Fabrication and Characterization of a Miniaturized 15-MHz Side-Looking Phased-Array Transducer Catheter.

This paper describes the development of a miniaturized 15-MHz side-looking phased-array transducer catheter. The array features a 2-2 linear composite with 64 piezoelectric elements mechanically diced into a piece of PMN-30%PT single crystal and separated by non-conductive epoxy kerfs at a 50-µm pitch, yielding a total active aperture of 3.2 mm in the azimuth direction and 1.8 mm in the elevation direction, with an elevation natural focal depth of 8.1 mm. The array includes non-conductive epoxy backing and two front matching layers. A custom flexible circuit connects the array piezoelectric elements to a bundle of 64 individual 48-AWG micro-coaxial cables enclosed within a 1.5-m long 10F catheter. Performance characterization was evaluated via finite element analysis simulations and afterwards compared against obtained measurement results, which showed an average center frequency of 17.7 MHz, an average bandwidth of 52.2% at -6 dB, and crosstalk less than -30 dB. Imaging of a tungsten fine-wire phantom resulted in axial and lateral spatial resolutions of approximately 90 µm and 420 ìm, respectively. The imaging capability was further evaluated with colorectal tissue-mimicking phantoms, demonstrating the potential suitability of the proposed phased-array transducer for the intraoperative assessment of surgical margins during minimally invasive colorectal surgery procedures.

Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and Beta Defensin-Containing Anti-Aging Skin Care Regimen With Clinical, Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation.

BACKGROUND/OBJECTIVES: Anti-aging strategies utilizing stem cells are in the forefront. Alpha and beta defensins are natural immune peptides that have been shown to activate an LGR6-positive stem cell locus in the hair follicle, identified as the source of most new epidermal cells during acute wound healing. We investigated the ability of biomimetic alpha and beta defensin molecules, supplemented with supportive cosmetic ingredients, formulated into three skin care products, at improving the structure and function of aging skin. METHODS: A participant- and investigator -blinded, placebo-controlled, multi-center trial was performed in outpatient settings. Forty-four healthy female subjects, aged 41-71 years, skin types I-V, completed the study with 2/3 receiving full formula and 1/3 receiving the placebo formula. A skin care regimen of 3 products (serum, cream, and mask) containing alpha-defensin 5 and beta-defensin 3, and other cosmetic ingredients, was applied to the face, post-auricular, and neck skin two times per day for 12 weeks in those receiving full formula, whereas the placebo group received the identically packaged regimen without the active ingredients. Methods of evaluation included histopathology and immunohistochemistry (7 subjects), clinical evaluation of pores, superficial and deep wrinkles based on Griffiths scale, and high-resolution photography (all subjects). In addition, a subset of 15 patients were evaluated with the QuantifiCare system (3-dimensional imaging and skin care scores for evenness, pores, oiliness) and Cortex measurements (high-resolution skin ultrasound, TEWL, elasticity, color, and hydration). Data points for evaluation included baseline, 6 weeks, and 12 weeks. All patients used the same sunscreen and cleanser, which was provided to them. RESULTS: The full formula regimen caused a significantly (P equals 0.027) increased thickness of the epidermis as seen in histology, not seen in the placebo group, with no signs of inflammation. No excessive cell proliferation was detected in either group as measured by Ki67-immunohistochemistry. Reduction in visible pores, superficial wrinkles, oiliness, pigmentation, and improvement of skin evenness, were statistically significant. A trend for improvement was also observed in skin elasticity, TEWL, and hydration; these did not achieve statistical significance. Ultrasound and histopathology demonstrated increases in dermal thickness in individual patients, without statistical significance. Comprehensive improvement in all 5 parameters, including visible pores, hyperpigmentation, superficial and deep wrinkles, and epidermal thickness, was statistically significant when the subset of participants assigned for histology in full formula group was compared with the placebo group participants. CONCLUSIONS: A 3-product skin care regimen containing alpha and beta defensins globally improves the visual appearance and structure of aging skin without irritation, dryness, or inflammation. Specifically, this regimen increases epidermal thickness, reduces appearance of pores, reduces wrinkles, and reduces melanin. This skin care regimen stimulates rejuvenation without evidence of increase of a marker of carcinogenic stimulation. This data is consistent with the hypothesis that a defensin-containing skin care regimen activates the body's own dormant stem cells to generate healthy new epidermal cells.

