Imaging Contrast Research Articles

Visualization of rat tendon in three dimensions using micro-Computed Tomography

Micro-computed tomography (CT) is an X-ray-based imaging modality that produces three-dimensional (3D), high-resolution images of whole-mount tissues, but is typically limited to dense tissues, such as bone. The X-rays readily pass-through tendons, rendering them transparent. Contrast-enhancing chemical stains have been explored, but their use to improve contrast in different tendon types and across developmental stages for micro-CT imaging has not been systematically evaluated. Therefore, we investigated how phosphotungstic acid (PTA) staining and tissue hydration impacts tendon contrast for micro-CT imaging. We showed that PTA staining increased X-ray absorption of tendon to enhance tissue contrast and obtain 3D micro-CT images of immature (postnatal day 21) and sexually mature (postnatal day 50) rat tendons within the tail and hindlimb. Further, we demonstrated that tissue hydration state following PTA staining significantly impacts soft tissue contrast. Using this method, we also found that tail tendon fascicles appear to cross between fascicle bundles. Ultimately, contrast-enhanced 3D micro-CT imaging will lead to better understanding of tendon structure, and relationships between the bone and soft tissues.• Simple tissue fixation and staining technique enhances soft tissue contrast for tendon visualization using micro-CT.• 3D tendon visualization in situ advances understanding of musculoskeletal tissue structure and organization.

Association of Gene Expression and Tremor Network Structure.

Transcriptomic changes in the essential tremor (ET)-associated cerebello-thalamo-cortical "tremor network" and their association to brain structure have not been investigated. The aim was to characterize molecular changes associated with network-level imaging-derived phenotypes (IDP) found in ET. We performed an imaging-transcriptomic study in British adults using imaging-genome-wide association study summary statistics (UK Biobank "BIG40" cohort; n = 33,224, aged 40-69 years). We imputed imaging-transcriptomic associations for 184 IDPs and analyzed functional enrichment of gene modules and aggregate network-level phenotypes. Validation was performed in cerebellar-tissue RNA-sequencing data from ET patients and controls (n = 55). Among 237,896 individual predicted gene expression levels for 6063 unique genes/transcripts, we detected 2269 genome-wide significant associations (Bonferroni P < 2.102e-7, 0.95%). These were concentrated in intracellular volume fraction measures of white matter pathways and in genes with putative links to tremor (MAPT, ARL17A, KANSL1, SPPL2C, LRRC37A4P, PLEKHM1, and FMNL1). Whole-tremor-network cortical thickness was associated with a gene module linked to mitochondrial organization and protein quality control (r = 0.91, P = 2e-70), whereas white-gray T1-weighted magnetic resonance imaging (MRI) contrast in the tremor network was associated with a gene module linked to sphingolipid synthesis and ethanolamine metabolism (r = -0.90, P = 2e-68). Imputed association effect sizes and RNA-sequencing log-fold change in the validation dataset were significantly correlated for cerebellar peduncular diffusion MRI phenotypes, and there was a close overlap of significant associations between both datasets for gray matter phenotypes (χ2 = 6.40, P = 0.006). The identified genes and processes are potential treatment targets for ET, and our results help characterize molecular changes that could in future be used for patient treatment selection or prognosis prediction. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dual-time-point dynamic 68Ga-PSMA-11 PET/CT for parametric imaging generation in prostate cancer.

