Search

Background Gastrectomy with extended (D2) lymphadenectomy is considered standard of care for gastric cancer to provide the best possible outcomes and pathologic staging. However, D2 gastrectomy is a technically demanding operation and reported to be associated with increased complications and mortality. Application of sentinel lymph node (SLN) concept in gastric cancer has the potential to reduce patient morbidity; however, SLN techniques are not established for gastrectomy, in part due to lack of practical tracers. An effective and convenient tracer with enhanced SLN accumulation is critically needed. Methods Mannose-labelled magnetic tracer ‘FerroTrace’ and fluorescent dye indocyanine green (ICG) were injected laparoscopically into the stomach submucosa of 8 healthy swine under general anaesthesia. Intraoperative fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while preoperative T2-weighted MRI and ex vivo magnetometer probe measurements were used to identify nodes containing FerroTrace. Lymphadenectomy was performed either robotically (n = 2) or via laparotomy (n = 6). Results Mixing ICG and FerroTrace ensured concurrence of fluorescent and magnetic signals in SLNs. An initial trial with robotic dissection removed all magnetic LNs (n = 4). In the subsequent laparotomy study that targeted all ICG-LNs based on intraoperative fluorescence imaging, dissection removed an average of 4.7 ± 1.2 fluorescent, and 2.0 ± 1.3 magnetic LNs per animal. Both MRI and magnetometer detected 100% of SLNs (n = 7). FerroTrace demonstrated high specificity to SLNs, which contained 76 ± 30% of total lymphotropic iron, and 88 ± 20 % of the overall magnetometer signal. Conclusions Through utilisation of this dual tracer approach, SLNs were identified via preoperative MRI, visualised intraoperatively with fluorescence imaging, and confirmed with a magnetometer. This combination pairs the sensitivity of ICG with SLN-specific FerroTrace and can be used for reliable SLN detection in gastric cancer, with potential applications in neoadjuvant therapy. Graphical abstract

In the context of Professional Technical Education, Dual Modality has been a commitment of the Chilean Ministry of Education to improve Professional Technical training in High School. The change has involved a curricular innovation around the development of basic competences where, in addition to the teacher and the traditional classroom, other agents and other scenarios that share the work of teaching concur. In this context, the research consigned, according to its objectives and methodological formulation, describes the characteristics of the Dual Professional Technical training of the Administration specialty of the Monseñor Guillermo Carlos Hartl Educational Complex of the Pitrufquén commune , in Chile . It is intended to investigate the effectiveness of the integrated curriculum through the assessment of achievement of the basic competencies of students who are in the 4th Middle Year of said specialty (with Dual mode), in direct relation to the required graduate and professional profile and in contrast, with that of students of the specialty of "Electricity", without the Dual Modality. No contexto da Educação Técnica Profissional, a modalidade dual tem sido um compromisso do Ministério da Educação do Chile para melhorar o treinamento Técnico Profissional no Ensino Médio. A mudança envolveu uma inovação curricular em torno do desenvolvimento de competências básicas onde, além do professor e da sala de aula tradicional, concorrem outros agentes e outros cenários que compartilham o trabalho de ensino. Neste contexto, a pesquisa consignada, de acordo com seus objetivos e formulação metodológica, descreve as características da formação Técnica Profissional Dual da especialidade de Administração do Complexo Educativo Monseñor Guillermo Carlos Hartl da comuna de Pitrufquén, no Chile. Pretende-se investigar a eficácia do currículo integrado através da avaliação do alcance das competências básicas dos alunos que estão no 4º Ano Médio da referida especialidade (com a modalidade Dual), em relação direta com o perfil profissional e de pós-graduação requerido e em contraste, com o dos alunos da especialidade "Eletricidade", sem a modalidade Dual.

In recent years, chimeric antigen receptor T (CAR T)‐cell therapy has shown great potential in treating haematologic disease, but no breakthrough has been achieved in solid tumours. In order to clarify the antitumour mechanism of CAR T cell in solid tumours, the pharmacokinetic (PK) and pharmacodynamic (PD) investigations of CD19 CAR T cell were performed in human leukaemic xenograft mouse models. For PK investigation, we radiolabelled CD19 CAR T cell with 89Zr and used PET imaging in the CD19‐positive and the CD19‐negative K562‐luc animal models. For PD evaluation, optical imaging, tumour volume measurement and DNA copy‐number detection were performed. Unfortunately, the qPCR results of the DNA copy number in the blood were below the detection limit. The tumour‐specific uptake was higher in the CD19‐positive model than in the CD19‐negative model, and this was consistent with the PD results. The preliminary PK and PD studies of CD19 CAR T cell in solid tumours are instructive. Considering the less efficiency of CAR T‐cell therapy of solid tumours with the limited number of CAR T cells entering the interior of solid tumours, this study is suggestive for the subsequent CAR T‐cell design and evaluation of solid tumour therapy.

