Glioblastoma Margin as a Diffusion Barrier Revealed by Photoactivation of Plasmonic Nanovesicles.

Glioblastoma (GBM) is the most complex and lethal primary brain cancer. Adequate drug diffusion and penetration are essential for treating GBM, but how the spatial heterogeneity in GBM impacts drug diffusion and transport is poorly understood. Herein, we report a new method, photoactivation of plasmonic nanovesicles (PANO), to measure molecular diffusion in the extracellular space of GBM. By examining three genetically engineered GBM mouse models that recapitulate key clinical features including the angiogenic core and diffuse infiltration, we found that the tumor margin has the lowest diffusion coefficient (highest tortuosity) compared with the tumor core and surrounding brain tissue. Analysis of the cellular composition shows that tortuosity in the GBM is strongly correlated with neuronal loss and astrocyte activation. Our all-optical measurement reveals the heterogeneous GBM microenvironment and highlights the tumor margin as a diffusion barrier for drug transport in the brain, with implications for therapeutic delivery.

Live Mapping of the Brain Extracellular Matrix and Remodeling in Neurological Disorders.

Live imaging of the brain extracellular matrix (ECM) provides vital insights into changes that occur in neurological disorders. Current techniques such as second or third-harmonic generation offer limited contrast for live imaging of the brain ECM. Here, a new method, pan-ECM via chemical labeling of extracellular proteins, is introduced for live brain ECM imaging. pan-ECM labels all major ECM components in live tissue including the interstitial matrix, basement membrane, and perineuronal nets. pan-ECM enables in vivo observation of the ECM heterogeneity between the glioma core and margin, as well as the assessment of ECM deterioration under stroke condition, without ECM shrinkage from tissue fixation. These findings indicate that the pan-ECM approach is a novel way to image the entire brain ECM in live brain tissue with optical resolution. pan-ECM has the potential to advance the understanding of ECM in brain function and neurological diseases.

Glioblastoma Margin as a Diffusion Barrier Revealed by Photoactivation of Plasmonic Nanovesicles.

Glioblastoma (GBM) is the most complex and lethal adult primary brain cancer. Adequate drug diffusion and penetration are essential for treating GBM, but how the spatial heterogeneity in GBM impacts drug diffusion and transport is poorly understood. Herein, we report a new method, photoactivation of plasmonic nanovesicles (PANO), to measure molecular diffusion in the extracellular space of GBM. By examining three genetically engineered GBM mouse models that recapitulate key clinical features including angiogenic core and diffuse infiltration, we found that the tumor margin has the lowest diffusion coefficient (highest tortuosity) compared with the tumor core and surrounding brain tissue. Analysis of the cellular composition shows that the tortuosity in the GBM is strongly correlated with neuronal loss and astrocyte activation. Our all-optical measurement reveals the heterogeneous GBM microenvironment and highlights the tumor margin as a diffusion barrier for drug transport in the brain, with implications for therapeutic delivery.

Optical blood-brain-tumor barrier modulation expands therapeutic options for glioblastoma treatment.

The treatment of glioblastoma has limited clinical progress over the past decade, partly due to the lack of effective drug delivery strategies across the blood-brain-tumor barrier. Moreover, discrepancies between preclinical and clinical outcomes demand a reliable translational platform that can precisely recapitulate the characteristics of human glioblastoma. Here we analyze the intratumoral blood-brain-tumor barrier heterogeneity in human glioblastoma and characterize two genetically engineered models in female mice that recapitulate two important glioma phenotypes, including the diffusely infiltrative tumor margin and angiogenic core. We show that pulsed laser excitation of vascular-targeted gold nanoparticles non-invasively and reversibly modulates the blood-brain-tumor barrier permeability (optoBBTB) and enhances the delivery of paclitaxel in these two models. The treatment reduces the tumor volume by 6 and 2.4-fold and prolongs the survival by 50% and 33%, respectively. Since paclitaxel does not penetrate the blood-brain-tumor barrier and is abandoned for glioblastoma treatment following its failure in early-phase clinical trials, our results raise the possibility of reevaluating a number of potent anticancer drugs by combining them with strategies to increase blood-brain-tumor barrier permeability. Our study reveals that optoBBTB significantly improves therapeutic delivery and has the potential to facilitate future drug evaluation for cancers in the central nervous system.

