Combined ARFI and Shear Wave Imaging of Prostate Cancer: Optimizing Beam Sequences and Parameter Reconstruction Approaches.

This study demonstrates the implementation of a shear wave reconstruction algorithm that enables concurrent acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) of prostate cancer and zonal anatomy. The combined ARFI/SWEI sequence uses closely spaced push beams across the lateral field of view and simultaneously tracks both on-axis (within the region of excitation) and off-axis (laterally offset from the excitation) after each push beam. Using a large number of push beams across the lateral field of view enables the collection of higher signal-to-noise ratio (SNR) shear wave data to reconstruct the SWEI volume than is typically acquired. The shear wave arrival times were determined with cross-correlation of shear wave velocity signals in two dimensions after 3-D directional filtering to remove reflection artifacts. To combine data from serially interrogated lateral push locations, arrival times from different pushes were aligned by estimating the shear wave propagation time between push locations. Shear wave data acquired in an elasticity lesion phantom and reconstructed using this algorithm demonstrate benefits to contrast-to-noise ratio (CNR) with increased push beam density and 3-D directional filtering. Increasing the push beam spacing from 0.3 to 11.6 mm (typical for commercial SWEI systems) resulted in a 53% decrease in CNR. In human in vivo data, this imaging approach enabled high CNR (1.61-1.86) imaging of histologically-confirmed prostate cancer. The in vivo images had improved spatial resolution and CNR and fewer reflection artifacts as a result of the high push beam density, the high shear wave SNR, the use of multidimensional directional filtering, and the combination of shear wave data from different push beams.

Prostate Cancer Detection Using 3-D Shear Wave Elasticity Imaging.

Transrectal ultrasound (TRUS) B-mode imaging provides insufficient sensitivity and specificity for prostate cancer (PCa) targeting when used for biopsy guidance. Shear wave elasticity imaging (SWEI) is an elasticity imaging technique that has been commercially implemented and is sensitive and specific for PCa. We have developed a SWEI system capable of 3-D data acquisition using a dense acoustic radiation force (ARF) push approach that leads to enhanced shear wave signal-to-noise ratio compared with that of the commercially available SWEI systems and facilitates screening of the entire gland before biopsy. Additionally, we imaged and assessed 36 patients undergoing radical prostatectomy using 3-D SWEI and determined a shear wave speed threshold separating PCa from healthy prostate tissue with sensitivities and specificities akin to those for multiparametric magnetic resonance imaging fusion biopsy. The approach measured the mean shear wave speed in each prostate region to be 4.8 m/s (Young's modulus E = 69.1 kPa) in the peripheral zone, 5.3 m/s (E = 84.3 kPa) in the central gland and 6.0 m/s (E = 108.0 kPa) for PCa with statistically significant (p < 0.0001) differences among all regions. Three-dimensional SWEI receiver operating characteristic analyses identified a threshold of 5.6 m/s (E = 94.1 kPa) to separate PCa from healthy tissue with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of 81%, 82%, 69%, 89% and 0.84, respectively. Additionally, a shear wave speed ratio was assessed to normalize for tissue compression and patient variability, which yielded a threshold of 1.11 to separate PCa from healthy prostate tissue and was accompanied by a substantial increase in specificity, PPV and AUC, where the sensitivity, specificity, PPV, NPV and AUC were 75%, 90%, 79%, 88% and 0.90, respectively. This work illustrates the feasibility of using 3-D SWEI data to detect and localize PCa and demonstrates the benefits of normalizing for applied compression during data acquisition for use in biopsy targeting studies.

Deep Convolutional Neural Networks for Displacement Estimation in ARFI Imaging.

Ultrasound elasticity imaging in soft tissue with acoustic radiation force requires the estimation of displacements, typically on the order of several microns, from serially acquired raw data A-lines. In this work, we implement a fully convolutional neural network (CNN) for ultrasound displacement estimation. We present a novel method for generating ultrasound training data, in which synthetic 3-D displacement volumes with a combination of randomly seeded ellipsoids are created and used to displace scatterers, from which simulated ultrasonic imaging is performed using Field II. Network performance was tested on these virtual displacement volumes, as well as an experimental ARFI phantom data set and a human in vivo prostate ARFI data set. In the simulated data, the proposed neural network performed comparably to Loupas's algorithm, a conventional phase-based displacement estimation algorithm; the rms error was [Formula: see text] for the CNN and 0.73 [Formula: see text] for Loupas. Similarly, in the phantom data, the contrast-to-noise ratio (CNR) of a stiff inclusion was 2.27 for the CNN-estimated image and 2.21 for the Loupas-estimated image. Applying the trained network to in vivo data enabled the visualization of prostate cancer and prostate anatomy. The proposed training method provided 26 000 training cases, which allowed robust network training. The CNN had a computation time that was comparable to Loupas's algorithm; further refinements to the network architecture may provide an improvement in the computation time. We conclude that deep neural network-based displacement estimation from ultrasonic data is feasible, providing comparable performance with respect to both accuracy and speed compared to current standard time-delay estimation approaches.

