Dual-modality Imaging Research Articles

BSA-templated synthesis of Ir/Gd bimetallic oxide nanotheranostics for MR/CT imaging-guided photothermal and photodynamic synergistic therapy.

Precision medicine urges the development of theranostics which can efficiently integrate precise diagnosis and effective therapy. In this study, a facile synthesis of Ir/Gd bimetallic oxide nanotheranostics (termed BSA@Gd2O3/IrO2 NPs) with good biocompatibility was demonstrated using a biomineralization method where bovine serum albumin (BSA) served as a versatile template. BSA@Gd2O3/IrO2 NPs exhibited high longitudinal relaxivity (5.2 mM-1 s-1) and X-ray absorption capability (14.5 Hu mM-1), illustrating them to be a good contrast agent for magnetic resonance (MR) and computed tomography (CT) dual-modal imaging. Moreover, BSA@Gd2O3/IrO2 NPs can act as not only a photothermal conversion agent with ultrahigh efficiency (66.7%) as well as a good photosensitizer, but also an effective catalase to decompose endogenous H2O2 to produce O2, thus relieving hypoxia and enhancing the phototherapeutic effect. Both in vitro and in vivo experiments demonstrated the high effectiveness of BSA@Gd2O3/IrO2 NPs in MR/CT dual-modal imaging and photothermal and photodynamic synergistic tumor treatments. This work sheds new light on the development of versatile nanotheranostic systems using mild and robust biomineralization methods.

Artificially intelligent differential diagnosis of enlarged lymph nodes with random vector functional link network plus.

Differential diagnosis of enlarged lymph nodes (ELNs) is essential for the treatment of related patients. Though multi-modal ultrasound including B-mode, Doppler ultrasound, elastographyand contrast-enhanced ultrasound (CEUS)can enhance diagnostic performance for ELNs, the scenario of having only single or dual modal data is often encountered. In this study, an artificially intelligent diagnosis model based on the learning using privileged information was proposed to aid in differential diagnosis of ELNs in the case of single or dual modal images. In our model, B-mode, or combined with another modality, was used as the standard information (SI) and other modalities were used as the privileged information (PI). The model was constructed through the combination of the SI and PI in the training stage. By learning from the training samples, a random vector functional link network with privileged information (RVFL+) was obtained, which was used to classify the testing samples of solely the SI. Results showed that the accuracy, precision and Youden's index of the RVFL+ model, using B-mode with elastography as the SI and CEUS as the PI, reached 78.4%, 92.4% and 54.9%, increased by 14.0%, 8.4% and 24.5% compared with the model using B-mode as the SI without the PI. The method based on the LUPI can improve the diagnostic performance for ELNs.

Carbon dots as a new class of multifunctional nanomaterial in mesenchymal stem cells: opportunities and challenges.

Mesenchymal stem cells (MSCs) have long been regarded as a potential treatment in regenerative medicine. However, due to the lack of effective methods to track and regulate the behavior of implanted MSCs, their application has been greatly limited. Carbon dots (CDs), as a new type of zero-dimensional carbon-based nanomaterial, have attracted extensive attention as nanoprobes, carriers and agents. The focus of this review is to clarify the noninvasive tracing of MSCs by CD-based nanoprobes, including conventional and dual modality imaging, and introduce several means to adjust the labeling performance. The effects of CDs on the differentiation behavior of MSCs and their underlying mechanism are summarized. As an excellent delivery carrier, CDs can easily carry genes and direct MSCs to differentiate. Other biological effects of CDs as agents, such as anti-inflammatory, antibacterial, photodynamic and photothermal effects, are also introduced. Finally, the significant therapeutic effect of the combination of CDs and MSCs, the existing problems of CDs and the future development direction are proposed. This review aims to inform researchers in materials science, biology and medicine to fully exploit the potential of CDs and purposefully modified MSCs, so as to provide some ideas for the application of engineered cell therapy in clinical transformation.