Improving diagnostic accuracy for probable and definite Ménière's disease using magnetic resonance imaging.

PURPOSE: To determine whether magnetic resonance imaging (MRI) can improve diagnostic accuracy for definite and probable Ménière's disease (MD) based on perilymphatic enhancement (PE) and endolymphatic hydrops (EH). METHODS: 363 patients with unilateral MD (probable MD, n = 75 and definite MD, n = 288) were recruited. A three-dimensional zoomed imaging technique with parallel transmission SPACE real inversion recovery was performed 6 h after intravenous gadolinium injection to investigate the presence of PE and to evaluate the grading and location of EH. PE and EH characteristics were analyzed and compared between the probable and definite MD groups. RESULTS: The cochlear and vestibular EH grading on the affected side was more severe in the definite MD group than that in the probable MD group (P < 0.001). The EH locations within the inner ear on the affected side also differed between the two groups (χ2 = 81.15, P < 0.001). The signal intensity ratio (SIR) on the affected side was significantly higher in the definite MD group than in the probable MD group (t = 2.18, P < 0.05). The assessment of the combination of PE and EH parameters within the inner ear revealed a higher area under the curve (AUC) in the definite MD group (0.82) compared with the AUCs of the parameters assessed alone. CONCLUSION: The assessment of a combination of PE and EH parameters improved the diagnostic accuracy for probable and definite MD, suggesting that MRI findings may be clinically useful in the diagnosis of MD.

pan-ECM: live brain extracellular matrix imaging with protein-reactive dye.

The brain extracellular matrix (ECM), consisting of proteins and glycosaminoglycans, is a critical scaffold in the development, homeostasis, and disorders of the central nervous system (CNS) and undergoes remodeling in response to environmental cues. Live imaging of brain ECM structure represents a native view of the brain ECM but, until now, remains challenging due to the lack of a robust fluorescent labeling approach. Here, we developed a pan-ECM method for labeling the entire (Greek: pan) brain ECM network by screening and delivering a protein-reactive dye into the brain. pan-ECM enables imaging of ECM compartments in live brain tissue, including the interstitial matrix, basement membrane (BM), and perineuronal nets (PNNs), and even the ECM in glioblastoma and stroke mouse brains. This approach provides access to the structure and dynamics of the ECM and enhances our understanding of the complexities of the brain ECM and its contribution to brain health and disease.

Toward dynamic, anisotropic, high-resolution, and functional measurement in the brain extracellular space.

Diffusion of substances in the brain extracellular space (ECS) is important for extrasynaptic communication, extracellular ionic homeostasis, drug delivery, and metabolic waste clearance. However, substance diffusion is largely constrained by the geometry of brain ECS and the extracellular matrix. Investigating the diffusion properties of substances not only reveals the structural information of the brain ECS but also advances the understanding of intercellular signaling of brain cells. Among different techniques for substance diffusion measurement, the optical imaging method is sensitive and straightforward for measuring the dynamics and distribution of fluorescent molecules or sensors and has been used for molecular diffusion measurement in the brain. We mainly discuss recent advances of optical imaging-enabled measurements toward dynamic, anisotropic, high-resolution, and functional aspects of the brain ECS diffusion within the last 5 to 10 years. These developments are made possible by advanced imaging, such as light-sheet microscopy and single-particle tracking in tissue, and new fluorescent biosensors for neurotransmitters. We envision future efforts to map the ECS diffusivity across the brain under healthy and diseased conditions to guide the therapeutic delivery and better understand neurochemical transmissions that are relevant to physiological signaling and functions in brain circuits.

