Microwave-induced thermoacoustic imaging with functional nanoparticles

As an emerging hybrid imaging modality,microwave-induced thermoacoustic imaging(MTAI),using microwaves as the excitation source and ultrasonic signals as the information carrier for combining the characteristics of high contrast of electromagnetic imaging and high resolution of ultrasound imaging,has shown broad prospects in biomedical and clinical applications.The imaging contrast depends on the microwave-absorption coe±cient of the endogenous imaged tissue and the injected MTAI contrast agents.With systemically introduced functional nanoparticles,MTAI contrast and sensitivity can be further improved,and enables visualization of biological processes in vivo.In recent years,functional nanoparticles for MTAI have been developed to improve the performance and application range of MTAI in biomedical applications.This paper reviews the recent progress of functional nanoparticles for MTAI and their biomedical applications.The challenges and future directions of microwave thermoacoustic imaging with functional nanoparticles in theeld of translational medicine are discussed.

Prospects of microwave-induced thermoacoustic imaging

Microwave-induced thermoacoustic imaging(MTAI)has advantages including the large imaging depth,high imaging resolution,high imaging contrast,and fast imaging speed.The thermoacoustic(TA)group of South China Normal University has dedicated to developing TA imaging for more than a decade and has made many breakthroughs.This review introduces these breakthroughs from two aspects including the improvement in techniques and the exploration of applications.On the technological level,there are ultrashort microwave pulse(USMP)-inducedTA imaging that can improve the imaging resolution,nonlinear thermoacoustic imaging(NTAI)that can improve the imaging contrast,polarized microwave-inducedthermoacoustic imaging(P-MTAI)that can obtain cellular-level alignment information,and more convenient and accurate handheld and multimodal probes.On the application side,the optimization and expansion have been carried out,mainly concentrating on breast and myocardial imaging.Finally,several current research directions are introduced,including the application of P-MTAI on joint imaging and research on whole-body imaging of small animals.

Quantitative tracing of bioprobes by simultaneously monitoring radiative and nonradiative relaxations

Bioprobe based on fluorescence is widely used in biological and medical research due to its high sensitivity and selectivity.Yet,its quantification in vivo is complicated and often compromised by the interaction between the fluorophore with the environmental factors,as well as the optical scattering and absorption by the tissue.A high florescence quantum yield and minimal interference by the environment are key requirements for designing an effective bioprobe,and the prerequisitions severely limit the available options.We propose that a comprehensive evaluation of potential bioprobe can be achieved by simultaneously measuring both radiative and nonradiative transitions,the two fundamental and complementary pathways for the energy de-excitation.This approach will not only improve the accuracy of the quantification by catching the information from a broader spectrum of the energy,but also provide additional information of the probe environment that often impacts the balance between the two forms of the energy transition.This work first analyzes the underlying mechanism of the hypothesis.The practical feasibility is then tested by means of simultaneous measurements of photoacoustic signal for the non-radiative and fluorescence for the radiative energy processes,respectively.It is demonstrated that the systematic evaluation of the probe energy de-excitation results in an improved quantitative tracing of a bioprobe in complex environment.

Traditional Chinese medicine of Salvia miltiorrhiza Bunge: a review of phytochemistry, pharmacology and pharmacokinetics

Salvia miltiorrhiza Bunge,known as red sage or Danshen,is commonly applied in Chinese herbal therapeutics for various biological effects.In 25-220 C.E.,the earliest Chinese Materia Medica referred to as Shengong’s Classic of Materia Medica(Eastern Han Dynasty of China,200 C.E.)initially documented Salvia miltiorrhiza Bunge.Currently,Salvia miltiorrhiza Bunge is one of the most frequently prescribed traditional Chinese medicines in clinics for antidiabetic,antianxiety,antihypertensive,antidepressant,antilipidemic,antiarrhythmic,and anticancer effects.Undoubtedly,it is best known for improving and promoting blood circulation;thus,its recommendation for use in cardiovascular disorders.Regarding this article,important information was sourced both manually and electronically using patent compendium and databases,including Google Scholar,herbal plant monographs,Hindawi,PubMed,Embase,CNKI,pharmacopoeias,Springer,etc.Well-concise details and discussions on the botany,traditional medicinal uses,chemical constituents-phytochemistry,pharmacokinetics,pharmacology,and toxicology information are presented.In perspective,understanding the comprehensive information of the above-stated fields with regards to Salvia miltiorrhiza Bunge would yield an additional positive knowledge on areas that need urgent attention and identify gaps in research and safety for future consideration.

