Multimodal Imaging Applications Research Articles

Novel facets of multifunctional Ag@Fe3O4 core-shell nanoparticles for multimodal imaging applications

Biocompatible nanoparticles, with magnetic cores and optically active shells, acting as multifunctional materials with a core size of 6 nm encapsulated in silver shells of varying thickness were synthesized through a novel single phase microemulsion method. Incorporation of silver shells onto the magnetite core enhances the intensity of the highest luminescence peak observed for magnetite by a significant luminescence enhancement factor. A blue photoluminescence peak observed in the visible region of spectrum brightens further with the increase in the thickness of silver shell. The magnetic properties of these core-shell nanomaterials show superparamagnetic behavior at room temperature, which is a mandatory criterion for MRI contrast enhancement agents. The hyperthermic response of synthesized magnetite nanoparticles elevates its temperature to 43 °C in a sharp span of time, which is above the desired temperature for the therapeutic application of these multifunctional nanomaterials. These excellent optical and magnetic properties, of the material having a size range suitable for cellular uptake, make it a potential candidate for both diagnostic and therapeutic uses in biomedical applications.

Application of aptamers for in vivo molecular imaging and theranostics.

Nucleic acid aptamers are small three-dimensional structures of oligonucleotides selected to bind to a target of interest with high affinity and specificity. In vitro, aptamers already compete with antibodies to serve as imaging probes, e.g. for microscopy or flow cytometry. However, they are also increasingly used for in vivo molecular imaging. Accordingly, aptamers have been evaluated over the last twenty years in almost every imaging modality, including single photon emission computed tomography, positron emission tomography, magnetic resonance imaging, fluorescence imaging, echography, and x-ray computed tomography. This review focuses on the studies that were conducted in vivo with aptamer-based imaging probes. It also presents how aptamers have been recently used to develop new types of probes for multimodal imaging and theranostic applications.

Ultrasound Technology for Molecular Imaging: From Contrast Agents to Multimodal Imaging.

Ultrasound (US) takes advantage of ultrasound contrast agents (UCAs) to further increase the sensitivity and specificity of monitoring at the cellular level, which has had a considerable effect on the modern molecular imaging field. Gas-filled microbubbles (MBs) as UCAs in the bloodstream generate resonant volumetric oscillations in response to rapid variations in acoustic pressure, which are related to both the acoustic parameters of applied ultrasound and the physicochemical properties of the contrast agents. Nanoscale UCAs have been developed and have attracted much attention due to their utility in detecting extravascular lesions. Ultrasound molecular assessment is achieved by binding disease-specific ligands to the surface of UCAs, which have been designed to target tissue biomarkers in the area of interest, such as blood vessels, inflammation, or thrombosis. Additionally, the development of multimodal imaging technology is conducive for integration of the advantages of various imaging techniques to acquire additional diagnostic information. In this review paper, the present status and the critical issues for developing ultrasound contrast agents and multimodal imaging applications are described. Conventional MB UCAs are first introduced, including their research material, diagnostic applications, and intrinsic limitations. Then, recent progress in developing targeted UCAs and phase-inversion contrast agents for diagnostic purposes is discussed. Finally, we review the present status and the critical issues for developing ultrasound-based multimodal imaging applications and summarize the existing challenges and future prospects.

Preparation and characterization of alginate based-fluorescent magnetic nanoparticles for fluorescence/magnetic resonance multimodal imaging applications

Simple and versatile methodologies have been reported that customize the surface of superparamagnetic iron oxide (SPIO) nanoparticles and impart additional fluorescence capabilities to these contrast agents. Herein, we present the rational design, synthesis, characterization, and biological applications of a new magnetic-based fluorescent probe. The dual modality imaging protocol was developed by labeling fluorophore with alginate natural polymers that have excellent biocompatibility and biodegradability, and using gelification method to form nanocomposites containing SPIO. The formation of alginate-based fluorescent magnetic (AFM) nanoparticles was observed in spherical and elliptical forms with a diameter of less than 500 nm by a transmission electron microscope (TEM). The fluorescent wavelength band in the range of 560 nm was also confirmed in the UV–visible spectrophotometer. In this study, we demonstrate that the multi-tasking design of AFM nanoparticles provides an ideal platform for building balanced dual-image probes of magnetic resonance imaging and optical imaging.

