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Objectives: This study was designed to investigate whether focused ultrasound (FUS) treatment with a higher mechanical index (MI) can enhance the effects of combined chemotherapy more than with a lower MI, and to evaluate the feasibility of the chemotherapy combined with FUS at a higher MI as an alternative treatment protocol.Methods: Mice in the first study were divided into six groups: control, chemotherapy only (GEM), two groups treated with FUS only at two different MIs, and two groups treated with chemotherapy and FUS (GEM + FUS). Mice were treated with a single-session treatment; one session consisted of three weekly treatments and 1 week of follow-up monitoring. In the second study, mice were assigned to two groups (GEM, GEM + FUS) and treated with four treatment sessions.Results: In the single-session treatment, tumor growth was most effectively suppressed in GEM + FUS group with a higher MI. Tumor growth rate was significantly lower in GEM + FUS group than in GEM group for multiple-session treatment. Specifically, three of ten mice in GEM + FUS group showed complete remission.Conclusions: This study demonstrated that FUS at a higher MI can enhance chemotherapy outcomes more than at a lower MI and demonstrated the potential of FUS in combination with chemotherapy as a new cancer treatment protocol.Key Points: • Combined treatment of chemotherapy and focused ultrasound can effectively suppress tumor growth. • For the focused ultrasound treatment conditions used in this study, focused ultrasound with relatively higher mechanical index shows more enhanced therapeutic outcomes than with the lower mechanical index. • Combination therapy shows the possibility as a new cancer treatment protocol. [ABSTRACT FROM AUTHOR]

Pulmonary capillary hemorrhage (PCH) can be induced by diagnostic ultrasound-a potential safety issue. Anesthetized rats were intubated for intermittent positive-pressure ventilation (IPPV) with 0 end-expiratory pressure, +4 cm H2O end-expiratory pressure (PEEP) and -4 cm H2O end-expiratory pressure (NEEP). Rats were imaged at 7.6 MHz with a Philips HDI 5000 ultrasound machine. The output was low (mechanical index [MI] = 0.22) for aiming and then was raised for 5 min in 20 different exposure groups with n = 8. Peak rarefactional pressure amplitudes were measured in water and de-rated for chest attenuation. The PCH areas were measured on the lung surface. At 2.2 MPa, PCH was 9.3 ± 6.6 mm2 for IPPV, 1.6 ± 3.2 mm2 for PEEP (p <0.001) and 26.8 ± 6.4 mm2 for NEEP (p <0.001). Thresholds were 1.3 MPa for IPPV, 2.1 MPa for PEEP and 1.0 MPa for NEEP. The small ventilator pressures subtracted or added to trans-capillary stress generated by diagnostic ultrasound pulses, virtually eliminating PCH for PEEP but enhancing PCH for NEEP. [ABSTRACT FROM AUTHOR]

Owing to new regulations starting from 2025, all commercial canal boats have to comply to zero local emission standards in Amsterdam. It is therefore vital that a clear emission indicator is made available for vessels with a varying operational profile, such as canal boats. In this paper, it is argued that current indicators, such as the Energy Efficiency Design Index, are not suitable for these (passenger) vessels. This paper proposes environmental performance indicators that can quantify emissions, (non-dimensional) energy and fuel usage based on an operational profile set in the design phase. This profile includes part load operation and auxiliary consumers and it can compare new designed concepts with current baseline vessels based on the ‘benefit for society’ of different vessel types. In the proposed environmental performance indicators, several operational modes can be defined, in contrast with the currently proposed Energy Efficiency Design Index, which is a point index at 75% of installed power. To gauge not only local emissions but also global emissions, the environmental performance indicator methodology is used to determine a minimum efficiency from any power generation method. This minimum efficiency follows from a comparison between baseline vessels and concepts that are more energy efficient and emission friendly. The proposed environmental performance indicators were validated using measurements on typical propulsion configurations of canal boats in Amsterdam. Three full electric concepts were designed and compared with the measured baseline vessels. As full electric concepts do not have local emissions, the method of power generation must satisfy the requirement to have less global emissions than the mechanical baseline. Furthermore, an energy efficiency of at least 33% is calculated from a fossil-fuelled land-based power plant (including transport) to the boundary from quay to boat to be required for newly designed electric concepts to be more energy efficient than the mechanical baseline. [ABSTRACT FROM AUTHOR]