J Drugs Dermatol. 2018;17(4):426-441.

Design of matching layers for high-frequency ultrasonic transducers.

Matching the acoustic impedance of high-frequency (≥100 MHz) ultrasound transducers to an aqueous loading medium remains a challenge for fabricating high-frequency transducers. The traditional matching layer design has been problematic to establish high matching performance given requirements on both specific acoustic impedance and precise thickness. Based on both mass-spring scheme and microwave matching network analysis, we interfaced metal-polymer layers for the matching effects. Both methods hold promises for guiding the metal-polymer matching layer design. A 100 MHz LiNbO3 transducer was fabricated to validate the performance of the both matching layer designs. In the pulse-echo experiment, the transducer echo amplitude increased by 84.4% and its -6dB bandwidth increased from 30.2% to 58.3% comparing to the non-matched condition, demonstrating that the matching layer design method is effective for developing high-frequency ultrasonic transducers.

Dual-element needle transducer for intravascular ultrasound imaging.

A dual-element needle transducer for intravascular ultrasound imaging has been developed. A low-frequency element and a high-frequency element were integrated into one device to obtain images which conveyed both low- and high-frequency information from a single scan. The low-frequency element with a center frequency of 48 MHz was fabricated from the single crystal form of lead magnesium niobate-lead titanate solid solution with two matching layers (MLs) and the high frequency element with a center frequency of 152 MHz was fabricated from lithium niobate with one ML. The measured axial and lateral resolutions were 27 and [Formula: see text], respectively, for the low-frequency element, and 14 and [Formula: see text], respectively, for the high-frequency element. The performance of the dual-element needle transducer was validated by imaging a tissue-mimicking phantom with lesion-mimicking area, and ex vivo rabbit aortas in water and rabbit whole blood. The results suggest that a low-frequency element effectively provides depth resolved images of the whole vessel and its adjacent tissue, and a high-frequency element visualizes detailed structure near the surface of the lumen wall in the presence of blood within the lumen. The advantages of a dual-element approach for intravascular imaging are also discussed.

Angled-focused 45 MHz PMN-PT single element transducer for intravascular ultrasound imaging.

A transducer with an angled and focused aperture for intravascular ultrasound imaging has been developed. The acoustic stack for the angled-focused transducer was made of PMN-PT single crystal with one matching layer, one protective coating layer, and a highly damped backing layer. It was then press-focused to a desired focal length and inserted into a thin needle housing with an angled tip. A transducer with an angled and unfocused aperture was also made, following the same fabrication procedure, to compare the performance of the two transducers. The focused and unfocused transducers were tested to measure their center frequencies, bandwidths, and spatial resolutions. Lateral resolution of the angled-focused transducer (AFT) improved more than two times compared to that of the angled-unfocused transducer (AUT). A tissue-mimicking phantom in water and a rabbit aorta tissue sample in rabbit blood were scanned using AFT and AUT. Imaging with AFT offered improved contrast, over imaging with AUT, of the tissue-mimicking phantom and the rabbit aorta tissue sample by 23 dB and 8 dB, respectively. The results show that AFT has strong potential to provide morphological and pathological information of coronary arteries with high resolution and high contrast.

Conviction for ill-treatment may deter whistleblowing.

Proposals to prosecute nurses who wilfully neglect patients could discourage staff from raising concerns about poor care, nurse leaders in Wales were warned.

Frequency-wavenumber processing for infrasound distributed arrays.

The work described herein discusses the application of a frequency-wavenumber signal processing technique to signals from rectangular infrasound arrays for detection and estimation of the direction of travel of infrasound. Arrays of 100 sensors were arranged in square configurations with sensor spacing of 2 m. Wind noise data were collected at one site. Synthetic infrasound signals were superposed on top of the wind noise to determine the accuracy and sensitivity of the technique with respect to signal-to-noise ratio. The technique was then applied to an impulsive event recorded at a different site. Preliminary results demonstrated the feasibility of this approach.

