Comprehensive Comparison of Image Quality Aspects Between Conventional and Plane-Wave Imaging Methods on a Commercial Scanner.

Coherent plane-wave compound imaging (CPWCI) is used as alternative for conventional focused imaging (CFI) to increase frame rates linearly with the ratio number of imaging lines to steering angles. In this study, the image quality was compared between CPWCI and CFI, and the effect of steering angles (range and number) and beamforming strategies was evaluated in CPWCI. In automated breast volume scanners (ABVSs), which suffer from reduced volume rates, CPWCI might be an excellent candidate to replace CFI. Therefore, the image quality of CFI currently in ABVS and CPWCI was also compared in an in vivo breast lesion. Images were obtained by a Siemens Sequoia ultrasound system, and two transducers (14L5 and 10L4) in a CIRS multipurpose phantom (040GSE) and a breast lesion. Phantom results showed that contrast sensitivity and resolution, axial resolution, and generalized contrast-to-noise ratio (gCNR; imaging depths <45 mm) were similar for most imaging sequences. CNR (imaging depths ≥45 mm), penetration, and lateral resolution were significantly improved for CPWCI (15 angles) compared to CFI for both transducers. In CPWCI, certain combinations of steering angles and beamforming methods yielded improved gCNR (small angles and delay-and-sum) or lateral resolution (large angles and Lu's-fk). Image quality seemed similar between CPWCI and CFI (three angles incoherent compounded as in ABVS) by visual inspection of the in vivo breast lesion images.

Deep Bleeder Acoustic Coagulation (DBAC)-part II: in vivo testing of a research prototype system.

BACKGROUND: Deep Bleeder Acoustic Coagulation (DBAC) is an ultrasound image-guided high-intensity focused ultrasound (HIFU) method proposed to automatically detect and localize (D&L) and treat deep, bleeding, combat wounds in the limbs of soldiers. A prototype DBAC system consisting of an applicator and control unit was developed for testing on animals. To enhance control, and thus safety, of the ultimate human DBAC autonomous product system, a thermal coagulation strategy that minimized cavitation, boiling, and non-linear behaviors was used. MATERIAL AND METHODS: The in vivo DBAC applicator design had four therapy tiles (Tx) and two 3D (volume) imaging probes (Ix) and was configured to be compatible with a porcine limb bleeder model developed in this research. The DBAC applicator was evaluated under quantitative test conditions (e.g., bleeder depths, flow rates, treatment time limits, and dose exposure time limits) in an in vivo study (final exam) comprising 12 bleeder treatments in three swine. To quantify blood flow rates, the "bleeder" targets were intact arterial branches, i.e., the superficial femoral artery (SFA) and a deep femoral artery (DFA). D&L identified, characterized, and targeted bleeders. The therapy sequence selected Tx arrays and determined the acoustic power and Tx beam steering, focus, and scan patterns. The user interface commands consisted of two buttons: "Start D&L" and "Start Therapy." Targeting accuracy was assessed by necropsy and histologic exams and efficacy (vessel coagulative occlusion) by angiography and histology. RESULTS: The D&L process (Part I article, J Ther Ultrasound, 2015 (this issue)) executed fully in all cases in under 5 min and targeting evaluation showed 11 of 12 thermal lesions centered on the correct vessel subsection, with minimal damage to adjacent structures. The automated therapy sequence also executed properly, with select manual steps. Because the dose exposure time limit (t dose ≤ 30 s) was associated with nonefficacious treatment, 60-s dosing and dual-dosing was also pursued. Thrombogenic evidence (blood clotting) and collagen denaturation (vessel shrinkage) were found in necropsy and histologically in all targeted SFAs. Acute SFA reductions in blood flow (20-30 %) were achieved in one subject, and one partial and one complete vessel occlusion were confirmed angiographically. The complete occlusion case was achieved with a dual dose (90 s total exposure) with focal intensity ≈500 W/cm(2) (spatial average, temporal average). CONCLUSIONS: While not meeting all in vivo objectives, the overall performance of the DBAC applicator was positive. In particular, D&L automation workflow was verified during each of the tests, with processing times well under specified (10 min) limits, and all bleeder branches were detected and localized. Further, gross necropsy and tissue examination confirmed that the HIFU thermal lesions were coincident with the target vessel locations in over 90 % of the multi-array dosing treatments. The SFA/DFA bleeder models selected, and the protocols used, were the most suitable practical model options for the given DBAC anatomical and bleeder requirements. The animal models were imperfect in some challenging aspects, including requiring tissue-mimicking material (TMM) standoffs to achieve deep target depths, thereby introducing device-tissue motion, with resultant imaging artifacts. The model "bleeders" involved intact vessels, which are subject to less efficient heating and coagulation cascade behaviors than true puncture injuries.

Deep bleeder acoustic coagulation (DBAC)-Part I: development and in vitro testing of a research prototype cuff system.

