Miniaturized preamplifier integration in ultrasound transducer design for enhanced photoacoustic imaging.

Photoacoustic imaging (PAI) utilizes the photoacoustic effect to record both vascular and functional characteristics of a biological tissue. Photoacoustic signals have typically low amplitude that cannot be read efficiently by data acquisition systems. This necessitates the use of one or more amplifiers. These amplifiers are somewhat bulky (e.g., the ZFL-500LN+, Mini-Circuits, USA, or 351A-3-50-NI, Analog Modules Inc., USA). Here, we describe the fabrication and development process of a transducer with a built-in low-noise preamplifier that is encased within the transducer housing. This new, to the best of our knowledge, design could be advantageous for applications where a compact transducer + preamplifier is required. We demonstrate the performance of this compact detection unit in a laser scanning photoacoustic microscopy system by imaging a rat ear ex vivo and a rat brain vasculature in vivo.

Compressed Sensing for Biomedical Photoacoustic Imaging: A Review.

Photoacoustic imaging (PAI) is a rapidly developing emerging non-invasive biomedical imaging technique that combines the strong contrast from optical absorption imaging and the high resolution from acoustic imaging. Abnormal biological tissues (such as tumors and inflammation) generate different levels of thermal expansion after absorbing optical energy, producing distinct acoustic signals from normal tissues. This technique can detect small tissue lesions in biological tissues and has demonstrated significant potential for applications in tumor research, melanoma detection, and cardiovascular disease diagnosis. During the process of collecting photoacoustic signals in a PAI system, various factors can influence the signals, such as absorption, scattering, and attenuation in biological tissues. A single ultrasound transducer cannot provide sufficient information to reconstruct high-precision photoacoustic images. To obtain more accurate and clear image reconstruction results, PAI systems typically use a large number of ultrasound transducers to collect multi-channel signals from different angles and positions, thereby acquiring more information about the photoacoustic signals. Therefore, to reconstruct high-quality photoacoustic images, PAI systems require a significant number of measurement signals, which can result in substantial hardware and time costs. Compressed sensing is an algorithm that breaks through the Nyquist sampling theorem and can reconstruct the original signal with a small number of measurement signals. PAI based on compressed sensing has made breakthroughs over the past decade, enabling the reconstruction of low artifacts and high-quality images with a small number of photoacoustic measurement signals, improving time efficiency, and reducing hardware costs. This article provides a detailed introduction to PAI based on compressed sensing, such as the physical transmission model-based compressed sensing method, two-stage reconstruction-based compressed sensing method, and single-pixel camera-based compressed sensing method. Challenges and future perspectives of compressed sensing-based PAI are also discussed.

Compound Acoustic Radiation Force Impulse Imaging of Bovine Eye by Using Phase-Inverted Ultrasound Transducer.

In general, it is difficult to visualize internal ocular structure and detect a lesion such as a cataract or glaucoma using the current ultrasound brightness-mode (B-mode) imaging. This is because the internal structure of the eye is rich in moisture, resulting in a lack of contrast between tissues in the B-mode image, and the penetration depth is low due to the attenuation of the ultrasound wave. In this study, the entire internal ocular structure of a bovine eye was visualized in an ex vivo environment using the compound acoustic radiation force impulse (CARFI) imaging scheme based on the phase-inverted ultrasound transducer (PIUT). In the proposed method, the aperture of the PIUT is divided into four sections, and the PIUT is driven by the out-of-phase input signal capable of generating split-focusing at the same time. Subsequently, the compound imaging technique was employed to increase signal-to-noise ratio (SNR) and to reduce displacement error. The experimental results demonstrated that the proposed technique could provide an acoustic radiation force impulse (ARFI) image of the bovine eye with a broader depth-of-field (DOF) and about 80% increased SNR compared to the conventional ARFI image obtained using the in-phase input signal. Therefore, the proposed technique can be one of the useful techniques capable of providing the image of the entire ocular structure to diagnose various eye diseases.

Lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation.

Ultrasound-driven bioelectronics could offer a wireless scheme with sustainable power supply; however, current ultrasound implantable systems present critical challenges in biocompatibility and harvesting performance related to lead/lead-free piezoelectric materials and devices. Here, we report a lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation, which integrates two developed lead-free sandwich porous 1-3-type piezoelectric composite elements with enhanced harvesting performance in a flexible printed circuit board. The implant is ultrasonically powered through a portable external dual-frequency transducer and generates programmable biphasic stimulus pulses in clinically relevant frequencies. Furthermore, we demonstrate ultrasound-driven implants for long-term biosafety therapy in deep brain stimulation through an epileptic rodent model. With biocompatibility and improved electrical performance, the lead-free materials and devices presented here could provide a promising platform for developing implantable ultrasonic electronics in the future.

Nanorefractive index transducer using a ring cavity with an internal h-shaped cavity grounded on Fano resonance.

Building on the Fano resonance observation, a new refractive index transducer structure at the nanoscale is proposed in this article, which is a refractive index transducer consisting of a metal-insulator-metal (MIM) waveguide structure coupled with a ring cavity internally connected to an h-shaped structure (RCIhS). Using an analytical method based on COMSOL software and finite element method (FEM), the effect of different geometric parameters of the structure on the trans-mission characteristics of the system is simulated and analyzed, which in turn illustrates the effect of the structural parameters on the output Fano curves. As simulation results show, the internally connected h-shaped structure is an influential component in the Fano resonance. By optimizing the geometrical parameters of the structure, the system finally accomplishes a sensitivity (S) of 2400 nm/RIU and a figure of merit (FOM) of 68.57. The sensor has also been demonstrated in the realm of temperature detection, having tremendous potential for utilization in future nano-sensing and optically integrated systems.

In-vitro effects of novel periodontal scalers with a planar ultrasonic piezoelectric transducer on periodontal biofilm removal, dentine surface roughness, and periodontal ligament fibroblasts adhesion.

OBJECTIVES: To compare ultrasonic scaler prototypes based on a planar piezoelectric transducer with different working frequencies featuring a titanium (Ti-20, Ti-28, and Ti-40) or stainless steel (SS-28) instrument, with a commercially available scaler (com-29) in terms of biofilm removal and reformation, dentine surface roughness and adhesion of periodontal fibroblasts. MATERIALS AND METHODS: A periodontal multi-species biofilm was formed on specimens with dentine slices. Thereafter specimens were instrumented with scalers in a periodontal pocket model or left untreated (control). The remaining biofilms were quantified and allowed to reform on instrumented dentine slices. In addition, fibroblasts were seeded for attachment evaluation after 72 h of incubation. Dentine surface roughness was analyzed before and after instrumentation. RESULTS: All tested instruments reduced the colony-forming unit (cfu) counts by about 3 to 4 log10 and the biofilm quantity (each p < 0.01 vs. control), but with no statistically significant difference between the instrumented groups. After 24-hour biofilm reformation, no differences in cfu counts were observed between any groups, but the biofilm quantity was about 50% in all instrumented groups compared to the control. The attachment of fibroblasts on instrumented dentine was significantly higher than on untreated dentine (p < 0.05), with the exception of Ti-20. The dentine surface roughness was not affected by any instrumentation. CONCLUSIONS: The planar piezoelectric scaler prototypes are able to efficiently remove biofilm without dentine surface alterations, regardless of the operating frequency or instrument material. CLINICAL RELEVANCE: Ultrasonic scalers based on a planar piezoelectric transducer might be an alternative to currently available ultrasonic scalers.

Bioresorbable, wireless, passive sensors for continuous pH measurements and early detection of gastric leakage.

Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time monitoring of pH with fast response time (within 1 hour) over a clinically relevant period (up to 7 days) and timely detection of simulated gastric leaks in animal models. These concepts have broad potential applications for temporary sensing of relevant biomarkers during critical risk periods following diverse types of surgeries.

