Design of Point-of-Care Ultrasound Device to be Used in at-Home Setting - A Holistic Approach.

The primary purpose of this work was to design and implement a compact, battery-powered, fully wearable applicator for delivering therapeutic low-frequency (20-40kHz), low-intensity (100mW/cm2 ISPTP) (LFLI) ultrasound to enable treatment of chronic wounds in home setting. Such a device does not currently exist, and in addition to engineering aspects associated with electromechanical design, its implementation requires a novel approach involving consideration of feedback received not only from healthcare professionals, but also caregivers. One strong motivation for the novel design approach is to enable individuals with chronic wounds to enhance self-care management of wounds in the home setting instead of a hospital or outpatient clinic setting. In the home setting, the device may be exposed to physical maltreatment, requiring precautions with respect to its sturdiness. Although the holistic approach presented have been applied to the design of an applicator for chronic wounds, the design considerations and execution are transferable to any device targeted for home use. The implementation exemplified here examines transformation of an early, relatively fragile design into a robust, time-programmable, safe tool. The modification, which includes comprehensive reconfiguration and redesign of the electronics driving a piezoelectric transducer is presented along with methodology devised with the field feedback obtained from focus groups. This feedback evinced that in addition to electrical engineering, an extensive background in mechanical engineering, material science, biology, and clinical practice is needed to fabricate an end-user friendly, quality-of-life improving, ergonomic device.

A Miniature Ultrasound Source for Neural Modulation.

This work describes a unique ultrasound (US) exposure system designed to create very localized ( [Formula: see text]) sound fields at operating frequencies that are currently being used for preclinical US neuromodulation. This system can expose small clusters of neuronal tissue, such as cell cultures or intact brain structures in target animal models, opening up opportunities to examine possible mechanisms of action. We modified a dental descaler and drove it at a resonance frequency of 96 kHz, well above its nominal operating point of 28 kHz. A ceramic microtip from an ultrasonic wire bonder was attached to the end of the applicator, creating a 100- [Formula: see text] point source. The device was calibrated with a polyvinylidene difluoride (PVDF) membrane hydrophone, in a novel, air-backed, configuration. The experimental results were confirmed by simulation using a monopole model. The results show a consistent decaying sound field from the tip, well-suited to neural stimulation. The system was tested on an existing neurological model, Drosophila melanogaster, which has not previously been used for US neuromodulation experiments. The results show brain-directed US stimulation induces or suppresses motor actions, demonstrated through synchronized tracking of fly limb movements. These results provide the basis for ongoing and future studies of US interaction with neuronal tissue, both at the level of single neurons and intact organisms.

Hydrophone Measurements for Biomedical Ultrasound Applications: A Review.

This article presents basic principles of hydrophone measurements, including mechanisms of action for various hydrophone designs, sensitivity and directivity calibration procedures, practical considerations for performing measurements, signal processing methods to correct for both frequency-dependent sensitivity and spatial averaging across the hydrophone sensitive element, uncertainty in hydrophone measurements, special considerations for high-intensity therapeutic ultrasound, and advice for choosing an appropriate hydrophone for a particular measurement task. Recommendations are made for information to be included in hydrophone measurement reporting.

Characterization of Ultrasound Surgical Devices.

This article is a review of the techniques for characterizing ultrasound surgical devices, as a guide to those undertaking a program of measurement, and as a basis for further standardization of those methods. The review covers both acoustic and nonacoustic measurements, with an emphasis on proper techniques, devices, and analyses according to the IEC Standard 61847. Low-frequency hydrophone measurements are presented, which are centered on simple acoustic theory. Inertial cavitation measurements are described based on detailed analyses of shock wave propagation. Cutting force tests are also presented as a basis for determining relative performance characteristics and determining mechanisms of action. Example data from each type of test are given. Comparison between acoustic output measurements, in vitro data, and clinical outcomes help establish that inertial cavitation is the predominant mechanism of soft tissue erosion and emulsification. The test results also demonstrate approaches to improving efficiency while minimizing undesired effects. Finally, recommendations are made for updates to the 61847 Standard and for other device labeling that would improve patient safety.

Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy.

OBJECTIVE: Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing. METHODS: Neuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others. RESULTS: With respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS. SIGNIFICANCE: This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm2 may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits.

Combining Visible Light and Non-Focused Ultrasound Significantly Reduces Propionibacterium acnes Biofilm While Having Limited Effect on Host Cells.