A Meta-Analysis of Soccer Injuries on Artificial Turf and Natural Grass.

The goal of this investigation was to determine if playing or training on third-generation artificial turf (AT) surfaces increases the incidence rate of injuries compared to natural grass (NG) surfaces. This was accomplished by a meta-analysis performed on previously published research. Eight studies met the criteria of competitive soccer players, participation on both surfaces, and presentation of both exposure time and injury occurrence. Exposure time and injury incidence values were used to generate injury rate ratios (IRRs, AT/NG) for all injuries as well as specific injuries. Subgroup analyses were also performed by condition (match or training), gender, and age (youth or adult). The overall IRR was 0.86 (P < 0.05) suggesting a lower injury risk on AT than NG. However, there was considerable heterogeneity between studies. Analyses of individual injuries and subgroups found that in many cases IRR values were significantly less than 1.0. In no case was the IRR significantly greater than 1.0. Based on this, it appears that the risk of sustaining an injury on AT under some conditions might be lowered compared to NG. However, until more is known about how issues such as altered playing styles affect injury incidence, it is difficult to make firm conclusions regarding the influence of AT on player safety.

Crosstalk reduction for high-frequency linear-array ultrasound transducers using 1-3 piezocomposites with pseudo-random pillars.

The goal of this research was to develop a novel diced 1-3 piezocomposite geometry to reduce pulse-echo ring down and acoustic crosstalk between high-frequency ultrasonic array elements. Two PZT-5H-based 1-3 composites (10 and 15 MHz) of different pillar geometries [square (SQ), 45° triangle (TR), and pseudo-random (PR)] were fabricated and then made into single-element ultrasound transducers. The measured pulse-echo waveforms and their envelopes indicate that the PR composites had the shortest -20-dB pulse length and highest sensitivity among the composites evaluated. Using these composites, 15-MHz array subapertures with a 0.95λ pitch were fabricated to assess the acoustic crosstalk between array elements. The combined electrical and acoustical crosstalk between the nearest array elements of the PR array subapertures (-31.8 dB at 15 MHz) was 6.5 and 2.2 dB lower than those of the SQ and the TR array subapertures, respectively. These results demonstrate that the 1-3 piezocomposite with the pseudo-random pillars may be a better choice for fabricating enhanced high-frequency linear-array ultrasound transducers; especially when mechanical dicing is used.

A high-frequency linear ultrasonic array utilizing an interdigitally bonded 2-2 piezo-composite.

This paper describes the development of a high-frequency 256-element linear ultrasonic array utilizing an interdigitally bonded (IB) piezo-composite. Several IB composites were fabricated with different commercial and experimental piezoelectric ceramics and evaluated to determine a suitable formulation for use in high-frequency linear arrays. It was found that the fabricated fine-scale 2-2 IB composites outperformed 1-3 IB composites with identical pillar- and kerf-widths. This result was not expected and lead to the conclusion that dicing damage was likely the cause of the discrepancy. Ultimately, a 2-2 composite fabricated using a fine-grain piezoelectric ceramic was chosen for the array. The composite was manufactured using one IB operation in the azimuth direction to produce approximately 19-µm-wide pillars separated by 6-µm-wide kerfs. The array had a 50 µm (one wavelength in water) azimuth pitch, two matching layers, and 2 mm elevation length focused to 7.3 mm using a polymethylpentene (TPX) lens. The measured pulse-echo center frequency for a representative array element was 28 MHz and -6-dB bandwidth was 61%. The measured single-element transmit -6-dB directivity was estimated to be 50°. The measured insertion loss was 19 dB after compensating for the effects of attenuation and diffraction in the water bath. A fine-wire phantom was used to assess the lateral and axial resolution of the array when paired with a prototype system utilizing a 64-channel analog beamformer. The -6-dB lateral and axial resolutions were estimated to be 125 and 68 µm, respectively. An anechoic cyst phantom was also imaged to determine the minimum detectable spherical inclusion, and thus the 3-D resolution of the array and beamformer. The minimum anechoic cyst detected was approximately 300 µm in diameter.

