Folic acid-mediated hollow Mn 3 O 4 nanocomposites for in vivo MRI/FLI monitoring the metastasis of gastric cancer.

BACKGROUND: Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis. METHODS: In this paper, we constructed a new type of hollow Mn 3 O 4 nanocomposites, Mn 3 O 4 @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of T 1 -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite. RESULTS: This report demonstrates that Mn 3 O 4 @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future. CONCLUSIONS: In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.

High-temperature PTT/CDT coordination nanoplatform realizing exacerbated hypoxia for enhancing hypoxia-activated chemotherapy to overcome tumor drug resistance.

BACKGROUND: Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the uneven distribution of oxygen in solid tumor and insufficient hypoxia in the tumor microenvironment greatly limit its therapeutic efficacy. RESULTS: In this paper, a novel AQ4N-Mn(II)@PDA coordination nanoplatform was designed and functionalized with GMBP1 to target drug-resistant tumor cells. Its excellent photothermal conversion efficiency could achieve local high-temperature photothermal therapy in tumors, which could not only effectively exacerbate tumor hypoxia and thus improve the efficacy of hypoxia-activated chemotherapy of AQ4N but also significantly accelerate Mn2+-mediated Fenton-like activity to enhance chemodynamic therapy. Moreover, real-time monitoring of blood oxygen saturation through photoacoustic imaging could reflect the hypoxic status of tumors during treatment. Furthermore, synergistic treatment effectively inhibited tumor growth and improved the survival rate of mice bearing orthotopic drug-resistant tumors. CONCLUSIONS: This study not only provided a new idea for PTT combined with hypoxia-activated chemotherapy and CDT for drug-resistant tumors but also explored a vital theory for real-time monitoring of hypoxia during treatment.

PriTKT: A Blockchain-Enhanced Privacy-Preserving Electronic Ticket System for IoT Devices.

Electronic tickets (e-tickets) are gradually being adopted as a substitute for paper-based tickets to bring convenience to customers, corporations, and governments. However, their adoption faces a number of practical challenges, such as flexibility, privacy, secure storage, and inability to deploy on IoT devices such as smartphones. These concerns motivate the current research on e-ticket systems, which seeks to ensure the unforgeability and authenticity of e-tickets while simultaneously protecting user privacy. Many existing schemes cannot fully satisfy all these requirements. To improve on the current state-of-the-art solutions, this paper constructs a blockchain-enhanced privacy-preserving e-ticket system for IoT devices, dubbed PriTKT, which is based on blockchain, structure-preserving signatures (SPS), unlinkable redactable signatures (URS), and zero-knowledge proofs (ZKP). It supports flexible policy-based ticket purchasing and ensures user unlinkability. According to the data minimization and revealing principle of GDPR, PriTKT empowers users to selectively disclose subsets of (necessary) attributes to sellers as long as the disclosed attributes satisfy ticket purchasing policies. In addition, benefiting from the decentralization and immutability of blockchain, effective detection and efficient tracing of double spending of e-tickets are supported in PriTKT. Considering the impracticality of existing e-tickets schemes with burdensome ZKPs, we replace them with URS/SPS or efficient ZKP to significantly improve the efficiency of ticket issuing and make it suitable for use on smartphones.

Dynamic Privacy-Preserving Anonymous Authentication Scheme for Condition-Matching in Fog-Cloud-Based VANETs.

Secure group communication in Vehicle Ad hoc Networks (VANETs) over open channels remains a challenging task. To enable secure group communications with conditional privacy, it is necessary to establish a secure session using Authenticated Key Agreement (AKA). However, existing AKAs suffer from problems such as cross-domain dynamic group session key negotiation and heavy computational burdens on the Trusted Authority (TA) and vehicles. To address these challenges, we propose a dynamic privacy-preserving anonymous authentication scheme for condition matching in fog-cloud-based VANETs. The scheme employs general Elliptic Curve Cryptosystem (ECC) technology and fog-cloud computing methods to decrease computational overhead for On-Board Units (OBUs) and supports multiple TAs for improved service quality and robustness. Furthermore, certificateless technology alleviates TAs of key management burdens. The security analysis indicates that our solution satisfies the communication security and privacy requirements. Experimental simulations verify that our method achieves optimal overall performance with lower computational costs and smaller communication overhead compared to state-of-the-art solutions.

Cobalt Ferrite-Gossypol Coordination Nanoagents with High Photothermal Conversion Efficiency Sensitizing Chemotherapy against Bcl-2 to Induce Tumor Apoptosis.