To investigate the optimal dual-time-point (DTP) approaches using dynamic 68Ga-PSMA-11 PET/CT imaging to generate parametric images for prostate cancer patients. Fifteen patients with prostate cancer were intravenously administered 68Ga-PSMA-11 of 181.9 ± 47.2MBq, followed by an immediate 60min dynamic PET/CT scan. List-mode data were reconstructed into 25 timeframes (6 × 10s, 8 × 30s, and 11 × 300s) and corrected for motion and partial volume effect. DTP parametric images were generated using different interval time points of 5min and 10min, with a minimum of 30min time interval. Net influx rates (Ki) were calculated through the fitting of a single irreversible two-tissue compartmental model. Intraclass correlation coefficient (ICC) values between DTP protocols and 60min Ki were obtained. Lesion-to-background ratios (LBRs) of Ki and standardized uptake value (SUV) images in each DTP protocol were determined. The DTP protocol of 5-10min with a 40-45min interval showed the highest ICC of 0.988 compared with the 60min Ki, whereas the ICC values for the intervals of 0-5min with 55-60min and 0-10min with 50-60min were 0.941. The LBRs of the 60min Ki, 5-10min with 40-45min Ki, 0-5min with 55-60min Ki, 0-10min with 50-60min Ki, SUVmean, and SUVmax images were 29.53 ± 27.33, 13.05 ± 15.28, 45.15 ± 53.11, 45.52 ± 70.31, 19.77 ± 23.43, and 25.06 ± 30.07, respectively. The 0-5min with 55-60min DTP parametric imaging exhibits a comparable Ki to 60min parametric imaging and remarkable image quality and contrast than SUV imaging, enhancing prostate cancer diagnosis while maintaining time efficiency.

Digital histological staining of tissue slide images from optical coherence microscopy

The convergence of staining-free optical imaging and digital staining technologies has become a central focus in digital pathology, presenting significant advantages in streamlining specimen preparation and expediting the rapid acquisition of histopathological information. Despite the inherent merits of optical coherence microscopy (OCM) as a staining-free technique, its widespread application in observing histopathological slides has been constrained. This study introduces a novel approach by combining wide-field OCM with digital staining technology for the imaging of histopathological slides. Through the optimization of the histology slide production process satisfying the ground growth for digital staining as well as pronounced contrast for OCM imaging, successful imaging of various mouse tissues was achieved. Comparative analyses with conventional staining-based bright field images were executed to evaluate the proposed methodology's efficacy. Moreover, the study investigates the generalization of digital staining color appearance to ensure consistent histopathology, considering tissue-specific and thickness-dependent variations.

Dual-targeted delivery of temozolomide by multi-responsive nanoplatform via tumor microenvironment modulation for overcoming drug resistance to treat glioblastoma.

Glioblastoma (GBM) is the most aggressive primary brain tumor with low survival rate. Currently, temozolomide (TMZ) is the first-line drug for GBM treatment of which efficacy is unfortunately hindered by short circulation time and drug resistance associated to hypoxia and redox tumor microenvironment. Herein, a dual-targeted and multi-responsive nanoplatform is developed by loading TMZ in hollow manganese dioxide nanoparticles functionalized by polydopamine and targeting ligands RAP12 for photothermal and receptor-mediated dual-targeted delivery, respectively. After accumulated in GBM tumor site, the nanoplatform could respond to tumor microenvironment and simultaneously release manganese ion (Mn2+), oxygen (O2) and TMZ. The hypoxia alleviation via O2 production, the redox balance disruption via glutathione consumption and the reactive oxygen species generation, together would down-regulate the expression of O6-methylguanine-DNA methyltransferase under TMZ medication, which is considered as the key to drug resistance. These strategies could synergistically alleviate hypoxia microenvironment and overcome TMZ resistance, further enhancing the anti-tumor effect of chemotherapy/chemodynamic therapy against GBM. Additionally, the released Mn2+ could also be utilized as a magnetic resonance imaging contrast agent for monitoring treatment efficiency. Our study demonstrated that this nanoplatform provides an alternative approach to the challenges including low delivery efficiency and drug resistance of chemotherapeutics, which eventually appears to be a potential avenue in GBM treatment.

Coupling Gold Nanospheres into Nanochain Constructs for High-Contrast, Longitudinal Photoacoustic Imaging.