Multiparametric Ultrasound for Targeting Prostate Cancer: Combining ARFI, SWEI, QUS and B-Mode.

Diagnosing prostate cancer through standard transrectal ultrasound (TRUS)-guided biopsy is challenging because of the sensitivity and specificity limitations of B-mode imaging. We used a linear support vector machine (SVM) to combine standard TRUS imaging data with acoustic radiation force impulse (ARFI) imaging data, shear wave elasticity imaging (SWEI) data and quantitative ultrasound (QUS) midband fit data to enhance lesion contrast into a synthesized multiparametric ultrasound volume. This SVM was trained and validated using a subset of 20 patients and tested on a second subset of 10 patients. Multiparametric US led to a statistically significant improvements in contrast, contrast-to-noise ratio (CNR) and generalized CNR (gCNR) when compared with standard TRUS B-mode and SWEI; in contrast and CNR when compared with MF; and in CNR when compared with ARFI. ARFI, MF and SWEI also outperformed TRUS B-mode in contrast, with MF outperforming B-mode in CNR and gCNR as well. ARFI, although only yielding statistically significant differences in contrast compared with TRUS B-mode, captured critical qualitative features for lesion identification. Multiparametric US enhanced lesion visibility metrics and is a promising technique for targeted TRUS-guided prostate biopsy in the future.

Field-only surface integral equations: scattering from a perfect electric conductor.

A field-only boundary integral formulation of electromagnetics is derived without the use of surface currents that appear in the Stratton-Chu formulation. For scattering by a perfect electrical conductor (PEC), the components of the electric field are obtained directly from surface integral equation solutions of three scalar Helmholtz equations for the field components. The divergence-free condition is enforced via a boundary condition on the normal component of the field and its normal derivative. Field values and their normal derivatives at the surface of the PEC are obtained directly from surface integral equations that do not contain divergent kernels. Consequently, high-order elements with fewer degrees of freedom can be used to represent surface features to a higher precision than the traditional planar elements. This theoretical framework is illustrated with numerical examples that provide further physical insight into the role of the surface curvature in scattering problems.

Field-only surface integral equations: scattering from a dielectric body.

An efficient field-only nonsingular surface integral method to solve Maxwell's equations for the components of the electric field on the surface of a dielectric scatterer is introduced. In this method, both the vector wave equation and the divergence-free constraint are satisfied inside and outside the scatterer. The divergence-free condition is replaced by an equivalent boundary condition that relates the normal derivatives of the electric field across the surface of the scatterer. Also, the continuity and jump conditions on the electric and magnetic fields are expressed in terms of the electric field across the surface of the scatterer. Together with these boundary conditions, the scalar Helmholtz equation for the components of the electric field inside and outside the scatterer is solved by a fully desingularized surface integral method. Compared with the most popular surface integral methods based on the Stratton-Chu formulation or the Poggio-Miller-Chew-Harrington-Wu-Tsai (PMCHWT) formulation, our method is conceptually simpler and numerically straightforward because there is no need to introduce intermediate quantities such as surface currents, and the use of complicated vector basis functions can be avoided altogether. Also, our method is not affected by numerical issues such as the zero-frequency catastrophe and does not contain integrals with (strong) singularities. To illustrate the robustness and versatility of our method, we show examples in the Rayleigh, Mie, and geometrical optics scattering regimes. Given the symmetry between the electric field and the magnetic field, our theoretical framework can also be used to solve for the magnetic field.

On the derivation of the Smoluchowski result of electrophoretic mobility.

One of the most enduring, broadly applicable and widely used theoretical results of electrokinetic theory is the Smoluchowski expression for the electrophoretic mobility. It is a limiting form that holds for any solid particle of arbitrary shape in an electrolyte of any composition provided the thickness of the electrical double layer is "infinitely" thin compared to the particle size and the particle has uniform surface potential. The familiar derivation of this result that is a simplified version of the original Smoluchowski analysis in 1903, considers the motion of the electrolyte adjacent to a planar surface. The theory is deceptively simple but as a result much of the interesting physics and characteristic hydrodynamic behavior around the particle have been obscured, leading to a significantly incorrect picture of the fluid velocity profile near the particle surface. This paper provides a derivation of this key theoretical result by starting from Smoluchowski's original 1903 analysis but brings out overlooked details of the hydrodynamic features near and far from the particle that have not been canvassed in detail. The objective is to draw together all the key physical features of the electrophoretic problem in the thin double layer regime to provide an accessible and complete exposition of this important result in colloid science.