Elevated Hemoglobin A1c Is Associated With Leaky Plaque Neovasculature as Detected by Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Patients with diabetes have accelerated atherosclerosis progression, but the underlying mechanisms are not fully understood. Dynamic contrast-enhanced magnetic resonance imaging has allowed in vivo characterization of plaque neovasculature, which plays a critical role in plaque progression. We aimed to evaluate the impact of diabetes on carotid plaque neovasculature as assessed by dynamic contrast-enhanced magnetic resonance imaging. METHODS: Patients with recent ischemic stroke and ipsilateral carotid plaque underwent multicontrast magnetic resonance imaging for characterizing plaque morphology and dynamic contrast-enhanced magnetic resonance imaging for pharmacokinetic parameters of plaque neovasculature, including transfer constant (Ktrans, reflecting flow, endothelial surface area, and permeability) and fractional plasma volume (νp). RESULTS: Sixty-five patients were enrolled, including 30 patients with diabetes (years since diagnosis: median 5.0 [interquartile range, [3.0-12.0]) and 35 patients without diabetes. Subjects with diabetes had a greater plaque burden and a higher prevalence of high-risk characteristics. Additionally, carotid plaques in the subjects with diabetes showed higher Ktrans than those in the subjects without diabetes (0.100±0.048 min-1 versus 0.067±0.042 min-1, P=0.005) but νp was numerically lower in the subjects with diabetes (5.2±3.7% versus 6.2±4.3%, P=0.31). The association of diabetes with high Ktrans (ß=0.033, P=0.005) was independent of patient and plaque characteristics and remained largely intact after adjusting for serum lipids, glucose, or hs-CRP (high-sensitivity C-reactive protein). However, it became nonexistent after adjusting for hemoglobin A1c (ß=-0.010, P=0.49). CONCLUSIONS: Dynamic contrast-enhanced magnetic resonance imaging of carotid plaques suggested that plaque neovasculature in patients with diabetes is leaky, indicating enhanced capability of bringing blood constituents and facilitating extravasation of inflammatory cells, erythrocytes, and plasma proteins. Leaky plaque neovasculature correlated with hemoglobin A1c and may play a role in accelerated atherosclerosis progression in diabetes.

Is Doppler Echocardiography Adequate for Surgical Planning of Single Ventricle Patients?

PURPOSE: Surgical planning has shown great potential for optimizing outcomes for patients affected by single ventricle (SV) malformations. Phase-contrast magnetic resonance imaging (PC-MRI) is the routine technique used for flow acquisition in the surgical planning paradigm. However, PC-MRI may suffer from possible artifacts in certain cases; furthermore, this technology may not be readily available for patients in low and lower-middle-income countries. Therefore, this study aims to investigate the effectiveness of using Doppler echocardiography (echo-Doppler) for flow acquisitions of SV surgical planning. METHODS: This study included eight patients whose blood flow data was acquired by both PC-MRI and echo-Doppler. A virtual surgery platform was used to generate two surgical options for each patient: (1) a traditional Fontan conduit and (2) a Y-graft. Computational fluid dynamics (CFD) simulations were conducted using the two flow acquisitions to assess clinically relevant hemodynamic metrics: indexed power loss (iPL) and hepatic flow distribution (HFD). RESULTS: Differences exist in flow data acquired by PC-MRI and echo-Doppler, but no statistical significance was obtained. Flow fields, therefore, exhibit discrepancies between simulations using flow acquisitions by PC-MRI and echo-Doppler. In virtual surgery, the two surgical options were ranked based on these metrics. No difference was observed in the ranking of surgical options between using different flow acquisitions. CONCLUSION: Doppler echocardiography is an adequate alternative approach to acquire flow data for SV surgical planning. This finding encourages broader usage of SV surgical planning with echo-Doppler when MRI may present artifacts or is not available, especially in low and lower-middle-income countries.

Metal Ions Doping for Boosting Luminescence of Lanthanide-Doped Nanocrystals.

