Hierarchically Nanostructured Hybrid Platform for Tumor Delineation and Image‐Guided Surgery via NIR‐II Fluorescence and PET Bimodal Imaging

Bimodal imaging with fluorescence in the second near infrared window (NIR‐II) and positron emission tomography (PET) has important significance for tumor diagnosis and management because of complementary advantages. It remains challenging to develop NIR‐II/PET bimodal probes with high fluorescent brightness. Herein, bioinspired nanomaterials (melanin dot, mesoporous silica nanoparticle, and supported lipid bilayer), NIR‐II dye CH‐4T, and PET radionuclide ⁶⁴Cu are integrated into a hybrid NIR‐II/PET bimodal nanoprobe. The resultant nanoprobe exhibits attractive properties such as highly uniform tunable size, effective payload encapsulation, high stability, dispersibility, and biocompatibility. Interestingly, the incorporation of CH‐4T into the nanoparticle leads to 4.27‐fold fluorescence enhancement, resulting in brighter NIR‐II imaging for phantoms in vitro and in situ. Benefiting from the fluorescence enhancement, NIR‐II imaging with the nanoprobe is carried out to precisely delineate and resect tumors. Additionally, the nanoprobe is successfully applied in tumor PET imaging, showing the accumulation of the nanoprobe in a tumor with a clear contrast from 2 to 24 h postinjection. Overall, this hierarchically nanostructured platform is able to dramatically enhance fluorescent brightness of NIR‐II dye, detect tumors with NIR‐II/PET imaging, and guide intraoperative resection. The NIR‐II/PET bimodal nanoprobe has high potential for sensitive preoperative tumor diagnosis and precise intraoperative image‐guided surgery.     

SPECT reconstruction with sub‐sinogram acquisitions

Described herein are the advantages of using sub‐sinograms for single photon emission computed tomography image reconstruction. A sub‐sinogram is a sinogram acquired with an entire data acquisition protocol, but in a fraction of the total acquisition time. A total‐sinogram is the summation of all sub‐sinograms. Images can be reconstructed from the total‐sinogram or from sub‐sinograms and then be summed to produce the final image. For a linear reconstruction method such as the filtered backprojection algorithm, there is no advantage of using sub‐sinograms. However, for nonlinear methods such as the maximum likelihood (ML) expectation maximization algorithm, the use of sub‐sinograms can produce better results. The ML estimator is a random variable, and one ML reconstruction is one realization of the random variable. The ML solution is better obtained via the mean value of the random variable of the ML estimator. Sub‐sinograms can provide many realizations of the ML estimator. We show that the use of sub‐sinograms can produce better estimations for the ML solution than can the total‐sinogram and can also reduce the statistical noise within iteratively reconstructed images. © 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 247–252, 2011;     

A semiparametric technique for the multi‐response optimization problem

Multi‐response optimization (MRO) in response surface methodology is quite common in applications. Before the optimization phase, appropriate fitted models for each response are required. A common problem is model misspecification and occurs when any of the models built for the responses are misspecified resulting in an erroneous optimal solution. The model robust regression (MRR) technique, a semiparametric method, has been shown to be more robust to misspecification than either parametric or nonparametric methods. In this study, we propose the use of MRR to improve the quality of model estimation and adapt its fits of each response to the desirability function approach, one of the most popular MRO techniques. A case study and simulation studies are presented to illustrate the procedure and to compare the semiparametric method with the parametric and nonparametric methods. The results show that MRR performs much better than the other two methods in terms of model comparison criteria in most situations during the modeling stage. In addition, the simulated optimization results for MRR are more reliable during the optimization stage. Copyright © 2010 John Wiley & Sons, Ltd.     

Reassembly of 89Zr‐Labeled Cancer Cell Membranes into Multicompartment Membrane‐Derived Liposomes for PET‐Trackable Tumor‐Targeted Theranostics

Nanoengineering of cell membranes holds great potential to revolutionize tumor‐targeted theranostics, owing to their innate biocompatibility and ability to escape from the immune and reticuloendothelial systems. However, tailoring and integrating cell membranes with drug and imaging agents into one versatile nanoparticle are still challenging. Here, multicompartment membrane‐derived liposomes (MCLs) are developed by reassembling cancer cell membranes with Tween‐80, and are used to conjugate ⁸⁹Zr via deferoxamine chelator and load tetrakis(4‐carboxyphenyl) porphyrin for in vivo noninvasive quantitative tracing by positron emission tomography imaging and photodynamic therapy (PDT), respectively. Radiolabeled constructs, ⁸⁹Zr‐Df‐MCLs, demonstrate excellent radiochemical stability in vivo, target 4T1 tumors by the enhanced permeability and retention effect, and are retained long‐term for efficient and effective PDT while clearing gradually from the reticuloendothelial system via hepatobiliary excretion. Toxicity evaluation confirms that the MCLs do not impose acute or chronic toxicity in intravenously injected mice. Additionally, ⁸⁹Zr‐labeled MCLs can execute rapid and highly sensitive lymph node mapping, even for deep‐seated sentinel lymph nodes. The as‐developed cell membrane reassembling route to MCLs could be extended to other cell types, providing a versatile platform for disease theranostics by facilely and efficiently integrating various multifunctional agents.     