Mobile-surface bubbles and droplets coalesce faster but bounce stronger.

Enhancing the hydrodynamic interfacial mobility of bubbles and droplets in multiphase systems is expected to reduce the characteristic coalescence times and thereby affect the stability of gas or liquid emulsions that are of wide industrial and biological importance. However, by comparing the controlled collision of bubbles or water droplets with mobile or immobile liquid interfaces, in a pure fluorocarbon liquid, we demonstrate that collisions involving mobile surfaces result in a significantly stronger series of rebounds before the rapid coalescence event. The stronger rebound is explained by the lower viscous dissipation during collisions involving mobile surfaces. We present direct numerical simulations to confirm that the observed rebound is enhanced with increased surface mobility. These observations require a reassessment of the role of surface mobility for controlling the dynamic stability of gas or liquid emulsion systems relevant to a wide range of processes, from microfluidics and pharmaceuticals to food and crude oil processing.

The unusual fluid dynamics of particle electrophoresis.

The classical problem of the electrophoretic motion of a spherical particle has been treated theoretically by Overbeek in his 1941 PhD thesis and almost 40 years later by O'Brien & White. Although both approaches used identical assumptions, the details are quite different. Overbeek solved for the pressure, velocity fields as well as the electrostatic potential, whereas O'Brien & White obtained the electrophoretic mobility without the need to consider the pressure and velocity explicitly. In this paper, we establish the equivalence of these two approaches that allow us to show that the tangential component of the fluid velocity has a maximum near the surface of the particle and outside the double layer, the velocity decays as 1/r3, where r is the distance from the sphere, instead of 1/r in normal Stokes flow. Associated with this behavior is that of an irrotational outer flow field. This is consistent with the fact that a sphere moving with a constant electrophoretic velocity experiences zero net force. A study of the forces on the particle also provides a physical explanation of the independence of the electrophoretic mobility on the electrostatic boundary conditions or dielectric permittivity of the particle. These results are important in situations where inter-particle interaction is considered, for instance, in electrokinetic deposition.

Right-Sided Versus Left-Sided Pneumonectomy After Induction Therapy for Non-Small Cell Lung Cancer.

BACKGROUND: A right-sided pneumonectomy after induction therapy for non-small cell lung cancer (NSCLC) has been shown to be associated with significant perioperative risk. We examined the effect of laterality on long-term survival after induction therapy and pneumonectomy using the National Cancer Data Base. METHODS: Perioperative and long-term outcomes of patients who underwent pneumonectomy after induction chemotherapy, with or without radiotherapy, from 2004 to 2014 in the National Cancer Data Base were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. RESULTS: During the study period, 1,465 patients (right, 693 [47.3%]; left, 772 [52.7%]) met inclusion criteria. Right-sided pneumonectomy was associated with significantly higher 30-day (8.2% [57 of 693] vs 4.2% [32 of 772], p < 0.01) and 90-day mortality (13.6% [94 of 693] vs 7.9% [61 of 772], p < 0.01), and right-sided pneumonectomy was a predictor of higher 90-day mortality (odds ratio, 2.23; p < 0.01). However, overall 5-year survival between right and left pneumonectomy was not significantly different in unadjusted (37.6% [95% confidence interval {CI}, 0.34 to 0.42] vs 35% [95% CI, 0.32 to 0.39], log-rank p = 0.94) or multivariable analysis (hazard ratio, 1.07; 95% CI, 0.92 to 1.25; p = 0.40). A propensity score-matched analysis of 810 patients found no significant differences in 5-year survival between the right-sided versus left-sided groups (34.7% [95% CI, 0.30 to 0.40] vs 34.1%, [95% CI, 0.29 to 0.39], log-rank p = 0.86). CONCLUSIONS: In this national analysis, right-sided pneumonectomy after induction therapy was associated with a significantly higher perioperative but not worse long-term mortality compared to a left-sided procedure.

Coalescence Dynamics of Mobile and Immobile Fluid Interfaces.

