonator based cell separation device (Applikon, The Netherlands). Both systems are equally well-suited for stable, long-term high cell density perfusion cell culture and provide industrial scalability and high yields. For products such as the recombinant ASB, high perfusion rates and therefore short product bioreactor residence times may be of additional benefit.

In vitro thrombolysis enhanced by standing and travelling ultrasound wave fields.

Success of thrombolytic therapy depends on penetration of recombinant tissue plasminogen activator (rt-PA) into clots. Ultrasound (US) of therapeutic quality accelerates thrombolysis in vitro. As yet, only the effects of travelling acoustic waves on thrombolysis have been investigated, and the impact of standing acoustic waves has been neglected. In the present study, we examined the effects of standing and travelling US wave fields applied continuously for 1 h (frequency 2 MHz, acoustic intensity 1.2 W/cm(2)) on thrombolysis enhancement by measuring clot weight reduction and concentration of fibrin degradation product D-dimer (FDP-DD) produced from clots subjected to rt-PA. The level of FDP-DD was 1.8 times greater in travelling than in standing acoustic waves. Thrombolysis enhancement was 46.0 +/- 20.8% in standing and 116.8 +/- 23.1% in travelling acoustic waves. Travelling waves enhanced thrombolysis significantly more (p < 0.0001) than did standing waves.

A capacitance ultrasonic transducer for high-temperature applications.

This paper introduces a novel ultrasonic capacitance transducer for operation at elevated gas temperatures of several hundred degrees Celsius. The transducer design is based on a metallic membrane foil and a backplate made of an electrically conducting substrate coated with an insulation layer. Guidelines are given for selecting suitable materials for the membrane foil, the backplate substrate, and the coating. Manufacturing techniques applied for fabrication of different transducer types are described in detail. Transducers tested were composed of titanium substrates with insulation layers of silicon nitride or of silicon substrates with silicon oxide coatings. Experimental setup and test procedures are described. Results of transducer characterization and performance tests at elevated temperatures are presented and discussed. Transducer functionality is proven for air temperatures of up to 500 degrees C.

Field programmable gate array-assigned complex-valued computation and its limits.

We discuss how leveraging Field Programmable Gate Array (FPGA) technology as part of a high performance computing platform reduces latency to meet the demanding real time constraints of a quantum optics simulation. Implementations of complex-valued operations using fixed point numeric on a Virtex-5 FPGA compare favorably to more conventional solutions on a central processing unit. Our investigation explores the performance of multiple fixed point options along with a traditional 64 bits floating point version. With this information, the lowest execution times can be estimated. Relative error is examined to ensure simulation accuracy is maintained.

Measurement of retinal blood flow in the rat by combining Doppler Fourier-domain optical coherence tomography with fundus imaging.

A wide variety of ocular diseases are associated with abnormalities in ocular circulation. As such, there is considerable interest in techniques for quantifying retinal blood flow, among which Doppler optical coherence tomography (OCT) may be the most promising. We present an approach to measure retinal blood flow in the rat using a new optical system that combines the measurement of blood flow velocities via Doppler Fourier-domain optical coherence tomography and the measurement of vessel diameters using a fundus camera-based technique. Relying on fundus images for extraction of retinal vessel diameters instead of OCT images improves the reliability of the technique. The system was operated with an 841-nm superluminescent diode and a charge-coupled device camera that could be operated at a line rate of 20 kHz. We show that the system is capable of quantifying the response of 100% oxygen breathing on the retinal blood flow. In six rats, we observed a decrease in retinal vessel diameters of 13.2% and a decrease in retinal blood velocity of 42.6%, leading to a decrease in retinal blood flow of 56.7%. Furthermore, in four rats, the response of retinal blood flow during stimulation with diffuse flicker light was assessed. Retinal vessel diameter and blood velocity increased by 3.4% and 28.1%, respectively, leading to a relative increase in blood flow of 36.2%. The presented technique shows much promise to quantify early changes in retinal blood flow during provocation with various stimuli in rodent models of ocular diseases in rats.