Recent Progress in Synthesis and Functionalization of Multimodal Fluorescent-Magnetic Nanoparticles for Biological Applications

There is a great interest in the development of new nanomaterials for multimodal imaging applications in biology and medicine. Multimodal fluorescent-magnetic based nanomaterials deserve particular attention as they can be used as diagnostic and drug delivery tools, which could facilitate the diagnosis and treatment of cancer and many other diseases. This review focuses on the recent developments of magnetic-fluorescent nanocomposites and their biomedical applications. The recent advances in synthetic strategies and approaches for the preparation of fluorescent-magnetic nanocomposites are presented. The main biomedical uses of multimodal fluorescent-magnetic nanomaterials, including biological imaging, cancer therapy and drug delivery, are discussed, and prospects of this field are outlined.

Multifunctional bacterial imaging and therapy systems.

Bacterial infections have severely affected human health, leading to a considerable number of human deaths. Inevitably direct and indirect contacts with medical devices, food packing and daily supplies with harmful bacteria are among the major transmission routes of bacterial infections. Effective bacterial theranostic systems that combine diagnostic functions and therapeutic effects have received extensive attention due to their excellent features including high efficiency, real-time performance and low drug resistance. In this review article, we summarize the recent advances of antibacterial materials including natural antibacterial compounds, quaternary ammonium polymers, and inorganic or hybrid nanoparticles with the dual functions of detection and imaging. In particular, multiple imaging modalities and antibacterial modalities are systematically discussed in order to provide a better understanding of modern theranostics.

Multimodal imaging for a theranostic approach in a murine model of B-cell lymphoma with engineered nanoparticles

Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.

Macroscale multimodal imaging reveals ancient painting production technology and the vogue in Greco-Roman Egypt

Macroscale multimodal chemical imaging combining hyperspectral diffuse reflectance (400–2500 nm), luminescence (400–1000 nm), and X-ray fluorescence (XRF, 2 to 25 keV) data, is uniquely equipped for noninvasive characterization of heterogeneous complex systems such as paintings. Here we present the first application of multimodal chemical imaging to analyze the production technology of an 1,800-year-old painting and one of the oldest surviving encaustic (“burned in”) paintings in the world. Co-registration of the data cubes from these three hyperspectral imaging modalities enabled the comparison of reflectance, luminescence, and XRF spectra at each pixel in the image for the entire painting. By comparing the molecular and elemental spectral signatures at each pixel, this fusion of the data allowed for a more thorough identification and mapping of the painting’s constituent organic and inorganic materials, revealing key information on the selection of raw materials, production sequence and the fashion aesthetics and chemical arts practiced in Egypt in the second century AD.

PEGylated crosslinked hyaluronic acid nanoparticles designed through a microfluidic platform for nanomedicine.

A high versatile microfluidic platform is proposed to design, in a one-step strategy, PEGylated crosslinked hyaluronic acid nanoparticles (cHANPs) entrapping a magnetic resonance imaging contrast agent and a dye for multimodal imaging applications. Clinically relevant biomaterials were shaped in the form of spherical NPs through a microfluidic flow focusing approach. A comparison between post processing and simultaneous PEGylation is reported to evaluate the potentiality of the chemical decoration of the cHANPs in microfluidics. An accurate control of the NPs in terms of size, PEGylation and loading was obtained. Furthermore, in vitro cell viability is reported and their ability to boost the magnetic resonance imaging signal is also confirmed. The proposed microfluidic approach reveals its ability to overcome several limitations of the traditional processes and to become an easy-to-use platform for theranostic applications.