Indocyanine green loaded graphene oxide for high-e±cient photoacoustic tumor therapy

Photoacoustic therapy,using the photoacoustic efect of agents for selectively kling tumor cells,has shown pronising for treat ing tumor.Utilization of high optical absorption probes can help to effectively improve the photoacoustic ther apy efficiency.Herein,we report a novel high-absorpt:ion photoacoustic probe that is composed of indocyanine green(ICG)and gr aphene oxide(GO),entitled GO-ICG,for photoacoustic ther apy.The attached ICG with narrow absorption spectral profile has strong optical absorption in the infrared region.The absorption spectrum of the GO-ICG solution reveals that the GO-ICG particles exhibited a 10-fold higher absorbance at 780 nm(its peak absorbance)as compared with GO.Importantly,ICG's fluorescence is quenched by GO via fuorescence resonance energy transfer.As a result,GO-ICG can high efficiently convert the absorbed light energy to acoustic wave under pulsed laser irradiation.We further demonstrate that GO-ICG can produce stronger photoacoustic wave than the GO and ICG alone.Moreover,we conjugate this contrast agent with integrin 0。As mono dlonal antibody to molecularly target the U87-MG human glioblastoma cells for selective tumor cell killing.Finally,our results testify that the photoacoustic therapy eficiency of GO-ICG is higher than the existing photoacoustic therapy agent.Our work demonstrates that GO-ICG is a high efficiency photo-acoustic therapy agent.This novel photoacoustic probe is likely to be an available candidate for tumor therapy.

Photoacoustic molecular imaging with functional nanoparticles

Photoacoustic imaging(PAI)breaks through the optical di®usion limit by making use of the PA e®ect.By converting incident photons into ultrasonic waves,PAI combines high contrast of optical imaging and high spatial resolution in depth tissue of ultrasound imaging in a single imaging modality.This imaging modality has now shown potential for molecular imaging,which enables visualization of biological processes with systemically introduced functional nanoparticles.In the current review,the potentials of di®erent optical nanoprobes as PAI contrast agents were elucidated and discussed.

Bounds for Average toward the Resonance Barrier for GL(3)×GL(2)Automorphic Forms

Let f be a fixed Maass form for SL_3(Z)with Fourier coefficients A_(f)(m,n).Let g be a Maass cusp form for SL_2(G)with Laplace eigenvalue(1/4)+k^(2) and Fourier coefficientλ_(g)(n),or a holomorphic cusp form of even weight k.Denote by S_(X)(f×g,α,β)a smoothly weighted sum of A_(f)(1,n)λ_(g)(n)e(αn~β)for X 0 are fixed real numbers.The subject matter of the present paper is to prove non-trivial bounds for a sum of S_(X)(f×g,α,β)over g as k tends to∞with X.These bounds for average provide insight for the corresponding resonance barriers toward the Hypothesis S as proposed by Iwaniec,Luo,and Sarnak.

Epidemiological characteristics of thyroid nodules and risk factors for malignant nodules： a retrospective study from 6 304 surgical cases

Background The prevalence of thyroid nodules （TN） is increasing rapidly.This study analyzed the epidemiological and clinical characteristics of TN in surgically treated patients and identified the risk factors for malignant nodules （MN） to provide more understanding of the differential diagnosis of TN.Methods A total of 6 304 TN cases who underwent thyroid surgery were included in this retrospective study.The clinical data were collected to evaluate the clinical and epidemiological characteristics and related risk factors for MN.The nature of TN （benign nodules （BN） or MN）,medical records,laboratory data,and imaging data were analyzed.The risk factors for MN were screened using Spearman＇s rank correlation analysis and nonconditional binary Logistic regression analysis.Results The number of surgically treated TN cases increased yearly.A total of 34.33％ of cases were MN and 65.67％ were BN.Up to 56.74％ of these cases underwent unnecessary surgery.Among the MN cases,papillary thyroid carcinoma accounted for 94％,in which 46.71％ coexisted with benign thyroid disease and 32.28％ with multiple foci.Single-related factor analysis showed that age,employment,disease duration,history of breast nodules and/or hypertension,the levels of serum thyroid-stimulating hormone （TSH）,thyroglobulin antibody （TgAb）,and thyroid peroxidase antibody （TPoAb）,and ultrasound features of TN were related to MN.Stepwise nonconditional binary Logistic regression analysis showed that 13 factors may be the independent risk factors for MN,including ＜40 years old,previous history of breast nodules and/or hypertension,disease duration ＜1 month,employment,hypoechoic nodule,irregular nodules,nodule calcification,solid echo nodule,fuzzy boundary,rich blood flow within nodules,abnormal lymph nodes around the neck,nodule diameter ＜1 cm,and abnormally high TgAb.Conclusions Our results demonstrate a rapid increase in surgically treated TN cases and ratio of MN and indicate unnecessary surgeries in some cases.This study also suggest that age,duration of thyroid disease,history of breast disease and/or hypertension,the levels of serum TSH,TgAb,and TPoAb,and ultrasound features of TN are related to MN,and some of these factors may be the risk factors for MN.

