Bimodal Imaging Research Articles

Carbon nano dot decorated copper nanowires for SERS-Fluorescence dual-mode imaging/anti-microbial activity and enhanced angiogenic activity.

Copper nanoparticles are explored significantly for their antimicrobial activity, especially for antibiotic-resistant strain infections. However, copper has severe toxic responses and mostly it is due to its generation capability of reactive oxygen species (ROS) molecules while interacting with invitro or invivo systems. In the current study, wire shaped copper nanostructures were synthesized via microwave irradiation with single step doping of carbon nanodots (CDs). The synthesized material (CuCs) was characterized by UV-Vis spectroscopy, fluorescence spectroscopy, FTIR, TEM, FESEM, XRD, DLS, and XPS. The fluorescence spectroscopy, microscopy and Raman spectroscopy results suggested CuCs to work well as a bi-modal imaging nanoprobe (fluorescence/SERS). The cell culture studies prove significant cytocompatibility and ROS scavenging property of the samples with respect to control. Further, CuCs-gelatin nanocomposite thin films were prepared and implanted into rodent deep wound model. The histological study has showed enhanced angiogenesis in the subcutaneous region. The results were validated by immuno-histochemistry. The ROS scavenging and enhanced angiogenesis were validated via gene expression studies and a HIF-α induced enhanced angiogenesis mechanism was also proposed for better wound healing.

Novel Oxygen-Deficient Zirconia (ZrO2-x) for Fluorescence/Photoacoustic Imaging-Guided Photothermal/Photodynamic Therapy for Cancer.

Theranostic nanoplatforms that integrate therapy and diagnosis in a single composite have become increasingly attractive in the field of precise and efficient tumor treatment. Herein, a novel oxygen-deficient zirconia (ZrO2-x) nanosystem based on the conjugation of thiol-polyethylene glycol-amine (SH-PEG-NH2) and chlorin e6 (Ce6) was elaborately designed and established for efficacious photothermal/photodynamic therapy (PTT/PDT) and fluorescence/photoacoustic (FL/PA) bimodal imaging for the first time. The crystalline-disordered, PEGylated ZrO2-x nanoparticles (ZP NPs) displayed strong optical absorption in the near-infrared (NIR) window and were featured with significant photothermal conversion capacity. The ZP NPs were further covalently conjugated with Ce6 to form ZrO2-x@PEG/Ce6 (ZPC) NPs, which displayed a long circulatory half-life, efficient tumor accumulation, and outstanding FL/PA imaging performance. Moreover, the nanocomposites effectively generated cytotoxic intracellular reactive oxygen species (ROS) responsive to laser activation. Both cell studies and animal experiments explicitly demonstrated that ZPC NPs mediated remarkable tumor ablation with minimal systemic toxicity thanks to their tumor-specific PTT/PDT effect. Collectively, these findings may open up new avenues to broaden the application of oxygen-deficient ZrO2-x nanostructures as high-performance photothermal agents in tumor theranostics through rational design and accurate control of their physiochemical properties.

Differential Diagnosis and Precision Therapy of Two Typical Malignant Cutaneous Tumors Leveraging Their Tumor Microenvironment: A Photomedicine Strategy.

Elevated hydrogen peroxide (H2O2) in biological tissues is generally recognized to be relevant to the carcinogenesis process that regulates the proliferative activity of cancer cells and the transformation of malignant features. Inspired by this observation, it can be hypothesized that imaging H2O2 in the tumor microenvironment (TME) could help diagnose tumor types and malignancy, and even guide precise therapy. Thus, in this study, a noninvasive photomedicine strategy is demonstrated that leverages the different levels of H2O2 in the TME, and two representative skin cancers, malignant melanoma (MM, clinically higher incidence of metastasis and recurrence) and cutaneous squamous cell carcinoma (cSCC, relatively less dangerous), are differentially diagnosed. The working probe used here is one we previously developed, namely, intelligent H2O2 responsive ABTS-loaded HRP@Gd nanoprobes (iHRANPs). In this study, iHRANPs have advantages over ratiometric imaging due to their bimodal imaging elements, in which the inherent magnetic resonance imaging (MR) mode can be used as the internal imaging reference and the H2O2 responsive photoacoustic (PA) imaging modality can be used for differential diagnosis. Results showed that after intravenous injection of iHRANPs, the tumor signals on both MM and cSCC are obviously enhanced without significant difference under the MR modality. However, under the PA modality, MM and cSCC can be easily distinguished with obvious variations in signal enhancement. Particularly, guided by PA imaging, photothermal therapy (PTT) can be precisely applied on MM, and a strong antitumor effect was achieved owing to the excessive H2O2 in the TME of MM. Furthermore, exogenous H2O2 was injected into cSCC to remedy H2O2 deficiency in the TME of cSCC, and an evident therapeutic efficacy on cSCC can also be realized. This study demonstrated that MM can be differentially diagnosed from cSCC by noninvasive imaging of H2O2 in the TME with iHRANPs; meanwhile, it further enabled imaging-guided precision PTT ablation, even for those unsatisfactory tumor types (cSCC) through exogenously delivering H2O2.