Dual-modal molecular imaging and therapeutic evaluation of coronary microvascular dysfunction using indocyanine green-doped targeted microbubbles.

Coronary microvascular dysfunction (CMD), which causes a series of cardiovascular diseases, seriously endangers human health. However, precision diagnosis of CMD is still challenging due to the lack of sensitive probes and complementary imaging technologies. Herein, we demonstrate indocyanine green-doped targeted microbubbles (named T-MBs-ICG) as dual-modal probes for highly sensitive near-infrared (NIR) fluorescence imaging and high-resolution ultrasound imaging of CMD in mouse models. In vitro results show that T-MBs-ICG can specifically target fibrin, a specific CMD biomarker, via the cysteine-arginine-glutamate-lysine-alanine (CREKA) peptide modified on the surface of microbubbles. We further employ T-MBs-ICG to achieve NIR fluorescence imaging of injured myocardial tissue in a CMD mouse model, leading to a signal-to-background ratio (SBR) of up to 50, which is 20 fold higher than that of the non-targeted group. Furthermore, ultrasound molecular imaging of T-MBs-ICG is obtained within 60 s after intravenous injection, providing molecular information on ventricular and myocardial structures and fibrin with a resolution of 1.033 mm × 0.466 mm. More importantly, we utilize comprehensive dual-modal imaging of T-MBs-ICG to evaluate the therapeutic efficacy of rosuvastatin, a cardiovascular drug for the clinical treatment of CMD. Overall, the developed T-MBs-ICG probes with good biocompatibility exhibit great potential in the clinical diagnosis of CMD.

NIR-II fluorescence and PA imaging guided activation of STING pathway in photothermal therapy for boosting cancer immunotherapy by theranostic thermosensitive liposomes.

Photothermal immunotherapy has shown great potential for efficient cancer treatment. However, the immunosuppressive tumor microenvironment forms a heavy barrier for photothermal-induced anti-tumor immunity by inhibiting dendritic cell (DC) maturation and cytotoxic T cell response. Moreover, the lack of reliable spatiotemporal imaging modalities makes photothermal immunotherapy difficult to guide tumor ablation and monitor therapeutic outcomes in real time. Herein, we designed a theranostic thermosensitive liposome (PLDD) as a versatile nanoplatform to boost the adaptive anti-tumor immunity of photothermal immunotherapy and to achieve multiple bioimaging modalities in a real-time manner. PLDD contains two major functional components: a multifunctional photothermal agent (DTTB) and an immune potentiator STING pathway agonist (DMXAA). Upon irradiation, the heat generated by DTTB induced the immunogenic cell death (ICD) of the tumor and dissociated the structure of thermosensitive liposome to release DMXAA, which ultimately activated the STING pathway and promoted the ICD-induced immune response by increasing DC cell maturation and T cell recruitment. Moreover, the DTTB in PLDD displayed excellent second near-infrared (NIR-II) fluorescence and photoacoustic (PA) dual-modal imaging, which provided omnibearing information on the tumor and guided the subsequent therapeutic operation. Therefore, this versatile PLDD with light-triggered promotion of anti-tumor immunity and multiple spatiotemporal imaging profiles holds great potential for the future development of cancer immunotherapy.

131I labeled pH-responsive gold nanoparticles for bimodal tumor diagnosis

• Preparation of pH-responsive 131 I-labeled gold nano-particle molecular probe. • Aggregation of gold nanoparticles was explored based on the tumor microenvironment. • Dual-modality imaging further improves the diagnostic efficacy of tumors. Considering that each diagnostic method exhibits its disadvantages, such as the poor spatial resolution of SPECT and limited penetration depth of PA imaging, the development of a diagnosis integrated agent with dual-modality imaging performance is of great research interest. Herein, an interesting triggered mechanism, release, and aggregation of radiolabeled Au NPs were explored for tumor diagnosis based on the effect of H + in the tumor microenvironment. In vitro experiments reveal that the pH-responsive Au NPs exhibit an obvious accumulation effect and local surface plasmon resonance (LSPR) coupling effect and generate strong NIR absorption and can be used as the PA imaging agent. Importantly, Au aggregation only appears in the acid tumor microenvironment and displays excellent tumor SPECT diagnostic and photoacoustic imaging performance in vivo. This work provides a new synergistic strategy for SPECT and PA bimodal imaging to further improve the diagnostic efficacy of tumors.

