Alleviation of Cyclophosphamide-induced Hemorrhagic Cystitis by Dietary Pomegranate: A Comparative Experimental Study With Mesna.

In this study, we investigated the effects of pomegranate on alleviating cyclophosphamide-induced hemorrhagic cystitis (HC). Initially, 16 Sprague-Dawley rats were allocated into 4 groups: group 1 (control), group 2 (CP) in which HC was induced by cyclophosphamide; group 3 (CP+M), HC-induced rats that received Mesna regimen, and group 4 (CP+P), which compromised rats that had been on a 14-day diet of pomegranate juice before HC induction. Cystometry was performed a few hours before euthanasia; after euthanasia, aortic blood samples and bladder tissue samples were obtained to perform TUNEL assay, and histopathologic and biochemical assessments. Urodynamic findings revealed that mean detrusor pressure in CP+P was significantly lower compared with that in CP and CP+M (P<0.05). Histopathologically, urothelium destruction and inflammation were lower in CP+P and CP+M compared with that in CP. Collagen destruction was less prominent in CP+P compared with that in CP and CP+M. Tissue and plasma levels of malondialdehyde were significantly lower in CP+P versus CP (P<0.05). Catalase activity and total protein thiol group levels in plasma and bladder tissue were higher in CP+P versus CP (P<0.05). The TUNEL positivity in CP+P was significantly weaker than that in CP, indicating less DNA fragmentation and apoptosis. Pomegranate's characteristics could significantly affect the inflammatory and destructive process of hemorrhagic cystitis.

MagSonic: Hybrid Magnetic-Ultrasonic Wireless Interrogation of Millimeter-Scale Biomedical Implants With Magnetoelectric Transducer.

Wireless interrogation (power and data transfer) of biomedical implants, miniaturized to millimeter (mm) dimensions, is critical for their chronic operation. Achieving simultaneous wireless power and data transfer at deep sites reliably within safety limits for closed-loop sensing/actuation functions of mm-sized implants is challenging. To enable this operation, a hybrid magnetic-ultrasonic interrogation approach (called MagSonic) is realized through a single magnetoelectric (ME) transducer at the implant that can generate and receive both magnetic field and ultrasound. The fabricated mm-sized bar-shaped ME transducer (5.2×2×1.6 mm3) operates at acoustic wave resonance, functioning at sub-MHz frequencies. For the first time, we demonstrate wireless power reception through one modality (magnetic field or ultrasound) and simultaneous uplink data transmission using the other. At 40 mm depth, the MagSonic link could achieve 100 kbps uplink data rate (bit error rate ≤ 10-5) using 190 pJ/bit transmitted energy and 8 mW delivered power in tissue. The robustness of the MagSonic interrogation link against power carrier interference and misalignments is also demonstrated.

A Study on Ultrasonic Wireless Power Transfer With Phased Array for Biomedical Implants.

This article presents the design, fabrication, and sensitivity analysis of an ultrasound (US) wireless power transfer (WPT) link using an external phased array. Optimal beam focusing and steering is needed for efficient, safe, and reliable US WPT to biomedical implants with millimeter (mm) dimensions. Therefore, the main contributions of this work include the investigation of the 1) performance of the US WPT link using different mm-sized US receivers, 2) effect of different types of errors in the delay profile of the beamforming system on the delivered power, and 3) implant's localization. In measurements, the fabricated 0.94 MHz, 32-element array (39.48 × 9.6 × 2 mm3) driven by 25 V pulses with beam focusing and steering capability up to 50 mm depth and ±60o angle could deliver power to different mm-sized US receivers within the FDA safety limit of 720 mW/cm2. Specifically, several US transducers with a 1 mm dimension (sphere, cubic, disc shape) and 2 mm dimension (disc shape) received 0.095 mW, 0.25 mW, 0.22 mW, and 0.53 mW, respectively, at a 30 mm depth (0o steering angle). Among these transducers, the sphere shape transducer featured less sensitivity to misalignments. A random error in the phased array delays had a more drastic effect on delivered power reduction. For implant's localization, the measurement results demonstrated comparable power delivery by measuring pulse delays of only 5 elements (out of 32 elements) using 4 different interpolation methods.

Design and Optimization of Ultrasonic Links With Phased Arrays for Wireless Power Transmission to Biomedical Implants.