Design and fabrication of highly effective, targeted, intelligent and multifunctional innovative theranostic agents with innovative alternative materials become pressing concerns. Nanoparticles are suitable for the incorporation of multifunction by modulating such a specific structure in a nanoscale and have been developed as multifunctional intelligent contrast agent theranostic nanoplatform on account of being performed multifunctional integration easily, for instance, controlled release function, targeting function, multi-stimuli sensitive function, biocompatibility, bio-degradation and other functions for promoting performance, effectiveness and efficiency. In this work, the CdTe@SiO2@CeO2 core-shell nanoparticles were synthesized and assessed as a pH responsive dual-modality imaging contrast agent. The CdTe@SiO2 core was participated as fluorescent label and the CeO2 shell was partaken as CT tag. As a latent auxiliary scheme, this study explored the dual-modality combination between fluorescence imaging and CT imaging to localize tumor on the xenograft tumor models. All assessments acknowledged that this CdTe@SiO2@CeO2 core-shell nanoparticle was an effective dual-modality contrast medium for tumor mapping on murine tumor models.

Modern-day diamond sorting is achieved through the application of X-ray luminescence (XRL) and X-ray transmission (XRT) techniques. Sorting with XRL is limited to the class range of 1.25 mm to 32 mm because of self-absorption associated with larger diamonds, greater than 32mm. The effect of self-absorption is also a high-energy phenomenon in XRL. XRT is limited to sorting large size diamonds as the technique suffers poor contrast for diamonds smaller than 10mm. XRT measurements are immune to self-absorption for all sample sizes, while XRL measurements have good contrast for particles smaller than 32mm. The applications of these techniques have hitherto been used independently of each other and have subsequently progressed mutually exclusively. Here we analytically show a new paradox of a dual-modality X-ray diamond sorting combining XRL and XRT techniques' strengths. Key features of our new paradoxical model performance are contrast mitigation for small particles and self-absorption rejection for a large particle at high energy as well as improved particle detectability and classification.

Because of the intrinsic defects of traditional treatment of cancer, it is quite needed to construct novel theranostic nanoagents that can not only improve the accuracy of imaging diagnosis but also achieve highly efficient therapy of cancer. Herein, we fabricated polydopamine-functionalized ammonium holmium fluoride nanocomposites (AHF@PDA) for dual-modality bioimaging (magnetic resonance imaging (MRI) and computed tomography (CT)) owing to the high X-ray attenuation feature and magnetic property of Ho3+. Moreover, PDA shell endows AHF@PDA with excellent photothermal conversion performances and robust biocompatibility, leading to good treatment effect in vitro and in vivo. All above positive results certify that AHF@PDA have good potential as theranostic agents for clinical application in the future.

Photoacoustic (PA) imaging has emerged as a promising bio-imaging technique due to its non-invasive visualization of lesions at great penetration depths. Fluorescence (FL) imaging in the second near-infrared window (NIR-II, 1000–1700 nm) achieves a higher imaging resolution and lower background signals compared to NIR-I. However, the single imaging method possesses its own disadvantages. Thus, we have demonstrated ZIF-8–IR820–MnPc–HA nanoparticles (ZIMH NPs) that can achieve visualization and localization of tumors in mice models with the help of a dual-modality PA/NIR-II FL imaging performance. Meanwhile, these excellent nanoparticles also induce the efficient generation of singlet oxygen (1O2) upon 808 nm laser illumination, and display excellent photodynamic therapy efficacy in cells, further indicating their potential application for in vivo PDT. In ZIMH NPs, hyaluronic acid (HA) impressively acts as a “sponge”, enhancing the generation of 1O2 and facilitating the cellular therapeutic effects. We believe that ZIF-8–IR820–MnPc–HA NPs present a brand-new strategy for the exploration of efficient PDT photosensitizers with dual-modality imaging performance for use in various biomedical applications.

OBJECTIVES 1: Describe subacute facial nerve paralysis after salvage stereotactic radiosurgery (SRS). 2: To analyze predictors of facial nerve weakness after dual modality treatment. PATIENTS Adult patients with Vestibular Schwannoma who underwent sub-total resection (STR) followed by salvage radiation. INTERVENTIONS Microsurgical resection of VS, stereotactic radiosurgery, intensity-modulated radiotherapy, proton radiotherapy. MAIN OUTCOME MEASURES Serial facial nerve function (House-Brackmann scale). RESULTS Thirteen patients who underwent dual modality treatment for large VS were included (mean age = 43.6 years, 77% females). The mean pre-operative tumor volume was 11.7 cm3 (SD = 6.5) and the immediate mean post-operative remnant volume was 1.5 cm3 (SD = 1.4) with a mean extent of resection of 86.7% (SD = 9.5). The mean salvage-free interval was 20.8 months (SD = 13.3). All patients had excellent one-year FN outcome (HB grade 1, 2) after resection. Three patients developed subacute facial nerve weakness after salvage SRS (4.2-9.4 months after SRS). This paralysis responded to high dose systemic steroids and no surgical interventions for facial rehabilitation were required. At last follow up (mean 61.6 months, SD = 28.5), facial nerve function was favorable (HB grade 1-2 in 12 patients and HB grade 3 in 1 patient). There were no significant associations between various predictors and subacute deterioration of facial nerve function after SRS. CONCLUSIONS Sub-acute transient facial nerve dysfunction can develop infrequently over a variable time frame after post-operative salvage SRS and usually responds to steroids. Patients should be adequately counseled about potential of transient deterioration of facial nerve function after salvage SRS.