Demonstration Study of Reflector-Based Volumetric Speed-of-Sound Imaging With Linear Ultrasound Arrays.

Conventional B-mode ultrasound imaging has difficulty in delineating homogeneous soft tissues with similar acoustic impedances, as the reflectivity depends on the acoustic impedance at the interface. As a quantitative imaging biomarker sensitive to alteration of biomechanical properties, speed-of-sound (SoS) holds promising potential for tissue and disease differentiation such as delineation of different breast tissue types with similar acoustic impedance. Compared to two-dimensional (2D) SoS images, three-dimensional (3D) volumetric SoS images achieved through a full-angle ultrasound scan can reveal more intricate morphological structures of tissues; however, they generally require a ring transducer. In this study, we introduce a 3D SoS reconstruction system that utilizes hand-held linear arrays instead. This system employs a passive reflector positioned opposite the linear arrays, serving as an echogenic reference for time-of-flight (ToF) measurements, and a high-definition camera to track the location corresponding to each group of transmit-receive data. To merge these two streams of ToF measurements and location tracking, a voxel-based reconstruction algorithm is implemented. Experimental results with gelatin phantom and ex vivo tissue have demonstrated the stability of our proposed method. Moreover, the results underscore the potential of this system as a complementary diagnostic modality, particularly in the context of diseases such as breast cancer.

Pinecone derived hierarchical carbon nanostructure as a transducer in a solid-state ion-selective electrode for in vivo analysis of calcium ion.

Monitoring extracellular calcium ion (Ca2+) chemical signals in neurons is crucial for tracking physiological and pathological changes associated with brain diseases in live animals. Potentiometry based solid-state ion-selective electrodes (ISEs) with the assist of functional carbon nanomaterials as ideal solid-contact layer could realize the potential response for in vitro and in vivo analysis. Herein, we employ a kind of biomass derived porous carbon as a transducing layer to prompt efficient ion to electron transduction while stabilizes the potential drift. The eco-friendly porous carbon after activation (APB) displays a high specific area with inherit macropores, micropores, and large specific capacitance. When employed as transducer in ISEs, a stable potential response, minimized potential drift can be obtained. Benefiting from these excellent properties, a solid-state Ca2+ selective carbon fiber electrodes (CFEs) with a sandwich structure is constructed and employed for real time sensing of Ca2+ under electrical stimulation. This study presents a new approach to develop sustainable and versatile transducers in solid-state ISEs, a crucial way for in vivo sensing.

SIMUS3: An open-source simulator for 3-D ultrasound imaging.

BACKGROUND AND OBJECTIVE: Computational Ultrasound Imaging (CUI) has become increasingly popular in the medical ultrasound community, facilitated by free simulation software. These tools enable the design and exploration of transmit sequences, transducer arrays, and signal processing. We recently introduced SIMUS, a frequency-based ultrasound simulator within the open-source MUST toolbox, which offers numerical advantages and allows easy consideration of frequency-dependent factors. In response to the growing interest in simulating ultrasound imaging with 2-D matrix arrays, we present 3-D versions, PFIELD3 and SIMUS3. METHOD: The linear acoustic equations driving these functions are described, with theoretical assumptions reviewed for user guidance. RESULTS: Comparative analyses with Field II, using a 32×32 element 3-MHz matrix array, highlight the performance of PFIELD3 and SIMUS3 under various transmission conditions. CONCLUSIONS: This work extends the capabilities of existing CUI tools and provides researchers with valuable resources for advanced ultrasound simulations.

Development of a Small-Footprint 50 MHz Linear Array: Fabrication and Micro-Ultrasound Imaging Demonstration.