A high-frequency annular-array transducer using an interdigital bonded 1-3 composite.

This paper reports the design, fabrication, and characterization of a 1-3 composite annular-array transducer. An interdigital bonded (IB) 1-3 composite was prepared using two IB operations on a fine-grain piezoelectric ceramic. The final composite had 19-µm-wide posts separated by 6-µm-wide polymer kerfs. A novel method to remove metal electrodes from polymer portions of the 1-3 composite was established to eliminate the need for patterning and aligning the electrode on the composite to the electrodes on a flexible circuit. Unloaded epoxy was used for both the matching and backing layers and a flexible circuit was used for interconnect. A prototype array was successfully fabricated and tested. The results were in reasonable agreement with those predicted by a circuit-analogous model. The average center frequency estimated from the measured pulse-echo responses of array elements was 33.5 MHz and the -6-dB fractional bandwidth was 57%. The average insertion loss recorded was 14.3 dB, and the maximum crosstalk between the nearest-neighbor elements was less than -37 dB. Images of a wire phantom and excised porcine eye were obtained to show the capabilities of the array for high-frequency ultrasound imaging.

Design and fabrication of PZN-7%PT single crystal high frequency angled needle ultrasound transducers.

A high-frequency angled needle ultrasound transducer with an aperture size of 0.4 x 0.56 mm2 was fabricated using a lead zinc niobate-lead titanate (PZN- 7%PT) single crystal as the active piezoelectric material. The single crystal was bonded to a conductive silver particle matching layer and a conductive epoxy backing material through direct contact curing. A parylene outer matching layer was formed by vapor deposition. Angled needle probe configuration was achieved by dicing at 45 degrees to the single crystal poling direction to satisfy a clinical request for blood flow measurement in the posterior portion of the eye. The electrical impedance magnitude and phase of the transducer were 42 Omega and -63 degrees , respectively. The measured center frequency and the fractional bandwidth at -6 dB were 43 MHz and 45%, respectively. The two-way insertion loss was approximately 17 dB. Wire phantom imaging using fabricated PZN-7%PT single crystal transducers was obtained and spatial resolutions were assessed.

Measurement of sarcoplasmic reticulum Ca2+ ATPase activity using high-performance liquid chromatography.

The goal of this investigation was to develop an assay whereby we could measure changes in ATP, ADP, and phosphocreatine (PCr) during stimulation of the sarcoplasmic reticulum (SR) Ca2+ ATPase. After stopping the enzyme reaction, compounds were extracted by perchloric acid and separated by reversed-phase high-performance liquid chromatography (HPLC). Absorbance of ATP and ADP was monitored at 260 nm, and detection of PCr was done at 205 nm. Chromatograms show that peaks associated with each compound are clearly separated and easily detected. The SR Ca2+ ATPase assay was run for various time periods and using varying free [Ca2+]. The changes in ATP and ADP contents were linear with increasing time and varied as expected with increasing free [Ca2+]. The ATPase activities determined using changes in ATP and ADP were nearly identical to those determined using previously established assays. When PCr was added to the assay, we were able to confirm that the Ca2+ ATPase uses ATP that is synthesized locally from PCr via creatine kinase (CK). The results indicate that this is a valid and reliable method for examining SR Ca2+ ATPase activity and for investigating its interaction with CK.

Functional overload attenuates plantaris atrophy in tumor-bearing rats.