Ultrasound (US) is an attractive modality for wireless power transfer (WPT) to biomedical implants with millimeter (mm) dimensions. To compensate for misalignments in WPT to a mm-sized implant (or powering a network of mm-sized implants), a US transducer array should electronically be driven in a beamforming fashion (known as US phased array) to steer focused US beams at different locations. This paper presents the theory and design methodology of US WPT links with phased arrays and mm-sized receivers (Rx). For given constraints imposed by the application and fabrication, such as load (RL) and focal distance (F), the optimal geometries of a US phased array and Rx transducer, as well as the optimal operation frequency (fc) are found through an iterative design procedure to maximize the power transfer efficiency (PTE). An optimal figure of merit (FoM) related to PTE is proposed to simplify the US array design. A design example of a US link is presented and optimized for WPT to a mm-sized Rx with a linear array. In measurements, the fabricated 16-element array (10.9×9×1.7 mm3) driven by 100 V pulses at fc of 1.1 MHz with optimal delays for focusing at F = 20 mm generated a US beam with a pressure output of 0.8 MPa. The link could deliver up to 6 mW to a ∼ 1 mm3 Rx with a PTE of 0.14% (RL = 850 Ω). The beam steering capability of the array at -45o to 45o angles was also characterized.

32 Element Piezoelectric Micromachined Ultrasound Transducer (PMUT) Phased Array for Neuromodulation.

Interest in utilizing ultrasound (US) transducers for non-invasive neuromodulation treatment, including for low intensity transcranial focused ultrasound stimulation (tFUS), has grown rapidly. The most widely demonstrated US transducers for tFUS are either bulk piezoelectric transducers or capacitive micromachine transducers (CMUT) which require high voltage excitation to operate. In order to advance the development of the US transducers towards small, portable devices for safe tFUS at large scale, a low voltage array of US transducers with beam focusing and steering capability is of interest. This work presents the design methodology, fabrication, and characterization of 32-element phased array piezoelectric micromachined ultrasound transducers (PMUT) using 1.5 µm thick Pb(Zr0.52 Ti0.48)O3 films doped with 2 mol% Nb. The electrode/piezoelectric/electrode stack was deposited on a silicon on insulator (SOI) wafer with a 2 µm silicon device layer that serves as the passive elastic layer for bending-mode vibration. The fabricated 32-element PMUT has a central frequency at 1.4 MHz. Ultrasound beam focusing and steering (through beamforming) was demonstrated where the array was driven with 14.6 V square unipolar pulses. The PMUT generated a maximum peak-to-peak focused acoustic pressure output of 0.44 MPa at a focal distance of 20 mm with a 9.2 mm and 1 mm axial and lateral resolution, respectively. The maximum pressure is equivalent to a spatial-peak pulse-average intensity of 1.29 W/cm2, which is suitable for tFUS application.

Design and Optimization of Ultrasound Phased Arrays for Large-Scale Ultrasound Neuromodulation.

Low-intensity transcranial focused ultrasound stimulation (tFUS), as a noninvasive neuromodulation modality, has shown to be effective in animals and even humans with improved millimeter-scale spatial resolution compared to its noninvasive counterparts. But conventional tFUS systems are built with bulky single-element ultrasound (US) transducers that must be mechanically moved to change the stimulation target. To achieve large-scale ultrasound neuromodulation (USN) within a given tissue volume, a US transducer array should electronically be driven in a beamforming fashion (known as US phased array) to steer focused ultrasound beams towards different neural targets. This paper presents the theory and design methodology of US phased arrays for USN at a large scale. For a given tissue volume and sonication frequency (f), the optimal geometry of a US phased array is found with an iterative design procedure that maximizes a figure of merit (FoM) and minimizes side/grating lobes (avoiding off-target stimulation). The proposed FoM provides a balance between the power efficiency and spatial resolution of a US array in USN. A design example of a US phased array has been presented for USN in a rat's brain with an optimized linear US array. In measurements, the fabricated US phased array with 16 elements (16.7×7.7×2 mm3), driven by 150 V (peak-peak) pulses at f = 833.3 kHz, could generate a focused US beam with a lateral resolution of 1.6 mm and pressure output of 1.15 MPa at a focal distance of 12 mm. The capability of the US phased array in beam steering and focusing from -60o to 60o angles was also verified in measurements.