Humans normally integrate multiple haptic signals during dexterous manipulation with the natural limb. Operating telerobots such as surgical robots and upper-limb prostheses removes this multimodality feedback. While considerable research has focused on single-modality haptic feedback and discrete multimodality haptic feedback, little is known regarding the utility of continuous multimodality feedback. Here, we present an experimental framework designed to explore continuous multimodality haptic feedback for dexterous manipulation. Participants performed a grasp-and-hold task in a virtual environment with either direct or myoelectric control under different haptic feedback conditions: no feedback, vibrotactile feedback of object slip, squeeze feedback of grip force, and combined vibrotactile and squeeze feedback. Results from preliminary pilot studies highlight the gap in knowledge surrounding the potential utility of continuous multimodality feedback in differing telerobot control scenarios.

The purpose of this study was to develop and preliminarily evaluate phospholipid-shelled nanodroplets (NDs) encapsulating perfluoropentane (PFP) and radioactive 64Cu as a hybrid positron emission tomography (PET)-ultrasound (US) probe. PFP NDs were fabricated by mixing liquid-phase PFP with a phospholipid solution. The 64Cu was encapsulated into the NDs in a size-controlled manner by exploiting the hydrophobicity of 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) using a vial mixer and an extruder. The fabricated 64Cu-loaded PFP NDs (64Cu-PFP NDs) were evaluated using in vitro/in vivo PET-computed tomography (PET-CT), US imaging and transmission electron microscopy. In the in vitro PET images, the 64Cu-PFP NDs were observed as a hot spot in the lower section of the test tube. In the acquired US images, the mean region of interest brightness values of 64Cu-PFP NDs were revealed by their strong echo image. In a tumor-bearing mouse animal model, tumor uptake of the 64Cu-PFP NDs was low, that is, approximately 65%, compared with that of only free 64Cu, as determined by PET-delayed imaging analysis. The dual-function concept of the NDs is expected to contribute to the prognosis and effectiveness of therapy by fusing the science and technology of nuclear medicine and US.

Dagger shaped gold particles have been electrodeposited on surfaces of conductive indium tin oxide (ITO) films. The optical extinction of these AuND@ITO substrates extends from the near-IR to long ...

Microbubbles (MBs) stabilized by particle surfactants (i.e., Pickering bubbles) have better thermodynamic stability compared to MBs stabilized by small molecules as a result of steric hindrance against coalescence, higher diffusion resistance, and higher particle desorption energy. In addition, the use of particles to stabilize MBs that are typically used as an ultrasound (US) contrast agent can also introduce photoacoustic (PA) properties, thus enabling a highly effective dual-modality US and PA contrast agent. Here, we report the use of partially reduced and functionalized graphene oxide as the sole surfactant to stabilize perfluorocarbon gas bubbles in the preparation of a dual-modality US and PA agent, with high contrast in both imaging modes and without the need for small-molecule or polymer additives. This approach offers an increase in loading of the PA agent without destabilization and increased thickness of the MB shell compared to traditional systems, in which the focus is on adding a PA agent to existing MB formulations.

Mesenchymal stem cells (MSCs) have shown potential as an innovative treatment for pulmonary fibrosis (PF), due to their capability to ameliorate the inflammation and moderate the deterioration of P...

Carbon nanomaterials have flourished for cancer therapy for decades. However, their practical applications on clinical bases still pose a challenge to address the dilemma of metabolism in vivo. In this study, an attempt is made to design a degradable carbon-silica nanocomposite (CSN) with immunoadjuvant property, which could undergo an enzyme-free degradation process into small particles (∼5 nm) and facilitate its clinical application. CSN harbors photothermal and photodynamic properties and as an immunoadjuvant would help to generate tumor-associated antigens and mature dendritic cells (DCs). Potent antitumor effects have been achieved in both 4T1 and patient-derived xenograft tumor models with tumor inhibition efficiencies of 93.2% and 92.5%, respectively. We believe that this strategy will benefit the possible clinical translation and carbon-silica-nanomaterial-based cancer therapy.

The traditional method of labeling the nonpalpable breast cancer is placing a guidewire or metal marker guided by ultrasound or stereographic mammogram prior to surgery. However, the wire localization has a risk of displacement and could be an obstacle in the surgical course. To avoid these issues, we tried to combine the near-infrared (NIR) fluorescence dye dioctadecyltetramethyl indotricarbocyanine iodide (DiR) and microbubbles (MBs) to realize the dual-modality imaging for breast cancer microfoci intraoperative identification and guidance as a more efficient workflow. First, 24 mice were divided into three groups, injected with DiR nanoparticles (NPs), DiR MBs, and DiR MBs + ultrasound (US), and then, in vivo and ex vivo NIR fluorescence imaging was conducted. The distinction of fluorescence imaging intensity at the tumor site among the three groups was statistically significant (P < 0.001). Group 3 (DiR MBs + US) exhibited the highest fluorescence imaging intensity; the distinctions between group 3 an...