Investigation of salt precipitation dynamic in porous media by X-ray and Neutron dual-modality imaging

In this work, a new dual modality monitoring technique is presented to demonstrate its interest to investigate the salt precipitation dynamics induced by gas flow-through drying. It consists of imaging simultaneously a core flood using both Neutron and X-ray beams. A method to calibrate and process the two signals is presented. It takes advantage of the difference in attenuation between the two ionizing radiations to quantify the different phase saturations and compositions as well as the reduction of porosity caused by salt precipitation. A set of experiments has been conducted at the NeXT-Grenoble beamline of the Institute Laue-Langevin facilities (ILL, France). Experiments were conducted on a homogeneous rock sample of Bentheimer sandstone using dry nitrogen and a 100 g/L KBr brine. The two first experiments aimed to calibrate the dual modality for the different phases. The last two experiments have been conducted with a brine capillary contact maintained at the gas outlet. Experimental data have given new insights into the organization of the three phases (the brine, the gas, and the precipitated salt) when a salt bank is formed in the sample. These quantities computed using dual-modality imaging show great similarities with published work. The salt accumulation was used to estimate the flow rate of brine pumped through the capillary contact to compensate for the brine evaporation in the gas phase. Observations have shown that a reduction of the initial porosity in some sections of the sample by 12–14% was enough to trigger a gas draw-down characterized by the migration of the salt toward the gas inlet. In some conditions (low gas inlet pressure for example), the rise of the water could be fast enough to form a second salt bank higher in the sample. It has been observed that the formation of the second salt bank could spread the precipitated salt in a less damaging configuration for the gas flow, triggering a phase of gas build-up characterized by the withdrawal of the water. These phases of gas draw-down and build-up could alternate until the sample clogs.

Starvation-assisted and photothermal-thriving combined chemo/chemodynamic cancer therapy with PT/MR bimodal imaging.

Chemodynamic therapy (CDT) reflects a novel reactive oxygen species (ROS)-related cancer therapeutic approach. However, CDT monotherapy is often limited by weak efficacy and insufficient endogenous H2O2. Herein, a multifunctional combined bioreactor (MnFe-LDH/MTX@GOx@Ta, MMGT) relying on MnFe-layered double hydroxide (MnFe-LDH) loaded with methotrexate (MTX) and coated with glucose oxidase (GOx)/tannin acid (Ta) is established for applications in H2O2 self-supply and photothermal enhanced chemo/chemodynamic combined therapy along with photothermal (PT) /magnetic resonance (MR) dual-modality imaging ability for cancer treatment. Once internalized into tumor cells, MMGT achieves starvation therapy by catalyzing the oxidation of glucose with GOx, accompanied by the regeneration of H2O2, enabling a Fenton-like reaction to accomplish GOx catalytic amplified CDT. Moreover, MMGT manifests significant tumor-killing ability through improved CDT performance with outstanding photothermal conversion efficiency (η = 52.2%) under 808 nm laser irradiation. In addition, the release of Mn2+ from MnFe-LDH in a solid tumor can significantly enhance T1-contrast MR imaging signals. Combined with MnFe-LDH-induced PT imaging under 808 nm laser irradiation, a dual-modality imaging directed theranostic nanoplatform has been developed. The present study provides a new strategy to design H2O2 self-supply and ROS evolving NIR light-absorption theranostic nanoagent for highly efficient and combined chemo/chemodynamic cancer treatment.

Biodegradable germanium nanoparticles as contrast agents for near-infrared-II photoacoustic imaging.

