Optimization of 3D Passive Acoustic Mapping Image Metrics: Impact of Sensor Geometry and Beamforming Approach.

Three-dimensional passive acoustic mapping (PAM) with matrix arrays typically suffers from high demands on the receiving electronics and high computational load. In our study, we investigated, both numerically and experimentally, the influence of matrix array aperture size, element count, and beamforming approaches on defined image metrics. With a numerical Vokurka model, matrix array acquisitions of cavitation signals were simulated. In the experimental part, two 32 × 32 matrix arrays with different pitches and aperture sizes were used. After being reconstructed into 3D cavitation maps, defined metrics were calculated for a quantitative comparison of experimental and numerical data. The numerical results showed that the enlargement of the aperture from 5 to 40 mm resulted in an improvement of the full width at half maximum (FWHM) by factors of 6 and 13 (in lateral and axial dimension, respectively). A larger array sparsity influenced the point spread function (PSF) only slightly, while the grating lobe level (GLL) remained more than 12 dB below the main lobe. These results were successfully experimentally confirmed. To further reduce the GLL caused by array sparsity, we adapted a non-linear filter from optoacoustics for use in PAM. In combination with the delay, multiply, sum, and integrate (DMSAI) algorithm, the GLL was decreased by 20 dB for 64-element reconstructions, resulting in levels that were identical to the fully populated matrix reconstruction levels.

Encapsulation of Capacitive Micromachined Ultrasonic Transducers (CMUTs) for the Acoustic Communication between Medical Implants.

The aim of this work was to extend conventional medical implants by the possibility of communication between them. For reasons of data security and transmitting distances, this communication should be realized using ultrasound, which is generated and detected by capacitive micromachined ultrasonic transducers (CMUTs). These offer the advantage of an inherent high bandwidth and a high integration capability. To protect the surrounding tissue, it has to be encapsulated. In contrast to previous results of other research groups dealing with the encapsulation of CMUTs, the goal here is to integrate the CMUT into the housing of a medical implant. In this work, CMUTs were designed and fabricated for a center frequency of 2 MHz in water and experimentally tested on their characteristics for operation behind layers of Polyether ether ketone (PEEK) and titanium, two typical materials for the housings of medical implants. It could be shown that with silicone as a coupling layer it is possible to operate a CMUT behind the housing of an implant. Although it changes the characteristics of the CMUT, the setup is found to be well suited for communication between two transducers over a distance of at least 8 cm.

Portable Ultrasound Research System for Use in Automated Bladder Monitoring with Machine-Learning-Based Segmentation.

We developed a new mobile ultrasound device for long-term and automated bladder monitoring without user interaction consisting of 32 transmit and receive electronics as well as a 32-element phased array 3 MHz transducer. The device architecture is based on data digitization and rapid transfer to a consumer electronics device (e.g., a tablet) for signal reconstruction (e.g., by means of plane wave compounding algorithms) and further image processing. All reconstruction algorithms are implemented in the GPU, allowing real-time reconstruction and imaging. The system and the beamforming algorithms were evaluated with respect to the imaging performance on standard sonographical phantoms (CIRS multipurpose ultrasound phantom) by analyzing the resolution, the SNR and the CNR. Furthermore, ML-based segmentation algorithms were developed and assessed with respect to their ability to reliably segment human bladders with different filling levels. A corresponding CNN was trained with 253 B-mode data sets and 20 B-mode images were evaluated. The quantitative and qualitative results of the bladder segmentation are presented and compared to the ground truth obtained by manual segmentation.

Evaluation of a Developed MRI-Guided Focused Ultrasound System in 7 T Small Animal MRI and Proof-of-Concept in a Prostate Cancer Xenograft Model to Improve Radiation Therapy.