Microwave–assisted synthesis of water–disperse and biocompatible NaGdF4: Yb,Ln@NaGdF4 nanocrystals for UCL/CT/MR multimodal imaging

In this paper, we have developed a series of rare earth fluoride nanocrystals (NCs) that can be used for multimodal imaging applications. Three highly monodisperse and water dispersible NaGdF4:Yb,Ln@NaGdF4 (Ln=Er, Tm, Ho) upconversion luminescence (UCL) NCs with an average size of 75nm were prepared using a facile and efficient microwave–assisted solvothermal reaction in ethylene glycol (EG). The morphology, crystal structures, size distributions and zeta potentials of the resulting NCs were fully characterized by transmission electron microscopy (TEM), X–ray diffraction (XRD) and Nano–ZS90 Zetasizer. The obtained NaGdF4:Yb,Ln@NaGdF4 (Ln=Er, Tm, Ho) NCs could emit bright blue, green and red luminescence in water upon laser excitation at 980nm. Furthermore, these core–shell NCs exhibited low cytotoxicity for HeLa and C9H2 cells, separately. Moreover, these NCs also displayed excellent Hounsfield units (HU) values in X–ray computed tomography (CT) imaging and high relaxivity parameters (r1) in magnetic resonance (MR) imaging in vitro. Thus, these small, water–dispersible and biocompatible NCs show excellent potential as contrast agents for UCL/CT/MR multimodal imaging and other biomedical applications.

Hybrid Core-Shell (HyCoS) Nanoparticles produced by Complex Coacervation for Multimodal Applications

Multimodal imaging probes can provide diagnostic information combining different imaging modalities. Nanoparticles (NPs) can contain two or more imaging tracers that allow several diagnostic techniques to be used simultaneously. In this work, a complex coacervation process to produce core-shell completely biocompatible polymeric nanoparticles (HyCoS) for multimodal imaging applications is described. Innovations on the traditional coacervation process are found in the control of the reaction temperature, allowing a speeding up of the reaction itself, and the production of a double-crosslinked system to improve the stability of the nanostructures in the presence of a clinically relevant contrast agent for MRI (Gd-DTPA). Through the control of the crosslinking behavior, an increase up to 6 times of the relaxometric properties of the Gd-DTPA is achieved. Furthermore, HyCoS can be loaded with a high amount of dye such as ATTO 633 or conjugated with a model dye such as FITC for in vivo optical imaging. The results show stable core-shell polymeric nanoparticles that can be used both for MRI and for optical applications allowing detection free from harmful radiation. Additionally, preliminary results about the possibility to trigger the release of a drug through a pH effect are reported.

In vivo pentamodal tomographic imaging for small animals.

Multimodality molecular imaging emerges as a powerful strategy for correlating multimodal information. We developed a pentamodal imaging system which can perform positron emission tomography, bioluminescence tomography, fluorescence molecular tomography, Cerenkov luminescence tomography and X-ray computed tomography successively. Performance of sub-systems corresponding to different modalities were characterized. In vivo multimodal imaging of an orthotopic hepatocellular carcinoma xenograft mouse model was performed, and acquired multimodal images were fused. The feasibility of pentamodal tomographic imaging system was successfully validated with the imaging application on the mouse model. The ability of integrating anatomical, metabolic, and pharmacokinetic information promises applications of multimodality molecular imaging in precise medicine.