Compact high-frequency arrays are of interest for clinical and preclinical applications in which a small-footprint or endoscopic device is needed to reach the target anatomy. However, the fabrication of compact arrays entails the connection of several dozens of small elements to the imaging system through a combination of flexible printed circuit boards at the array end and micro-coaxial cabling to the imaging system. The methods currently used, such as wire bonding, conductive adhesives, or a dry connection to a flexible circuit, considerably increase the array footprint. Here, we propose an interconnection method that uses vacuum-deposited metals, laser patterning, and electroplating to achieve a right-angle, compact, reliable connection between array elements and flexible-circuit traces. The array elements are thickened at the edges using patterned copper traces, which increases their cross-sectional area and facilitates the connection. We fabricated a 2.3 mm by 1.7 mm, 64-element linear array with elements at a 36 µm pitch connected to a 4 cm long flexible circuit, where the interconnect adds only 100 µm to each side of the array. Pulse-echo measurements yielded an average center frequency of 55 MHz and a -6 dB bandwidth of 41%. We measured an imaging resolution of 35 µm in the axial direction and 114 µm in the lateral direction and demonstrated the ex vivo imaging of porcine esophageal tissue and the in vivo imaging of avian embryonic vasculature.

Flexible large-area ultrasound arrays for medical applications made using embossed polymer structures.

With the huge progress in micro-electronics and artificial intelligence, the ultrasound probe has become the bottleneck in further adoption of ultrasound beyond the clinical setting (e.g. home and monitoring applications). Today, ultrasound transducers have a small aperture, are bulky, contain lead and are expensive to fabricate. Furthermore, they are rigid, which limits their integration into flexible skin patches. New ways to fabricate flexible ultrasound patches have therefore attracted much attention recently. First prototypes typically use the same lead-containing piezo-electric materials, and are made using micro-assembly of rigid active components on plastic or rubber-like substrates. We present an ultrasound transducer-on-foil technology based on thermal embossing of a piezoelectric polymer. High-quality two-dimensional ultrasound images of a tissue mimicking phantom are obtained. Mechanical flexibility and effective area scalability of the transducer are demonstrated by functional integration into an endoscope probe with a small radius of 3 mm and a large area (91.2×14 mm2) non-invasive blood pressure sensor.

Development of an MR-Guided Focused Ultrasound (MRgFUS) Lesioning Approach for the Fornix in the Rat Brain.

OBJECTIVE: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. METHODS: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n = 7 lesions) was compared to a craniectomy approach (n = 22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histologic methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. RESULTS: Comparing a motorized adjustment system (∼1 mm precision, n = 17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n = 14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. CONCLUSIONS: The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

Evaluation of Dual-Frequency Switching HIFU for Optimizing Superficial Ablation.

OBJECTIVE: Dual-frequency high-intensity focused ultrasound (HIFU) thermal ablation is an exceptionally promising technique for treating tumors due to its precision and effectiveness. However, there are still a few studies on improving the accuracy and efficiency of HIFU in superficial ablation applications. This study proposes a method utilizing dual frequency switching ultrasound (DFSU) to enhance the efficiency and precision of superficial treatments. METHODS: A dual-frequency HIFU transducer operating at 4.5 MHz and 13.7 MHz was designed, and a dual-frequency impedance matching network was designed to optimize electro-acoustic conversion efficiency. Phantom and ex vivo tests were conducted to measure and compare thermal lesion areas and temperature rises caused by single-frequency ultrasound (SFU) and DFSU. RESULTS: In both phantom and ex vivo tests, the utilization of DFSU resulted in larger lesion areas compared to SFU. Moreover, DFSU provided improved control and versatility, enabling precise and efficient ablation. CONCLUSION: DFSU exhibits the ability to generate larger ablation areas in superficial tissue compared to SFU, and DFSU allows flexible control over the ablation area and temperature rise rate. The acoustic power deposition of HIFU can be optimized to achieve precise ablation.

Histoplasty Modification of the Tumor Microenvironment in a Murine Preclinical Model of Breast Cancer.