BACKGROUND: Bleeding from limb injuries is a leading cause of death on the battlefield, with deep wounds being least accessible. High-intensity focused ultrasound (HIFU) has been shown capable of coagulation of bleeding (cautery). This paper describes the development and refereed in vitro evaluation of an ultrasound (US) research prototype deep bleeder acoustic coagulation (DBAC) cuff system for evaluating the potential of DBAC in the battlefield. The device had to meet quantitative performance metrics on automated operation, therapeutic heating, bleeder detection, targeting accuracy, operational time limits, and cuff weight over a range of limb sizes and bleeder depths. These metrics drove innovative approaches in image segmentation, bleeder detection, therapy transducers, beam targeting, and dose monitoring. A companion (Part II) paper discusses the in vivo performance testing of an animal-specific DBAC system. MATERIALS AND METHODS: The cuff system employed 3D US imaging probes ("Ix") for detection and localization (D&L) and targeting, with the bleeders being identified by automated spectral Doppler analysis of flow waveforms. Unique high-element-count therapeutic arrays ("Tx") were developed, with the final cuff prototype having 21 Tx's and 6 Ix's. Spatial registration of Ix's and Tx's was done with a combination of image-registration, acoustic time-of-flight measurement, and tracking of the cuff shape via a fiber optic sensor. Acoustic radiation force impulse (ARFI) imaging or thermal strain imaging (TSI) at low-power doses were used to track the HIFU foci in closed-loop targeting. Recurrent neural network (RNN) acoustic thermometry guided closed-loop dosing. The cuff was tested on three phantom "limb" sizes: diameters = 25, 15, and 7.5 cm, with bleeder depths from 3.75 to 12.5 cm. "Integrated Phantoms" (IntP) were used for assessing D&L, closed-loop targeting, and closed-loop dosing. IntPs had surrogate arteries and bleeders, with blood-mimicking fluids moved by a pulsatile pump, and thermocouples (TCs) on the bleeders. Acoustic dosing was developed and tested using "HIFU Phantoms" having precisely located TCs, with end-of-dose target ∆T = 33-58 °C, and skin temperature ∆T ≤ 20 °C, being required. RESULTS: Most DBAC cuff performance requirements were met, including cuff weight, power delivery, targeting accuracy, skin temperature limit, and autonomous operation. The automated D&L completed in 9 of 15 tests (65 %), detecting the smallest (0.6 mm) bleeders, but it had difficulty with the lowest flow (3 cm/sec) bleeders, and in localizing bleeders in the smallest (7.5 cm) phantoms. D&L did not complete within the 9-min limit (results ranged 10-21 min). Closed-loop targeting converged in 20 of 31 tests (71 %), and closed-loop dosing power shut-off at preset ∆Ts was operational. SUMMARY AND CONCLUSION: The main performance objectives of the prototype DBAC cuff were met, however the designs required a number of challenging new technology developments. The novel Tx arrays exhibited high power with significant beam steering and focusing flexibility, while their integrated electronics enabled the required compact, lightweight configurability and simplified driving controls and cable/connector architecture. The compounded 3D imaging, combined with sophisticated software algorithms, enabled automated D&L and initial targeting and closed-loop targeting feedback via TSI. The development of RNN acoustic thermometry made possible feedback-controlled dosing. The lightweight architecture required significant design and fabrication effort to meet mechanical functionalities. Although not all target specifications were met, future engineering solutions addressing these performance deficiencies are proposed. Lastly, the program required very complex limb test phantoms and, while very challenging to develop, they performed well.

Protective effects of (-)-epigallocatechin-3-gallate against TNF-α-induced lung inflammation via ROS-dependent ICAM-1 inhibition.

Oxidative stresses are considered to play an important role in the induction of cell adhesion molecules and proinflammatory cytokines implicated in inflammatory processes. Heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS)-3 exert several biological functions, including antiapoptotic and anti-inflammatory effects. Here, we report that HO-1 and SOCS-3 were induced in A549 cells and human pulmonary alveolar epithelial cells (HPAEpiCs) treated with (-)-epigallocatechin-3-gallate (EGCG). EGCG protected against tumor necrosis factor (TNF)-α-mediated lung inflammation by down-regulation of oxidative stress and intercellular adhesion molecule (ICAM)-1 expression in A549 cells or HPAEpiCs and the lungs of mice. EGCG inhibited TNF-α-induced ICAM-1 expression, THP-1 cells adherence, pulmonary hematoma and leukocyte (eosinophils and neutrophils) count in bronchoalveolar lavage fluid in mice. In addition, EGCG also attenuated TNF-α-induced oxidative stress, p47(phox) translocation, MAPKs activation, and STAT-3 and activating transcription factor (ATF)2 phosphorylation. EGCG also reduced the formation of a TNFR1/TRAF2/Rac1/p47(phox) complex. Moreover, in this study, the observed suppression of TNF-α-stimulated ICAM-1 expression and reactive oxygen species (ROS) generation by EGCG was abrogated by transfection with siRNA of SOCS-3 or HO-1. These results suggested that HO-1 or SOCS-3 functions as a suppressor of TNF-α signaling, not only by inhibiting adhesion molecules expression but also by diminishing intracellular ROS production and STAT-3 and ATF2 activation in A549 cells or HPAEpiCs and the lungs of mice.