PET probe with Aggregation Induced Emission characteristics for the specific turn-on of aromatase

Aromatase is an attractive target for the diagnosis and treatment of breast cancer. To combine the anti-photobleaching properties of Aggregation Induced Emission (AIE) with the high sensitivity and whole-body imaging characteristics of positron emission tomography (PET), we designed a bifunctional complexing agent with AIE characteristics by modifying the structure of tetraphenylethene, which is linked with triazole derivatives capable of complexing with natGa3+/68Ga3+ to obtain [natGa/68Ga] 2 for targeting the aromatase. [natGa] 2 has typical AIE characteristics, which can form uniform nanomicelles above the critical micelle concentration, and illuminate estrogen receptor (+) MCF-7 cells. [natGa] 2 itself is almost nonemissive in PBS buffer solution, but it turns on its fluorescence upon interaction with human aromatase, with a detection limit of 0.15 μg/mL [68Ga] 2 is easy to prepare and has high stability. Compared to the estrogen receptor that is negatively expressed by MDA-MB-231 cells, MCF-7 cells positively expressing estrogen have a higher uptake of [natGa] 2. The distribution of aromatase in a tumor can be co-localized by using [68Ga] 2. These results can be used to effectively assess estrogen receptor status and aromatase levels at the cellular level. We anticipate that this research could provide a new strategy for the fabrication of PET probes with AIE characteristics, providing useful probes for PET- FL (Fluorescence imaging) bimodal imaging.

77P - Red-blood-cell-membrane-enveloped magnetic nanoclusters as a biomimetic theranostic nanoplatform for bimodal imaging guided cancer photothermal therapy

BackgroundDue to their intrinsic thermal and magnetic resonance imaging properties, magnetic nanoparticles (MNCs) have attracted more and more attention in the biomedical field. However, relatively weak photothermal conversion (PTC) efficiency and low tumor homing capacity has hampered its further application in vivo. MethodsTo solve these problems, we modified near-infrared (NIR) light-absorbing materials onto the surface of MNCs to increase PTC efficiency and increase MNCs tumor homing capacity by coated red blood cell (RBC) membranes. ResultsOur data show that after being loaded with NIR cypate molecules, the as-prepared Cyp-MNCs showed remarkably increased NIR absorbance and resultant PTC efficiency compared with the MNCs. By disguising itself, Cyp-MNCs coated with erythrocyte membranes inherit the long circulation characteristics of RBCs to improve the MNCs’ tumor homing capacity. By tracking the NIR fluorescence of cypate under an in vivo fluorescence imaging system, we discovered that such Cyp-MNC@RBCs upon intravenous injection show significantly improved tumor homing capacity compared with bare cypate-loaded MNCs. The antitumor efficiency of biomimetic Cyp-MNC@RBCs was particularly prominent and was superior to biomimetic MNC@RBCs. Additionally, fluorescence and T2-weighted magnetic resonance imaging (MRI) functionalities were all retained attributable to Cyp-MNC@RBCs cores. ConclusionsOur study would provide a promising procedure for other similarly enhanced photothermal treatments by increasing PTC efficincies and improving tumor-homing capacity. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

A Melanin-Based Natural Antioxidant Defense Nanosystem for Theranostic Application in Acute Kidney Injury.