Accurate diagnosis of cancer at an early stage is the key to reduce cancer mortality and improve survival. PET imaging has high sensitivity but low spatial resolution, while CT imaging has good spatial location information. Therefore, the combination of PET and CT imaging can provide complementary advantages to achieve accurate early diagnosis of tumors. However, currently developed PET or CT imaging agents have only a single function. Here, we designed and constructed a self-assembled lipid nanocapsule encapsulated with iodixanol and labeled with self-chelated

The Droplet family of tools provides novice programmers with a dual-modality environment to learn, offering both blocks and text representations of code. Our showpiece will highlight the next generation of tools in this family, including the launch of Pencil.io, Amphibian 2.0, and work on the development of Lilypad, the next evolution of Droplet. Lilypad will integrate a frame-based editor, which will facilitate study and deployment of dual-modality instruction in later CS coursework and, potentially, industry applications.

In the context of Professional Technical Education, Dual Modality has been a commitment of the Chilean Ministry of Education to improve Professional Technical training in High School. The change has involved a curricular innovation around the development of basic competences where, in addition to the teacher and the traditional classroom, other agents and other scenarios that share the work of teaching concur. In this context, the research consigned, according to its objectives and methodological formulation, describes the characteristics of the Dual Professional Technical training of the Administration specialty of the Monseñor Guillermo Carlos Hartl Educational Complex of the Pitrufquén commune , in Chile . It is intended to investigate the effectiveness of the integrated curriculum through the assessment of achievement of the basic competencies of students who are in the 4th Middle Year of said specialty (with Dual mode), in direct relation to the required graduate and professional profile and in contrast, with that of students of the specialty of "Electricity", without the Dual Modality.

A combination of pre- and intraoperative sentinel lymph node (SLN) mapping techniques has been suggested to optimize SLN detection. A novel liposomal nanoparticle, Nanotrast-CF800 (CF800), utilizes computed tomography lymphography (CTL) and near infrared fluorescence imaging (NIRF) for image-guided surgery and SLN mapping. This novel tracer agent has not been evaluated in companion animals. The objective of this study was to evaluate the feasibility and efficacy of CF800 for SLN mapping in the oral cavity of healthy dogs and to report any local adverse effects. Six healthy adult purpose-bred research dogs randomly received either 1 mL (group 1) or 2 mL (group 2) of CF800 injected into the submucosa at the level of the right canine maxillary tooth. CTL and percutaneous NIRF were performed at 1, 3, and 10 minutes, then 1, 2, 4, 7, and 10 days post-injection (p.i). Overall, both CTL and NIRF identified SLNs in all dogs. The overall peak mean contrast enhancement of the SLNs was 73.98 HU (range 63.45-86.27 HU) at 2 days p.i. Peak fluorescence of the SLN occurred at 1 day p.i. The agent was retained within the SLN for at least 7 days for CTL and 4 days for NIRF. No adverse effects were observed. Local administration of CF800 was simple and feasible for the detection of SLNs using CTL+NIRF in the head and neck of healthy dogs and was not associated with significant local adverse events.

State-of-the-art object detection systems for autonomous driving achieve promising results in clear weather conditions. However, such autonomous safety critical systems also need to work in degrading weather conditions, such as rain, fog and snow. Unfortunately, most approaches evaluate only on the KITTI dataset, which consists only of clear weather scenes. In this paper we address this issue and perform one of the most detailed evaluation on single and dual modality architectures on data captured in real weather conditions. We analyse the performance degradation of these architectures in degrading weather conditions. We demonstrate that an object detection architecture performing good in clear weather might not be able to handle degrading weather conditions. We also perform ablation studies on the dual modality architectures and show their limitations., Accepted for publication at ITSC 2021

Tracking signaling H2S in live mice demands responsive imaging with fine tissue imaging depth and low interferences from tissue scattering/autofluorescence and probe concentration. With complementary advantages of fluorescence and photoacoustic (PA) imaging, optical/PA dual-modality imaging was suggested for in/ex vivo H2S imaging. Therefore, a meso-benzoyloxyltricarboheptamethine cyanine, HS-CyBz, was prepared as the first ratiometric optical/PA dual-modality probe for H2S, profiting from a keto-enol transition sensing mechanism. Tail intravenous injection of this probe leads to probe accumulation in the liver of mice, and the endogenous H2S upregulation triggered by S-adenosyl-l-methionine has been verified by ratiometric optical/PA imaging, suggesting the promising potential of this ratiometric dual-modality imaging.

superstructures has enormous potential in material sciences and engineering. Despite the potential, controlled assembly of different kinds of NPs into spatially addressable hybrid configurations still remains a formidable challenge. Herein, we report a simple and universal strategy for DNA-mediated assembly of CdTe quantum dots (QDs) and lanthanide-doped upconversion nanoparticles (UCNPs). Such DNA-QD/UCNPs heterostructures not only maintains both fluorescent properties of QDs and upconversion luminescence behaviors of UCNPs, but also offers a polyvalent DNA surface, allowing for targeted dual-modality imaging of cancer cells using an aptamer. The hetero-assembly mediated by the DNA − inorganic interfacial interaction may provide a scalable way to fabricate hybrid superstructures of both theoretical and practical interests.