Photoacoustic (PA) imaging using contrast agents with strong near-infrared-II (NIR-II, 1000-1700 nm) absorption enables deep penetration into biological tissue. Besides, biocompatibility and biodegradability are essential for clinical translation. Herein, we developed biocompatible and biodegradable germanium nanoparticles (GeNPs) with high photothermal stability as well as strong and broad absorption for NIR-II PA imaging. We first demonstrate the excellent biocompatibility of the GeNPs through experiments, including the zebrafish embryo survival rates, nude mouse body weight curves, and histological images of the major organs. Then, comprehensive PA imaging demonstrations are presented to showcase the versatile imaging capabilities and excellent biodegradability, including in vitro PA imaging which can bypass blood absorption, in vivo dual-wavelength PA imaging which can clearly distinguish the injected GeNPs from the background blood vessels, in vivo and ex vivo PA imaging with deep penetration, in vivo time-lapse PA imaging of a mouse ear for observing biodegradation, ex vivo time-lapse PA imaging of the major organs of a mouse model for observing the biodistribution after intravenous injection, and notably in vivo dual-modality fluorescence and PA imaging of osteosarcoma tumors. The in vivo biodegradation of GeNPs is observed not only in the normal tissue but also in the tumor, making the GeNPs a promising candidate for clinical NIR-II PA imaging applications.

Modulation of hypoxia and redox in the solid tumor microenvironment with a catalytic nanoplatform to enhance combinational chemodynamic/sonodynamic therapy.

The efficacy of reactive oxygen species-mediated therapy is generally limited by hypoxia and overexpressed glutathione (GSH) in the tumor microenvironment (TME). To address these issues, herein, a smart Mn3O4/OCN-PpIX@BSA nanoplatform is rationally developed to enhance the combinational therapeutic efficacy of chemodynamic therapy (CDT) and sonodynamic therapy (SDT) through TME modulation. For constructing the catalytic nanoplatform (Mn3O4/OCN-PpIX@BSA), Mn3O4 nanoparticles were grown in situ on oxidized g-C3N4 (OCN) nanosheets, and the as-prepared Mn3O4/OCN nano-hybrids were then successively loaded with protoporphyrin (PpIX) and coated with bovine serum albumin (BSA). The catalase-like Mn3O4 nanoparticles are able to effectively catalyze the overexpressed endogenous H2O2 to produce O2, which could relieve hypoxia and improve the therapeutic effect of combinational CDT/SDT. The decomposition of Mn3O4 by GSH enables the release of Mn2+ ions, which not only facilitates good T1/T2 dual-modal magnetic resonance imaging for tumor localization but also results in the depletion of GSH and the Mn2+-driven Fenton-like reaction, thus further amplifying the oxidative stress and achieving improved therapeutic efficacy. It is worth noting that the Mn3O4/OCN-PpIX@BSA nanocomposites exhibit minimal toxicity to normal tissues at therapeutic doses. These positive findings provide a new strategy for the convenient construction of TME-regulating smart theranostic nanoagents to improve the therapeutic outcomes towards malignant tumors effectively.

Orthogonal integration of holographic and fluorescent dual images based on energy transfer from liquid crystals to a photocleavable AIEgen

Orthogonal integration of holographic and fluorescent dual-mode optical images with facile tunable emission colors has been achieved by precisely controlling the Förster resonance energy transfer and photocleavage reaction of an AIEgen.

Phosphorus core-shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters.

Nanoplatforms with amplified passive tumor targeting and enhanced protein resistance can evade unnecessary uptake by the reticuloendothelial system and achieve high tumor retention for accurate tumor theranostics. To achieve this goal, we here constructed phosphorus core-shell tecto dendrimers (CSTDs) with a rigid aromatic backbone core as a nanoplatform for enhanced fluorescence and single-photon emission computed tomography (SPECT) dual-mode imaging of tumors. In this study, the phosphorus P-G2.5/G3 CSTDs (G denotes generation) were partially conjugated with tetraazacyclododecane tetraacetic acid (DOTA), cyanine5.5 (Cy5.5) and 1,3-propane sulfonate (1,3-PS) and then labeled with 99mTc. The formed P-G2.5/G3-DOTA-Cy5.5-PS CSTDs possess good monodispersity with a particle size of 10.1 nm and desired protein resistance and cytocompatibility. Strikingly, compared to the counterpart material G3/G3-DOTA-Cy5.5-PS with both the core and shell components being soft poly(amidoamine) dendrimers, the developed P-G2.5/G3-DOTA-Cy5.5-PS complexes allow for more efficient cellular uptake and more significant penetration in 3-dimensional tumor spheroids in vitro, as well as more significant tumor retention and accumulation for enhanced dual-mode fluorescence and SPECT (after labelling with 99mTc) tumor imaging in vivo. Our studies suggest that the rigidity of the core for the constructed CSTDs matters in the amplification of the tumor enhanced permeability retention (EPR) effect for improved cancer nanomedicine development.

A supramolecular near-infrared nanophotosensitizer from host-guest complex of lactose-capped pillar[5]arene with aza-BODIPY derivative for tumor eradication

A supramolecular NIR nanophotosensitizer for dual-modal imaging and ablation of tumors was constructed by loading disulfiram (DSF) into the vesicle from host–guest complex of lactose-capped pillar[5]arene (LacP5) with aza-BODIPY derivative (BSTA).

Photo-sonodynamic therapy mediated with OLI_NPs to induce HPV16E7-specific immune response and inhibit cervical cancer in a Tc-1-grafted murine model.

Cervical carcinoma is the fourth most common gynecological cancer. Here we reported the synthesis of oxygen-carried and lipopolysaccharide (LPS)/ indocyanine green (ICG)-loaded nanoparticles (OLI_NPs) for photo-sonodynamic therapy (PSDT) mediated combination therapy to induce systemic antitumor immune responses. We effectively built a new nanoparticle system, a multifunctional nanoagent that integrated the ability of dual-model imaging and therapy for tumors. In this study, we confirmed that OLI_NPs can act as a multifunctional platform that enables not only to diagnose tumors conveniently but also to efficiently provide treatment of in situ tumors, permitting simultaneous dual-mode imaging and localization of the therapy in combination with PSDT-mediated drug release. Furthermore, our combined strategy could effectively depress the tumor development and extend mouse life by the combination of inducing immunogenic cell death (ICD) with encapsulated LPS. In conclusion, combining therapy of OLI_NPs plus PSDT can induce anti-tumor immune responses and tumor antigen-specific immunity in a common TC-1 graft tumor model. Therefore, this combination therapy is a viable technique for cervical cancer treatment.

Persistent luminescent metal-organic framework nanocomposite enables autofluorescence-free dual modal imaging-guided drug delivery.

Molecular imaging-guided therapy was essential for realizing precise cancer intervention, while designing an imaging platform to achieve autofluorescence-free imaging for dual modal imaging-guided drug delivery remains a challenge. Near-infrared persistent luminescence nanoparticles (NIR PLNPs) were promising for tumor imaging due to no background interference from the tissue. Herein, a persistent luminescent metal-organic framework (PLNPs@MIL-100(Fe)) is prepared via a layer-by-layer method for dual-modal imaging-guided drug delivery. The PLNPs@MIL-100(Fe) exhibit NIR persistent luminescence emitting and T2-weighted signal, achieving precise in vivo dual-modal imaging of tumor-bearing mice by providing high spatial resolution MR imaging and autofluorescence-free NIR imaging. The porous MIL-100(Fe) shell provides PLNPs@MIL-100(Fe) with up to 87.1% drug loading capacity and acid-triggered drug release for drug delivery. We envision that the proposed PLNPs@MIL-100(Fe) platform would provide an effective approach for precise tumor imaging and versatile drug delivery.