Coalescence dynamics between deformable bubbles and droplets can be dramatically affected by the mobility of the interfaces with fully tangentially mobile bubble-liquid or droplet-liquid interfaces expected to accelerate the coalescence by orders of magnitude. However, there is a lack of systematic experimental investigations that quantify this effect. By using high speed camera imaging we examine the free rise and coalescence of small air-bubbles (100 to 1300 µm in diameter) with a liquid interface. A perfluorocarbon liquid, PP11, is used as a model liquid to investigate coalescence dynamics between fully mobile and immobile deformable interfaces. The mobility of the bubble surface was determined by measuring the terminal rise velocity of small bubbles rising at Reynolds numbers, Re, less than 0.1 and the mobility of free PP11 surface by measuring the deceleration kinetics of the small bubble toward the interface. Induction or film drainage times of a bubble at the mobile PP11-air surface were found to be more than 2 orders of magnitude shorter compared to the case of bubble and an immobile PP11-water interface. A theoretical model is used to illustrate the effect of hydrodynamics and interfacial mobility on the induction time or film drainage time. The results of this study are expected to stimulate the development of a comprehensive theoretical model for coalescence dynamics between two fully or partially mobile fluid interfaces.

Long-term Survival After Surgery Compared With Concurrent Chemoradiation for Node-negative Small Cell Lung Cancer.

OBJECTIVE: To determine whether surgery with adjuvant chemotherapy offers a survival advantage over concurrent chemoradiation for patients with cT1-2N0M0 small cell lung cancer (SCLC). BACKGROUND: Although surgery with adjuvant chemotherapy is the recommended treatment for patients with cT1-2N0M0 SCLC per international guidelines, there have been no prospective or retrospective studies evaluating the impact of surgery versus optimal medical management for cT1-2N0M0 SCLC. METHODS: Outcomes of patients with cT1-2N0M0 SCLC who underwent surgery with adjuvant chemotherapy or concurrent chemoradiation in the National Cancer Data Base (2003-2011) were evaluated using Cox proportional hazards analyses and propensity-score-matched analyses. RESULTS: During the study period, 681 (30%) patients underwent surgery with adjuvant chemotherapy and 1620 (70%) underwent concurrent chemoradiation. After propensity-score matching, all 14 covariates were well balanced between the surgery (n = 501) and concurrent chemoradiation (n = 501) groups. Surgery was associated with a higher overall survival (OS) than concurrent chemoradiation (5-year OS 47.6% vs 29.8%, P < 0.01). To minimize selection bias due to comorbidities, we limited the propensity-matched analysis to 492 patients with no comorbidities; surgery remained associated with a higher OS than concurrent chemoradiation (5-year OS 49.2% vs 32.5%, P < 0.01). CONCLUSIONS: In a national analysis, surgery with adjuvant chemotherapy was used in the minority of patients for early stage SCLC. Surgery with adjuvant chemotherapy for node-negative SCLC was associated with improved long-term survival when compared to concurrent chemoradiation. These results suggest a significant underuse of surgery among patients with early stage SCLC and support an increased role of surgery in multimodality therapy for cT1-2N0M0 SCLC.

Field-only integral equation method for time domain scattering of electromagnetic pulses.

The scattering of electromagnetic pulses is described using a non-singular boundary integral method to solve directly for the field components in the frequency domain, and Fourier transform is then used to obtain the complete space-time behavior. This approach is stable for wavelengths both small and large relative to characteristic length scales. Amplitudes and phases of field values can be obtained accurately on or near material boundaries. Local field enhancement effects due to multiple scattering of interest to applications in microphotonics are demonstrated.

Self-determined shapes and velocities of giant near-zero drag gas cavities.

Minimizing the retarding force on a solid moving in liquid is the canonical problem in the quest for energy saving by friction and drag reduction. For an ideal object that cannot sustain any shear stress on its surface, theory predicts that drag force will fall to zero as its speed becomes large. However, experimental verification of this prediction has been challenging. We report the construction of a class of self-determined streamlined structures with this free-slip surface, made up of a teardrop-shaped giant gas cavity that completely encloses a metal sphere. This stable gas cavity is formed around the sphere as it plunges at a sufficiently high speed into the liquid in a deep tank, provided that the sphere is either heated initially to above the Leidenfrost temperature of the liquid or rendered superhydrophobic in water at room temperature. These sphere-in-cavity structures have residual drag coefficients that are typically less than [Formula: see text] those of solid objects of the same dimensions, which indicates that they experienced very small drag forces. The self-determined shapes of the gas cavities are shown to be consistent with the Bernoulli equation of potential flow applied on the cavity surface. The cavity fall velocity is not arbitrary but is uniquely predicted by the sphere density and cavity volume, so larger cavities have higher characteristic velocities.

Space-time domain solutions of the wave equation by a non-singular boundary integral method and Fourier transform.