Thermally confined shell coating amplifies the photoacoustic conversion efficiency of nanoprobes

Efficient probes/contrast agents are highly desirable for good-performance photoacoustic （PA） imaging, where the PA signal amplitude of a probe is dominated by both its optical absorption and the conversion efficiency from absorbed laser energy to acoustic waves. Nanoprobes have a unique micro- mechanism of PA energy conversion due to the size effect, which, however, has not been quantitatively demonstrated and effectively utilized. Here, we present quantitative simulations of the PA signal production process for plasmon- mediated nanoprobes based on the finite element analysis method, which were performed to provide a deep understanding of their PA conversion micromechanism. Moreover, we propose a method to amplify the PA conversion efficiency of nanoprobes through the use of thermally confined shell coating, which allows the active control of the conversion efficiency beyond that of conventional probes. Additionally, we deduced the dependence of the conversion efficiency on the shell properties. Gold-nanoparticles/polydimethylsiloxane nanocomposites were experimentally synthesized in the form of gel and microfilms to verify our idea and the simulation results agreed with the experiments. Our work paves the way for the rational design and optimization of nanoprobes with improved conversion efficiency.

Defect-rich titanium nitride nanoparticle with high microwaveacoustic conversion efficiency for thermoacoustic imaging-guided deep tumor therapy

Pulse microwave excite thermoacoustic(TA)shockwave to destroy tumor cells in situ.This has promising applications for precise tumor therapy in deep tissue.Nanoparticle(NP)with high microwave-acoustic conversion is the key to enhance the efficiency of therapy.In this study,we firstly developed defect-rich titanium nitride nanoparticles(TiN NPs)for pulse microwave excited thermoacoustic(MTA)therapy.Due to a large number of local structural defects and charge carriers,TiN NPs exhibit excellent electromagnetic absorption through the dual mechanisms of dielectric loss and resistive loss.With pulsed microwave irradiation,it efficiently converts the microwave energy into shockwave via thermocavitation effect,achieving localized mechanical damage of mitochondria in the tumor cell and yielding a precise antitumor effect.In addition to the therapeutic function,the NP-mediated TA process also generates images that provide valuable information,including tumor size,shape,and location for treatment planning and monitoring.The experimental results showed that the TiN NPs could be efficiently accumulated in the tumor via intravenous infusion.With the deep tissue penetration characteristics of microwave,the proposed TiN-mediated MTA therapy effectively and precisely cures tumors in deep tissue without any detectable side effects.The results indicated that defect-rich TiN NPs are promising candidates for tumor therapy.

A Two-Level Cross-Sectional Optimization Approach for Automotive Body Concept Design

Concept design is vital important in development of auto-body and it has great effects on later design work.In this paper,a twolevel cross-sectional optimization approach is presented to shorten concept design cycles.First,an exact structural analysis approach for spatial semi-rigid framed structures,i.e.,the transfer stiffness matrix method proposed in our previous study,is adopted for both static and dynamic analyses of body-in-white(BIW)structure.A two-level cross-sectional optimization approach is then proposed for an automotive BIW lightweight design,and genetic algorithm is used to solve the optimization models.Afterward,an object-oriented MATLAB toolbox,using distributed parallel computing techniques,is developed to promote the concept design of the BIW structure.Finally,relevant numerical examples demonstrate the validity and accuracy of the proposed method.

Polarization microwave-induced thermoacoustic imaging for quantitative characterization of deep biological tissue microstructures

Polarization optical imaging can be used to characterize anisotropy in biological tissue microstructures and has been demonstrated to be a powerful tool for clinical diagnosis. However, the approach is limited by an inability to image targets deeper than ~1 mm due to strong optical scattering in biological tissues. As such, we propose a novel polarization microwave-induced thermoacoustic imaging(P-MTAI) technique to noninvasively detect variations in deep tissue by exploiting the thermoacoustic signals induced by four pulsed microwaves of varying polarization orientations. The proposed P-MTAI method overcomes the penetration limits of conventional polarization optical imaging and provides submillimeter resolution over depths of several centimeters. As part of the paper, the structural characteristics of tissues were quantified using a new parameter, the degree of microwave absorption anisotropy. P-MTAI was also applied to the noninvasive detection of morphological changes in cardiomyocytes as they transitioned from ordered to disordered states, providing a potential indication of myocardial infarction.

Photoacoustic-immune therapy with a multi-purpose black phosphorus-based nanoparticle

Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue,inhibit metastases,and prevent tumor relapses,are the ultimate goals in the battle against cancer.We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic(PA)therapy with checkpoint-blockade immunotherapy.With the mitochondria targeting nanoparticle,PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor.More importantly,PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses.When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4,the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy.Furthermore,the number of memory T cells detected in the spleen is increased,and these cells inhibit tumor recurrence.This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity.