Biomedical Imaging Applications Research Articles

Reduction Triggered In Situ Polymerization in Living Mice.

"Smart" biomaterials that are responsive to physiological or biochemical stimuli have found many biomedical applications for tissue engineering, therapeutics, and molecular imaging. In this work, we describe in situ polymerization of activatable biorthogonal small molecules in response to a reducing environment change in vivo. We designed a carbohydrate linker- and cyanobenzothiazole-cysteine condensation reaction-based small molecule scaffold that can undergo rapid condensation reaction upon physiochemical changes (such as a reducing environment) to form polymers (pseudopolysaccharide). The fluorescent and photoacoustic properties of a fluorophore-tagged condensation scaffold before and after the transformation have been examined with a dual-modality optical imaging method. These results confirmed the in situ polymerization of this probe after both local and systemic administration in living mice.

Rare earth element doped hydroxyapatite luminescent bioceramics contrast agent for enhanced biomedical imaging and therapeutic applications

The design and synthesis of alternative biocompatible, luminescent bioimaging agent for application in diagnostics imaging and preventive medicine is very important for the future of biomedicine. With an advanced flexible structure of hydroxyapatite (HAp), rare earth ions (Gd3+, Eu3+) were doped to achieve an enhanced luminescent optical property. A facile wet co-precipitation method was employed to dope Gd3+, and Eu3+ on host HAp structure (Eux-Gdx-HAp). Different sophisticated characterization instruments, such as powder X-Ray diffraction, Fourier transformed infrared (FTIR) spectroscopy, micro Raman spectroscopy, Thermogravimetric-differential thermal analysis (TG-DTA), Brunauer-Emmett-Teller (BET) surface area analysis confirms the hexagonal crystal structure, functional groups, high thermal stability, with large surface area and average pore size. The optical properties were measured by diffusive reflectance spectroscopy (DRS), photoluminescence (PL) spectroscopy, and fluorescence imaging. The enhanced luminescence could be observed due to “Gd–Eu” co-doping, which causes energy transfer (6IJof Gd3+→5HJof Eu3+) under 273 nm excitation with possible combination effect of the cooperative up-conversion and subsequent energy transfer under 394 nm excitation respectively. The in vitro study confirms the intracellular nontoxic behavior of Eux-Gdx-HAp nanocrystals with good biocompatibility. Further in vivo studies with Eux-Gdx-HAp nanocrystals confirms the cell labelling and in vivo imaging capabilities. The synthesized biocompatible, nontoxic Eux-Gdx-HAp nanomaterials has the potential to act as a luminescence enhanced contrast agent for biomedical fluorescent imaging applications.

Metal-organic frameworks-based nanozymes for combined cancer therapy

• This review summarized the recent progress in metal-organic frameworks (MOFs)-based nanozymes for cancer combination therapy. • The fundamental catalysis mechanisms and general synthetic strategies for MOFs-based nanozymes were discussed. • The progress was described with four new categories based on the characteristic factors in tumor microenvironment. • The current challenges and perspectives of these smart nanoplatforms on the future research directions were proposed. Nanomaterials with enzyme-like catalytic activity, named as nanozymes, have aroused wide research interest owing to their striking merits bridging nanotechnology and biology. Metal-organic frameworks (MOFs) are a novel class of porous inorganic-organic hybrid materials made from metal ions/clusters and organic ligands, and have shown great prospect in the construction of novel nanozymes, making the as-emerged MOFs-based nanozymes promising candidates for biosensing, biocatalysis, biomedical imaging, and therapeutic applications. In this feature article, we tend to systematically summarize the recent process concerning MOFs-based nanozymes for combined cancer therapy, which emerged as a new trend in clinical oncology in view of the synergistic therapeutic efficacy and reduced side effects originating from different treatments. Firstly, classic kinds of MOFs-based nanozymes are briefly described with representatives for catalysis mechanism analysis. Secondly, general strategies for construction of MOFs-based nanozymes are discussed. Thirdly, recent advances in the application of MOFs-based nanozymes for dual or triple combination of therapeutic modalities have been reviewed in detail with a particular emphasis focusing upon underlying synergistic mechanisms involved in each combination formulation. Finally, current challenges and future perspectives of MOFs-based nanozymes with a view to maximizing their great potential in the research of translational medicine are also discussed. It is highly expected that our demonstration on this evolving area will play a more important role in the field of the personalized nanomedicine in combating cancer.