Objective The aim of this paper is to study the theranostic potential of 5-Aminolevulinic Acid (5-ALA)in dentistry. Methods Photodynamic inactivation (PDI) and fluorescence spectroscopy of Streptococcus sanguis, and laser induced fluorescence (LIF) of several decayed teeth were performed using 5-ALA. Results In the absence of 5-ALA, 15 min illumination of the bacteria by the means of an LED light source led to only 1.16% viability reduction. On the other hand, 5-ALA revealed remarkable dark toxicity at concentrations above 20 μM. Furthermore, the synergistic effects of 10 μM 5-ALA and illumination by the light source for 5 and 15 min intervals led respectivelyto0.74log10 and 1.69log10 reduction of viability. Also, fluorescence spectroscopy of the bacteria showed a direct relationship between emission line intensity at 620 nm and the concentration of 5-ALA. In dental experiments, following exposing tooth with 40 mM 5-ALA, a significant autofluorescence growth was observed just in the decayed parts. Conclusion Based on the strong dual modality of 5-ALA to annihilate cariogenic bacteria through photodynamic inactivation and enhancing LIF intensity for identification of dental caries, 5-ALA is proposed as a theranostic agent in dentistry.

While cancer is one of the most studied disorders in humans; a complete cure or prognosis has not yet been developed. Nearly 40% of the current population will suffer from this deadly disease. Scientists all across the globe strive to innovate new technologies and therapies to treat this disease. However, these innovations are often short-lived owing to the dynamic genetic mutations of cancer cells and the need to overcome eventual cancer cell/tumor resistance. Therefore, there is an immense need for innovation and to build on the current treatment options to develop a near perfect system to help tackle cancer. In this article, we review a drug delivery system in the form of Quantum Dots (QDs), which are nano-sized fluorescent particles, capable of diagnosing and delivering molecules to cancer cells in-vivo. In this review, we highlight different types of QDs, characterization methods, and how microfluidics can be used as a tool to improve their functionality. We then focus on the applications of QDs as diagnostics, drug delivery systems, or a tool to study biological phenomena. Finally, we discuss the current limitations of QDs and future challenges.

This study examined how practicing instructional designers manage cognitive load in a standardized scenario as they select and implement instructional strategies, message design, content sequencing, delivery medium, and technology within various domains with learners at different levels of expertise. The study employed a quasi-experimental, mixed methods design to gain insight into how practicing instructional designers perceive their awareness of strategies to manage cognitive load and implement those strategies within a standardized design scenario. The results of the study indicated that both novice and expert practitioners frequently used several strategies to manage extraneous load (worked examples, completion tasks, and dual modality) as prescribed by theory, as well as the simple-to-complex presentation strategy to manage intrinsic load. While participants frequently acknowledged differences in the levels of learner expertise within the instructional scenario, few employed strategies prescribed to address the expertise reversal effect as outlined by theory. Based on the results of this study, we present a framework to assist designers with managing for cognitive load in their everyday design practices.

Demands on effective diagnosis and therapy, especially in the antibacterial field, are increasing. This study presents multifunctional Fe3O4@NaGdF4:Yb:Er-HMME (Fe@UCNP-HMME) nanoparticles for applications in bioimaging as well as photodynamic therapy (PDT)/sonodynamic therapy (SDT). We constructed a core-shell structure of Fe3O4 and upconversion nanoparticles (UCNPs) for T2-weighted MRI and upconversion luminescence (UCL) imaging both in vitro and in vivo. Moreover, we modified the surface of the Fe@UCNPs with the photo/sonosensitizer hematoporphyrin monomethyl ether (HMME), which could be excited to produce 1O2 for photo/sonodynamic antimicrobial chemotherapy (PACT). Furthermore, deep tissue penetration of UCL and ultrasound led to the temporal induction of cytotoxicity when applied to drug-resistant Gram(+) and Gram(−) bacteria, by which these pathogens were efficiently killed through damage of the cell wall structure. In summary, we developed a multifunctional Fe@UCNP-HMME-based platform for both dual-modality imaging and photo/sonodynamic antimicrobial chemotherapy, employing its complementary array of UCL, T2-MRI, and 1O2 production properties to kill bacteria (100%) through PDT and SDT. Our experimental results verify the excellent potential of Fe@UCNP-HMME for applications in diagnosis and therapy.

Kunyan He,1 Haitao Ran,2,3 Zhongzhen Su,1 Zhigang Wang,2,3 Maoping Li,4 Lan Hao3 1Ultrasound Department, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, People’s Republic of China; 2Ultrasound Department, The second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China; 3The Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing 400010, People’s Republic of China; 4Ultrasound Department, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China Purpose: The objective of this study was to develop a multifunctional contrast agent for bioimaging and synergistic high-intensity focused ultrasound (HIFU) therapy to achieve theranostic.Materials and methods: A novel type of perfluorohexane-encapsulated fullerene (PFH-C60) nanosphere was successfully developed via a vacuum ultrasonic emulsification and centrifugation method and subsequently used in ultrasound/computed tomography (CT) dual-modality and HIFU ablation of dissected bovine livers. In addition, transmission electron microscopic examination was employed to detect structural changes in the target tissue for HIFU ablation.Results: The use of composite nanospheres effectively enhanced ultrasound and CT imaging. Moreover, the HIFU ablation of dissected bovine livers was also significantly enhanced.Conclusion: Composite nanospheres demonstrate potential theranostic application as a multifunctional contrast agent for dual-modality biological imaging and highly efficient synergistic imaging-guided HIFU ablation. Keywords: microbubble, noninvasive therapy, double modal imaging, sonodynamic effects, synergistic ablation efficiency