The general space-time evolution of the scattering of an incident acoustic plane wave pulse by an arbitrary configuration of targets is treated by employing a recently developed non-singular boundary integral method to solve the Helmholtz equation in the frequency domain from which the space-time solution of the wave equation is obtained using the fast Fourier transform. The non-singular boundary integral solution can enforce the radiation boundary condition at infinity exactly and can account for multiple scattering effects at all spacings between scatterers without adverse effects on the numerical precision. More generally, the absence of singular kernels in the non-singular integral equation confers high numerical stability and precision for smaller numbers of degrees of freedom. The use of fast Fourier transform to obtain the time dependence is not constrained to discrete time steps and is particularly efficient for studying the response to different incident pulses by the same configuration of scatterers. The precision that can be attained using a smaller number of Fourier components is also quantified.

Surgery Versus Optimal Medical Management for N1 Small Cell Lung Cancer.

BACKGROUND: Adjuvant chemotherapy has been demonstrated to improve the outcomes of patients with N1 non-small cell lung cancer. It is unknown whether patients previously thought to have unresectable small cell lung cancer (SCLC) may have tumors amenable to surgery if adjuvant therapies can be given. This study was undertaken to evaluate whether surgery, in the setting of modern adjuvant therapies, can be beneficial for patients with N1-positive SCLC. METHODS: Patients with clinical T1-3 N1 M0 SCLC who underwent concurrent chemoradiation versus surgery and adjuvant therapy in the National Cancer Data Base from 2003 to 2011 were examined. Overall survival was assessed using Kaplan-Meier and Cox proportional hazards analysis and propensity score-matched analysis. RESULTS: Of 1,041 patients with cT1-3 N1 M0 SCLC who met inclusion criteria, 96 patients (9%) underwent surgery and adjuvant chemotherapy with or without radiation and 945 (91%) underwent concurrent chemoradiation alone. Multivariable Cox modeling demonstrated that surgery with adjuvant chemotherapy with or without radiation (hazard ratio 0.74, 95% confidence interval: 0.56 to 0.97) was associated with improved survival compared with concurrent chemoradiation. After propensity matching, surgery with adjuvant chemotherapy with or without radiation was associated with improved 5-year survival compared with concurrent chemoradiation (31.4% versus 26.3%). CONCLUSIONS: In an analysis of a national population-based cancer database, surgery followed by adjuvant chemotherapy with or without radiation for cT1-3 N1 SCLC had improved outcomes compared with concurrent chemoradiation. These results support the re-evaluation of the role of surgery in multimodality therapy for N1 SCLC in a clinical trial setting.

Leidenfrost Vapor Layers Reduce Drag without the Crisis in High Viscosity Liquids.

The drag coefficient C_{D} of a solid smooth sphere moving in a fluid is known to be only a function of the Reynolds number Re and diminishes rapidly at the drag crisis around Re∼3×10^{5}. A Leidenfrost vapor layer on a hot sphere surface can trigger the onset of the drag crisis at a lower Re. By using a range of high viscosity perfluorocarbon liquids, we show that the drag reduction effect can occur over a wide range of Re, from as low as ∼600 to 10^{5}. The Navier slip model with a viscosity dependent slip length can fit the observed drag reduction and wake shape.

A robust and accurate formulation of molecular and colloidal electrostatics.

This paper presents a re-formulation of the boundary integral method for the Debye-Hückel model of molecular and colloidal electrostatics that removes the mathematical singularities that have to date been accepted as an intrinsic part of the conventional boundary integral equation method. The essence of the present boundary regularized integral equation formulation consists of subtracting a known solution from the conventional boundary integral method in such a way as to cancel out the singularities associated with the Green's function. This approach better reflects the non-singular physical behavior of the systems on boundaries with the benefits of the following: (i) the surface integrals can be evaluated accurately using quadrature without any need to devise special numerical integration procedures, (ii) being able to use quadratic or spline function surface elements to represent the surface more accurately and the variation of the functions within each element is represented to a consistent level of precision by appropriate interpolation functions, (iii) being able to calculate electric fields, even at boundaries, accurately and directly from the potential without having to solve hypersingular integral equations and this imparts high precision in calculating the Maxwell stress tensor and consequently, intermolecular or colloidal forces, (iv) a reliable way to handle geometric configurations in which different parts of the boundary can be very close together without being affected by numerical instabilities, therefore potentials, fields, and forces between surfaces can be found accurately at surface separations down to near contact, and (v) having the simplicity of a formulation that does not require complex algorithms to handle singularities will result in significant savings in coding effort and in the reduction of opportunities for coding errors. These advantages are illustrated using examples drawn from molecular and colloidal electrostatics.