With the developing need for luminous materials with better performance, lanthanide-doped nanocrystals have been widely studied for their unique luminescence properties such as their narrow bandwidth emission, excellent chemical stability, and photostability, adjustable emission color, high signal-to-background ratio, deeper tissue penetration with less photo-damage, and low toxicity, etc., which triggered enthusiasm for research on the broad applications of lanthanide-doped nanocrystals in bioimaging, anti-counterfeiting, biosensing, and cancer diagnosis and treatment. Considerable progress has been made in the past few decades, but low upconversion luminescence efficiency has been a hindrance in achieving further progress. It is necessary to summarize the recently relevant literature and find solutions to improve the efficiency. The latest experimental and theoretical studies related to the deliberate design of rare earth luminescent nanocrystals have, however, shown the development of metal ion-doped approaches to enhance the luminescent intensity. Host lattice manipulation can enhance the luminescence through increasing the asymmetry, which improves the probability of electric dipole transition; and the energy transfer modulation offers a reduced cross-relaxation pathway to improve the efficiency of the energy transfer. Based on the mechanisms of host lattice manipulation and energy transfer modulation, a wide range of enhancements at all wavelengths or even within a particular wavelength have been accomplished with an enhancement of up to a hundred times. In this mini review, we present the strategy of metal ion-doped lanthanide nanocrystals to cope with the issue of enhancing luminescence, overview the advantages and tricky challenges in boosting the luminescence, and provide a potential trend of future study in this field.

Lanthanide nanoparticles with efficient near-infrared-II emission for biological applications.

The near-infrared II (NIR-II) light (1000-1700 nm) possesses deep penetration capability and high signal-to-noise ratios due to the advances of low autofluorescence and scattering in biological tissues. Differing from the traditional NIR-II-emitting nanoprobes such as carbon nanotubes (CNT), organic dyes, quantum dots (QDs), and polymer dots (PDs), lanthanide-doped NPs feature the characteristic of excellent photo-and-chemical stability, sharp emission peaks, longer lifetime, and larger anti-Stokes shift. These merits have impelled the development of NIR-II-emitting lanthanide NPs in biomedical applications at a terrific speed. In this mini-review, we discuss how to design efficient NIR-II-emitting lanthanide NPs and summarize their recent progress in bioimaging, therapy, and biosensing. Moreover, the limitations and future opportunities of NIR-II-emitting lanthanide NPs are also discussed.

The Bioavailability, Biodistribution, and Toxic Effects of Silica-Coated Upconversion Nanoparticles in vivo.

Lanthanide-doped upconversion nanoparticles can convert long wavelength excitation radiation to short wavelength emission. They have great potential in biomedical applications, such as bioimaging, biodetection, drug delivery, and theranostics. However, there is little information available on their bioavailability and biological effects after oral administration. In this study, we systematically investigated the bioavailability, biodistribution, and toxicity of silica-coated upconversion nanoparticles administrated by gavage. Our results demonstrate that these nanoparticles can permeate intestinal barrier and enter blood circulation by microstructure observation of Peyer's patch in the intestine. Comparing the bioavailability and the biodistribution of silica-coated upconversion nanoparticles with oral and intravenous administration routes, we found that the bioavailability and biodistribution are particularly dependent on the administration routes. After consecutive gavage for 14 days, the body weight, pathology, Zn and Cu level, serum biochemical analysis, oxidative stress, and inflammatory cytokines were studied to further evaluate the potential toxicity of the silica-coated upconversion nanoparticles. The results suggest that these nanoparticles do not show overt toxicity in mice even at a high dose of 100 mg/kg body weight.

Retrospective Study of Hemodynamic Changes Before and After Carotid Stenosis Formation by Vessel Surface Repairing.

Prospective observation of hemodynamic changes before and after the formation of atherosclerotic stenosis in the carotid artery is difficult. Thus, a vessel surface repairing method was used for retrospective hemodynamic study before and after atherosclerotic stenosis formation in carotid artery. The three-dimensional geometry of sixteen sinus atherosclerotic stenosis carotid arteries were repaired and restored as normal arteries. Computational fluid dynamics analysis was performed to estimate wall shear stress (WSS), velocity and vortex in atherosclerosis-free areas and sinus in stenosis-repaired carotid artery. The analysis was also performed in the stenotic segment and upstream and downstream of stenosis in stenotic carotid artery. Compared to the atherosclerosis-free areas in stenosis-repaired carotid artery, sinus presented significantly lower WSS (P < 0.05), lower velocity (P < 0.05) and apparent vortex. Compared to the sinus, the WSS in the upstream of stenosis was lower (P < 0.05), while in the downstream area was similar (P = 0.87), both upstream and downstream of stenosis demonstrated similar velocity to sinus (P = 0.76 and P = 0.36, respectively) and apparent vortex. Atherosclerosis-prone areas including normal carotid sinus and upstream and downstream of stenosis in stenotic carotid artery were subjected to lower WSS and velocity as well as apparent vortex, thereby might be associated with the formation and progress of atherosclerosis.