BACKGROUND: Late stage cancer malignancies may result in severe skeletal muscle wasting, fatigue and reduced quality of life. Resistance training may attenuate these derangements in cancer patients, but how this hypertrophic response relates to normal muscle adaptations in healthy subjects is unknown. Here, we determined the effect of resistance training on muscle mass and myosin heavy chain (MHC) isoform composition in plantaris muscles from tumor-bearing (TB) rats. METHODS: Age- and gender-matched Buffalo rats were used for all studies (n = 6/group). Suspensions of Morris Hepatoma MH7777 cells or normal saline were injected subcutaneously into the dorsum. Six weeks after cell implantation, muscles from TB rats were harvested, weighed and processed for ATP-independent proteasome activity assays. Once tumor-induced atrophy had been established, subgroups of TB rats underwent unilateral, functional overload (FO). Healthy, sham-operated rats served as controls. After six weeks, the extent of plantaris hypertrophy was calculated and MHC isoform compositions were determined by gel electrophoresis. RESULTS: Six weeks of tumor growth reduced body mass and the relative masses of gastrocnemius, plantaris, tibialis anterior, extensor digitorum longus, and diaphragm muscles (p < or = 0.05). Percent reductions in body mass had a strong, negative correlation to final tumor size (r = -0.78). ATP-independent proteasome activity was increased in plantaris muscles from TB rats (p < or = 0.05). In healthy rats, functional overload (FO) increased plantaris mass ~44% compared to the contralateral control muscle, and increased the relative percentage of MHC type I and decreased the relative percentage of MHC type IIb compared to the sham-operated controls (p < or = 0.05). Importantly, plantaris mass was increased ~24% in TB-FO rats and adaptations to MHC isoform composition were consistent with normal, resistance-trained muscles. CONCLUSION: Despite significant skeletal muscle derangements due to cancer, muscle retains the capacity to respond normally to hypertrophic stimuli. Specifically, when challenged with functional overload, plantaris muscles from TB rats displayed greater relative mass, increased percentages of MHC type I and decreased percentages of MHC type IIb. Therefore, resistance training paradigms should provide relative morphological and functional benefits to cancer patients suffering from muscle wasting.

Development of a 35-MHz piezo-composite ultrasound array for medical imaging.

This paper discusses the development of a 64-element 35-MHz composite ultrasonic array. This array was designed primarily for ocular imaging applications, and features 2-2 composite elements mechanically diced out of a fine-grain high-density Navy Type VI ceramic. Array elements were spaced at a 50-micron pitch, interconnected via a custom flexible circuit and matched to the 50-ohm system electronics via a 75-ohm transmission line coaxial cable. Elevation focusing was achieved using a cylindrically shaped epoxy lens. One functional 64-element array was fabricated and tested. Bandwidths averaging 55%, 23-dB insertion loss, and crosstalk less than -24 dB were measured. An image of a tungsten wire target phantom was acquired using a synthetic aperture reconstruction algorithm. The results from this imaging test demonstrate resolution exceeding 50 microm axially and 100 microm laterally.

Modified Exeter technique in revision hip surgery: does distal fixation of the stem affect allograft transformation?

Promising results have made the Exeter technique a valuable alternative in hip replacement revision. However, even with this technique, subsidence remains a difficult problem because it may lead to additional revision if it is not mild and self-limited. We propose a technical modification that achieves primary stability by cementing the distal portion of the stem directly to the host bone. We conducted a prospective study on 45 hips. After an average of 46 (range, 18-72) months of follow-up monitoring, no hips required or underwent revision for aseptic loosening of the prosthesis. Four stems subsided <5 mm. In each case, distal cementation was only fair, so implant strength was decreased. Allograft transformation occurred in 36 hips and was associated with host bone remodeling in 11. This technical modification appears to be reliable, as satisfactory distal cementation was achieved in 41 hips (91%), and the modification did not interfere with allograft transformation.

Is postexercise hypotension related to excess postexercise oxygen consumption through changes in leg blood flow?

After a single bout of aerobic exercise, oxygen consumption remains elevated above preexercise levels [excess postexercise oxygen consumption (EPOC)]. Similarly, skeletal muscle blood flow remains elevated for an extended period of time. This results in a postexercise hypotension. The purpose of this study was to explore the possibility of a causal link between EPOC, postexercise hypotension, and postexercise elevations in skeletal muscle blood flow by comparing the magnitude and duration of these postexercise phenomena. Sixteen healthy, normotensive, moderately active subjects (7 men and 9 woman, age 20-31 yr) were studied before and through 135 min after a 60-min bout of upright cycling at 60% of peak oxygen consumption. Resting and recovery VO2 were measured with a custom-built dilution hood and mass spectrometer-based metabolic system. Mean arterial pressure was measured via an automated blood pressure cuff, and femoral blood flow was measured using ultrasound. During the first hour postexercise, VO2 was increased by 11 +/- 2%, leg blood flow was increased by 51 +/- 18%, leg vascular conductance was increased by 56 +/- 19%, and mean arterial pressure was decreased by 2.2 +/- 1.0 mmHg (all P <0.05 vs. preexercise). At the end of the protocol, VO2 remained elevated by 4 +/- 2% (P <0.05), whereas leg blood flow, leg vascular conductance, and mean arterial pressure returned to preexercise levels (all P >0.7 vs. preexercise). Taken together, these data demonstrate that EPOC and the elevations in skeletal muscle blood flow underlying postexercise hypotension do not share a common time course. This suggests that there is no causal link between these two postexercise phenomena.