Bacterial biofilms are highly resistant to antibiotics and have been implicated in the etiology of 60%-80% of chronic microbial infections. We tested a novel combination of low intensity ultrasound and blue light against biofilm and planktonic bacteria. A laboratory prototype was built which produced both energies uniformly and coincidently from a single treatment head, impinging upon a 4.45 cm2 target. To demonstrate proof of concept, Propionibacterium acnes biofilms were cultured on Millicell hanging inserts in 6-well plates. Hanging inserts with biofilms were treated in a custom exposure chamber designed to minimize unwanted ultrasound reflections. Coincident delivery of both energies demonstrated synergy over either alone, killing both stationary planktonic and biofilm cultures of P. acnes. Reduction in biofilm bacteria was dose dependent on exposure time (i.e., energy delivered). P. acnes biofilms were significantly reduced by dual energy treatment (p < 0.0001), with a >1 log10 reduction after a 5 min (9 J/cm2) and >3 log10 reduction after a 30 min (54 J/cm2) treatment (p < 0.05). Mammalian cells were found to be unaffected by the treatment. Both the light and the ultrasound energies are at levels previously cleared by the FDA. Therefore, this combination treatment could be used as a safe, efficacious method to treat biofilm related syndromes.

Design, Development, and Operation of a Low-Intensity Focused Ultrasound Pulsation (LIFUP) System for Clinical Use.

Noninvasive low-intensity focused ultrasound pulsation (LIFUP) neuromodulation provides a unique approach to both investigating and treating the brain. This work describes a well-calibrated, simple-to-use ultrasound stimulation system for neuromodulation studies. It provides a single-element 650-kHz transducer design and a straightforward control mechanism, with extensive calibration and internal electronic monitoring to prevent unwanted over or under treatment. One goal of this approach is to relieve researchers of many of the details associated with developing their own exposure equipment. A unique transducer positioning system and distinctive MRI fiducial targets simplify alignment and targeting. The system design, control software, calibration, and alignment techniques are described in detail. Examples of transducer targeting and neurostimulation using the system are provided.

Fundamentals of High-Resolution Ultrasound in Breast Implant Screening for Plastic Surgeons.

This article introduces the plastic surgeon to the basics of high-resolution ultrasound (HRUS) for screening breast implants. It describes how HRUS has become an accepted alternative to MRI for screening and diagnosis, and how plastic surgeons should use this new technology for the benefit of their patients and their practices. Basic principles, technology, and nomenclature are presented. Key steps to obtaining diagnostic images of breast implants are reviewed, including typical artifacts and sources of error. Imaging examples are presented. The article ends with a review and a step-by-step guide for plastic surgeons looking to use the technology.

Challenges and regulatory considerations in the acoustic measurement of high-frequency (>20 MHz) ultrasound.

This article examines the challenges associated with making acoustic output measurements at high ultrasound frequencies (>20 MHz) in the context of regulatory considerations contained in the US Food and Drug Administration industry guidance document for diagnostic ultrasound devices. Error sources in the acoustic measurement, including hydrophone calibration and spatial averaging, nonlinear distortion, and mechanical alignment, are evaluated, and the limitations of currently available acoustic measurement instruments are discussed. An uncertainty analysis of acoustic intensity and power measurements is presented, and an example uncertainty calculation is done on a hypothetical 30-MHz high-frequency ultrasound system. This analysis concludes that the estimated measurement uncertainty of the acoustic intensity is +73%/-86%, and the uncertainty in the mechanical index is +37%/-43%. These values exceed the respective levels in the Food and Drug Administration guidance document of 30% and 15%, respectively, which are more representative of the measurement uncertainty associated with characterizing lower-frequency ultrasound systems. Recommendations made for minimizing the measurement uncertainty include implementing a mechanical positioning system that has sufficient repeatability and precision, reconstructing the time-pressure waveform via deconvolution using the hydrophone frequency response, and correcting for hydrophone spatial averaging.

Acute adipocyte viability after third-generation ultrasound-assisted liposuction.