Assessment of hemodynamic parameters distribution in normal carotid artery by using computational fluid dynamics based on CE-MRA data / Avaliação da distribuição dos parâmetros hemodinâmicos na artéria carótida normal utilizando a dinâmica de fluidos computacional baseada em dados CE-MRA

This study was to analyze the in vivo distribution of wall shear stress (WSS), velocity and inplane pressure difference in normal carotid artery by using computational fluid dynamics (CFD) based on contrastenhanced MRA (CE-MRA) data and to determine whether there were differences in these hemodynamic parameters between atherosclerosis-free and atherosclerosis-prone areas. CE-MRA was performed on 16 normal carotid arteries to obtain carotid three-dimensional surface data. CFD analysis was then performed to estimate those parameters in atherosclerosis-free (distal common carotid artery and distal internal carotid artery) and atherosclerosis-prone (carotid bifurcation) areas. One-way analysis of variance (ANOVA) was conducted to analyze differences among these three areas. CFD analysis revealed that WSS and velocity were significantly lower in carotid bifurcation compared to distal common carotid artery (CCA) (P =0.011, P <0.001, respectively) and distal internal carotid artery (ICA) (P <0.001, P <0.001, respectively). While in-plane pressure difference was significantly higher in carotid bifurcation compared to distal CCA (P <0.001) and distal ICA (P =0.005). Hemodynamic environment in carotid bifurcation of normal carotid artery which assessed by using CFD analysis appeared to be with lower WSS and lower velocity, while with higher in-plane pressure difference. These characterizations might facilitate the initiation of atherosclerosis.

Este estudo teve como objetivo analisar a distribuição in vivo da tensão de cisalhamento da parede (WSS), velocidade e plano diferença de pressão na artéria carótida normal usando dinâmica de fluidos computacional (CFD) baseada em contraste Dados do MRA (CE-MRA) e para determinar se houve diferenças nesses parâmetros hemodinâmicos entre áreas livres de aterosclerose e propensas à aterosclerose. O CE-MRA foi realizado em 16 artérias carótidas normais para obter dados de superfície tridimensional da carótida. A análise CFD foi então realizada para estimar esses parâmetros em livre de aterosclerose (artéria carótida comum distal e artéria carótida interna distal) e propensa a aterosclerose (carótida bifurcação). Análise de variância unidirecional (ANOVA) foi realizada para analisar as diferenças entre essas três áreas. A análise de CFD revelou que o WSS e a velocidade foram significativamente menores na bifurcação carotídea em comparação com a comum distal artéria carótida (ACC) (P = 0,011, P <0,001, respectivamente) e artéria carótida interna distal (ACI) (P <0,001, P <0,001, respectivamente). Enquanto a diferença de pressão no plano foi significativamente maior na bifurcação carotídea em comparação com a CCA distal (P <0,001) e ICA distal (P = 0,005). Ambiente hemodinâmico na bifurcação carotídea da artéria carótida normal que avaliada por meio de análise de CFD parece estar com menor WSS e menor velocidade, enquanto com maior pressão no plano diferença. Essas caracterizações podem facilitar o início da aterosclerose.

Controlled optical characteristics of lanthanide doped upconversion nanoparticles for emerging applications.

Lanthanide-doped upconversion nanoparticles (UCNPs) can convert long wavelength excitation radiation in the near-infrared region to higher energy emission radiation from ultraviolet to near-infrared. The anti-Stokes luminescence process will result in high tissue penetration depth, low background noise and low photo-damage in bioimaging applications. Considering these excellent optical performances, UCNPs have been considered as the next generation of fluorescent probes for sensing and bioimaging based on near-infrared light stimulation. In this mini review, we highlight the recent advances of UCNPs in the field of emerging applications, such as dye sensitized UCNPs, photogene regulation, anti-counterfeiting, and super-resolution imaging, which depend on the optical modulation. Finally, we discuss the challenges and opportunities in the development of these new applications.

