Signal Enhancement Research Articles

Fluorophore signal detection and imaging enhancement in high refractive index nanowire biosensors

Abstract Semiconductor nanowires are an efficient platform for fluorescence-based biosensors. Here, we model how a GaP nanowire (i) enhances the excitation intensity at the position of the fluorophore attached to the nanowire sidewall, (ii) enhances the probability to collect photons emitted from the fluorophore, and (iii) through the Purcell effect increases the quantum yield of the fluorophore. With optimized design, we can reach a larger than 102 enhancement in signal. We also model imaging-based detection. There, waveguiding in the nanowire beats the limitations set by the depth of view in conventional microscopy, enabling the use of a long nanowire to enhance the binding-area for fluorophores. As an example, we can focus to the top of a 4000 nm long nanowire and reach a 25 times sharper image from a fluorophore at the bottom of the nanowire, as compared to such a 4000 nm defocusing in a conventional planar biosensor platform.

Hydrophilic Shape‐Memory Nanozyme Aerogel for the Development of a Reusable and Signal‐Amplified Sensor

AbstractNanozymes hold great promise for biosensing applications, yet their practical implementation is hampered by limitations in signal enhancement, reusability, and device integration. Herein, the development of a hydrophilic shape‐memory nanozyme aerogel that addresses these challenges is reported. The aerogel platform is constructed by embedding chitosan‐protected platinum nanoparticles (Pt‐CS NPs), which exhibit intrinsic peroxidase (POD) activity, within a polyacrylic acid (PAA) aerogel matrix. This hybrid Pt‐CS/PAA aerogel retains the shape‐memory effect of the PAA component as well as the POD activity of the Pt‐CS NPs. Importantly, the aerogel exhibits differential adsorption behaviors toward the two distinct POD oxidation products, oxidized 3,3′,5,5′‐tetramethyl‐benzidine (oxTMB) and oxidized 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (oxABTS), driven by their differing electrostatic potentials with the aerogel. By integrating the shape‐memory effect, nanozyme catalysis, and exceptional probe adsorption performance, the aerogel enables the realization of the signal‐amplified or reusable nanozyme‐based assay, when employing TMB and ABTS as chromogenic substrates, respectively. Furthermore, the aerogel architecture allows for straightforward deviceization, transforming nanozyme‐based analysis from conventional test paper formats into practical, reusable sensing devices. This work establishes a generalizable blueprint for engineering smart nanozyme materials with shape memory characteristics, opening up new avenues for developing advanced biosensing platforms with enhanced performance and user‐friendly operability.

Gadopiclenol Enables Reduced Gadolinium Dose While Maintaining Quality of Pulmonary Arterial Enhancement for Pulmonary MRA: An Opportunity for Improved Safety and Sustainability.

Pulmonary magnetic resonance angiography (MRA) is an imaging method with proven utility for the exclusion of pulmonary embolism and avoids the need for ionizing radiation and iodinated contrast agents. High-relaxivity gadolinium-based contrast agents (GBCAs), such as gadopiclenol, can be used to reduce the required gadolinium dose for pulmonary MRA. The aim of this study was to compare the contrast enhancement performance of gadopiclenol with an established gadobenate dimeglumine-enhanced pulmonary MRA protocol. In this retrospective single-center study, data from 152 patients who underwent pulmonary MRA at 1.5 T were analyzed. Imaging was performed with either 0.05 mmol/kg gadopiclenol (n = 75) or 0.1 mmol/kg gadobenate dimeglumine (n = 77), using dedicated multiphasic imaging protocols with precontrast, pulmonary arterial phase, immediate delayed phase, and a low flip-angle T1-weighted spoiled gradient echo acquisition. Subjective image quality evaluation was performed blinded by 2 radiologists on a 5-point Likert scale. For the estimation of interrater reliability, Cohen weighted κ was calculated. For semiquantitative assessment, signal intensities were measured in the pulmonary arteries, and relative signal enhancement was calculated. Data from groups were compared with Mann-Whitney U tests using Bonferroni corrections. Signal enhancement relative to precontrast in the first-pass pulmonary arterial phase was higher with 0.05 mmol/kg gadopiclenol compared with 0.1 mmol/kg gadobenate dimeglumine (20.0-fold ± 5.6-fold vs 17.8-fold ± 5.8-fold; P = 0.015). Readers observed no difference in subjective rating in terms of intravascular contrast, peripheral vessel depiction, and diagnostic confidence with substantial interrater reliability (Cohen κ = 0.73 [95% confidence interval: 0.57-0.89], 0.65 [0.55-0.75], and 0.74 [0.65-0.84], all P's < 0.001). No severe adverse events were recorded for any clinical MRA examination. The high-relaxivity contrast agent gadopiclenol can facilitate a reduction in gadolinium dose by 50% without compromising contrast enhancement for pulmonary MRA. This approach may enhance the safety and sustainability of pulmonary MRA in the long term.