Regional hemodynamics during postexercise hypotension. I. Splanchnic and renal circulations.

Moderate exercise elicits a relative postexercise hypotension that is caused by an increase in systemic vascular conductance. Previous studies have shown that skeletal muscle vascular conductance is increased postexercise. It is unclear whether these hemodynamic changes are limited to skeletal muscle vascular beds. The aim of this study was to determine whether the splanchnic and/or renal vascular beds also contribute to the rise in systemic vascular conductance during postexercise hypotension. A companion study aims to determine whether the cutaneous vascular bed is involved in postexercise hypotension (Wilkins BW, Minson CT, and Halliwill JR. J Appl Physiol 97: 2071-2076, 2004). Heart rate, arterial pressure, cardiac output, leg blood flow, splanchnic blood flow, and renal blood flow were measured in 13 men and 3 women before and through 120 min after a 60-min bout of exercise at 60% of peak oxygen uptake. Vascular conductances of leg, splanchnic, and renal vascular beds were calculated. One hour postexercise, mean arterial pressure was reduced (79.1 +/- 1.7 vs. 83.4 +/- 1.8 mmHg; P < 0.05), systemic vascular conductance was increased by approximately 10%, leg vascular conductance was increased by approximately 65%, whereas splanchnic (16.0 +/- 1.8 vs. 18.5 +/- 2.4 ml.min(-1).mmHg(-1); P = 0.13) and renal (20.4 +/- 3.3 vs. 17.6 +/- 2.6 ml.min(-1).mmHg(-1); P = 0.14) vascular conductances were unchanged compared with preexercise. This suggests there is neither vasoconstriction nor vasodilation in the splanchnic and renal vasculature during postexercise hypotension. Thus the splanchnic and renal vascular beds neither directly contribute to nor attenuate postexercise hypotension.

Skeletal muscle sarcoplasmic reticulum glycogen status influences Ca2+ uptake supported by endogenously synthesized ATP.

The purpose of this investigation was to determine whether there is a link between sarcoplasmic reticulum (SR) glycogen status and SR Ca2+ handling. In this investigation, skeletal muscle SR was purified from female Sprague-Dawley rats (200-250 g). Glycogen was extracted from the SR purified from one hindlimb, whereas the SR purified from the contralateral limb served as control. Before removal of the tissue, the animals were anesthetized with an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (10 mg/kg). Both alpha-amylase treatment (AM) and removal of EDTA from the homogenization and storage buffers reduced the amount of glycogen associated with the SR (P < 0.05). AM treatment reduced the glycogen phosphorylase content of SR (P < 0.05). In contrast, creatine kinase (CK) and pyruvate kinase (PK) contents were increased after both glycogen extraction protocols (P < 0.05). Under exogenous ATP conditions, both AM and EDTA-free (EF) treatments resulted in an increase in Ca2+-stimulated ATPase activity when normalized to sarco(endo)plasmic reticulum calcium-ATPase (SERCA) content (P < 0.05). CK and PK-supported SR Ca2+ uptake was decreased (P < 0.05) in the AM group when normalized to SERCA and CK or SERCA and PK content, respectively. AM was more effective than the EF for extracting glycogen associated with purified SR. Glycogen extraction alters the yield of purified SR proteins and must be taken into account when investigating SR calcium handling. Removal of glycogen from purified SR causes a change in Ca2+-handling properties as measured by ATPase and uptake activities.