Core-shell and co-doped nanoscale metal-organic particles (NMOPs) obtained via post-synthesis cation exchange for multimodal imaging and synergistic thermo-radiotherapy

Nanoscale metal-organic particles (NMOPs) have recently shown great promise in the area of nanomedicine owing to their tunable compositions, highly enriched functionalities, well-defined sizes/shapes and intrinsic biodegradability. Herein, we describe the fabrication of NMOPs with both core-shell and co-doped structures via a post-synthesis cation exchange method for applications in multimodal imaging and combined photothermal and radiation therapy of cancer. Template NMOPs containing Mn2+ and IR825, a near-infrared (NIR) dye, are first synthesized and then mixed with Hf4+ to obtain core-shell and co-doped Mn/Hf-IR825 NMOPs depending on the dose of added Hf4+ ions. In these NMOPs, Mn2+ offers strong T1 magnetic resonance (MR) contrast, Hf4+ is a high-Z element with excellent computed tomography signal enhancement ability and radio-sensitization capability, and IR825 exhibits rather high NIR absorbance. After coating with polydopamine (PDA) and further conjugation with polyethylene glycol (PEG), the co-doped Mn/Hf-IR825@PDA-PEG particles (NMOP-PEG) showed efficient tumor-homing ability after intravenous injection, as illustrated by MR and photoacoustic (PA) imaging. Utilizing NMOP-PEG achieved excellent tumor killing efficacy through in vivo photothermal and radiation synergistic therapy in our mouse tumor model experiments. Importantly, our NMOP-PEG showed no appreciable toxicity to the treated mice and could be efficiently excreted. Our work presents a facile method to fabricate NMOP-PEG with multi-component structures as a biodegradable, multifunctional nanoplatform for multimodal image-guided combination cancer therapy.

The application of multimodal molecular imaging in the diagnosis of dementia with Lewy bodies

Objective To evaluate the value of multimodal molecular imaging in the diagnosis of dementia with Lewy bodies (DLB). Methods Five patients with probable DLB received detailed clinical data collection, neuropsychological tests, head MRI examination, 11 C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropane ( 11 C-β-CFT) PET, 11 C-Pittsburgh compound B ( 11 C-PIB) PET and 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET examination. Results Cognitive dysfunction and visual hallucinations were prominent symptoms in patients with DLB. 11 C-β-CFT PET showed that the radioactive uptake significantly reduced in bilateral putamen and caudate nuclei. 11 C-PIB PET showed increased radioactive retention in bilateral frontal, temporal, parietal and occipital cortex with various degrees. 18 F-FDG PET showed glucose hypometabolism in bilateral parietal and occipital cortex. Conclusions Multimodal molecular imaging greatly improves the specificity of clinical diagnosis of DLB, and it is expected to achieve accurate diagnosis before death. DOI: 10.3969/j.issn.1672-6731.2017.01.009

All‐in‐One Theranostic Nanoplatform Based on Hollow TaOx for Chelator‐Free Labeling Imaging, Drug Delivery, and Synergistically Enhanced Radiotherapy

Despite extensive use of radiotherapy in cancer treatment, there has been huge demand to improve its efficacy and accuracy in tumor destruction. To this end, nanoparticle‐based radiosensitizers, particularly those with high‐Z elements, have been explored to enhance radiotherapy. Meanwhile, imaging is an essential tool prior to the individual planning of precise radiotherapy. Here, hollow tantalum oxide (H‐TaOx) nanoshells are prepared using a one‐pot template‐free method and then modified with polyethylene glycol (PEG), yielding H‐TaOx‐PEG nanoshells for imaging‐guided synergistically enhanced radiotherapy. H‐TaOx‐PEG nanoshells show strong intrinsic binding with metal ions such as Fe3+ and 99mTc4+ upon simple mixing, enabling magnetic resonance imaging and single photon emission computed tomography imaging, respectively, which are able to track in vivo distribution of those nanoshells and locate the tumor. With mesoporous shells and large cavities, those H‐TaOx‐PEG nanoshells show efficient loading of 7‐ethyl‐10‐hydroxycamptothecin (SN‐38), a hydrophobic chemotherapeutic drug. By means of the radiosensitization effect of Ta to deposit X‐ray energy inside tumors, as well as SN‐38‐induced cell cycle arrest into radiation‐sensitive phases, H‐TaOx‐PEG@SN‐38 can offer remarkable synergistic therapeutic outcome in the combined chemoradiotherapy. Without appreciable systemic toxicity, such hollow‐TaOx nanostructure may therefore find promising applications in multimodal imaging and enhanced cancer radiotherapy.