Structural parameters play a crucial role in determining the electromagnetic and thermal responses of gold nanoconstructs (GNCs) at near-infrared (NIR) wavelengths. Therefore, developing GNCs for reliable, high-contrast photoacoustic imaging has been focused on adjusting structural parameters to achieve robust NIR light absorption with photostability. In this study, we introduce an efficient photoacoustic imaging contrast agent: gold sphere chains (GSCs) consisting of plasmonically coupled gold nanospheres. The chain geometry results in enhanced photoacoustic signal generation originating from outstanding photothermal characteristics compared to traditional gold contrast agents, such as gold nanorods. Furthermore, the GSCs produce consistent photoacoustic signals at laser fluences within the limits set by the American National Standards Institute. The exceptional photoacoustic response of GSCs allows for high-contrast photoacoustic imaging over multiple imaging sessions. Finally, we demonstrate the utility of our GSCs for molecular photoacoustic cancer imaging, both in vitro and in vivo, through the integration of a tumor-targeting moiety.

Bionic Scotopic Adaptation Transistors for Nighttime Low Illumination Imaging.

Human vision excels in perceiving nighttime low illumination due to biological feedforward adaptation. Replicating this ability in biomimetic vision using solid-state devices has been highly sought after. However, emulating scotopic adaptation, entailing a confluence of efficient photoexcitation and dynamic carrier modulation, presents formidable challenges. Here, we demonstrate a low-power and bionic scotopic adaptation transistor by coupling a light-absorption layer and an electron-trapping layer at the bottom of the semiconducting channel, enabling simultaneous achievement of efficient generation of free photocarriers and adaptive carrier accumulation within a single device. This innovation empowers our transistor to exhibit sensitivity-potentiated characteristics after adaptation, detecting scotopic-level illumination (0.001 lx) with exceptional photosensitivity up to 103 at low voltages below 2 V. Moreover, we have successfully replicated diverse scotopic vision functions, encompassing time-dependent visual threshold enhancement, light intensity-dependent adaptation index, imaging contrast enhancement for nighttime low illumination imaging, opening an opportunity for artificial night vision.

Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging

BackgroundThe general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape.ResultsIn this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments.ConclusionsWe believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.Graphical

Green synthesis and optimization of iron oxide nanoparticles as MRI contrast agent

Iron nanoparticles (FeNPs) derived from herbal plants are being explored as potential magnetic resonance imaging (MRI) contrast agents due to their biocompatibility and ability to perform targeted drug delivery. For the first time, the usage of various novel combinations of leaf extracts such as those of Azadirachta indica and Piper betle and extracts of two other Ayurvedic herbs – namely, Asparagus racemosus and Symplocos – was attempted for eco-friendly green synthesis of FeNPs. The nanoparticles were coated onto nanofibers made from a banana pseudo-stem (FENPs-NF) to enhance their biocompatibility. The synthesis process was optimized using response surface methodology, and techniques such as ultraviolet–visible (UV–Vis) spectroscopy, vibrating-sample magnetometry, atomic absorption spectroscopy (AAS), field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX) and Fourier transform infrared spectroscopy (FT-IR) were used for characterization. Hemolytic and immune cell assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and MRI analysis were carried out. A peak at 325 nm observed in UV–Vis spectroscopy, AAS, FE-SEM, EDX and FT-IR proved the presence of FeNPs. Hemolytic and immune cell assays indicated biocompatibility, and the MTT assay (MCF-7) showed inhibition at 250 μg/ml. FeNPs and FeNPs-NF showed a good signal loss in MRI analysis at 1.5 T, proving their contrast agent nature. Thus, FeNPs synthesized from herbal plant sources may open a new door for potential application in the biomedical field as a chemical-free and biocompatible MRI contrast agent.

Highly focused beam generated with a height tuned micro-optical structure for high contrast microscopic imaging

Light sheet illumination technology improves the signal-to-noise ratio, resolution, and reduces scattered backgrounds for biological microscopic detection system. Here, we developed a novel micro-optical structure to produce a focused and uniform beam for the enhancement of imaging contrast. The beam intensity and working distance can be modified by adjusting the height and period of the structure. Our experiments successfully recorded structured light illumination, demonstrating the ability of the structure to capture high-contrast imaging data. We compared the light fields generated with and without the structure to assess the imaging quality, revealing a maximum 4.78-fold improvement in the signal-to-noise ratio. This work provides a potential method for high-resolution and high-contrast light sheet fluorescence microscopic detection.