Acute kidney injury (AKI) is frequently associated with oxidative stress and causes high mortality annually in clinics. Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for the treatment of AKI. Herein, a novel biomedical use of the endogenous biopolymer melanin as a theranostic natural antioxidant defense nanoplatform for AKI is reported. In this study, ultrasmall Mn2+-chelated melanin (MMP) nanoparticles are easily prepared via a simple coordination and self-assembly strategy, and further incorporated with polyethylene glycol (MMPP). In vitro experiments reveal the ability of MMPP nanoparticles to scavenge multiple toxic reactive oxygen species (ROS) and suppress ROS-induced oxidative stress. Additionally, in vivo results from a murine AKI model demonstrate preferential renal uptake of MMPP nanoparticles and a subsequent robust antioxidative response with negligible side effects according to positron emission tomography/magnetic resonance (PET/MR) bimodal imaging and treatment assessment. These results indicate that the effectiveness of MMPP nanoparticles for treating AKI suggests the potential efficacy of melanin as a natural theranostic antioxidant nanoplatform for AKI, as well as other ROS-related diseases.

Hierarchically Nanostructured Hybrid Platform for Tumor Delineation and Image-Guided Surgery via NIR-II Fluorescence and PET Bimodal Imaging.

Bimodal imaging with fluorescence in the second near infrared window (NIR-II) and positron emission tomography (PET) has important significance for tumor diagnosis and management because of complementary advantages. It remains challenging to develop NIR-II/PET bimodal probes with high fluorescent brightness. Herein, bioinspired nanomaterials (melanin dot, mesoporous silica nanoparticle, and supported lipid bilayer), NIR-II dye CH-4T, and PET radionuclide 64 Cu are integrated into a hybrid NIR-II/PET bimodal nanoprobe. The resultant nanoprobe exhibits attractive properties such as highly uniform tunable size, effective payload encapsulation, high stability, dispersibility, and biocompatibility. Interestingly, the incorporation of CH-4T into the nanoparticle leads to 4.27-fold fluorescence enhancement, resulting in brighter NIR-II imaging for phantoms in vitro and in situ. Benefiting from the fluorescence enhancement, NIR-II imaging with the nanoprobe is carried out to precisely delineate and resect tumors. Additionally, the nanoprobe is successfully applied in tumor PET imaging, showing the accumulation of the nanoprobe in a tumor with a clear contrast from 2 to 24 h postinjection. Overall, this hierarchically nanostructured platform is able to dramatically enhance fluorescent brightness of NIR-II dye, detect tumors with NIR-II/PET imaging, and guide intraoperative resection. The NIR-II/PET bimodal nanoprobe has high potential for sensitive preoperative tumor diagnosis and precise intraoperative image-guided surgery.

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) for dual-modality imaging of intracranial glioblastoma via EGFRvIII targeting.

In this work, a peptide-modified, biodegradable, nontoxic, brain-tumor-targeting nanoprobe based on superparamagnetic iron oxide nanoparticles (SPIONs) (which have been commonly used as T2-weighted magnetic resonance (MR) contrast agents) was successfully synthesized and applied for accurate molecular MR imaging and sensitive optical imaging. PEPHC1, a short peptide which can specifically bind to epidermal growth factor receptor variant III (EGFRvIII) that is overexpressed in glioblastoma, was conjugated with SPIONs to construct the nanoprobe. Both in vitro and in vivo MR and optical imaging demonstrated that the as-constructed nanoprobe was effective and sensitive for tumor targeting with desirable biosafety. Given its desirable properties such as a 100 nm diameter (capable of penetration of the blood–brain barrier) and bimodal imaging capability, this novel and versatile multimodal nanoprobe could bring a new perspective for elucidating intracranial glioblastoma preoperative diagnosis and the accuracy of tumor resection.

Yolk–Shell Structured Au Nanostar@Metal–Organic Framework for Synergistic Chemo-photothermal Therapy in the Second Near-Infrared Window

Light-sensitive yolk-shell nanoparticles (YSNs) as remote-controlled and stimuli-responsive theranostic platforms provide an attractive method for synergistic cancer therapy. Herein, a kind of novel stimuli-responsive multifunctional YSNs has been successfully constructed by integrating star-shaped gold (Au star) nanoparticles as the second near-infrared (NIR-II) photothermal yolks and biodegradable crystalline zeolitic imidazolate framework-8 (ZIF-8) as the shells. In this platform, a chemotherapeutic drug (doxorubicin hydrochloride, DOX) was encapsulated into the cavity, which can show the behavior of controlled release due to the degradation process of ZIF-8 in the mildly acidic tumor microenvironment. Upon the 1064 nm (NIR-II biowindow) laser irradiation, gold nanostar@ZIF-8 (Au@MOF) nanoparticles exhibited outstanding synergistic anticancer effect based on their photothermal and promoted cargo release properties. Moreover, the strong NIR region absorbance endows the Au@MOF of NIR thermal imaging and photoacoustic (PA) imaging properties. This work contributes to design a stimuli-responsive "all-in-one" nanocarrier that realizes bimodal imaging diagnosis and chemo-photothermal synergistic therapy.