Design of Thermoresponsive Polyamine Cross-Linked Perfluoropolyether Hydrogels for Imaging and Delivery Applications

Perfluorocarbons are versatile compounds with applications in 19F magnetic resonance imaging (MRI) and chemical conjugation to drugs and pH sensors. We present a novel thermoresponsive perfluorocarbon emulsion hydrogel that can be detected by 19F MRI. The developed hydrogel contains perfluoro(polyethylene glycol dimethyl ether) (PFPE) emulsion droplets that are stabilized through ionic cross-linking with polyethylenimine (PEI). Specifically, PFPE ester undergoes hydrolysis upon contact with aqueous PEI solution, resulting in an ionic bond between the PFPE acid and charged PEI amino groups. Due to the ionic nature of the PFPE/PEI bond, potassium buffer is required to preserve the hydrogel's pH and rheological and emulsion droplet stability. The presence of the surface cross-linked PFPE droplets does not affect the hydrogel's rheological behavior, drug loading, or drug release, and the hydrogel is nontoxic. We propose that the presented hydrogel can be adapted to a broad range of biomedical imaging and delivery applications.

Longer and Stronger: Improving Persistent Luminescence in Size-Tuned Zinc Gallate Nanoparticles by Alcohol-Mediated Chromium Doping.

Benefiting from near-infrared persistent luminescence, chromium-doped zinc gallate nanoparticles have become appealing for background-free biomedical imaging applications, where autofluorescence from adjacent tissues no longer poses a problem. Nevertheless, the synthesis of persistent luminescent nanoparticles with controllable and biologically appropriate size, high luminescence intensity, and long persistent duration remains very challenging. Herein, we report a solvothermal synthetic route for preparing differently sized ZnGa2O4:Cr nanoparticles with a particle size tunable from 4 to 31 nm and afterglow duration longer than 20 h. The route involves lower reaction temperatures and involves no reworking of the particles postsynthesis, providing materials that have far fewer unwanted defects and much higher luminescence yields (up to 51%). It was found that methanol played a paramount role in obtaining the Cr3+-doped ZnGa2O4 nanoparticles. The effects of methanol were discussed in combination with NMR spectroscopy studies and theoretical calculations, and the underlying alcohol-mediated growth and doping mechanisms were elucidated, which will be beneficial for developing highly persistent luminescent nanoparticles.

Imaging reconstruction through strongly scattering media by using convolutional neural networks

As an object passes through strongly scattering slab, it cannot be imaged, due to scattering slab scrambling the object information. In this paper, we employ convolutional neural network (CNN) to realize the imaging reconstruction in such a specific optical system where an object is located between two strongly scattering slabs. The influence of the thickness of the scattering slabs on the imaging reconstruction is investigated, in which we can obtain the imaging reconstruction from the object–speckle pairs of the object passing through the certain thickness of scattering slab, by using the trained CNN with the certain object–specklepairs. It is shown that good reconstructed images are achieved for three different thickness of the scattering slab. Moreover the so-called hybrid trained network is employed, in which we train the network by using totally 9000 object–speckle pairs from three sets of data, each set of data we selecting equal 3,000 pairs of object–speckle​ patterns, corresponding to the three different thickness of the rear scattering slabs. We find that hybrid trained network is capable of reconstructing the image from speckles taken from the three different scattering conditions Our approach may have applications in biomedical imaging.

Multiresponsive Nanoprobes for Turn-On Fluorescence/19F MRI Dual-Modal Imaging.