PURPOSE: To develop a noninvasive therapeutic approach able to alter the biophysical organization and physiology of the extracellular matrix (ECM) in breast cancer. MATERIALS AND METHODS: In a 4T1 murine model of breast cancer, histoplasty treatment with a proprietary 700-kHz multielement therapy transducer using a coaxially aligned ultrasound (US) imaging probe was used to target the center of an ex vivo tumor and deliver subablative acoustic energy. Tumor collagen morphology was qualitatively evaluated before and after histoplasty with second harmonic generation. Separately, mice bearing bilateral 4T1 tumors (n = 4; total tumors = 8) were intravenously injected with liposomal doxorubicin. The right flank tumor was histoplasty-treated, and tumors were fluorescently imaged to detect doxorubicin uptake after histoplasty treatment. Next, 4T1 tumor-bearing mice were randomized into 2 treatment groups (sham vs histoplasty, n = 3 per group). Forty-eight hours after sham/histoplasty treatment, tumors were harvested and analyzed using flow cytometry. RESULTS: Histoplasty significantly increased (P = .002) liposomal doxorubicin diffusion into 4T1 tumors compared with untreated tumors (2.12- vs 1.66-fold increase over control). Flow cytometry on histoplasty-treated tumors (n = 3) demonstrated a significant increase in tumor macrophage frequency (42% of CD45 vs 33%; P = .022) and a significant decrease in myeloid-derived suppressive cell frequency (7.1% of CD45 vs 10.3%; P = .044). Histoplasty-treated tumors demonstrated increased CD8+ (5.1% of CD45 vs 3.1%; P = .117) and CD4+ (14.1% of CD45 vs 11.8%; P = .075) T-cell frequency. CONCLUSIONS: Histoplasty is a nonablative focused US approach to noninvasively modify the tumor ECM, increase chemotherapeutic uptake, and alter the tumor immune microenvironment.

Recommendations for the Cleaning of Endocavity Ultrasound Transducers Between Patients.

The COVID-19 pandemic highlighted the importance of infection prevention and control measures for all medical procedures, including ultrasound examinations. As the use of ultrasound increases across more medical modalities, including point-of-care ultrasound, so does the risk of possible transmission from equipment to patients and patients to patients. This is particularly relevant for endocavity transducers, such as trans-vaginal, trans-rectal and trans-oesophageal, which could be contaminated with organisms from blood, mucosal, genital or rectal secretions. This article proports to update the WFUMB 2017 guidelines which focussed on the cleaning and disinfection of trans-vaginal ultrasound transducers between patients.

Cavitation-induced pressure saturation: a mechanism governing bubble nucleation density in histotripsy.

Objective.Histotripsy is a noninvasive focused ultrasound therapy that mechanically disintegrates tissue by acoustic cavitation clouds. In this study, we investigate a mechanism limiting the density of bubbles that can nucleate during a histotripsy pulse. In this mechanism, the pressure generated by the initial bubble expansion effectively negates the incident pressure in the vicinity of the bubble. From this effect, the immediately adjacent tissue is prevented from experiencing the transient tension to nucleate bubbles. Approach.A Keller-Miksis-type single-bubble model was employed to evaluate the dependency of this effect on ultrasound pressure amplitude and frequency, viscoelastic medium properties, bubble nucleus size, and transducer geometric focusing. This model was further combined with a spatial propagation model to predict the peak negative pressure field as a function of position from a cavitating bubble.Main results. The single-bubble model showed the peak negative pressure near the bubble surface is limited to the inertial cavitation threshold. The predicted bubble density increased with increasing frequency, tissue viscosity, and transducer focusing angle. The simulated results were consistent with the trends observed experimentally in prior studies, including changes in density with ultrasound frequency and transducerF-number.Significance.The efficacy of the therapy is dependent on several factors, including the density of bubbles nucleated within the cavitation cloud formed at the focus. These results provide insight into controlling the density of nucleated bubbles during histotripsy and the therapeutic efficacy.

Inducing cavitation within hollow cylindrical radially polarized transducers for intravascular applications.