BACKGROUND: Although clinical evidence of successful autologous fat transfer (AFT) using third-generation ultrasound-assisted liposuction (UAL) is readily available, no study has quantified adipocyte viability using standardized methods. OBJECTIVES: The authors assess acute adipocyte viability following fat aspiration as a first step in determining the overall efficacy of using third-generation UAL for AFT. METHODS: Lipoaspirate samples were collected from patients who underwent elective liposuction procedures at multiple surgery centers. Patients with a history of bleeding disorders, diabetes, human immunodeficiency virus, or lipoatrophy disorders were excluded. The UAL system (VASER; Sound Surgical Technologies, Inc, Louisville, Colorado) was set at 60% amplitude in pulsed mode with vacuum aspiration of 15 in Hg or less. Laboratory analysis included free lipid volume, viability via lipolysis and propidium iodide staining, and cytological analysis, including cell surface protein examination and hematoxylin and eosin staining. RESULTS: The lipolysis assay revealed metabolically active adipocytes with a mean (SD) correlative viability of 85.1% (11%). Direct measures of acute viability via propidium iodide staining resulted in a mean (SD) viability measure of 88.7% (3.5%). Both mean values are within the historical range reported from syringe and vacuum-assisted lipoaspiration. Aqueous and lipid contents were favorably reduced after washing and filtering (Puregraft system; Cytori Therapeutics, Inc, San Diego, California). Cellular phenotypes identified were primarily white blood cells or vascular endothelial and vascular associated cells. CONCLUSIONS: Adipose tissue acquired via third-generation UAL is viable at harvest and is potentially a suitable source for autologous fat grafts. These results confirm reported clinical successes utilizing third-generation ultrasound lipoaspirate for AFT.

CLOTBUST-hands free: initial safety testing of a novel operator-independent ultrasound device in stroke-free volunteers.

BACKGROUND AND PURPOSE: We aimed to evaluate safety and tolerability of a novel operator-independent ultrasound device among stroke-free volunteers. METHODS: A headframe containing 18 ultrasound transducers (each operating at 2 MHz, pulsed-wave) was used to expose both temporal windows and the suboccipital window. The transmission characteristics were set to emulate the acoustic characteristics of the exposure levels in the Combined Lysis of Thrombus in Brain Ischemia using Transcranial Ultrasound and Systemic tPA (CLOTBUST) trial and to never exceed Food and Drug Administration mandated diagnostic ultrasound exposure limits. Volunteers underwent 2 hours of insonation with transducer activation one at a time. Safety was captured using serial neurological examinations and pre- and postinsonation MRI for detection of the blood brain barrier permeability. RESULTS: A total of 15 volunteers (40% men; 49 ± 16 years; 27% black; all pre-exposure National Institutes of Health Stroke Scale scores 0) were enrolled. Five volunteers received pulsed-wave ultrasound via the best pair temporal transducers, 5 via sequential activation of the suboccipital transducers, and 5 via sequential activation of all bilateral temporal and suboccipital transducers. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure, and at 24 hours, and no abnormality of the blood brain barrier was found on any of the MRIs. CONCLUSIONS: Our novel device was well tolerated by stroke-free volunteers and did not cause any neurological dysfunction nor did it affect blood brain barrier integrity. The safety and efficacy of the device are now being tested in stroke patients receiving intravenous tissue-type plasminogen activator in phase II-III clinical trials.

Comparison of harvest and processing techniques for fat grafting and adipose stem cell isolation.

BACKGROUND: Variability in harvest and processing technique may impact the success of fat grafting. This study compared properties of fat grafts produced by differing methods and assessed volume retention of the grafted tissue in a nude mouse model. METHODS: In phase I, fat was harvested by either suction-assisted lipoaspiration or ultrasound-assisted lipoaspiration and then filtered using two different pore sizes. Graft material was analyzed for average parcel size; relative oil, fat, and aqueous fractions; and stromal vascular fraction yield. Filtrands and filtrates were injected into athymic nude mice. In phase II, lipoaspirate harvested by suction-assisted lipoaspiration only was processed by centrifugation, cotton gauze rolling, or filtration, and then studied in a similar manner. RESULTS: Fat harvested by ultrasound- and suction-assisted lipoaspiration had comparable stromal vascular fraction counts and graft retention in vivo. Ultrasound-assisted lipoaspiration released only slightly more oil than suction-assisted lipoaspiration; filtering with either 500- or 800-µm pore size effectively removed fluid and oil. Centrifugation, cotton-gauze rolling, and filtration also effectively removed fluid and oil. In vivo graft retention and stromal vascular fraction yield was highest with the cotton gauze method. Histologic analysis of all explants showed intact adipose tissue. CONCLUSIONS: Ultrasound- and suction-assisted lipoaspiration yielded similar retention of fat grafts in a xenograft model. Processing with cotton gauze rolling may be best suited for grafting cosmetically sensitive areas of the body in which optimal retention is critical and lower total graft volumes are needed. Filtration and centrifugation both effectively removed fluid fractions and resulted in comparable graft retention, and are more feasible when larger volumes are required.