Multiresponsive nanoprobes are highly desirable for low background and highly sensitive imaging in biomedical applications. Herein, we design a glutathione (GSH)/pH dual-responsive nanoprobe capable of both fluorescence imaging in cells and 19F magnetic resonance imaging (19F MRI) in deep tissue, by encapsulating manganese oleate (Mn(OA)2) on the surface of fluorinated fluorescent quantum dots (F-ZnS:Mn2+). In this approach, Mn(OA)2 serves as an efficient quencher of both fluorescence and 19F MRI signal. Both the fluorescence and 19F MRI signal can be turned on by introducing glutathione (GSH) that breaks up the Mn-O bonds within Mn(OA)2 under weak acidity conditions (e.g., pH 6.0). The imaging results in cells and mice suggest that this novel strategy can offer a promising nanoprobe for turn-on fluorescence/19F MRI dual-modal tumor imaging.

Simple synthesis of photoluminescent carbon dots from a marine polysaccharide found in shark cartilage

Abstract Background For more than a decade, water-soluble, eco-friendly, biocompatible, and low-toxicity fluorescent nanomaterials have received considerable attention for their numerous in vivo and in vitro applications in biomedical imaging, disease diagnostics, and environmental monitoring. Owing to their tunable photoluminescence properties, carbon-based luminescent nanomaterials have shown great potential in bioimaging, photocatalysis, and biosensing among other applications. Results Marine environments provide excellent resources for the fabrication of these nanomaterials, because many marine organisms contain interesting trigger organic compounds that can be used as precursors. Herein, we synthesize multi-color emissive carbon dots (CDs) with an intrinsic photoluminescence quantum yield of 20.46%. These nanostructures were achieved through the one-step hydrothermal treatment of marine polysaccharide chondroitin sulfate, obtained from shark cartilage, in aqueous solution. Conclusions We successfully demonstrate the low toxicity of our marine resource-derived CDs in zebrafish, and provide an initial assessment of their possible use as a bioimaging agent. Notably, the newly synthesized CDs localize in the intestines of zebrafish larvae, thereby indicating their biocompatibility and potential use as in vivo dyes. How to cite: Kim KW, Choi TY, Kwon YM, et al. Simple synthesis of photoluminescent carbon dots from a marine polysaccharide found in shark cartilage. Electron J Biotechnol 2020;47. https://doi.org/10.1016/j.ejbt.2020.07.003 .

Germanium iodide mediated synthesis of nanodiamonds from adamantane “seeds” under moderate high-pressure high-temperature conditions

There is an emerging demand for nanodiamonds with controlled structures or shapes for applications in biomedical imaging and sensing. Synthetic conditions proceeding at less harsh temperatures and pressures are considered crucial to control nanodiamond formation process. We report a germanium iodide (GeI4) mediated synthesis of nanodiamonds from diamondoid molecules and alkane hydrocarbon under moderate high-pressure high-temperature (m-HPHT) conditions. For the first time, GeI4 is used to generate nanodiamonds at 3.5 GPa and 500 °C, which is considerably lower than the conditions reported for common HPHT methods for nanodiamond synthesis. The strategy reported herein allows synthesizing nanodiamonds based on well-defined molecular precursors, which paves the way to a bottom-up diamond synthesis designed at a molecular level.

Biomacromolecular fluorescent nanoparticles co-assembled by bovine serum albumin and DNA segments for living cell imaging

Fluorescent nanoparticles have been widely used in the field of biomedical engineering because they are usually biocompatible, cost-effective and homogeneously uniform. In this study, we describe a biomacromolecular fluorescent nanoparticle prepared with a facile disolvating process using bovine serum albumin, DNA segments and SYBR Green I. The obtained co-assemblies, termed DNA@BSA nanoparticles, had a narrow and relatively uniform size distribution with an average size of about 122 nm and the PDI value 0.087. Cellular uptake results demonstrated well internalization of DNA@BSA nanoparticles by the Michigan Cancer Foundation-7 (MCF-7) cells. Together with the fluorescent tag of SYBR Green I molecules, DNA@BSA nanoparticles accumulated in the cell cytoplasm after cellular internalization enabled the MCF-7 cells for fluorescent imaging. This study provided a new strategy for constructing biomacromolecular fluorescent nanoparticles for applications in biomedical engineering and biomedical imaging.