Objectives: Pulmonary diagnostic ultrasound (US) can induce pulmonary capillary hemorrhage (PCH) in mammals. This singular biological effect of diagnostic US imaging was discovered more than 25 years ago but remains poorly understood. Our objective here was to investigate rapid infusion of intravenous fluids as a possible stressor for capillaries, which might enhance pulmonary diagnostic US‐induced PCH. Methods: Rats were anesthetized with Telazol (Zoetis, Inc, Kalamazoo, MI), which yielded relatively low pulmonary diagnostic US‐induced PCH, or Telazol and xylazine, which yielded relatively high pulmonary diagnostic US‐induced PCH. Groups of rats were not infused or infused either with normal saline, 10% mannitol, or 5% albumin. Rats were scanned in a warmed water bath with B‐mode US for 5 minutes with a 7.6‐MHz linear array set to different mechanical index values to obtain exposure response information. Pulmonary capillary hemorrhage was observed as comet tail artifacts in the image and measured on the lung surface. Results: For Telazol anesthesia, all of the PCH results were very low, with no significant differences at the maximum output with an in situ peak rarefactional pressure amplitude of 2.1 MPa (on‐screen mechanical index, 0.9). The addition of xylazine to the Telazol anesthetic significantly enhanced the PCH (P < .001) without infusion and likewise for the mannitol and albumin infusion. Saline infusion eliminated this enhancement, with significantly reduced PCH for Telazol‐plus‐xylazine anesthesia (P < .001); however, both mannitol and albumin infusion resulted in significantly more PCH than saline infusion (P < .01). Conclusions: These results show PCH dependence on the specific intravenous infusion fluid and illustrate the complex importance of physiologic parameters for US‐induced PCH. [ABSTRACT FROM AUTHOR]

Objective This article aims to determine if the number of maternal ultrasound scans where the highest thermal (TI) or mechanical (MI) indices recorded during obstetrical ultrasound exceed 1.0 were associated with neonatal anthropometric measurements. Study Design A prospective cohort of 2,334 nonobese low-risk pregnant women from 12 U.S. clinical sites underwent a total of six ultrasound scans, for which the highest TI and MI values were recorded. Neonatal anthropometric measurements were obtained within 12 to 24 hours of delivery. Multiple linear regression models adjusted for maternal race/ ethnicity, body mass index, weight gain, and gestational age were used to examine associations between the number of maternal ultrasounds during gestation with a TI or MI exceeding 1.0 and the mean change in neonatal anthropometry. Results Ultrasounds with TI or MI >1.0 were not associated with birth weight, neonatal length, nor head, chest, and abdominal circumferences. TI >1.0 was negatively associated with neonatal mid-upper arm and mid-upper thigh circumferences. MI >1.0 was negatively associated with neonatal skinfold measurements of the anterior thigh and triceps, and neonatal circumferences of the mid-upper thigh and umbilicus. Conclusion Prenatal ultrasound examinations in which TI or MI intermittently exceeded 1.0 did not identify a pattern of alterations of birth size. [ABSTRACT FROM AUTHOR]

A recently proposed two-criterion model for cavitational bioeffects in tissue with microbubbles (MBs) was tested. The glomerular capillary hemorrhage bioeffect was observed in rat kidney for contrast agent MB suspensions with mean diameters of 1.6, 3.1 and 5.5 µm. A diagnostic ultrasound machine was used at 3.6 MHz and 5.5 MHz for intermittent scans at power settings 2 dB apart. Petechial hemorrhage counts scored on the surface of the kidneys, and glomeruli were scored in histology. Thresholds for the petechial hemorrhage measurements were the same for the large and medium MB suspensions but substantially higher for the small MBs. For the histology, the medium MBs gave a higher threshold than the large MBs at 5.5 MHz. The pressure amplitude thresholds are in approximate agreement with theory, and the optimum MB size counterintuitively increased for increasing ultrasound frequency, as predicted. The two-criterion model of MB-associated capillary hemorrhage is supported. [ABSTRACT FROM AUTHOR]