Multifunctional Nanodroplets Encapsulating Naphthalocyanine and Perfluorohexane for Bimodal Image-Guided Therapy.

Although nanocarriers containing perfluorocarbon (PFC) have been widely investigated as an ultrasound (US) imaging agent and a high intensity focused ultrasound (HIFU) agent, these carriers have suffered from low stability and biocompatibility limiting their further biomedical applications. Here, we developed surface cross-linked polymer nanodroplets as a HIFU therapeutic agent guided by bimodal photoacoustic (PA) and US imaging. Pluronic F127 was reacted with 4-nitrophenyl chloroformate (NPC) and mixed with naphthalocyanine (Nc) in dichloromethane, which was added into the aqueous solution of amine-functionalized six-arm-branched poly(ethylene glycol) (PEG) to form an oil-in-water emulsion for the cross-linking reaction between the terminal NPC of Pluronic F127 and the primary amine of six-arm PEG. The resulting solution was sonicated with liquid perfluorohexane (PFH) to prepare PEG cross-linked Pluronic F127 nanoparticles encapsulating Nc and PFH (Nc/PFH@PCPN). Nc/PFH@PCPN appeared to be stable without any coalescence or vaporization in the physiological condition. Upon the application of HIFU, Nc/PFH@PCPN was vaporized and showed increased US intensity for 180 min. The Nc dye in the nanodroplets enabled the stable encapsulation of PFH and the bimodal US/PA imaging. In vivo PA/US image-guided HIFU ablation therapy confirmed that the nanodroplets increased the cavitation effect, induced necrosis and apoptosis of tumor cells, and reduced tumor growth significantly for 12 days. Taken together, the multifunctional Nc/PFH@PCPN was successfully developed as a new platform for PA/US image-guided HIFU therapy.

CT and CEST MRI bimodal imaging of the intratumoral distribution of iodinated liposomes.

To develop liposomes loaded with iodinated agents as nanosized CT/MRI bimodal contrast agents for monitoring liposome-mediated drug delivery. Rhodamine-labeled iodixanol (VisipaqueTM)-loaded liposomes (IX-lipo) were prepared and tested for their properties as a diamagnetic CEST contrast agent in vitro. Mice bearing subcutaneous CT26 colon tumors were injected i.v. with 1 g/kg (535 mg iodine/kg) IX-lipo, and in vivo CT and CEST MR images were acquired on day 3. CT and CEST MR images were also acquired for tumor-bearing mice co-injected with IX-lipo and tumor necrosis factor (TNF-α). In addition to CT contrast, IX-lipo exhibited a strong CEST contrast similar to its non-liposomal form, with a detectability of ~2 nM per liposome. Both CT imaging and CEST MRI showed that i.v. injection of IX-lipo resulted in a rim enhancement of CT26 tumors with a heterogeneous central distribution. In contrast, co-injection of TNF-α caused a significantly augmented CT/MRI contrast in the tumor center. The intratumoral biodistribution of IX-lipo correlated well to the rhodamine patterns observed with fluorescence microscopy. We have developed a CT/MRI bimodal imaging approach for monitoring the delivery and biodistribution of liposomes by loading them with the clinically approved X-ray/CT contrast agent iodixanol. Our approach may be easily adapted for other-FDA approved iodinated agents and thus has great translational potential.

Hybrid silica-coated Gd-Zn-Cu-In-S/ZnS bimodal quantum dots as an epithelial cell adhesion molecule targeted drug delivery and imaging system.