Early-Stage Detection of Melanoma Skin Cancer Using Contactless Millimeter-Wave Sensors

Studies show that the early (stage I) diagnosis of cancer increases the survival rate of patients, and significantly reduces treatment costs. Millimeter-wave radars can detect skin tumors based on the difference between the electrical properties of melanomas and healthy skin tissues. This paper proposes a low-power multitone continuous-wave radar design at 77GHz for biomedical imaging applications, to be used for skin cancer detection. The sensor implementation is based on a low-cost Miniature Hybrid Microwave Integrated Circuit (MHMIC) design. The entire sensor was integrated on a 0.127mm thin ceramic substrate. Two 16-element patch antenna arrays are implemented in the transmitter and receiver modules. The receiver is a six-port homodyne quadrature down-converter. The integrated power detectors are fabricated using HSCH-9161 Schottky diodes. The sensor was encapsulated in a metallic fixture with dimensions 35 by 45mm. Two cascaded amplifier circuits are designed and implemented for amplifying baseband voltages at the output of each power detector. The proposed radar design has the ability to detect the dielectic properties of tissues, making it suitable for the detection of melanomas with an accuracy on the order of tens of microns.

Ultrasmall Europium, Gadolinium, and Dysprosium Oxide Nanoparticles: Polyol Synthesis, Properties, and Biomedical Imaging Applications.

Imaging agents are crucial in diagnosing diseases. Ultrasmall lanthanide oxide (Ln2O3) nanoparticles (NPs) (Ln = Eu, Gd, and Dy) are promising materials as high-performance imaging agents because of their excellent magnetic, optical, and X-ray attenuation properties which can be applied as magnetic resonance imaging (MRI), fluorescence imaging (FI), and X-ray computed tomography (CT) agents, respectively. Ultrasmall Ln2O3 NPs (Ln = Eu, Gd, and Dy) are reviewed here. The reviewed topics include polyol synthesis, characterization, properties, and biomedical imaging applications of ultrasmall Ln2O3 NPs. Recently published papers were used as bibliographic databases. A polyol method is a simple and efficient one-pot synthesis for preparing ultrasmall Ln2O3 NPs. Ligand-coated ultrasmall Ln2O3 NPs have good colloidal stability, biocompatibility, and renal excretion ability suitable for in vivo imaging applications. Ultrasmall Eu2O3 NPs display photoluminescence in the red region suitable for use as FI agents. Ultrasmall Gd2O3 NPs have r1 values higher than those of commercial molecular contrast agents and r2/r1 ratios close to 1, which make them eligible for use as T1 MRI contrast agents. Ultrasmall Dy2O3 NPs exhibit high r2 and negligible r1 values, which make them suitable for use as T2 MRI contrast agents. All ultrasmall Ln2O3 NPs have high X-ray attenuation powers which make them suitable for use as CT contrast agents. Unmixed, mixed, or doped ultrasmall Ln2O3 NPs with different Ln are extremely useful for in vivo imaging applications in MRI, CT, FI, MRI-CT, MRI-FI, CT-FI, and MRI-CT-FI.

Transparent nano hydroxyapatite coated platform for bone cell imaging

Hydroxyapatite is an essential inorganic component of bone tissue which is important for bone cell biology. In laboratory, bone cells are routinely cultured on glass or plastic plates with lacking HA. Some commercial plates coated with HA are now available for investigating osteoclast bone resorption. However, the opaque nature of these plates limits further application to investigating bone cell biology. It is impossible to observe real-time interactions between hydroxyapatite and bone cells under microscope. In this study, glasses with HA nano-coating were prepared by the hydrothermal process. This nano-coating platform (HCP) offers a stage to image real-time interactions between hydroxyapatite and bone cells directly. The ease of fabrication and the repeatability of this platform approach could open a host of biomedical imaging applications in bone biology research as well as bone drug development. Different osteocytes were used to detect the biocompatibility and imaging advantages of the platform. The results showed that the platform could simulate the native bone environment and reflect the state of the bone cells accurately.