An activatable fluorescence probe for rapid detection and in situ imaging of β-galactosidase activity in cabbage roots under heavy metal stress

β-Galactosidase (β-gal), an enzyme related to cell wall degradation, plays an important role in regulating cell wall metabolism and reconstruction. However, activatable fluorescence probes for the detection and imaging of β-gal fluctuations in plants have been less exploited. Herein, we report an activatable fluorescent probe based on intramolecular charge transfer (ICT), benzothiazole coumarin-bearing β-galactoside (BC-βgal), to achieve distinct in situ imaging of β-gal in plant cells. It exhibits high sensitivity and selectivity to β-gal with a fast response (8 min). BC-βgal can be used to efficiently detect the alternations of intracellular β-gal levels in cabbage root cells with considerable imaging integrity and imaging contrast. Significantly, BC-βgal can assess β-gal activity in cabbage roots under heavy metal stress (Cd2+, Cu2+, and Pb2+), revealing that β-gal activity is negatively correlated with the severity of heavy metal stress. Our work thus facilitates the study of β-gal biological mechanisms.

Chiral Pyclen-Based Heptadentate Chelates as Highly Stable MRI Contrast Agents.

In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.

CT-Visible Microspheres Enable Whole-Body In Vivo Tracking of Injectable Tissue Engineering Scaffolds.

Targeted delivery and retention are essential requirements for implantable tissue-engineered products. Non-invasive imaging methods that can confirm location, retention, and biodistribution of transplanted cells attached to implanted tissue engineering scaffolds will be invaluable for the optimization and enhancement of regenerative therapies. To address this need, an injectable tissue engineering scaffold consisting of highly porous microspheres compatible with transplantation of cells is modified to contain the computed tomography (CT) contrast agent barium sulphate (BaSO4). The trackable microspheres show high x-ray absorption, with contrast permitting whole-body tracking. The microspheres are cellularized with GFP+ Luciferase+ mesenchymal stem cells and show in vitro biocompatibility. In vivo, cellularized BaSO4-loaded microspheres are delivered into the hindlimb of mice where they remain viable for 14 days. Co-registration of 3D-bioluminescent imagingand µCT reconstructions enable the assessment of scaffold material and cell co-localization. The trackable microspheres are also compatible with minimally-invasive delivery by ultrasound-guided transthoracic intramyocardial injections in rats. These findings suggest that BaSO4-loaded microspheres can be used as a novel tool for optimizing delivery techniques and tracking persistence and distribution of implanted scaffold materials. Additionally, the microspheres can be cellularized and have the potential to be developed into an injectable tissue-engineered combination product for cardiac regeneration.

Prostate-Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer.

The uptake of large (>10nm) non-targeted nanocarriers by bulk tumors is thought to be dominated by passive extravasation through porous tumor vessels and limited lymphatic drainage, the enhanced permeability and retention (EPR) effect. Prior studies demonstrated radiolabeled tumor-targeted and non-targeted 4-arm 40kDa star polyethylene glycol (StarPEG) polymers for cancer imaging. By adding small molecule ligands targeting prostate-specific membrane antigen (PSMA) to the StarPEG polymer, marked increase in tumor uptake, penetration and retention in the tumor core was observed. These prior studies support the application of imaging surrogates for the evaluation of targeted delivery of chemotherapeutic nanomedicines and the potential for therapy using analogous β-emitting radiopharmaceuticals. To evaluate the delivery and therapeutic efficacy of PSMA-targeted StarPEG nanocarriers, StarPEG nanodrugs with or without three copies of PSMA-targeting, ACUPA, ligands were designed and synthesized. One copy of the radiometal chelator, DOTA, was conjugated to each nanocarrier for labelling with b-emitting 177Lu, providing non-targeted [177Lu]PEG-(DOTA)1 and PSMA targeting [177Lu]PEG-(DOTA)1(ACUPA)3, for SPECT imaging and therapy. The radiolabeled nanodrugs were evaluated in vitro and in vivo using PSMA+ PC3-Pip and/or PSMA- PC3-Flu cell lines, subcutaneous xenografts and disseminated metastatic models. The nanocarriers PEG-(DOTA)1 and PEG-(DOTA)1(ACUPA)3 were efficiently radiolabeled with 177Lu with molar activities of 10.8-15.8 MBq/nmol. Along with excellent in vitro PSMA binding affinity (kD = 51.7nM in PC3-Pip cells), the targeted nanocarrier [177Lu]PEG-(DOTA)1(ACUPA)3 demonstrated excellent in vivo single-photon emission computed tomography (SPECT) imaging contrast with 21.3% ID/g uptake in PC3-Pip tumors at 192h post injection. Single doses of 18.5 MBq [177Lu]PEG-(DOTA)1(ACUPA)3 showed complete resolution of the PC3-Pip xenografts, without any regrowth up to 138 days. The StarPEG nanocarriers demonstrated high PSMA-targeted delivery of the therapeutic isotope 177Lu with excellent imaging contrast. The targeted nanocarrier eliminated subcutaneous and metastatic PC3-Pip tumors. Overall, these preclinical results demonstrated high treatment efficacy of the PSMA-targeted nanocarrier [177Lu]PEG-(DOTA)1(ACUPA)3 for prostate cancer, with potential for clinical translation. This article is protected by copyright. All rights reserved.