Dual-modal imaging probes based on fluorescence (FL) and magnetic resonance (MR) modalities have attracted great attention due to their ability to combine the target specificity and high penetration into body tissues. In this study, we developed a potent nanocarrier with an effective photoluminescent emission and MR imaging capacity to deliver the doxorubicin to breast cancer 4T1 cells. The nanocarrier was fabricated by coating of quantum dots (QDs) with mesoporous silica followed by amine functionalization of the silica surface. Then, the doxorubicin was loaded into the silica pores and biheterofunctional PEG was covalently bound to the surface of core-shell quantum dot mesoporous silica nanoparticles. In order to target the DOX-loaded nanoparticles, the EpCAM DNA aptamer was attached on the surface of the DOX-loaded PEGylated nanoparticles. The synthesized NPs were analyzed for their size distribution, morphology, zeta potential and magnetic susceptibility using HRTEM, SEM and VSM analysis. The QD-encapsulated mesoporous silica revealed spherical shapes with an average particle size of 100 nm. The maximum encapsulation efficacy of doxorubicin in the silica pores was 25%. The in vitro release assessment demonstrated the pH-sensitive release of doxorubicin from the designed formulations. The in vitro cytotoxicity assays indicated that the aptamer targeted nanoparticles showed greater cytotoxicity than both non-targeted NPs and free DOX toward 4T1 and MCF-7 cell lines. The in vivo studies in 4T1 tumor-bearing Balb/c mice demonstrated that EpCAM aptamer could specifically deliver the DOX-loaded nanoparticles into the tumor tissue and cause remarkable inhibition of tumor growth as compared to non-targeted formulation and free DOX. Moreover, the in vivo MR and fluorescent imaging in 4T1 tumor-bearing mice confirmed the accumulation and residence of targeted system in tumor tissue even 24 h post-injection. This work presents a novel system for preparing bimodal imaging theranostic NPs through hybridization of silica and magnetic-fluorescent quantum dots.

High-resolution bimodal imaging and potent antibiotic/photodynamic synergistic therapy for osteomyelitis with a bacterial inflammation-specific versatile agent

Unsatisfactory diagnosis and therapy of osteomyelitis are still common but challenging issues for clinicians. To overcome these problems, a bacterial inflammation-specific multifunctional agent, denoted bovine serum albumin-manganese dioxide-ubiquicidin29-41-indocyanine green (ICG) -gentamicin (BMUIG), was synthesized for combined high-resolution bimodal imaging and antibiotic/photodynamic therapy for osteomyelitis. BMUIG binding affinity and antibacterial ability were assessed by using Staphylococcus aureus (S. aureus). Photoacoustic/magnetic resonance imaging was performed on a mouse model of acute osteomyelitis after intravenous injection of BMUIG. Then, myelitis-bearing mice were treated with antibiotic/photodynamic combination therapy. BMUIG specifically targeted S. aureus in comparison with non-targeted agents. In the osteomyelitis model, the infection area was identified accurately and quickly through ICG-based photoacoustic imaging and Mn2+-based T1 magnetic resonance imaging after injection of BMUIG. Furthermore, the manganese dioxide in BMUIG reacted with the locally produced hydrogen peroxide under acidic inflammatory conditions, continuously generating oxygen for enhanced photodynamic therapy. In combination with low-dose gentamicin, a synergistic antibacterial effect was observed and bone infection was resolved. In summary, a non-invasive accurate diagnosis and effective synergistic therapy for osteomyelitis was successfully developed using a bacterial inflammation-specific versatile agent, which would provide a sound theranostic strategy for common infectious diseases. Statement of SignificanceOsteomyelitis is one of the most serious consequences in orthopedics. However, its inaccurate diagnosis and low-effective antibiotic treatment are still common but challenging issues for clinicians. To overcome these problems, we uniquely designed a bacterial inflammation-specific multifunctional nanoagent, bovine serum albumin-manganese dioxide-ubiquicidin29-41-indocyanine green-gentamicin (BMUIG), for high-resolution bimodal imaging and antibiotic/photodynamic combined therapy of osteomyelitis. Herein, high-resolution imaging technologies refer to classic magnetic resonance imaging and emerging photoacoustic imaging. Photodynamic therapy is subtly introduced because of its safe and effective killing mechanism, which can synergize the bactericidal effect of antibiotics. As a result, we successfully realize non-invasive accurate diagnosis and effective synergistic therapy for osteomyelitis by virtue of the bacterial inflammation-specific versatile agent, which will serve as a promising candidate for sound theranostics in common infectious diseases.

A Correlative Bimodal Surface Imaging Method to Assess Hyphae-Rock Interactions.

A Correlative Bimodal Surface Imaging Method to Assess Hyphae-Rock Interactions.