Epilepsy in multiple sclerosis: The role of temporal lobe damage

Background: Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. Objectives: To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. Methods: A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. Results: Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS (p< 0.05 for all comparisons). Conclusions: Compared to RRMS, RRMS/E showed more severe damage of temporal lobe, which exceeds what would be expected on the basis of the global GM damage observed.

Effect of Core/Shell Interface on Carrier Dynamics and Optical Gain Properties of Dual-Color Emitting CdSe/CdS Nanocrystals.

Two-color emitting colloidal semiconductor nanocrystals (NCs) are of interest for applications in multimodal imaging, sensing, lighting, and integrated photonics. Dual color emission from core- and shell-related optical transitions has been recently obtained using so-called dot-in-bulk (DiB) CdSe/CdS NCs comprising a quantum-confined CdSe core embedded into an ultrathick (∼7-9 nm) CdS shell. The physical mechanism underlying this behavior is still under debate. While a large shell volume appears to be a necessary condition for dual emission, comparison between various types of thick-shell CdSe/CdS NCs indicates a critical role of the interface "sharpness" and the presence of potential barriers. To elucidate the effect of the interface morphology on the dual emission, we perform side-by-side studies of CdSe/CdS DiB-NCs with nominally identical core and shell dimensions but different structural properties of the core/shell interface arising from the crystal structure of the starting CdSe cores (zincblende vs wurtzite). While both structures exhibit dual emission under comparable pump intensities, NCs with a zincblende core show a faster growth of shell luminescence with excitation fluence and a more readily realized regime of amplified spontaneous emission (ASE) even under "slow" nanosecond excitation. These distinctions can be linked to the structure of the core/shell interface: NCs grown from the zincblende cores contain a ∼3.5 nm thick zincblende CdS interlayer, which separates the core from the wurtzite CdS shell and creates a potential barrier for photoexcited shell holes inhibiting their relaxation into the core. This helps maintain a higher population of shell states and simplifies the realization of dual emission and ASE involving shell-based optical transitions.

Lasers for Optogenetics and Multimodal Microscopy

AbstractA new type of short‐pulse ultrafast laser sources provides extremely wide (680 — 1300 nm) wavelength tunability of the primary output as well as simultaneous high power (1.5 watts) output at 1040 nm. This combination makes lasers such as the Chameleon Discovery ideal for demanding multiphoton excitation applications in optogenetics, multimodal imaging, and other microscopy applications that need two independent wavelengths. In this article we will see why these applications benefit from this performance.

Radioactive Nanomaterials for Multimodality Imaging.

Nuclear imaging techniques, primarily including positron emission tomography and single-photon emission computed tomography, can provide quantitative information for a biological event in vivo with ultrahigh sensitivity; however, the comparatively low spatial resolution is their major limitation in clinical application. With the convergence of nuclear imaging with other imaging modalities like computed tomography, magnetic resonance imaging, and optical imaging, the hybrid imaging platforms can overcome the limitations of each individual imaging technique. Possessing versatile chemical linking ability and good cargo-loading capacity, radioactive nanomaterials can serve as ideal imaging contrast agents. Here, we provide a brief overview about the current state-of-the-art applications of radioactive nanomaterials in multimodality imaging. We present strategies for incorporation of radioisotope(s) into nanomaterials with the applications of radioactive nanomaterials in multimodal imaging. Advantages and limitations of radioactive nanomaterials for multimodal imaging applications are discussed. Finally, a future perspective of possible radioactive nanomaterial utilization is presented for improving diagnosis and patient management in a variety of diseases.

Facile and large-scale synthesis of active platform for multimodality imaging and cancer treatment applications

Facile and large-scale synthesis of active platform for multimodality imaging and cancer treatment applications