Thrombotic occlusions of large blood vessels are increasingly treated with catheter based mechanical approaches, one of the most prominent being to employ aspiration to extract clots through a hollow catheter lumen. A central technical challenge for aspiration catheters is to achieve sufficient suction force to overcome the resistance of clot material entering into the distal tip. In this study, we examine the feasibility of inducing cavitation within hollow cylindrical transducers with a view to ultimately using them to degrade the mechanical integrity of thrombus within the tip of an aspiration catheter. Hollow cylindrical radially polarized PZT transducers with 3.3/2.5 mm outer/inner diameters were assessed. Finite element simulations and hydrophone experiments were used to investigate the pressure field distribution as a function of element length and resonant mode (thickness, length). Operating in thickness mode (∼5 MHz) was found to be associated with the highest internal pressures, estimated to exceed 23 MPa. Cavitation was demonstrated to be achievable within the transducer under degassed water (10 %) conditions using hydrophone detection and high-frequency ultrasound imaging (40 MHz). Cavitation clouds occupied a substantial portion of the transducer lumen, in a manner that was dependent on the pulsing scheme employed (10 and 100 µs pulse lengths; 1.1, 11, and 110 ms pulse intervals). Collectively the results support the feasibility of achieving cavitation within a transducer compatible with mounting in the tip of an aspiration format catheter.

In vivo evaluation of focused ultrasound ablation surgery (FUAS)-induced coagulation using echo amplitudes of the therapeutic focused ultrasound transducer.

OBJECTIVE: Monitoring sensitivity of sonography in focused ultrasound ablation surgery (FUAS) is limited (no hyperechoes in ∼50% of successful coagulation in uterine fibroids). A more accurate and sensitive approach is required. METHOD: The echo amplitudes of the focused ultrasound (FUS) transducer in a testing mode (short pulse duration and low power) were found to correlate with the ex vivo coagulation. To further evaluate its coagulation prediction capabilities, in vivo experiments were carried out. The liver, kidney, and leg muscles of three adult goats were treated using clinical FUAS settings, and the echo amplitude of the FUS transducer and grayscale in sonography before and after FUAS were collected. On day 7, animals were sacrificed humanely, and the treated tissues were dissected to expose the lesion. Echo amplitude changes and lesion areas were analyzed statistically, as were the coagulation prediction metrics. RESULTS: The echo amplitude changes of the FUS transducer correlate well with the lesion areas in the liver (R = 0.682). Its prediction in accuracy (94.4% vs. 50%), sensitivity (92.9% vs. 35.7%), and negative prediction (80% vs. 30.8%) is better than sonography, but similar in specificity (80% vs. 100%) and positive prediction (100% vs. 100%). In addition, the correlation between tissue depth and the lesion area is not good (|R| < 0.2). Prediction performances in kidney and leg muscles are similar. CONCLUSION: The FUS echo amplitudes are sensitive to the tissue properties and their changes after FUAS. They are sensitive and reliable in evaluating and predicting FUAS outcomes.

Piezoelectric Multi-Channel Bilayer Transducer for Sensing and Filtering Ossicular Vibration.

This paper presents an acoustic transducer for fully implantable cochlear implants (FICIs), which can be implanted on the hearing chain to detect and filter the ambient sound in eight frequency bands between 250 and 6000 Hz. The transducer dimensions are conventional surgery compatible. The structure is formed with 3  × 3 × 0.36 mm active space for each layer and 5.2 mg total active mass excluding packaging. Characterization of the transducer is carried on an artificial membrane whose vibration characteristic is similar to the umbo vibration. On the artificial membrane, piezoelectric transducer generates up to 320.3 mVpp under 100 dB sound pressure level (SPL) excitation and covers the audible acoustic frequency. The measured signal-to-noise-ratio (SNR) of the channels is up to 84.2 dB. Sound quality of the transducer for fully implantable cochlear implant application is graded with an objective qualification method (PESQ) for the first time in the literature to the best of the knowledge, and scored 3.42/4.5.