Analysis of mechanical properties and its associated fracture surfaces in dual‐phase austempered ductile iron

This work aims at evaluating the fracture surfaces of tensile samples taken from a new kind of ductile iron referred to as ‘dual‐phase Austempered Ductile Iron (ADI)’, a material composed of ausferrite (regular ADI microstructure) and free (or allotriomorphic) ferrite. The tensile fracture surface characteristics and tensile properties of eight dual‐phase ADI microstructures, containing different relative quantities of ferrite and ausferrite, were studied in an alloyed ductile cast iron. Additionally, samples with fully ferritic and fully ausferritic (ADI) matrices were produced to be used as reference. Ferritic–pearlitic ductile irons (DI) were evaluated as well. For dual‐phase ADI microstructures, when the amount of ausferrite increases, tensile strength, yield stress and hardness do so too. Interesting combinations of strength and elongation until failure were found. The mechanisms of fracture that characterise DI under static uniaxial loading at room temperature are nucleation, growth and coalescence of microvoids. The fracture surface of fully ferritic DI exhibited an irregular topography with dimples and large deformation of the nodular cavities, characteristic of ductile fracture. Microstructures with small percentages of ausferrite (less than 20%) yielded better mechanical properties in relation to fully ferritic matrices. These microstructures presented regions of quasi‐cleavage fracture around last‐to‐freeze zones, related to the presence of ausferrite in those areas. As the amount of ausferrite increased, a decrease in nodular cavities deformation and a flatter fracture surface topography were noticed, which were ascribed to a higher amount of quasi‐cleavage zones. By means of a special thermal cycle, microstructures with pearlitic matrices containing a continuous and well‐defined net of allotriomorphic ferrite, located at the grain boundaries of recrystallised austenite, were obtained. The results of the mechanical tests leading to these microstructures revealed a significant enhancement of mechanical properties with respect to completely pearlitic matrices. The topographies of the fracture surfaces revealed a flat aspect and slightly or undeformed nodular cavities, as a result of high amount of pearlite. Still isolated dimple patterns associated to ferritic regions were observed.     

Segmentation for brain magnetic resonance images using dual‐tree complex wavelet transform and spatial constrained self‐organizing tree map

In brain MR images, the noise and low‐contrast significantly deteriorate the segmentation results. In this paper, we introduce a novel application of dual‐tree complex wavelet transform (DT‐CWT), and propose an automatic unsupervised segmentation method integrating DT‐CWT with self‐organizing map for brain MR images. First, a multidimensional feature vector is constructed based on the intensity, low‐frequency subband of DT‐CWT, and spatial position information. Then, a spatial constrained self‐organizing tree map (SCSOTM) is presented as the segmentation system. It adaptively captures the complicated spatial layout of the individual tissues, and overcomes the problem of overlapping gray‐scale intensities for different tissues. SCSOTM applies a dual‐thresholding method for automatic growing of the tree map, which uses the information from the high‐frequency subbands of DT‐CWT. The proposed method is validated by extensive experiments using both simulated and real T1‐weighted MR images, and compared with the state‐of‐the‐art algorithms. © 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 208–214, 2014     

Fatigue performance of dual‐phase steels for automotive wheel application

Fatigue performance of ferrite–martensite (FM) and ferrite–bainite (FB) dual‐phase (DP) steels used in automotive wheels has been compared in terms of (i) high‐cycle fatigue performance and failure mechanisms and (b) low‐cycle fatigue performance (Δε_t/2 = 0.002 to 0.01) and associated deformation mechanisms. FBDP steel exhibits moderately better high‐cycle fatigue performance, owing to delay in microcrack initiation. In FBDP steel, microcracks initiate predominantly along ferrite grain boundaries, while that at FB interface is significantly delayed in comparison with FMDP steel, where few microcracks appear at FM interface even below the endurance limit. During low‐cycle fatigue, however, FMDP steel performs considerably better than FBDP steel till Δε_t/2 ≤ 0.005 attributed to initial cyclic hardening, followed by cyclically stable behaviour exhibited by FMDP steel. In sharp contrast, at all Δε_t/2 > 0.002, FBDP steel undergoes continuous cyclic softening. The latter may cause undesirable deformation of wheels in service.     