Harmonic imaging techniques have been applied in ultrasonic elasticity imaging to obtain higher-quality tissue motion tracking data. However, harmonic tracking can be signal-to-noise ratio and penetration depth limited during clinical imaging, resulting in decreased yield of successful shear wave speed measurements. A logical approach is to increase the source pressure, but the in situ pressures used in diagnostic ultrasound have been subject to a de facto upper limit based on the Food and Drug Administration guideline for the mechanical index (MI <1.9). A recent American Institute of Ultrasound in Medicine report concluded that an in situ MI up to 4.0 could be warranted without concern for increased risk of cavitation in non-fetal tissues without gas bodies if there were a concurrent clinical benefit. This work evaluates the impact of using an elevated MI in harmonic motion tracking for hepatic shear wave elasticity imaging. The studies indicate that high-MI harmonic tracking increased shear wave speed estimation yield by 27% at a focal depth of 5 cm, with larger yield increase in more difficult-to-image patients. High-MI tracking improved harmonic tracking data quality by increasing the signal-to-noise ratio and decreasing jitter in the tissue motion data. We conclude that there is clinical benefit to use of elevated acoustic output in shear wave tracking, particularly in difficult-to-image patients. [ABSTRACT FROM AUTHOR]

Microbubbles are considered a promising tool for noninvasive estimation of local blood pressure. It is reported that the subharmonic scattering amplitude of microbubbles decreases by 9 to 12 dB when immersed in the media under an ambient pressure variation from 0 to 180 mmHg. However, the pressure sensitivity still needs to be improved to satisfy clinical diagnostic requirements. Here, we investigated the effects of acoustic parameters on the pressure sensitivity of microbubbles through measuring the acoustic attenuation and scattering properties of commercially available SonoVue microbubbles. Our results showed that the first harmonic, subharmonic, and ultraharmonic amplitudes of microbubbles were reduced by 6.6 dB, 10.9 dB, and 9.3 dB at 0.225 mechanical index (MI), 4.6 dB, 19.8 dB, and 12.3 dB at 0.25 MI, and 18.5 dB, 17.6 dB, and 12.6 dB at 0.3 MI, respectively, when the ambient pressure increased from 0 to 180 mmHg. Our finding revealed that a moderate MI (0.25⁻0.4) exciting microbubbles could significantly improve their sensitivities to detect ambient pressure.

Considering the use of physical and mechanical stimulation, such as low-intensity ultrasound for proliferation and differentiation of stem cells, it is essential to understand the physical and acoustical mechanisms of acoustic waves in vitro. Mechanical index is used for quantifying acoustic cavitation and the relationship between acoustic pressure and the frequency. In this study, modeling of the mechanical index was applied to provide treatment protocol and to understand the effective physical processes on reproducibility of stem cells. Due to low intensity of ultrasound, Rayleigh integral model has been used for acoustic pressure computation. The acoustic pressure and mechanical index equations are modeled and solved to estimate optimal mechanical index for 28, 40, 150 kHz and 1 MHz frequencies. This model are solved in different intensities and distances from transducer in cylindrical coordinates. Based on the results of the mechanical index, regions with threshold mechanical index of 0.7 were identified for extracting of radiation arrangement to cell medium. Acoustic pressure distribution along the axial and radial was extracted. In order to validate the results of the modeling, the acoustic pressure in the water and near field depth was measured by a piston hydrophone. Results of modeling and experiments show that the model is consistent well to experimental results with 0.91 and 0.90 correlation of coefficient (p < 0.05) for 1 MHz and 40 kHz. Low-intensity ultrasound with 0.40 mechanical index is more effective on enhancing the proliferation rate of the spermatogonia stem cells during the seven days of culture. In contrast, higher mechanical index has a harmful effect on the spermatogonial stem cells. Thus, considering cavitation threshold of different materials is necessary to find effective mechanical index ranges on proliferation for the used frequencies. This acoustic propagation model and ultrasound mechanical index assessments can be used with acceptable accuracy, for the extraction special arrangement of acoustic exposure used in biological conditions in vitro. This model provides proper treatment planning in vitro and in vivo by estimating the cavitation phenomenon. [ABSTRACT FROM AUTHOR]