Exploratory analysis of estimated acoustic peak rarefaction pressure, recanalization, and outcome in the transcranial ultrasound in clinical sonothrombolysis trial.

PURPOSE: Acoustic peak rarefaction pressure (APRP) is the main factor that influences ultrasound-enhanced thrombolysis. We sought to determine whether recanalization rate and functional outcomes in the Transcranial Ultrasound in Clinical SONothrombolysis (TUCSON) trial could be predicted by estimated in vivo APRP. METHODS: We developed an acoustic attenuation model to estimate the in vivo APRP at the arterial occlusion site in each subject of the TUCSON trial with CT scans eligible for measurements. Variables included temporal bone thickness, depth of arterial occlusion site, and average attenuation of skin and brain tissues. Recanalization was defined as partial or complete using the Thrombolysis in Brain Infarction flow grades. Functional independence was assessed at 3 months using the modified Rankin Scale score (mRS, 0-1). RESULTS: APRP was calculated in 20 acute ischemic stroke patients treated with sonothrombolysis (mean age, 64 ± 15 years, 65% men; median NIHSS score, 13; IQR, 6-17). The mean APRP was 30.2 ± 15.5 kPa (range, 8-68 kPa). Patients with persisting occlusion had nonsignificantly lower APRP than patients with partial or complete recanalization (25.2 ± 8.0 versus 32.3 ± 17.7 kPa; p = 0.228). Patients who were functionally independent at 3 months had nonsignificantly higher APRP than patients with worse outcome (35.1 ± 19.5 versus 25.9 ± 11.2 kPa; p = 0.217). CONCLUSIONS: Our exploratory analysis suggests a potentially important role of successful energy delivery to augment thrombolysis with 2-MHz ultrasound in acute ischemic stroke patients.

Prenatal exposure to ultrasound waves impacts neuronal migration in mice.

Neurons of the cerebral neocortex in mammals, including humans, are generated during fetal life in the proliferative zones and then migrate to their final destinations by following an inside-to-outside sequence. The present study examined the effect of ultrasound waves (USW) on neuronal position within the embryonic cerebral cortex in mice. We used a single BrdU injection to label neurons generated at embryonic day 16 and destined for the superficial cortical layers. Our analysis of over 335 animals reveals that, when exposed to USW for a total of 30 min or longer during the period of their migration, a small but statistically significant number of neurons fail to acquire their proper position and remain scattered within inappropriate cortical layers and/or in the subjacent white matter. The magnitude of dispersion of labeled neurons was variable but systematically increased with duration of exposure to USW. These results call for a further investigation in larger and slower-developing brains of non-human primates and continued scrutiny of unnecessarily long prenatal ultrasound exposure.

Ultrasonic-generated fluid velocity with Sovereign WhiteStar micropulse and continuous phacoemulsification.

PURPOSE: To evaluate and compare ultrasonic turbulence created by conventional and micropulse ultrasound technology. SETTING: Sonora Medical Systems, Longmont, Colorado, USA. METHODS: A high-resolution digital ultrasound probe imaged the zone around a phacoemulsification tip. Doppler analysis allowed determination of flow. The fluid velocity was measured at 4 levels of ultrasound power at a constant flow, comparing the ultrasonic conditions of continuous energy to WhiteStar micropulses. RESULTS: In addition to the normal baseline irrigation and aspiration, fluid movement was detected directly below the phaco tip, produced by a nonlinear effect known as acoustic streaming. Acoustic streaming increased with increased phacoemulsification power for both conditions. At each of the 4 levels of power, fluid velocity away from the tip was less with micropulse technology than with continuous phacoemulsification. CONCLUSIONS: The demonstrated decrease in acoustic streaming flow away from the phaco tip with Sovereign WhiteStar micropulse technology compared to conventional ultrasound provides an objective explanation for clinical observations of increased stability of nuclear fragments at the tip and less turbulence in the anterior chamber during phacoemulsification. This methodology can be used to examine and compare fluid flow and turbulence under a variety of clinically relevant conditions.