Adapting second‐order response surface designs to specific needs

Experimental design strategies most often involve an initial choice of a classic factorial or response surface design and adapt that design to meet restrictions or unique requirements of the system under study. One such experience is described here, in which the objective was to develop an efficient experimental design strategy that would facilitate building second‐order response models with excellent prediction capabilities. In development, careful consideration was paid to the desirable properties of response surface designs. Once developed, the proposed design was evaluated using Monte Carlo simulation to prove the concept, a pilot implementation of the design carried out to evaluate the accuracy of the response models, and a set of validation runs enacted to look for potential weaknesses in the approach. The purpose of the exercise was to develop a procedure to efficiently and effectively calibrate strain‐gauge balances to be used in wind tunnel testing. The current calibration testing procedure is based on a time‐intensive one‐factor‐at‐a‐time method. In this study, response surface methods were used to reduce the number of calibration runs required during the labor‐intensive heavy load calibration, to leverage the prediction capabilities of response surface designs, and to provide an estimate of uncertainty for the calibration models. Results of the three‐phased approach for design evaluation are presented. The new calibration process will require significantly fewer tests to achieve the same or improved levels of precision in balance calibration. Copyright © 2008 John Wiley & Sons, Ltd.     

Optimizing the design of a moderator-based neutron detector for a flat response curve in the 2–14 MeV energy range

The efficiency of a neutron detector with boron trifluoride proportional tubes embedded in a polyethylene moderator was simulated with a Monte Carlo program. A moderator structure where the detector had uniform sensitivity for neutrons from 2 to 14 MeV was determined by simulation. A counter was built based on the simulation results. The counter's efficiencies were calibrated with an Am–Be source and an accelerator that served as a D–D and D–T neutron source. Experimental neutron efficiencies of these sources are approximately uniform. The simulated model was validated by the consistent results between the calculated and experimental data.     

Toxic Reactive Oxygen Species Enhanced Synergistic Combination Therapy by Self‐Assembled Metal‐Phenolic Network Nanoparticles

Engineering functional nanomaterials with high therapeutic efficacy and minimum side effects has increasingly become a promising strategy for cancer treatment. Herein, a reactive oxygen species (ROS) enhanced combination chemotherapy platform is designed via a biocompatible metal‐polyphenol networks self‐assembly process by encapsulating doxorubicin (DOX) and platinum prodrugs in nanoparticles. Both DOX and platinum drugs can activate nicotinamide adenine dinucleotide phosphate oxidases, generating superoxide radicals (O₂^??). The superoxide dismutase‐like activity of polyphenols can catalyze H₂O₂ generation from O₂^??. Finally, the highly toxic HO^? free radicals are generated by a Fenton reaction. The ROS HO^? can synergize the chemotherapy by a cascade of bioreactions. Positron emission tomography imaging of ⁸⁹Zr‐labeled as‐prepared DOX@Pt prodrug Fe³⁺ nanoparticles (DPPF NPs) shows prolonged blood circulation and high tumor accumulation. Furthermore, the DPPF NPs can effectively inhibit tumor growth and reduce the side effects of anticancer drugs. This study establishes a novel ROS promoted synergistic nanomedicine platform for cancer therapy.     

Non‐linear random response of laminated composite shallow shells using finite element modal method

This paper investigates the large‐amplitude multi‐mode random response of thin shallow shells with rectangular planform at elevated temperatures using a finite element non‐linear modal formulation. A thin laminated composite shallow shell element and the system equations of motion are developed. The system equations in structural node degrees‐of‐freedom (DOF) are transformed into modal co‐ordinates, and the non‐linear stiffness matrices are transformed into non‐linear modal stiffness matrices. The number of modal equations is much smaller than the number of equations in structural node DOF. A numerical integration is employed to determine the random response. Thermal buckling deflections are obtained to explain the intermittent snap‐through phenomenon. The natural frequencies of the infinitesimal vibration about the thermally buckled equilibrium positions (BEPs) are studied, and it is found that there is great difference between the frequencies about the primary (positive) and the secondary (negative) BEPs. All three types of motion: (i) linear random vibration about the primary BEP, (ii) intermittent snap‐through between the two BEPs, and (iii) non‐linear large‐amplitude random vibration over the two BEPs, can be predicted. Copyright © 2006 John Wiley & Sons, Ltd.     