Ultrasound can lead to thermal and mechanical effects in interrogated tissues. We reviewed the literature to explore the evidence on ultrasound heating on fetal and neonatal neural tissue. The results of animal studies have suggested that ultrasound exposure of the fetal or neonatal brain may lead to a significant temperature elevation at the bone-brain interface above current recommended safety thresholds. Temperature increases between 4.3 and 5.6°C have been recorded. Such temperature elevations can potentially affect neuronal structure and function and may also affect behavioral and cognitive function, such as memory and learning. However, the majority of these studies were carried out more than 25 y ago using non-diagnostic equipment with power outputs much lower than those of modern machines. New studies to address the safety issues of cranial ultrasound are imperative to provide current clinical guidelines and safety recommendations. [ABSTRACT FROM AUTHOR]

Diagnostic ultrasound can induce pulmonary capillary hemorrhage (PCH) in rats and other mammals. This phenomenon represents the only clearly demonstrated biological effect of (non-contrast enhanced) diagnostic ultrasound and thus presents a uniquely important safety issue. However, the physical mechanism responsible for PCH remains uncertain more than 25 y after its discovery. Experimental research has indicated that neither heating nor acoustic cavitation, the predominant mechanisms for bioeffects of ultrasound, is responsible for PCH. Furthermore, proposed theoretical mechanisms based on gas-body activation, on alveolar resonance and on impulsive generation of liquid droplets all appear unlikely to be responsible for PCH, owing to unrealistic model assumptions. Here, a simple model based on the acoustical radiation surface pressure (ARSP) at a tissue-air interface is hypothesized as the mechanism for PCH. The ARSP model seems to explain some features of PCH, including the approximate frequency independence of PCH thresholds and the dependence of thresholds on biological factors. However, ARSP evaluated for experimental threshold conditions appear to be too weak to fully account for stress failure of pulmonary capillaries, gauging by known stresses for injurious physiologic conditions. Furthermore, consideration of bulk properties of lung tissue suggests substantial transmission of ultrasound through the pleura, with reduced ARSP and potential involvement of additional mechanisms within the pulmonary interior. Although these recent findings advance our knowledge, only a full understanding of PCH mechanisms will allow development of science-based safety assurance for pulmonary ultrasound. [ABSTRACT FROM AUTHOR]

Delivery of therapeutics to the intraocular space or to targeted tissues in the posterior segment is challenging because of the structural and dynamic barriers surrounding the eye. Previously, we reported the feasibility of using ultrasound (US) irradiation to deliver macromolecules to the posterior segment of the eye via the transscleral route, which consists of sclera as the outermost anatomic barrier. In this study, we found that although ultrasound increases scleral permeability for macromolecules, the scleral collagen arrangement remains undisturbed. In an ex vivo experiment, protein permeation across the sclera was significantly enhanced by ultrasound in the stable cavitation regime. The scleral collagen network was further examined by second harmonic generation imaging. Quantitative image analysis techniques were adopted to examine the density, anisotropy and interlacing pattern of collagen fibers before and after ultrasound irradiation. Repeated ultrasound applications did not induce significant changes in the arrangement of collagen fibrils at 40 kHz with a spatial average temporal average intensity (ISATA) <1.8 W/cm2. These parameters correspond to a mechanical index (MI) below 0.8 in our setting. These data suggested that enhanced permeation of macromolecules across the sclera was achieved without disturbing the collagen network of the sclera. This evidence supports that low-frequency, low-intensity ultrasound is a tolerable approach to transscleral drug delivery. [ABSTRACT FROM AUTHOR]