Engineering conductive covalent-organic frameworks enable highly sensitive and anti-interference molecularly imprinted electrochemical biosensor.

Covalent organic frameworks (COFs) have drawn great interest in electrochemical sensing. However, most are integrated as enrichment units or reaction carriers and are co-modified with metal nanomaterials. Few studies use the single pristine COFs as an electrochemical signal amplifier. Aza-fuzed π-conjugated COFs exhibit exceptional signal enhancement and are an effective electron transport layer for electrochemical sensing applications. In this work, different conductive aza-fuzed π-conjugated COFs were optimized by synthetic engineering. Among them, 2D crystalline COF4 with the highest conductivity (240 % via the bare electrodes) was used to modify the screen printing carbon electrode to construct a portable molecularly imprinted electrochemical biosensor for point-of-care glutathione detection. Compared with the conventional strategy of co-modifing with gold nanoparticles, the single conductive COF4 electrochemical sensor exhibited excellent detection performance and better selectivity for thiol interferents. Conductive COFs combining molecularly imprinted polymer provide a promising strategy for constructing low-cost, easy fabrication and operation, highly sensitive and selective electrochemical biosensors.

Field-Programmable Gate Array (FPGA)-Based Lock-In Amplifier System with Signal Enhancement: A Comprehensive Review on the Design for Advanced Measurement Applications.

Lock-in amplifiers (LIAs) are critical tools in precision measurement, particularly for applications involving weak signals obscured by noise. Advances in signal processing algorithms and hardware synthesis have enabled accurate signal extraction, even in extremely noisy environments, making LIAs indispensable in sensor applications for healthcare, industry, and other services. For instance, the electrical impedance measurement of the human body, organs, tissues, and cells, known as bioelectrical impedance, is commonly used in biomedical and healthcare applications because it is non-invasive and relatively inexpensive. Also, due to its portability and miniaturization capabilities, it has great potential for the development of new point-of-care and portable testing devices. In this document, we highlight existing techniques for high-frequency resolution and precise phase detection in LIA reference signals from field-programmable gate array (FPGA) designs. A comprehensive review is presented under the key requirements and techniques for single- and dual-phase digital LIA architectures, where relevant insights are provided to address the LIAs' digital precision in measurement system configurations. Furthermore, the document highlights a novel method to enhance the spurious-free dynamic range (SFDR), thereby advancing the precision and effectiveness of LIAs in complex measurement environments. Finally, we summarize the diverse applications of impedance measurement, highlighting the wide range of fields that can benefit from the design of high performance in modern measurement technologies.

Size-Dependent Cascade Enhancement of T1-T2 Dual-Modal MRI in Tumors.