Optically Transparent Focused Transducers for Combined Photoacoustic and Ultrasound Microscopy

PurposePhotoacoustic (PA) microscopy has emerged as a useful tool in biomedical imaging applications such as visualization of microvasculature and hemoglobin oxygen saturation, single-cell, and label-free imaging of organs including cancer. Since the ultrasound transducers used for PA signal detection are not optically transparent, the integration of optical and acoustic modules for coaxial alignment of laser and acoustic beam fields in PA microscopy is complex and costly.MethodsHere, we report a recently developed optically transparent focused transducer for combined PA and ultrasound (US) microscopy. All the acoustic layers including the acoustic lens are optically transparent, enabling simple integration of optical and acoustic modules for both imaging modalities.ResultsThe mean light transmittance of the transducer’s backing layer and acoustic lens and of the transducer itself were measured at 92%, 83%, and 66%, respectively. Results from in vitro and in vivo experiments demonstrated the transducer to be suitable for both US and PA imaging.ConclusionsThe results of this study represent a step toward efficient construction of probes for combined PA and US microscopy.

Theoretical investigation of optical intersubband transitions and infrared photodetection in β-(AlxGa1 − x)2O3/Ga2O3 quantum well structures

We provide theoretical consideration of intersubband transitions designed in the ultra-wide bandgap aluminum gallium oxide [(AlxGa1 − x)2O3]/gallium oxide (Ga2O3) quantum well system. Conventional material systems have matured into successful intersubband device applications such as large-area quantum well infrared photodetector (QWIP) focal plane arrays for reproducible imaging systems but are fundamentally limited via maximum conduction band offsets to mid- and long-wavelength infrared applications. Short- and near-infrared devices are technologically important to optical communication systems and biomedical imaging applications but are difficult to realize in intersubband designs for this reason. In this work, we use a first-principles approach to estimate the expansive design space of monoclinic β-(AlxGa1 − x)2O3/Ga2O3 material system, which reaches from short-wavelength infrared (1–3 μm) to far infrared (>30 μm) transition wavelengths. We estimate the performance metrics of two QWIPs operating in the long- and short-wavelength regimes, including an estimation of high room temperature detectivity (∼1011 Jones) at the optical communication wavelength λp = 1.55 μm. Our findings demonstrate the potential of the rapidly maturing (AlxGa1 − x)2O3/Ga2O3 material system to open the door for intersubband device applications.

Spectroelectrochemical Study of Organic-Inorganic Hybrid Nano-Molecular Clusters Exhibiting Voltage-Gated Fluorescence Switching and Electrochromism.

Polyhedral boranes especially the twelve vertex closo-dodecaborate and ten vertex closo-decaborate anions exhibit remarkably high thermal stability and resistance to oxidative degradation. Such high stability is attributed to the extensive delocalization of their framework bonding electrons, giving rise to three dimensional aromaticity. The substitution chemistry of polyhedral boron chemistry using aromatic ligands was previously limited in scope. However, we recently reported new and extensive polysubstitution chemistry for these ions. The structural characterization of these products revealed that up to ten of B-H vertices may be replaced with phenyl, substituted phenyl, or polycyclic aromatic hydrocarbons as ligands through the formation of stable boron-carbon bonds. The resulting organic-inorganic hybrid nano-molecular ions are pseudospherical whose diameters range between 1.3 – 3.5 nanometers depending on the ligands involved. These polyarylborane clusters are found to exhibit interesting electronic and spectroscopic properties, including high solution-phase fluorescence quantum yields, high molar absorptivities, and extraordinarily large stoke shifts. Furthermore, the fluorescence emission, excitation and absorption spectra for most of these products change reversibly upon applying product-specific electrochemical potentials, thus resulting in redox-controlled fluorescence switching and electrochromism. The properties of each polyarylborane depend upon the composition and the structure of the bound ligands, and these may be tailored through chemical modification of the surface. Our study suggest that these new nanomaterials may have the potential for applications in biomedical imaging and sensor development. This presentation will focus on the details of syntheses, structural characterization, electrochemical and spectroelectrochemical properties of polyarylboranes.