Accurate quantification of analyte using surface-enhanced Raman spectroscopy (SERS) is a desired, yet unfulfilled, ability that could enable a plethora of diagnostic- and defense-related applications. The major hurdles to overcome to achieve this goal are expensive manufacturing for highly ordered and reproducible substrates and low reproducibility of substrates produced through low cost methods. A technology that can set industry standards for manufacturing/processing of SERS substrates is still yet to be achieved. A dual-modality multisite sensing approach was developed, that overcomes the limitations experienced when fabricating bottom-up, reproducible, sensitive, and low-cost SERS substrates. Electrochemistry was combined with SERS for dual-modality sensing to improve precision by adding redundancy and encoding features, thus increasing measurement robustness and predictability. This technique works by calibrating SERS response with respect to active surface area, a parameter known to be proportional to charge, which can be estimated via electrochemical measurements. The dual-modality multisite measurement demonstrates at least 2.8× improvement in assay precision compared to the traditional single-site Raman measurements. The technique yields overall improved precision of measurement and is not limited to any particular SERS substrate or geometry, and thus it can be adapted and incorporated readily in any SERS sensing assay.

Optoacoustic imaging, based on the differences in optical contrast of blood hemoglobin and oxyhemoglobin, is uniquely suited for the detection of breast vasculature and tumor microvasculature with the inherent capability to differentiate hypoxic from the normally oxygenated tissue. We describe technological details of the clinical ultrasound (US) system with optoacoustic (OA) imaging capabilities developed specifically for diagnostic imaging of breast cancer. The combined OA/US system provides co-registered and fused images of breast morphology based upon gray scale US with the functional parameters of total hemoglobin and blood oxygen saturation in the tumor angiogenesis related microvasculature based upon OA images. The system component that enabled clinical utility of functional OA imaging is the hand-held probe that utilizes a linear array of ultrasonic transducers sensitive within an ultrawide-band of acoustic frequencies from 0.1 MHz to 12 MHz when loaded to the high-impedance input of the low-noise analog preamplifier. The fiberoptic light delivery system integrated into a dual modality probe through a patented design allowed acquisition of OA images while minimizing typical artefacts associated with pulsed laser illumination of skin and the probe components in the US detection path. We report technical advances of the OA/US imaging system that enabled its demonstrated clinical viability. The prototype system performance was validated in well-defined tissue phantoms. Then a commercial prototype system named Imagio™ was produced and tested in a multicenter clinical trial termed PIONEER. We present examples of clinical images which demonstrate that the spatio-temporal co-registration of functional and anatomical images permit radiological assessment of the vascular pattern around tumors, microvascular density of tumors as well as the relative values of the total hemoglobin [tHb] and blood oxygen saturation [sO2] in tumors relative to adjacent normal breast tissues. The co-registration technology enables increased accuracy of radiologist assessment of malignancy by confirming, upgrading and/or downgrading US categorization of breast tumors according to Breast Imaging Reporting And Data System (BI-RADS). Microscopic histologic examinations on the biopsied tissue of the imaged tumors served as a gold standard in verifying the functional and anatomic interpretations of the OA/US image feature analysis. Keywords: Optoacoustic, Photoacoustic, Ultrasound, Functional-anatomical imaging, Breast cancer, Diagnostics, Dual modality

Background: Pancreatic cancer (PC) is one of the most devastating types of cancers worldwide and has a remarkably poor survival rate, emphasizing the need for more effective strategies for the diagnosis and therapy of PC. Upconversion nanoparticles (UCNPs) have gained a privileged place in the biomedical field due to their outstanding properties. Besides, epithelial cell adhesion molecule (EpCAM) as one of the key biomarkers of pancreatic cancer stem cells, is a vital target for theranostic, diagnostic, and/or therapeutic intervention in nanomedicine. In this study, the theranostic nanosystem (EpCAM-UCMSNs-MX) was formed from the mesoporous silica-coated UCNPs functionalized with anti-EpCAM monoclonal antibody, and then one anticancer drug and photosensitizer, mitoxantrone (MX), was loaded into the mesoporous silica. The nanotheranostic system was used to target caner stem cells for realizing simultaneous dual-modality MR/UCL imaging and synergetic chemotherapy and NIR-triggered PDT. Results: After conducting series of characterizations, the nanotheranostic systems own superior uniform sphericity and long-time stability. In vitro and vivo experiments show the nanocomposites have good biocompatibility and can target caner stem cells to realize simultaneous dual-modality MR/UCL imaging. Furthermore, in comparison with UCMSNs-MX and free MX, MX-loaded UCMSNs conjugated with anti-EpCAM monoclonal antibody (EpCAM-UCMSNs-MX) are efficiently endocytosed by cancerous cells and show synergetic effect with PDT in vitro. In vivo experiments reconfirm the synergistic effects observed with the combination of EpCAM-UCMSNs-MX and PDT, which results in better treatment outcomes as compared to chemotherapy or NIR irradiation alone that fail to show any noticeable systemic toxicity.Conclusions: The resulting nanotheranostics were shown to target caner stem cells to confer simultaneous dual-modality MR/UCL imaging and induced intracellular reactive oxygen species exposed to 980 nm excitation, leading to synergetic chemotherapy and NIR-triggered PDT. These results offer a promising strategy for designing a multifunctional nanotheranostic system for dual-modality imaging-guided synergistic oncotherapy.