Currently, there is no conclusive evidence indicating that in situ self-assembled Gd nanostructures of varying sizes demonstrate distinct T1 and T2 signal enhancement capabilities. Furthermore, it remains uncertain whether size adjustment can effectively achieve enhanced T1-T2 dual-modal MRI. To address these uncertainties, a two-step in situ self-assembly strategy is developed. This approach began with a small-sized nanoprobe, Gd-TCO-P, with a hydrodynamic diameter (dH) of 16 ±3nm. This nanoprobe underwent alkaline phosphatase (ALP) cleavage and self-assembled intracellularly into short nanofibers termed Gd-NFs (dH: 200 ±51nm). The subsequent introduction of tetrazine-tetrazine crosslinked these Gd-NFs, leading to the formation of larger two-stage dendritic nanofibers known as Gd-TS-NFs (dH: 4371 ±236nm). This process achieves size-dependent enhancement of both T1 and T2 signals, which is validated through both in vitro and in vivo experiments, enabling precise long-term imaging of ALP-overexpressing tumors. This study not only provides valuable insights into the relationship between the size of in situ formed Gd nanostructures and T1/T2 MRI contrast enhancement, but also suggests a promising strategy for clinical applications of T1-T2 dual-modal MRI.

Label-Free Surface-Enhanced Raman Scattering for Genomic DNA Cytosine Methylation Reading.

DNA methylation has been widely studied with the goal of correlating the genome profiles of various diseases with epigenetic mechanisms. Multiple approaches have been developed that employ extensive steps, such as bisulfite treatments, polymerase chain reactions (PCR), restriction digestion, sequencing, mass analysis, etc., to identify DNA methylation. In this article, we report a facile label-free surface-enhanced Raman scattering (SERS) spectroscopy system that utilizes gold nanoparticles (AuNPs) for signal enhancement of methylated DNA. The key innovation of this work is to use anionic nanoparticles at a high ionic strength to introduce the aggregation of AuNPs with anionic DNA. When target methylated DNA is present, the presence of a methyl group in the cytosine C5 position of CpG sites induces a Raman peak at 1350 cm-1. Our amplification-free system has a limit of detection (LOD) of 5% and a limit of quantification (LOQ) of 16% with good specificity. The method was applied to determine the hypermethylated levels of the germline of colorectal cancer cell lines SW48 and SW480. Our simple label-free method holds the potential to read the disease-associated methylation of genomic DNA.

Attention rhythmically shapes sensory tuning.

Attention is key to perception and human behavior, and evidence shows that it periodically samples sensory information (<20Hz). However, this view has been recently challenged due to methodological concerns and gaps in our understanding of the function and mechanism of rhythmic attention. Here we used an intensive ∼22-hour psychophysical protocol combined with reverse correlation analyses to infer the neural representation underlying these rhythms. Participants (male/female) performed a task in which covert spatial (sustained and exploratory) attention was manipulated, and then probed at various delays. Our results show that sustained and exploratory attention periodically modulate perception via different neural computations. While sustained attention suppresses distracting stimulus features at the alpha (∼12Hz) frequency, exploratory attention increases the gain around task-relevant stimulus feature at the theta (∼6Hz) frequency. These findings reveal that both modes of rhythmic attention differentially shape sensory tuning, expanding the current understanding of the rhythmic sampling theory of attention.Significance statement For the past decade, low-frequency rhythms have been observed in attentional performance. Here, we go beyond description and assess the underlying neural computations in the sensory system. We used an intensive psychophysical protocol combined with reverse correlation analysis to infer the system's sensitivity to and selectivity for stimulus feature (orientation) across time, and for two attention modes, i.e., sustained and exploratory attention. Our results reveal that sustained and exploratory attention modes differentially shape the sensory tuning to stimulus features: respectively altering either noise suppression or signal enhancement rhythmically, leading to alternating periods of performance enhancement and decrement.

Mechanisms in thyroid eye disease - the TSH receptor interacts directly with the IGF-1 receptor.