Magnetic-responsive and targeted cancer nanotheranostics by PA/MR bimodal imaging-guided photothermally triggered immunotherapy

While theranostic nanoparticle (TNP)-based photothermal therapy (PTT) exhibits prominent promise for cancer therapy, metastatic cancers remain one of the main obstacles of effective PTT. Immunotherapy has been developed vigorously to inhibit metastatic cancers, but the heterogeneity of patients and the complexities of manufacturing cancer vaccines significantly hinder its further clinical applications. Herein, a photothermally triggered immunotherapeutic paradigm under imaging guidance was designed based on magnetic-responsive immunostimulatory nanoagents (MINPs) loaded with superparamagnetic iron oxide (SPIO) nanoparticles and cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs). The fabricated MINPs with the clinically approved components acted not only as a contrast agent for photoacoustic (PA)/magnetic resonance (MR) bimodal imaging but also as a magnetic-targeting therapeutic agent for photothermally triggered immunotherapy. Under external magnetic fields, the MINPs showed a great magnetic-targeting ability, leading to high accumulation of the photoabsorber (SPIO) and the immunoadjuvant (CpG ODNs) in the tumors for precise bimodal imaging guidance. More importantly, the excellent photothermal conversion effect of the MINPs upon near-infrared (NIR) exposure enabled the effective photothermal destruction of the primary tumors, releasing tumor-associated antigens and showing ‘autologous cancer vaccine’-like functions, thus activating robust antitumor immune responses, especially in the presence of CpG ODN-containing immunostimulatory nanoagents. Such generated immune responses can further attack the remaining tumors and distant metastatic tumors in mice. This work provides an imaging-guided photothermally triggered immunotherapeutic strategy based on multifunctional MINPs to effectively eliminate primary tumors and inhibit metastatic tumors simultaneously with high specificity, easy maneuverability and favorable biocompatibility. This strategy may potentially be applicable for precise individualized diagnosis and therapy of various tumors.

Fluorescent and magnetic stellate mesoporous silica for bimodal imaging and magnetic hyperthermia

There is currently a crucial need of innovative multifunctional nanoparticles combining, in one formulation, imaging and therapy capacities allowing thus an accurate diagnosis and a therapy monitored by imaging. Multimodal imaging will ensure to speed up diagnosis, and to increase its sensitivity, reliability and specificity for a better management of the disease. Combined with a therapeutic action, it will also enable to treat the disease in a specific personalized manner in feedback mode. The mastered design of such bioprobes as well as the demonstration of their efficiency are still challenges to face in nanomedicine. In this work, novel fluorescent and magnetic core–shell nanocomposites have been designed to ensure, in one nanoformulation, bimodal fluorescence and MRI imaging coupled with therapy by magnetic hyperthermia. They consist in the coating of a magnetic iron oxide (IO) core (ca.18nm diameter to ensure magnetic hyperthermia) by an original large pore stellate mesoporous silica (STMS) shell to produce uniform and mono-core magnetic core–shell nanocomposites denoted IO@STMS NPs. To confer fluorescence properties, CdSe/ZnS quantum dots (QDs) NPs were grafted inside the large pores of the IO@STMS nanocomposites. To provide biocompatibility and opsonization-resistance, a tightly-bound human serum albumin (HSA) coating is added around the nanocomposite using an original IBAM-based strategy. Cellular toxicity and non-specific cell–nanomaterial interactions allowed to determine a concentration range for safe application of these NPs. Cellular endosomes containing spontaneously-uptaken NPs displayed strong and photostable QD fluorescence signals while magnetic relaxivity measurements confirm their suitability as contrast agent for MRI. HeLa cell-uptaken NPs exposed to a magnetic field of 100kHz and 357Gauss (or 28.5kAm−1) display an outstanding 65% cell death at a very low iron concentration (1.25μgFemL−1), challenging current magnetic hyperthermia nanosystems. Furthermore, at the particularly demanding conditions of clinical use with low frequency and amplitude field (100kHz, 117Gauss or 9.3kAm−1), magnetic hyperthermia combined with the delivery of a chemotherapeutic drug, doxorubicin, allowed 46% cell death, which neither the drug nor the NPs alone yielded, evidencing thus the synergistic effect of this combined treatment.