Silicon nanoparticles with iron impurities for multifunctional applications

Crystalline silicon (Si) nanoparticles (NPs) doped with iron (Fe) in the range from 0.02 to 2.5 at.% were prepared by plasma-ablative synthesis and were investigated by means of the transmission electron microscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), infrared spectroscopy and nuclear magnetic resonance relaxometry. While the nanocrystal size in Si:Fe NPs did not depend significantly on Fe content, the hydrodynamic diameter of NPs in aqueous suspensions increases from 50 to 180[Formula: see text]nm. Both the transverse and longitudinal proton relaxation time were found to decrease in the prepared suspensions of Si:Fe NPs. Maximal shortening of the transverse relaxion was observed for Si:Fe NPs with 0.2 at.% of Fe and the relaxation rate was almost linearly proportional to the NP concentration. Both these findings and in vivo tests indicate that Si:Fe NPs are promising for biomedical applications in magnetic resonance imaging (MRI) and therapy of cancer.

FTIR microspectroscopy revealed biochemical changes in liver and kidneys as a result of exposure to low dose of iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) have biomedical and biotechnological applications in magnetic imaging, drug-delivery, magnetic separation and purification. The biocompatibility of such particles may be improved by covering them with coating. In presented paper the biochemical anomalies of liver and kidney occurring in animals exposed to d-mannitol-coated iron(III) oxide nanoparticles (M-IONPs) were examined with Fourier transform infrared (FTIR) microspectroscopy. The dose of IONPs used in the study was significantly lower than those used so far in other research. Liver and kidney tissue sections were analysed by chemical mapping of infrared absorption bands originating from proteins, lipids, compounds containing phosphate groups, cholesterol and cholesterol esters. Changes in content and/or structure of the selected biomolecules were evaluated by comparison of the results obtained for animals treated with M-IONPs with those from control group. Biochemical analysis of liver samples demonstrated a few M-IONPs induced anomalies in the organ, mostly concerning the relative content of the selected compounds. The biomolecular changes, following exposition to nanoparticles, were much more intense within the kidney tissue. Biochemical aberrations found in the organ samples indicated at increase of tissue density, anomalies in fatty acids structure as well as changes in relative content of lipids and proteins. The simultaneous accumulation of lipids, phosphate groups as well as cholesterol and cholesterol esters in kidneys of rats exposed to IONPs may indicate that the particles stimulated formation of lipid droplets within the organ.

Switchable Quarter-Wave Plate and Half-Wave Plate Based on Phase-Change Metasurface

Wave plates as important polarization control devices are widely used in the applications of biomedical imaging, fiber optical communication, astronomy, semiconductor industry and aerospace etc. To make the wave plate actively tunable, we propose a rectangular antenna-based metasurface based on the phase-changing material Ge2Sb2Te5 (GST) with high transmittance and polarization conversion rate. Before the GST phase transition, the metasurface operates as a quarter-wave plate in the wavelength range of 10.0–11.9 μm. After the GST turning into crystalline state, the metasurface operates as a half-wave plate in the wavelength range of 10.3–10.9 μm. The physical mechanism for the high transmittance efficiency and polarization conversion rate attributes to the combination of the electric dipole and magnetic dipole resonances. Moreover, the adjustable wavelength range can be further extended by changing the geometry of antenna-based GST to selectively enhancing or suppressing the electric and magnetic resonances. This work provides a new strategy for tunable wave plate, which would have the potential in the application of multi-functional integrated optical systems.

THz Pulsed Imaging in Biomedical Applications

Recent advances in technology have allowed the production and the coherent detection of sub-ps pulses of terahertz (THz) radiation. Therefore, the potentialities of this technique have been readily recognized for THz spectroscopy and imaging in biomedicine. In particular, THz pulsed imaging (TPI) has rapidly increased its applications in the last decade. In this paper, we present a short review of TPI, discussing its basic principles and performances, and its state-of-the-art applications on biomedical systems.