Level‐cut inhomogeneous filtered Poisson field for two‐phase microstructures

Level‐cut homogeneous filtered Poisson fields developed in (J. Appl. Phys. 2003; 94 (6):3762–3770) to model two‐phase microstructures are defined, and their properties are briefly reviewed. Filtered Poisson fields are sums of randomly scaled and oriented kernels that are centered at the points of homogeneous Poisson fields. The cuts of these fields above specified thresholds are called level‐cut homogeneous filtered Poisson fields. It is shown that an arbitrary inhomogeneous Poisson field becomes homogeneous if observed in new coordinates, and that the mapping relating inhomogeneous and homogeneous Poisson fields can be constructed in a simple manner. This mapping and the model in (J. Appl. Phys. 2003; 94 (6): 3762–3770) provide an efficient algorithm for generating arbitrary inhomogeneous two‐phase microstructures. Developments in (Int. J. Numer. Meth. Engng 2008; DOI: 10.1002/nme.2340 ), using arguments essentially identical to those in (J. Appl. Phys. 2003; 94 (6):3762–3770) to define and generate inhomogeneous Poisson fields, overlook the natural extension of results in (J. Appl. Phys. 2003; 94 (6): 3762–3770) to these fields provided by the mapping constructed in this paper. Copyright © 2008 John Wiley & Sons, Ltd.     

Aggregation‐Induced Dual‐Phosphorescence from Organic Molecules for Nondoped Light‐Emitting Diodes

Aggregation‐induced emission (AIE) is a beneficial strategy for generating highly effective solid‐state molecular luminescence without suffering losses in quantum yield. However, the majority of reported AIE‐active molecules exhibit only strong fluorescence, which is not ideal for electrical excitation in organic light‐emitting diodes (OLEDs). By introducing various substituent groups onto the biscarbazole compound, a series of molecular materials with aggregation‐induced phosphorescence (AIP) is designed, which exhibits two distinctly different phosphorescence bands and an absolute solid‐state room‐temperature phosphorescence quantum yield up to 64%. Taking advantage of the AIE feature, the AIP molecules are fabricated into OLEDs as a homogeneous light‐emitting layer, which allows for relatively small efficiency roll‐off and shows an external electroluminescence quantum yield of up to 5.8%, more than the theoretical limit for purely fluorescent OLED devices. The design showcases a promising strategy for the production of cost‐effective and highly efficient OLED technology.     

Worst‐case design in head impact crashworthiness optimization

This paper describes the solution of a worst‐case design optimization problem of head impact in automotive design. The worst‐case design process uses an optimization algorithm that can locate saddlepoints: points in the design space where the objective function is maximized with respect to some design variables (worst case) while it is minimized with respect to other design variables simultaneously. The worst‐case design methodology is first tested using two analytic functions. Both functions contain saddlepoints, while the second one also has a random analytic noise component and an integer variable. Thereafter, the methodology is applied to the worst‐case design of a crashworthiness head impact problem. The head impact problem contains both numerical noise and an integer variable. For the first analytical case, the effect of separability of the maximization and minimization variables is investigated by rotating the design variable axes. For the second analytical case, analytical noise in the form of a modified Griewank function and an integer variable is added. For the head impact problem, cases are presented where maximization and minimization are first performed separately, and then in a combined fashion to locate the saddle point. The case studies illustrate the power of this approach in the automotive occupant safety design field. Copyright © 2003 John Wiley & Sons, Ltd.     

Impact of Glutathione Modulation on Stability and Pharmacokinetic Profile of Redox‐Sensitive Nanogels

Nanoparticles degradable upon external stimuli combine pharmacokinetic features of both small molecules as well as large nanoparticles. However, despite promising preclinical results, several redox responsive disulphide‐linked nanoparticles failed in clinical translation, mainly due to their unexpected in vivo behavior. Glutathione (GSH) is one of the most evaluated antioxidants responsible for disulfide degradation. Herein, the impact of GSH on the in vivo behavior of redox‐sensitive nanogels under physiological and modulated conditions is investigated. Labelling of nanogels with a DNA‐intercalating dye and a radioisotope allows visualization of the redox responsiveness at the cellular and the systemic levels, respectively. In vitro, efficient cleavage of disulphide bonds of nanogels is achieved by manipulation of intracellular GSH concentration. While in vivo, the redox‐sensitive nanogels undergo, to a certain extent, premature degradation in circulation leading to rapid renal elimination. This instability is modulated by transient inhibition of GSH synthesis with buthioninsulfoximin. Altered GSH concentration significantly changes the in vivo pharmacokinetics. Lower GSH results in higher elimination half‐life and altered biodistribution of the nanogels with a different metabolite profile. These data provide strong evidence that decreased nanogel degradation in blood circulation can limit the risk of premature drug release and enhance circulation half‐life of the nanogel.