The pathogenesis of Thyroid Eye Disease (TED) has been suggested as due to signal enhancement in orbital fibroblasts as a result of autoantibody-induced, synergistic, interaction between the TSH receptor (TSHR) and the IGF-1 receptor (IGF-1R). This interaction has been explained by a "receptor cross talk", mediated via β-arrestin binding. Here, we have examined if this interaction can be mediated via direct receptor contact using modeling and experimental approaches. First, we docked a model of the leucine rich domain (LRD) of the TSHR ectodomain (ECD) to an available cryo-EM based structure of the active-state IGF-1R dimer and demonstrated the stability of the complex using molecular dynamics (MD) simulations. We then extended the complex with the full-length TSHR and the transmembrane helices of the IGF1R and a 3000 ns simulation also showed stability of this complex. We then performed co-immunoprecipitation studies with anti-TSHR and anti-IGF-1R antibodies using cells expressing the IGF-1R and the full-length TSHR and also cells that expressed the IGF-1R and only the TSHR-ECD and, therefore, unable to bind β-arrestin. These studies showed a 360 kD complex protein in the immunoprecipitation which was present in both the full-length TSHR and the TSHR-ECD-only expressing cells evidencing a direct interaction of receptors via their ectodomains in the absence of arrestin. Co-localized staining of TSHR and IGF1R in the TSHR-ECD cells further supported this direct interaction. These data showed that the TSHR and IGF-1R can interact directly and in the absence of β-arrestin binding. Understanding these interactions is important in the pathogenesis of TED and its therapeutic intervention.

A Magnetoelectric Distance Estimation System for Relative Human Motion Tracking.

Clinical motion analysis plays an important role in the diagnosis and treatment of mobility-limiting diseases. Within this assessment, relative (point-to-point) tracking of extremities could benefit from increased accuracy. Given the limitations of current wearable sensor technology, supplementary spatial data such as distance estimates could provide added value. Therefore, we propose a distributed magnetic tracking system based on early-stage demonstrators of novel magnetoelectric (ME) sensors. The system consists of two body-worn magnetic actuators and four ME sensor arrays (body-worn and fixed). It is enabled by a comprehensive signal processing framework with sensor-specific signal enhancement and a gradient descent-based system calibration. As a pilot study, we evaluated the technical feasibility of the described system for motion tracking in general (Scenario A) and for operation during treadmill walking (Scenario B). At distances of up to 60 cm, we achieved a mean absolute distance error of 0.4 cm during gait experiments. Our results show that the modular system is capable of centimeter-level motion tracking of the lower extremities during treadmill walking and should therefore be investigated for clinical gait parameter assessment.

Quantitative Analysis of Multi-Elements in a Micron-Sized Single Particle Based on Laser-Induced Breakdown Spectroscopy Signal Enhancement of an Optical Fiber Collimated System.

With rapid, energy-intensive, and coal-fueled economic growth, global air quality is deteriorating, and particulate matter pollution has emerged as one of the major public health problems worldwide. It is extremely urgent to achieve carbon emission reduction and air pollution prevention and control, aiming at the common problem of weak and unstable signals of characteristic elements in the application of laser-induced breakdown spectroscopy (LIBS) technology for trace element detection. In this study, the influence of the optical fiber collimation signal enhancement method on the LIBS signal was explored. Then, the influence of the LIBS signal enhancement system based on an optical fiber collimated system on LIBS spectral signal intensity and signal-to-noise ratio (SNR) was compared, and the influences of different spectral preprocessing methods and different variable selection methods on the prediction performance of the random forest (RF) calibration model were investigated. Finally, the Savitzky-Golay convolution derivative (SG)-variable importance projection (VIP)-mutual information (MI)-RF (Zn), first-order derivative (D1st)-variable importance measurement (VIM)-successive projections algorithm (SPA)-RF (Cu), and D1st-VIM-MI-RF (Ni) optimal models were constructed according to the optimal spectral preprocessing method and the optimal hybrid variable selection method. The prediction performances of their optimal RF model after SG-VIP-MI (Zn), D1st-VIM-SPA (Cu), and D1st-VIM-MI (Ni) spectral preprocessing and hybrid variable selection method are presented as follows: Zn (Rp2 = 0.9860; MREP = 0.0590), Cu (Rp2 = 0.9817; MREP = 0.0405), and Ni (Rp2 = 0.9856; MREP = 0.0875). The above results demonstrate that the RF calibration model based on the optical fiber collimated LIBS signal enhancement method, the optimal spectral preprocessing method, and variable selection strategy overcome the key problems of low SNR and low quantitative accuracy in single particle detection. It is expected to provide a theoretical basis and technical support for in situ online rapid monitoring of particulate matter.