Purpose: To develop a method for constructing customizable, multimodal quality control (QC) imaging phantoms based on 3D printing technology.Materials and Methods: Four phantoms were designed and constructed through 3D printing technology using three unique printing materials. Physical parameters of the 3D printed materials were evaluated, including density, shore hardness, porosity, deformation temperature, computed tomography (CT) number, absorption coefficient, and printing accuracy. Imaging performance of the phantoms was studied using MRI, CT, PET/MR, and PET/CT, and compared with conventional/commercial phantoms. Imaging assessments included high contrast resolution, low contrast resolution, uniformity, deformation, SNR, slice accuracy/slice thickness, location accuracy/laser alignment, CT number, relaxation time, and registration.Results: All three printing materials have a shore hardness of 90. The physical densities of these materials are 1.15 g/cm3, 0.76 g/cm3, and 1.27 g/cm3, respectively. The porosities are 9.09, 6.81, and 18.56%, respectively. The threshold temperature of deformation for the three materials is >105°C, which is higher than that of PMMA and silica gel. Imaging scans of the constructed phantoms for single modality scanners (MRI and CT) and dual-modality scanners (PET/MRI and PET/CT) were compared with those of the commercial phantoms. The standard deviation of the HU value uniformity test was Conclusion: 3D printed medical imaging phantoms allow for rapid, customized phantom fabrication for clinical situations across single and dual modality imaging platforms. Further imaging parameter analysis is underway to provide more quantitative evaluation of the proposed phantoms.

Gas microbubbles are an established clinical ultrasound contrast agent. They could also become a powerful MR intravascular contrast agent, but their low susceptibility-induced contrast requires high circulating concentrations or the addition of exogenous paramagnetic nanoparticles for MR detection. In order to detect clinical in vivo concentrations of raw microbubbles via MR, an alternative detection scheme must be used. HyperCEST is an NMR technique capable of indirectly detecting signals from very dilute molecules that exchange hyperpolarized (129)Xe and that are present at concentrations that fall well below the NMR detection threshold. Here, we use quantitative hyperCEST to show that microbubbles are very efficient hyperCEST agents. They can accommodate and saturate millions of (129)Xe atoms at a time, allowing for their indirect detection at concentrations as low as 10 femtomolar. The increased MR sensitivity to microbubbles achieved via hyperCEST can bridge the gap for microbubbles to become a dual modality contrast agent.

A dual-modal optical imaging system combining photoacoustic remote sensing (PARS) and swept-source optical coherence tomography (SS-OCT) is presented. The PARS subsystem utilized a pulsed excitation beam at 532 nm confocal with a low-coherence interrogation beam centered at 830 nm to detect photoacoustic signals. The OCT subsystem employs a 1060 nm VCSEL swept source with a 60 kHz A-scan rate and 8 μm axial resolution in tissue. Volumetric images were acquired from carbon fibers and in-vivo biological tissues. To our knowledge, this is the first study demonstrating a combination of SS-OCT with optical-resolution photoacoustic microscopy for in-vivo, non-contact imaging of tissues.

Integrating anticancer drugs and diagnostic agents in a polymer nanosystem is an emerging and promising strategy for improving cancer treatment. However, the development of multifunctional nanoparticles (NPs) for an "all-in-one" platform characterized by specific targeting, therapeutic efficiency, and imaging feedback remains an unmet clinical need. In this study, pH-responsive mixed-lanthanide-based multifunctional NPs were fabricated based on simple metal-ligand interactions for simultaneous cancer cell imaging and drug delivery. We investigated two new systems of alginate-polydopamine complexed with either terbium/europium or dysprosium/erbium oxide NPs (Tb/Eu@AlgPDA or Dy/Er@AlgPDA NPs). Tb/Eu@AlgPDA NPs were then functionalized with the tumor-targeting ligand folic acid (FA) and loaded with the anticancer drug doxorubicin (DOX) to form FA-Tb/Eu@AlgPDA-DOX NPs. Using such systems, the mussel-inspired property of PDA was introduced to improve tumor targetability and penetration, in addition to active targeting (via FA-folate receptor interactions). Determining the photoluminescence efficiency showed that the Tb/Eu@AlgPDA system was superior to the Dy/Er@AlgPDA system, presenting intense and sharp emission peaks on the fluorescence spectra. In addition, compared to Dy/Er@AlgPDA NPs (82.4%), Tb/Eu@AlgPDA NPs exhibited negligible cytotoxicity with93.3% HeLa cell viability found in MTT assays at NP concentrations of up to 0.50 mg/mL and high biocompatibility when incubated with zebrafish (

Aim: To design MRI/ultrasound (US) dual modality imaging probes with optimized size for prostate cancer imaging by targeting prostate-specific membrane antigen (PSMA). Materials & methods: The PSMA-targeting polypeptide-nanobubbles (PP-NBs) with core size of 400 and 700 nm were fabricated and evaluated. Results: With excellent physical property and specificity, PP-NBs of both core size could image PSMA expression in prostate cancer xenografts. Particularly, 400 nm PP-NBs generated higher PSMA-specific MRI/US dual modality contrast enhancement than 700 nm PP-NBs in correlation with histopathologic findings. Conclusion: Benefit from the smaller core size, 400 nm PP-NBs had higher permeability and specificity than 700 nm PP-NBs, hence producing better PSMA-specific MRI/US dual modality imaging.