Albumin-based nanoparticle for dual-modality imaging of the lymphatic system.

The lymphatic system is a complex network of lymphatic vessels, lymph nodes, and lymphoid organs. The current understanding of the basic mechanism and framework of the lymphatic system is relatively limited and not ideal for exploring the function of the lymphatic system, diagnosing lymphatic system diseases, and controlling tumor metastasis. Imaging modalities for evaluating lymphatic system diseases mainly include lymphatic angiography, reactive dye lymphatic angiography, radionuclide lymphatic angiography, computed tomography, and ultrasonography. However, these are insufficient for clinical diagnosis. Some novel imaging methods, such as magnetic resonance imaging, positron emission computed tomography, single-photon emission computed tomography, contrast-enhanced ultrasonography, and near-infrared imaging with agents such as cyanine dyes, can reveal lymphatic system information more accurately and in detail. We fabricated an albumin-based fluorescent probe for dual-modality imaging of the lymphatic system. A near-infrared cyanine dye, IR-780, was absorbed into bovine serum albumin (BSA), which was covalently linked to a molecule of diethylenetriaminepentaacetic acid to chelate gadolinium Gd3+. The fabricated IR-780@BSA@Gd3+ nanocomposite demonstrates strong fluorescence and high near-infrared absorption and can be used as a T1 contrast agent for magnetic resonance imaging. In vivo dual-modality fluorescence and magnetic resonance imaging showed that IR-780@BSA@Gd3+ rapidly returned to the heart through the lymphatic circulation after it was injected into the toe webs of mice, facilitating good lymphatic imaging. The successful fabrication of the new IR-780@BSA@Gd3+ nanocomposite will facilitate the study of the mechanism and morphological structure of the lymphatic system.

Design of a near-infrared fluoro-photoacoustic probe for rapid imaging of carboxylesterase in liver injury.

Carboxylesterase (CE) is crucial in metabolizing ester-containing biomolecules and is particularly significant in liver metabolic diseases. Herein, we present the first activatable NIRF/PA dual-mode imaging probe QHD-CE for detection of CE in vitro and in vivo. QHD-CE displays excellent sensitivity and selectivity for CE with a high reaction efficiency (∼90 min). By utilizing QHD-CE, the dynamic changes of CE in drug-induced liver injury and diabetic mice models were monitored.

A trade-off between ligand coating and crystallinity of Gd-doped ultrasmall CeO2 for improving relaxivity.

A Gd-doped ultrasmall CeO2 contrast agent was prepared with high longitudinal relaxivity (r1 = 10.1 mM-1 s-1, 7.0 T) through rationally regulating the crystallinity and surface coatings, providing a new paradigm for optimizing MRI performance. Moreover, responsive photoacoustic imaging (PAI) was established via tumor microenvironment-triggered oxidation, affording dual-modal imaging.

An NIR fluorescent/photoacoustic dual-mode probe of NADPH for tumor imaging.

A novel probe was synthesized with a turn-on NIR fluorescent (NIRF)/photoacoustic (PA) response to NADPH, which was successfully applied in both monitoring intracellular NADPH and dual-modal imaging of tumor-bearing mice. It exhibits good potential in studying and understanding the tumor energy metabolism and treatment process related to NADPH.

Investigation of a dual-mode algorithm for joint processing of infrared and visible images based on a Residual Network

A dual-mode algorithm for processing images of infrared and visible light based on the ResNet152 network to implement the process of recognizing the external environment of unmanned vehicles in low light conditions is developed. It is proposed to split the input image into low-frequency and high-frequency parts by using medium filtering and then combine the low-frequency parts. In this case, high-frequency parts are introduced into the ResNet network to obtain maps of multilayer features. The experimental results show that the target detection and recognition technology based on the processing of dual-mode images of infrared and visible light has higher accuracy and reliability than single-mode image detection and recognition. Keywords image processing, infrared imaging, visible light imaging, residual network