Evolving Characteristics of Gadolinium-Based Contrast Agents for MR Imaging: A Systematic Review of the Importance of Relaxivity.

Gadolinium-based contrast agents (GBCAs) are widely and routinely used to enhance the diagnostic performance of magnetic resonance imaging and magnetic resonance angiography examinations. T1 relaxivity (r1) is the measure of their ability to increase signal intensity in tissues and blood on T1-weighted images at a given dose. Pharmaceutical companies have invested in the design and development of GBCAs with higher and higher T1 relaxivity values, and "high relaxivity" is a claim frequently used to promote GBCAs, with no clear definition of what "high relaxivity" means, or general concurrence about its clinical benefit. To understand whether higher relaxivity values translate into a material clinical benefit, well-designed, and properly powered clinical studies are necessary, while mere in vitro measurements may be misleading. This systematic review of relevant peer-reviewed literature provides high-quality clinical evidence showing that a difference in relaxivity of at least 40% between two GBCAs results in superior diagnostic efficacy for the higher-relaxivity agent when this is used at the same equimolar gadolinium dose as the lower-relaxivity agent, or similar imaging performance when used at a lower dose. Either outcome clearly implies a relevant clinical benefit. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Semiconducting Polymers Based on Asymmetric Thiadiazoloquinoxaline for Augmented In Vivo NIR-II Photoacoustic Imaging.

A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 μm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.

Analysis and reduction of back-reflection straylight in laser ranging system

In the coaxial satellite laser ranging system or the other telescope-based measurement systems, the emitted beam produces backward reflection at the center of the secondary mirror, which affects the detector in the system. To reduce the impact of straylight, a new device for reduce the backward reflection of the secondary mirror has been proposed. The specific parameters of the device have been determined through numerical calculation and computer simulation. The device has been implemented in a 1.2 m laser ranging system and has been experimentally proven to reduce the laser straylight by 32.4 % with the single photon detector and there is an increase in the camera's contrast for target imaging, making it more effective to measuring the space target.