Double-mesoporous core-shell nanosystems based on platinum nanoparticles functionalized with lanthanide complexes for in vivo magnetic resonance imaging and photothermal therapy.

A double-mesoporous nanosystem was synthesized for treating as well as imaging cancer cells by using a simple and mild method. The mesoporous platinum (Pt) nanoparticles acting as a core show excellent photothermal effect under illumination with an 808 nm near infrared (NIR) laser. The mesoporous silica linked with a lanthanide (Gd) complex acting as a shell displays potential applications as a contrast agent for magnetic resonance imaging (MRI). The final mPt@mSiO2-GdDTPA nanosystems exhibit good biocompatibility in vitro and in vivo, when investigated by methyl thiazolyl tetrazolium assay and histological and serum biochemistry analysis. The investigation of the photothermal effect shows that the mPt@mSiO2-GdDTPA nanosystems exhibit an excellent photothermal therapy effect on HeLa cells and tumor-bearing mice. As theranostic agents, the nanosystems display a higher r1 value than the medical contrast agent magnevist and were successfully applied to in vivo MRI of Kunming mice. Therefore, the first systematic study on the photothermal effect of nanosystems based on mesoporous Pt nanoparticles does encourage the potential applications of metal nanoparticles and hybrid nanocomposites for cancer bioimaging and therapy.

Association between carotid plaque characteristics and acute cerebral infarction determined by MRI in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) might aggravate the carotid plaque vulnerability, and increase the risk for ischemic stroke. Few studies reported the acute stroke subtype with carotid plaque characteristics in T2DM patients. This study aimed to investigate the association between carotid plaque characteristics and acute cerebral infarct (ACI) lesion features determined by MRI in T2DM patients. METHODS: Patients with acute cerebrovascular syndrome in internal carotid artery territory were recruited. All patients were stratified into T2DM and non-T2DM groups and underwent both carotid and brain MRI scans. Ipsilateral carotid plaque morphological and compositional characteristics, intracranial and extracranial carotid artery stenosis were also determined. Stroke subtype based on the Trial of ORG 10172 in Acute Stroke Treatment classification and ACI lesion patterns were evaluated. RESULTS: Of the recruited 140 patients, 68 (48.6%) patients had T2DM (mean age 64.16 ± 11.38 years, 40 males). T2DM patients exhibited higher prevalence of carotid type IV-VI lesions, larger plaque burden as well as larger lipid-rich necrotic core (LRNC) compared with non-T2DM patients. Among the patients with carotid LRNC on symptomatic side, more concomitant large perforating artery infarct patterns and larger ACI size in the internal carotid artery territory were found in T2DM group than those in non-T2DM group. Carotid plaque with LRNC% > 22.0% was identified as an independent risk factor for the presence of ACI lesions confined to the carotid territory in T2DM patients, regardless of other risk factors. CONCLUSIONS: This study shows that more concomitant large perforating artery infarct patterns and larger ACI size in the internal carotid artery territory were found in the T2DM patients with ipsilateral carotid LRNC plaque than those in non-T2DM patients. Quantification of the carotid plaque characteristics, particularly the LRNC% by MRI has the potential usefulness for stroke risk stratification.

Evaluation of carotid plaque vulnerability in vivo: Correlation between dynamic contrast-enhanced MRI and MRI-modified AHA classification.