Bimodal Probe for Magnetic Resonance Imaging and Photoacoustic Imaging Based on a PCTA‐Derived Gadolinium(III) Complex and ZW800–1

One of the most widely used techniques to obtain anatomical information is magnetic resonance imaging (MRI). Despite its high resolution, it has a low sensitivity which could be enhanced by coupling MRI with a more sensitive technique such as photoacoustic imaging (PAI). The development of a bimodal agent could thus lead to hybrid images with a high anatomical resolution provided by MRI and a precise localization of the contrast agent thanks to PAI. The probes used in this work are a gadolinium(III) complex derived from PCTA‐[12] for MRI and the ZW800–1 fluorophore for PAI. These two organic parts have been attached to a L‐lysine derivative which has a third site for potential conjugation to a biovector, thus opening the field of targeted probes for molecular imaging. Preliminary relaxometric and photoacoustic characterizations indicate that this bimodal agent is a promising compound for bimodal imaging.

Tetraphenylporphyrin‐based dual‐functional medical agent for magnetic resonance and fluorescence imaging

A bimodal magnetic resonance imaging contrast agent, TPP‐M‐Gd, was developed by modifying tetraphenylporphyrin (TPP) with a small dendritic molecule as a ligand (M) to chelate gadolinium (Gd) ions. The ligand featured four carboxylate groups, which contributed to good water solubility and a strong combination with metal ions. The longitudinal relaxivity (R1) of the resulting agent was calculated to be 12.45 mM−1 s−1, which is much higher than that of DTPA‐Gd (4.49 mM−1 s−1). The magnetic resonance imaging experiments showed that the newly synthesized contrast agent could enhance T1‐weighted magnetic resonance imaging quality both in vitro and in vivo. In addition, TPP‐M‐Gd exhibited good fluorescent property as shown in cell imaging experiments. The cytotoxicity of TPP‐M‐Gd was even better than that of clinically approved DTPA‐Gd, which makes it a promising dual‐functional medical imaging agent to provide more detailed information about biological and disease‐related events.

Ultrasound-Based Diagnosis of Breast Tumor with Parameter Transfer Multilayer Kernel Extreme Learning Machine.

B-mode ultrasound (BUS) imaging is widely used for diagnosis of breast tumors. In recent years, another ultrasound modality, namely ultrasound elastography (UE), has also been successfully applied in clinical practice. Although the combination of bimodal ultrasound imaging can improve the diagnosis accuracy for breast tumors, the single-modal ultrasound-based diagnosis is more popular in clinical practice, especially in the rural areas. Since transfer learning (TL) can transfer knowledge from a source domain to a target domain to help train more effective model, we propose to develop a single-modal ultrasound-based computer-aided diagnosis (CAD) with the transferred information from an additional modality in this work. We propose a projective model (PM) based multilayer kernel extreme learning machine (ML-KELM-PM) algorithm, which performs the parameter transfer approach in classifier to perform TL in CAD. The experimental results on a bimodal ultrasound image dataset show that the proposed ML-KELM-PM algorithm outperforms all the compared algorithms for the single-modal ultrasound-based CAD for breast tumors.

Neutron Imaging at the ILL for Li-Ion Battery and Fuel Cell Research

NeXT-Grenoble is a Neutron and X-ray Tomography facility developed and now running in Grenoble, born from a collaboration between the University Grenoble Alpes and the European Neutron Source the Institut Laue-Langevin (ILL). This instrument combines the uniquely intense neutron flux offered by the ILL with laboratory X-ray tomography in order to obtain bi-modal imaging, thus taking advantage of the reciprocal benefits of each respective method. As a preliminary step, a medium resolution neutron radiography/tomography instrument was implemented in 2016 allowing users to perform successful material characterisations in a wide range of applications such as Li-batteries, proton-exchange membrane fuel cells, porous/geomaterials and medical prosthetics. The specific transmission proprieties of neutrons (low attenuation of metals compared with relatively high absorption in light elements such as lithium and hydrogen, and isotopic differentiation, e.g., between 6Li and 7Li or 1H and 2H) and the high flux of ILL’s reactor is now enabling researchers to take this type of tomographic set-up to its limits in terms of the inherent compromise between temporal and spatial resolution. In order to exploit the complimentarity of neutron and X-ray imaging, a laboratory X-ray ensemble has been integrated (see Figure 1) and is operational since 2018, along with an ensemble of high resolution neutron detectors. This has made possible for the first time full visualisation of in operando interactions between complex phenomena, notably in the domains of battery and hydrogen fuel cell research – examples of which will be shown here. Figure 1