ARISE I Consensus Review on the Management of Intracranial Aneurysms

BACKGROUND: Intracranial aneurysms (IAs) remain a challenging neurological diagnosis associated with significant morbidity and mortality. There is a plethora of microsurgical and endovascular techniques for the treatment of both ruptured and unruptured aneurysms. There is no definitive consensus as to the best treatment option for this cerebrovascular pathology. The Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts discussed best practices and the most promising approaches to improve the management of brain aneurysms. METHODS: A group of experts from academia, industry, and federal regulators convened to discuss updated clinical trials, scientific research on preclinical system models, management options, screening and monitoring, and promising novel device technologies, aiming to improve the outcomes of patients with IA. RESULTS: Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts suggested the incorporation of artificial intelligence to capture sequential aneurysm growth, identify predictors of rupture, and predict the risk of rupture to guide treatment options. The consensus strongly recommended nationwide systemic data collection of unruptured IA radiographic images for the analysis and development of machine learning algorithms for rupture risk. The consensus supported centers of excellence for preclinical multicenter trials in areas such as genetics, cellular composition, and radiogenomics. Optical coherence tomography and magnetic resonance imaging contrast–enhanced 3T vessel wall imaging are promising technologies; however, more data are needed to define their role in IA management. Ruptured aneurysms are best managed at large volume centers, which should include comprehensive patient management with expertise in microsurgery, endovascular surgery, neurology, and neurocritical care. CONCLUSIONS: Clinical and preclinical studies and scientific research on IA should engage high-volume centers and be conducted in multicenter collaborative efforts. The future of IA diagnosis and monitoring could be enhanced by the incorporation of artificial intelligence and national radiographic and biologic registries. A collaborative effort between academic centers, government regulators, and the device industry is paramount for the adequate management of IA and the advancement of the field.

A narrow-bandgap RuI3 nanoplatform to synergize radiotherapy, photothermal therapy, and thermoelectric dynamic therapy for tumor eradication

Therapeutic resistance is an essential challenge for nanotherapeutics. Herein, a narrow bandgap RuI3 nanoplatform has been constructed firstly to synergize radiotherapy (RT), photothermal therapy (PTT), and thermoelectric dynamic therapy (TEDT) for tumor eradication. Specifically, the photothermal performance of RuI3 can ablate tumor cells while inducing TEDT. Noteworthy, the thermoelectric effect is found firstly in RuI3, which can spontaneously generate an electric field under the temperature gradient, prompting carrier separation and triggering massive ROS generation, thus aggravating oxidative stress level and effectively inhibiting HSP-90 expression. Moreover, RuI3 greatly enhances X-ray deposition owing to its high X-ray attenuation capacity, resulting in a pronounced computed tomography imaging contrast and DNA damage. In addition, RuI3 possesses both catalase-like and glutathione peroxidase-like properties, which alleviate tumor hypoxia and reduce antioxidant resistance, further exacerbating 1O2 production during RT and TEDT. This integrated therapy platform combining PTT, TEDT, and RT significantly inhibits tumor growth. Statement of SignificanceRuI3 nanoparticles were synthesized for the first time. RuI3 exhibited the highest photothermal properties among iodides, and the photothermal conversion efficiency was 53.38%. RuI3 was found to have a thermoelectric effect, and the power factor could be comparable to that of most conventional thermoelectric materials. RuI3 possessed both catalase-like and glutathione peroxidase-like properties, which contributed to enhancing the effect of radiotherapy.

Magnetic Field-Optimized Paramagnetic Nanoprobe for T2/T1 Switchable Histopathological-Level MRI.

Traditional magnetic resonance imaging (MRI) contrast agents (CAs) are a type of "always on" system that accelerates proton relaxation regardless of their enrichment region. This "always on" feature leads to a decrease in signal differences between lesions and normal tissues, hampering their applications in accurate and early diagnosis. Herein, we report a strategy to fabricate glutathione (GSH)-responsive one-dimensional (1-D) manganese oxide nanoparticles (MONPs) with improved T2 relaxivities and achieve effective T2/T1 switchable MRI imaging of tumors. Compared to traditional contrast agents with high saturation magnetization to enhance T2 relaxivities, 1-D MONPs with weak Ms effectively increase the inhomogeneity of the local magnetic field and exhibit obvious T2 contrast. The inhomogeneity of the local magnetic field of 1-D MONPs is highly dependent on their number of primary particles and surface roughness according to Landau-Lifshitz-Gilbert simulations and thus eventually determines their T2 relaxivities. Furthermore, the GSH responsiveness ensures 1-D MONPs with sensitive switching from the T2 to T1 mode in vitro and subcutaneous tumors to clearly delineate the boundary of glioma and metastasis margins, achieving precise histopathological-level MRI. This study provides a strategy to improve T2 relaxivity of magnetic nanoparticles and construct switchable MRI CAs, offering high tumor-to-normal tissue contrast signal for early and accurate diagnosis.