An OMV-Based Nanovaccine as Antigen Presentation Signal Enhancer for Cancer Immunotherapy.

Antigen-presenting cells (APCs) process tumor vaccines and present tumor antigens as the first signals to T cells to activate anti-tumor immunity, which process requires the assistance of co-stimulatory second signals on APCs. The immune checkpoint programmed death ligand 1 (PD-L1) not only mediates the immune escape of tumor cells but also acts as a co-inhibitory second signal on APCs. The serious dysfunction of second signals due to the high expression of PD-L1 on APCs in the tumor body results in the inefficiency of tumor vaccines. To overcome this challenge, a previously established Plug-and-Display tumor vaccine platform based on bacterial outer membrane vesicles (OMVs) is developed into an "Antigen Presentation Signal Enhancer" (APSE) by surface-modifying PD-L1 antibodies (αPD-L1). While delivering tumor antigens, APSE can activate the expression of co-stimulatory second signals in APCs due to the high immunogenicity of OMVs. More importantly, the surface-modified αPD-L1 binds to the co-inhibitory signals PD-L1, potentially restoring CD80 function and ensuring efficient co-stimulatory second signals and activation of anti-tumor immunity. The results reveal the importance of PD-L1 blockage in the initiation process of anti-tumor immunity, and the second signal modulation capability of APSE can expand the application potential of cancer vaccines to less immunogenic malignancies.

Dolphin Whistle Signal Enhancement Using Nonconvex Time–Frequency Regularized Overlapping Group Shrinkage in Warm Shallow Water

Dolphin Whistle Signal Enhancement Using Nonconvex Time–Frequency Regularized Overlapping Group Shrinkage in Warm Shallow Water

The role of spin diffusion in endogenous metal ions DNP.

The sensitivity of solid state nuclear magnetic resonance spectroscopy can be enhanced via dynamic nuclear polarization (DNP) using unpaired electrons as polarizing agents. In metal ions based (MI)-DNP, paramagnetic metal ions are introduced as dopants into inorganic materials serving as endogenous polarizing agents. Having polarizing agents as part of the structure enables signal enhancements within the bulk of the material. Nuclear spins can be hyperpolarized either directly through their coupling to the polarizing agent or via homonuclear spin diffusion. In this work, we addressed what are the factors determining the relative sizes of the spin pools polarized by each of these two mechanisms and how changing their contribution to the polarization process affects the experimental outcome. Experimentally, we adjusted the spin diffusion rate through modifying the isotope ratio 6Li/7Li in otherwise identical samples, Li4Ti5O12 doped with paramagnetic Fe(III). DNP experiments on samples with typical content of polarizing agents for MI-DNP, corroborated by simulations, evidenced that while the efficiency of spin diffusion has large effects on the polarization buildup times, the enhancements remain largely unaffected.

Employing Triphenylene-Based, Layered, Conductive Metal-Organic Framework Materials as Electrochemical Sensors for Nitric Oxide in Aqueous Media.