PURPOSE: To noninvasively monitor carotid plaque vulnerability by exploring the relationship between pharmacokinetic parameters (PPs) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and plaque types based on MRI-modified American Heart Association (AHA) classification, as well as to assess the ability of PPs in discrimination between stable and vulnerable plaques suspected on MRI. MATERIALS AND METHODS: Of 70 consecutive patients with carotid plaques who volunteered for 3.0T MRI (3D time-of-flight [TOF], T1 -weighted, T2 -weighted, 3D magnetization-prepared rapid acquisition gradient-echo [MP-RAGE] and DCE-MRI), 66 participants were available for analysis. After plaque classification according to MRI-modified AHA Lesion-Type (LT), PPs (Ktrans , kep , ve , and vp ) of DCE-MRI were measured. The Extended Tofts model was used for calculation of PPs. For participants with multiple carotid plaques, the plaque with the worst MRI-modified AHA LT was chosen for analysis. Correlations between PPs and plaque types and the ability of these parameters to distinguish stable and vulnerable plaques suspected on MRI were assessed. RESULTS: Significant positive correlation between Ktrans and LT III to VI was found (ρ = 0.532, P < 0.001), as was the correlation between kep and LT III to VI (ρ = 0.409, P < 0.001). Stable and vulnerable plaques suspected on MRI could potentially be distinguished by Ktrans (sensitivity 83%, specificity 100%) and kep (sensitivity 77%, specificity 91%). CONCLUSION: Ktrans and kep from DCE-MRI can provide quantitative information to monitor plaque vulnerability in vivo and differentiate vulnerable plaques suspected on MRI from stable ones. These two parameters could be adopted as imaging biomarkers for plaque characterization and risk stratification. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:870-876.

Lanthanide (Gd(3+) and Yb(3+)) functionalized gold nanoparticles for in vivo imaging and therapy.

Nanoparticles are regularly used as contrast agents in bioimaging. Unlike other agents such as composite materials, nanoparticles can also be used for treating as well as imaging disease. Here we synthesized lanthanide functionalized gold nanoparticles that can be used for both imaging and therapy in vivo. That is a multifunctional nanoplatform was developed based on a simple and versatile method, by incorporating 10-nm gold nanoparticles and lanthanide ions (Gd(3+) and Yb(3+)), denoted as LnAu nanoparticles hereby. The LnAu nanoparticles were then surface-modified using a PEGylated amphiphilic polymer (C18MH-mPEG), and the resulting PEG modified LnAu nanoparticles (PEG-LnAu) display good monodispersion in water and good solubility in biological media. Due to the low toxicity in vitro and in vivo (as determined by a cell viability assay and histological and serum biochemistry analysis), the PEG-LnAu nanoparticles can be successfully applied to in vivo magnetic resonance imaging (MRI), in vivo computed tomography (CT) imaging and photothermal therapy (PTT) for tumor-bearing mice. Therefore, the present work developed an easy yet powerful strategy to combine lanthanide ions and gold nanoparticles to a unified nanoplatform for integrating bioimaging and therapy.

Nile Red Derivative-Modified Nanostructure for Upconversion Luminescence Sensing and Intracellular Detection of Fe(3+) and MR Imaging.

Iron ion (Fe(3+)) which is the physiologically most abundant and versatile transition metal in biological systems, has been closely related to many certain cancers, metabolism, and dysfunction of organs, such as the liver, heart, and pancreas. In this Research Article, a novel Nile red derivative (NRD) fluorescent probe was synthesized and, in conjunction with polymer-modified core-shell upconversion nanoparticles (UCNPs), demonstrated in the detection of Fe(3+) ion with high sensitivity and selectivity. The core-shell UCNPs were surface modified using a synthesized PEGylated amphiphilic polymer (C18PMH-mPEG), and the resulting mPEG modified core-shell UCNPs (mPEG-UCNPs) show good water solubility. The overall Fe(3+)-responsive upconversion luminescence nanostructure was fabricated by linking the NRD to the mPEG-UCNPs, denoted as mPEG-UCNPs-NRD. In the nanostructure, the core-shell UCNPs, NaYF4:Yb,Er,Tm@NaGdF4, serve as the energy donor while the Fe(3+)-responsive NRD as the energy acceptor, which leads to efficient luminescence resonance energy transfer (LRET). The mPEG-UCNPs-NRD nanostructure shows high selectivity and sensitivity for detecting Fe(3+) in water. In addition, benefited from the good biocompatibility, the nanostructure was successfully applied for detecting Fe(3+) in living cells based on upconversion luminescence (UCL) from the UCNPs. Furthermore, the doped Gd(3+) ion in the UCNPs endows the mPEG-UCNPs-NRD nanostructure with effective T1 signal enhancement, making it a potential magnetic resonance imaging (MRI) contrast agent. This work demonstrates a simple yet powerful strategy to combine metal ion sensing with multimodal bioimaging based on upconversion luminescence for biomedical applications.