Background Cardiac allograft vasculopathy is a combination of the development of de novo plaque and the progression of donor-transmitted plaque. Purpose This study aimed to evaluate the development of de novo plaque and the progression of donor-transmitted plaque within 12-month after heart transplantation (HTx) using serial intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The association between inflammatory cytokines and plaque progression was also examined. Methods We prospectively enrolled 40 recipients to conduct serial three-vessel IVUS and OCT analysis at 8-week and 12-month after HTx. De novo plaque was defined as having maximum intimal thickness (MIT) ≥0.5 mm at 12-month in the absence of donor-transmitted plaques (MIT ≥0.5 mm at 8-week). Serum cytokines were screened with a bead-based multiplex assay. Results A total of 13 de novo plaques (fibrous, n=10; fibroatheroma, n=3) were detected in eight recipients. Serum interleukin (IL)-31 at 8-week was associated with the development of de novo plaques (p=0.009). A total of 31 donor-transmitted plaques (fibrous, n=12; fibroatheroma, n=11; fibrocalcific, n=8) were detected in 17 recipients. Multiple regression analysis revealed that fibrous (p=0.026) and fibroatheroma (p=0.012) observed at 8-week were significantly associated with subsequent plaque progression within 12-month after HTx. ΔPlaque burden was significant higher in de novo plaque than donor-transmitted plaque (38.8% [29.6–41.2] versus 8.7% [1.3–13.6], p Conclusions In de novo plaques, fibrous plaque was the most common and macrophage accumulation was rarely observed. In donor-transmitted plaque, fibrous and fibroatheroma were independent predictor for the subsequent plaque progression. Serum interleukin-31 surge at subacute phase may play pathogenic role in cardiac allograft vasculopathy. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grants-in-Aid for Scientific Research (KAKENHI)

The second half of the Spring 2020 semester has been an unprecedented time globally due to the ongoing coronavirus disease 2019 (COVID-19). COVID-19 pandemic has forced more than one billion students out of school, has disrupted the world and led all university courses switched to online instruction social distancing actions taken to limit the spread of the virus. The aim of the present study is to evaluate the pandemic related changes for undergraduate students, to assess their perspectives related to their learning, experiences in two courses, and to discuss the far-reaching potential implications for the upcoming summer and fall semesters. An electronic survey was conducted to gather data on the student perceptions and learning characteristics of this transition from face-to-face (F2F) to online at a medium-sized university in the Southeast in the Spring 2020 semester. Nearly 88% of the participants indicated that the COVID-19 pandemic impacted their education, while 19% indicated that they prefer online over F2F learning. Furthermore, the online modality significantly increased attendance in General Biology I. Our study also showed that the usage of live conferencing and digital applications increased due to the pandemic. The current research fills the gap in the existing literature by providing the first study on the effects of the ongoing COVID-19 pandemic on undergraduate learning and experiences in the most unique dual modality of the Spring 2020 semester.

In this study, we will present the synthesis of self-assembled coupled Au nanorods (NRs) as substrates capable of supporting a dual modality of surface enhanced spectroscopies, SERS and SEIRAS. The AuNR arrays can be assembled either through vertical alignment or lateral alignment. We will present different assembly strategies for the Au NRs by adjusting the ionic strength of the Au NR solution. The goal is to rely on self-assembly to create organized and reproducible sensors for small molecule detection. Field enhancement criteria differs between SERS and SEIRAS. We will also present the finite-difference time-domain (FDTD) simulation of the multilayered AuNR array across visible and SWIR spectral region to explain some of the experimental observations.

Early detection of drug-induced acute kidney injury (AKI) is crucial for effective treatment and prevention of further injury. It remains challenging, however, because of the lack of activatable indicators with multimodality imaging capability that could increase the accuracy of diagnosis by mutual verification. Herein, we report an activatable probe, FDOCl-22, that enabled dual-modality detection of the early-stage drug-induced AKI. FDOCl-22 was completely soluble in water and highly sensitive to hypochlorous acid (HOCl). Dramatic increases of both near-infrared (NIR) emission and absorption were observed after reaction with HOCl. A correlation between HOCl concentration and drug-induced AKI was established using FDOCl-22 as a tool. As a consequence, the HOCl-activated probe was able to detect the early-stage drug-induced AKI by dual-modality imaging, irrespective of the drug stimulation time or dosage, by combining NIR fluorescence and photoacoustic imaging.

The presence of auditory and visual senses enables humans to obtain a profound understanding of the real-world scenes. While audio and visual signals are capable of providing scene knowledge individually, the combination of both offers a better insight about the underlying event. In this paper, we address the problem of audio-visual event localization where the goal is to identify the presence of an event that is both audible and visible in a video, using fully or weakly supervised learning. For this, we propose a novel Audio-Visual Interacting Network (AVIN) that enables inter as well as intra modality interactions by exploiting the local and global information of the two modalities. Our empirical evaluations confirm the superiority of our proposed model over the existing state-of-the-art methods, in both fully as well as weakly supervised learning tasks, thus asserting the efficacy of our joint-modeling.