This paper describes the first use of conductive metal-organic frameworks as the active material in the electrochemical detection of nitric oxide in aqueous solution. Four hexahydroxytriphenylene (HHTP)-based MOFs linked with first-row transition metal nodes (M = Co, Ni, Cu, Zn) were compared as thin-film working electrodes for promoting oxidation of NO using voltammetric and amperometric techniques. Cu- and Ni-linked MOF analogs provided signal enhancement of 5- to 7-fold over a control glassy carbon electrode (SANO = 6.7 ± 1.2 and 5.7 ± 1.1 for Ni3(HHTP)2 and Cu3(HHTP)2, respectively) for detecting micromolar concentrations of NO. Zinc-based MOF electrodes offered more limited enhancement (SANO = 3.1 ± 0.5), while the cobalt-based MOF analog had intrinsic redox activity at potentials close to NO oxidation, which interfered with sensing. Combining MOFs with a conductive polymer improved electrode stability under repeated electrochemical scanning (14 ± 3% decrease in signal over 10 scans). The stabilized Ni3(HHTP)2@polymer-coated electrodes were able to detect NO at physiologically relevant concentrations (LOD = 9.0 ± 4.8 nM) in amperometric sensing experiments, and exhibited moderate selectivity against ascorbic acid and nitrite (log kj,NO = -1.3 ± 0.3 and -0.83 ± 0.68 for ascorbic acid and nitrite, respectively). This study demonstrates that layered, conductive 2D MOFs have promising applicability for NO detection in aqueous environments.

Precise Sizing and Collision Detection of Functional Nanoparticles by Deep Learning Empowered Plasmonic Microscopy.

Single nanoparticle analysis is crucial for various applications in biology, materials, and energy. However, precisely profiling and monitoring weakly scattering nanoparticles remains challenging. Here, it is demonstrated that deep learning-empowered plasmonic microscopy (Deep-SM) enables precise sizing and collision detection of functional chemical and biological nanoparticles. Image sequences are recorded by the state-of-the-art plasmonic microscopy during single nanoparticle collision onto the sensor surface. Deep-SM can enhance signal detection and suppresses noise by leveraging spatio-temporal correlations of the unique signal and noise characteristics in plasmonic microscopy image sequences. Deep-SM can provide significant scattering signal enhancement and noise reduction in dynamic imaging of biological nanoparticles as small as 10nm, as well as the collision detection of metallic nanoparticle electrochemistry and quantum coupling with plasmonic microscopy. The high sensitivity and simplicity make this approach promising for routine use in nanoparticle analysis across diverse scientific fields.

Multifolding Vertical-Flow Electrochemical Paper-Based Devices with Tunable Dual Preconcentration for Enhanced Multiplexed Assays of Heavy Metals.

This work describes fully integrated multifolding electrochemical paper-based devices (ePADs) for enhanced multiplexed voltammetric determination of heavy metals (Zn(II), Cd(II), and Pb(II)) using tunable passive preconcentration. The paper devices integrate five circular sample preconcentration layers and a 3-electrode electrochemical cell. The hydrophobic barriers of the devices are drawn by pen-plotting with hydrophobic ink, while the electrodes are deposited by screen-printing. The devices exploit the wicking ability of cellulose paper to perform passive preconcentration of the target analytes, resulting in a ∼6-fold signal enhancement. For this purpose, drops of the sample are placed at the five sample pads of the preconcentration layers, the device is folded, and the target metals are eluted in a vertical-flow mode to the electrochemical cell, where they are measured directly by anodic stripping voltammetry (ASV). The working electrode of the ePADs is bulk-modified with bismuth citrate; during the ASV measurements, the bismuth precursor is converted to nanodomains of metallic bismuth at the surface of the working electrode. By combining the triplex signal amplification through passive preconcentration, electrochemical preconcentration, and judicious working electrode modification with in situ generated bismuth nanoparticles, ultrasensitive and multiplexed heavy metal assays can be achieved. Due to their high degree of integration, low cost, easy and fast fabrication, and sensitivity, the multifolding ePADs are particularly suitable for on-site heavy metals' monitoring applications.