Focused ultrasound (FUS) can be used to physiologically change or destroy tissue in a non-invasive way. A few commercial systems have clinical approval for the thermal ablation of solid tumors for the treatment of neurological diseases and palliative pain management of bone metastases. However, the thermal effects of FUS are known to lead to various biological effects, such as inhibition of repair of DNA damage, reduction in tumor hypoxia, and induction of apoptosis. Here, we studied radiosensitization as a combination therapy of FUS and RT in a xenograft mouse model using newly developed MRI-compatible FUS equipment. Xenograft tumor-bearing mice were produced by subcutaneous injection of the human prostate cancer cell line PC-3. Animals were treated with FUS in 7 T MRI at 4.8 W/cm2 to reach ~45 °C and held for 30 min. The temperature was controlled via fiber optics and proton resonance frequency shift (PRF) MR thermometry in parallel. In the combination group, animals were treated with FUS followed by X-ray at a single dose of 10 Gy. The effects of FUS and RT were assessed via hematoxylin-eosin (H&E) staining. Tumor proliferation was detected by the immunohistochemistry of Ki67 and apoptosis was measured by a TUNEL assay. At 40 days follow-up, the impact of RT on cancer cells was significantly improved by FUS as demonstrated by a reduction in cell nucleoli from 189 to 237 compared to RT alone. Inhibition of tumor growth by 4.6 times was observed in vivo in the FUS + RT group (85.3%) in contrast to the tumor volume of 393% in the untreated control. Our results demonstrated the feasibility of combined MRI-guided FUS and RT for the treatment of prostate cancer in a xenograft mouse model and may provide a chance for less invasive cancer therapy through radiosensitization.

Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model.

Focused ultrasound (FUS) is a non-invasive technique producing a variety of biological effects by either thermal or mechanical mechanisms of ultrasound interaction with the targeted tissue. FUS could bring benefits, e.g., tumour sensitisation, immune stimulation, and targeted drug delivery, but investigation of FUS effects at the cellular level is still missing. New techniques are commonly tested in vitro on two-dimensional (2D) monolayer cancer cell culture models. The 3D tumour model-spheroid-is mainly utilised to mimic solid tumours from an architectural standpoint. It is a promising method to simulate the characteristics of tumours in vitro and their various responses to therapeutic alternatives. This study aimed to evaluate the effects of FUS on human prostate and glioblastoma cancer tumour spheroids in vitro. The experimental follow-up enclosed the measurements of spheroid integrity and growth kinetics, DNA damage, and cellular metabolic activity by measuring intracellular ATP content in the spheroids. Our results showed that pulsed FUS treatment induced molecular effects in 3D tumour models. With the disruption of the spheroid integrity, we observed an increase in DNA double-strand breaks, leading to damage in the cancer cells depending on the cancer cell type.

A Novel Matrix-Array-Based MR-Conditional Ultrasound System for Local Hyperthermia of Small Animals.

OBJECTIVE: The goal of this work was to develop a novel modular focused ultrasound hyperthermia (FUS-HT) system for preclinical applications with the following characteristics: MR-compatible, compact probe for integration into a PET/MR small animal scanner, 3D-beam steering capabilities, high resolution focusing for generation of spatially confined FUS-HT effects. METHODS: For 3D-beam steering capabilities, a matrix array approach with 11 × 11 elements was chosen. For reaching the required level of integration, the array was mounted with a conductive backing directly on the interconnection PCB. The array is driven by a modified version of our 128 channel ultrasound research platform DiPhAS. The system was characterized using sound field measurements and validated using tissue-mimicking phantoms. Preliminary MR-compatibility tests were performed using a 7T Bruker MRI scanner. RESULTS: Four 11 × 11 arrays between 0.5 and 2 MHz were developed and characterized with respect to sound field properties and HT generation. Focus sizes between 1 and 4 mm were reached depending on depth and frequency. We showed heating by 4 °C within 60 s in phantoms. The integration concept allows a probe thickness of less than 12 mm. CONCLUSION: We demonstrated FUS-HT capabilities of our modular system based on matrix arrays and a 128 channel electronics system within a 3D-steering range of up to ±30°. The suitability for integration into a small animal MR could be demonstrated in basic MR-compatibility tests. SIGNIFICANCE: The developed system presents a new generation of FUS-HT for preclinical and translational work providing safe, reversible, localized, and controlled HT.

Hybrid Photoacoustic/Ultrasound Tomograph for Real-Time Finger Imaging.

We report a target-enclosing, hybrid tomograph with a total of 768 elements based on capacitive micromachined ultrasound transducer technology and providing fast, high-resolution 2-D/3-D photoacoustic and ultrasound tomography tailored to finger imaging. A freely programmable ultrasound beamforming platform sampling data at 80 MHz was developed to realize plane wave transmission under multiple angles. A multiplexing unit enables the connection and control of a large number of elements. Fast image reconstruction is provided by GPU processing. The tomograph is composed of four independent and fully automated movable arc-shaped transducers, allowing imaging of all three finger joints. The system benefits from photoacoustics, yielding high optical contrast and enabling visualization of finger vascularization, and ultrasound provides morphologic information on joints and surrounding tissue. A diode-pumped, Q-switched Nd:YAG laser and an optical parametric oscillator are used to broaden the spectrum of emitted wavelengths to provide multispectral imaging. Custom-made optical fiber bundles enable illumination of the region of interest in the plane of acoustic detection. Precision in positioning of the probe in motion is ensured by use of a motor-driven guide slide. The current position of the probe is encoded by the stage and used to relate ultrasound and photoacoustic signals to the corresponding region of interest of the suspicious finger joint. The system is characterized in phantoms and a healthy human finger in vivo. The results obtained promise to provide new opportunities in finger diagnostics and establish photoacoustic/ultrasound-tomography in medical routine.

A Novel Quantitative 500-MHz Acoustic Microscopy System for Ophthalmologic Tissues.

OBJECTIVE: This paper describes development of a novel 500-MHz scanning acoustic microscope (SAM) for assessing the mechanical properties of ocular tissues at fine resolution. The mechanical properties of some ocular tissues, such as lamina cribrosa (LC) in the optic nerve head, are believed to play a pivotal role in eye pathogenesis. METHODS: A novel etching technology was used to fabricate silicon-based lens for a 500-MHz transducer. The transducer was tested in a custom-designed scanning system on human eyes. Two-dimensional (2-D) maps of bulk modulus (K) and mass density (ρ) were derived using improved versions of current state-of-the-art signal processing approaches. RESULTS: The transducer employed a lens radius of 125 µm and had a center frequency of 479 MHz with a -6-dB bandwidth of 264 MHz and a lateral resolution of 4 µm. The LC, Bruch's membrane (BM) at the interface of the retina and choroid, and Bowman's layer (BL) at the interface of the corneal epithelium and stroma, were successfully imaged and resolved. Analysis of the 2-D parameter maps revealed average values of LC, BM, and BL with KLC = 2.81 ±0.17; GPa, KBM = 2.89 ±0.18; GPa, KBL = 2.6 ±0.09 ; GPa, ρ LC = 0.96 ±0.03 g/cm3; ρ BM = 0.97 ±0.04 g/cm3; ρ BL = 0.98 ±0.04 g/cm3. SIGNIFICANCE: This novel SAM was shown to be capable of measuring mechanical properties of soft biological tissues at microscopic resolution; it is currently the only system that allows simultaneous measurement of K, ρ, and attenuation in large lateral scales (field area >9 mm2) and at fine resolutions.

Calibrated Linear Array-Driven Photoacoustic/Ultrasound Tomography.

The anisotropic resolution of linear arrays, tools that are widely used in diagnostics, can be overcome by compounding approaches. We investigated the ability of a recently developed calibration and a novel algorithm to determine the actual radial transducer array distance and its misalignment (tilt) with respect to the center of rotation in a 2-D and 3-D tomographic setup. By increasing the time-of-flight accuracy, we force in-phase summation during the reconstruction. Our setup is composed of a linear transducer and a rotation and translation axis enabling multidimensional imaging in ultrasound and photoacoustic mode. Our approach is validated on phantoms and young mice ex vivo. The results indicate that application of the proposed analytical calibration algorithms prevents image artifacts. The spatial resolution achieved was 160 and 250 µm in photoacoustic mode of 2-D and 3-D tomography, respectively.

Measurement of skull bone thickness for bone-anchored hearing aids: an experimental study comparing both a novel ultrasound system (SonoPointer) and computed tomographic scanning to mechanical measurements.

HYPOTHESIS: A-mode ultrasound scanning with coded signals allows bone thickness measurements at the site of bone-anchored hearing aid surgery as compared to computed tomographic scanning and mechanical measurements. BACKGROUND: Adequate bone thickness is a prerequisite for successful, long-lasting osseointegration of titanium fixtures for bone-anchored hearing aids. Computed tomography can be used to measure bone thickness but has several drawbacks. MATERIAL: Bone thickness was measured at the site of bone-anchored hearing aids surgery in 28 formaldehyde-preserved human cadaver temporoparietal bones. Four blinded investigators used a hand-held, A-mode ultrasound system with direct coupling at 2.25 MHz transducer using coded signals (SonoPointer) and repeated the measurements twice. Comparisons were made with high-resolution computed tomographic scanning and mechanical micrometer caliper measurements. RESULTS: There was significant anatomical variation in the temporoparietal bones. Computed tomography was in good agreement with the mechanical reference. All specimens could be measured by the SonoPointer. The mean difference between the mechanical control and ultrasound scanning averaged for all measurements by all investigators was 0.3 mm (standard deviation, 1.2 mm). Trained ultrasound experts yielded better results (mean difference, 0.3 mm; standard deviation, 1.0 mm). Agreement was best for bone thickness up to 5 mm. Outliers occurred in bones thicker than 7.5 mm. CONCLUSION: The SonoPointer is a promising, noninvasive, hand-held tool for real-time measurement of bone thickness in bone-anchored hearing aid surgery, especially for children. Even disregarding the absolute thickness reading, the SonoPointer could be used to search intraoperatively for a local maximum of bone thickness.

Accuracy of ultrasound measurements for skull bone thickness using coded signals.

The knowledge of skull bone thickness would be helpful for a great variety of surgical interventions of the head. Ultrasound (US) can offer this information intraoperatively in real time. A-mode US measurements of skull bone thickness were performed with different pulse characteristics: 1) in water and 2) by directly coupling a 2.25-MHz US transducer integrated in a handpiece with a soft delay line using coded excitation (CE) (SonoPointer). Mechanical measurements by calipers served as controls. The specimen were 16 nonselected human cadaveric skull bones preserved with formaldehyde. The average difference between the bone thickness measured by the SonoPointer and the mechanical control measurements was 0.04 +/- 0.62 mm. The 95% limits of agreement between the two methods were -1.18 and 1.25 mm. However, even the gold standard of two repeated caliper measurements had limits of agreement of -0.4 and 0.42 mm. Using a standard US pulse in water, only 62.5% sample points were measurable, whereas the SonoPointer produced the thickness measurement in 97.9% of points. CE proved to be superior to single burst or needle US pulses. A-mode US measurements of skull bone thickness using the SonoPointer are feasible. It may provide valuable information on skull bone thickness, e.g., for osteosynthesis, calvarial split bone harvesting, implantation of hearing devices, osseointegrated titanium fixtures, and skull base surgery.

First 3D ultrasound scanning, planning, and execution of CT-free milling interventions with a surgical robot.

Surgical procedures with navigation or robot system support usually require pre-operative planning data. This data can be acquired with imaging techniques such as computed tomography (CT), the current gold standard due to its high precision. With such planning data, access trajectories, implant positions, individual milling paths etc. can be computed. We present a novel ultrasound-based method to generate equivalent 3D image data which is well-suited for many interventions, but less costly than the CT-based method. The method is demonstrated for robot-based implant bed milling in the lateral skull base, in a complete process consisting of infrared navigation registration, manual ultrasound scan path delineation, path smoothing and checking, robot-based ultrasound scan execution, 3D ultrasound volume reconstruction, implant position optimization, robot milling path planning, and intervention execution. This represents, to the best of our knowledge, the first time such a CT-free, 3D-ultrasound-based intervention has been demonstrated in the laboratory.