Carboxylated Graphene: An Innovative Approach to Enhanced IgA-SARS-CoV-2 Electrochemical Biosensing.

Biosensors harness biological materials as receptors linked to transducers, enabling the capture and transformation of primary biorecognition signals into measurable outputs. This study presents a novel carboxylation method for synthesizing carboxylated graphene (CG) under acidic conditions, enhancing biosensing capabilities. The characterization of the CG was performed using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, thermogravimetric analysis (TGA), and X-ray diffraction (XRD). We modified screen-printed carbon electrodes (SPCEs) with CG to immobilize the SARS-CoV-2 N-protein, facilitating targeted detection of IgA antibodies (IgA-SARS-CoV-2). The analytical performance was assessed via electrochemical techniques such as cyclic voltammetry and electrochemical impedance spectroscopy, confirming CG synthesis effectiveness and biosensor functionality. The developed biosensor efficiently detects IgA-SARS-CoV-2 across a dilution range of 1:1000 to 1:200 v/v in a phosphate-buffered saline (PBS) solution, with a limit of detection calculated at 1:1601 v/v. This device shows considerable potential because of its fast response time, miniaturized design facilitated by SPCEs, reduced sample volume requirements, high sensitivity and specificity, low detection limits, and signal enhancement achieved through nanomaterial integration.

A Single-Chain Peptide Probe Targeting Pathological Collagen for Precise Staging of Hepatic Fibrosis by MR Imaging.

Hepatic fibrosis, a chronic liver response to injury with potential severe outcomes like cirrhosis and liver cancer, necessitates urgent noninvasive diagnostic techniques to halt disease progression. We herein for the first time developed a single-chain peptide probe targeting pathological collagen for in vivo magnetic resonance imaging (MRI) of hepatic fibrosis. The novel (GhypO)10 probe, distinguished by its unique monomeric conformation achieved through Pro to (2S,4S)-hydroxyproline (hyp) substitution and subsequent disruption of hydrogen bonding, exhibits selectivity for pathological collagen over its intact counterpart in connective tissues. Fluorescence imaging of liver specimens from fibrotic models displayed a discernible relationship between pathological collagen levels and fibrosis stage. Moreover, T1-weighted MR images post Gd-GhypO administration revealed progressive signal enhancement congruent with fibrosis severity, corroborated by a corresponding increase in the contrast-to-noise ratio (ΔCNR). Biodistribution analysis indicates that Gd-GhypO has low Gd retention in the main organs 24 h postinjection, ensuring the probe's safety for molecular imaging. The Gd-GhypO probe therefore emerges as a potent tool for the precise, noninvasive delineation of hepatic fibrosis stages, offering significant implications for the diagnosis and management of liver fibrosis.

High H2 Solubility of Perfluorocarbon Solvents and Their Use in Reversible Polarization Transfer from para-Hydrogen.

This research uses perfluorocarbons (PFCs) as effective alternatives to traditional toxic solvents in reversible para-hydrogen-induced polarization (PHIP) for NMR signal enhancement. Hydrogen solubility in PFCs is shown here to be an order of magnitude higher than in typical organic solvents by determination of Henry's constants. We demonstrate how this high H2 solubility enables the PFCs to deliver substantial polarization transfer from para-hydrogen, achieving up to 2400-fold signal gains for 1H NMR detection and 67,000-fold (22% polarization) for 15N NMR detection at 9.4 T in substrates such as pyridine and nicotine. Notably, methylperfluorobutylether outperforms catalytic efficiency in methanol-d4 and dichloromethane-d2 for pyridine at low catalyst loadings. This makes PFCs particularly advantageous for applications demanding high NMR sensitivity. With high polarization efficiency and reduced toxicity, PFCs hold strong potential for expanding hyperpolarized NMR applications across the biomedical and analytical fields.