Gossypol is a chemotherapeutic drug that can inhibit the anti-apoptotic protein Bcl-2, but the existing gossypol-related nanocarriers cannot well solve the problem of chemotherapy resistance. Based on the observation that gossypol becomes black upon Fe3+ coordination, it is hypothesized that encasing gossypol in glyceryl monooleate (GMO) and making it coordinate cobalt ferrite will not only improve its photothermal conversion efficiency (PCE) but also help it enter tumor cells. As the drug loading content and drug encapsulation efficiency of gossypol are 10.67% (w/w) and 96.20%, the PCE of cobalt ferrite rises from 14.71% to 36.00%. The synergistic therapeutic effect finally induces tumor apoptosis with a tumor inhibition rate of 96.56%, which is 2.99 and 1.47 times higher than chemotherapy or photothermal therapy (PTT) alone. PTT generated by the GMO nanocarriers under the irradiation of 808 nm laser can weaken tumor hypoxia, thereby assisting gossypol to inhibit Bcl-2. In addition, the efficacy of nanocarriers is also evaluated through T2 -weighted magnetic resonance imaging. Observations of gossypol-induced apoptosis in tissue slices provide definitive proof of chemotherapy sensitization, indicating that such coordination nanocarriers can be used as an effective preclinical agent to enhance chemotherapy.

Rational design of NIR-II molecule-engineered nanoplatform for preoperative downstaging and imaging-guided surgery of orthotopic hepatic tumor.

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core "S-D-A-D-S" NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.

MF-Net: Automated Muscle Fiber Segmentation From Immunofluorescence Images Using a Local-Global Feature Fusion Network.

Histological assessment of skeletal muscle slices is very important for the accurate evaluation of weightless muscle atrophy. The accurate identification and segmentation of muscle fiber boundary is an important prerequisite for the evaluation of skeletal muscle fiber atrophy. However, there are many challenges to segment muscle fiber from immunofluorescence images, including the presence of low contrast in fiber boundaries in immunofluorescence images and the influence of background noise. Due to the limitations of traditional convolutional neural network-based segmentation methods in capturing global information, they cannot achieve ideal segmentation results. In this paper, we propose a muscle fiber segmentation network (MF-Net) method for effective segmentation of macaque muscle fibers in immunofluorescence images. The network adopts a dual encoder branch composed of convolutional neural networks and transformer to effectively capture local and global feature information in the immunofluorescence image, highlight foreground features, and suppress irrelevant background noise. In addition, a low-level feature decoder module is proposed to capture more global context information by combining different image scales to supplement the missing detail pixels. In this study, a comprehensive experiment was carried out on the immunofluorescence datasets of six macaques' weightlessness models and compared with the state-of-the-art deep learning model. It is proved from five segmentation indices that the proposed automatic segmentation method can be accurately and effectively applied to muscle fiber segmentation in shank immunofluorescence images.

Detector-trigger-based cardiac multiphase micro-CT imaging for small animals.

BACKGROUND: Micro-computed tomography is important in cardiac imaging for preclinical small animal models, but motion artifacts may appear due to the rapid heart rates. To avoid influence of motion artifacts, the prospective ECG gating schemes based on an X-ray source trigger have been investigated. However, due to the lack of pulsed X-ray exposure modes, high-resolution micro-focus X-ray sources do not support source triggering in most cases. OBJECTIVE: To develop a fast-cardiac multiphase acquisition strategy using prospective ECG gating for micro-focus X-ray tubes with a continuous emission mode. METHODS: The proposed detector-trigger-based prospective ECG gating acquisition scheme (DTB-PG) triggers the X-ray detector at the R peak of ECG, and then collects multiple phase projections of the heart in one ECG cycle by sequence acquisition. Cardiac multiphase images are reconstructed after performing the same acquisition in all views. The feasibility of this strategy was verified in multiphase imaging experiments of a phantom with 150 ms motion period and a mouse heart on a micro-focus micro-CT system with continuous emission mode. RESULTS: Using a high frame-rate CMOS detector, DTB-PG discriminates the positions of the motion phantom well in 10 different phases and enables to distinguish the changes in the cardiac volume of the mouse in different phases. The acquisition rate of DTB-PG is much faster than other prospective gating schemes as demonstrated by theoretical analysis. CONCLUSIONS: DTB-PG combines the advantages of prospective ECG gating strategies and X-ray detector-trigger mode to suppress motion artifacts, achieve ultra-fast acquisition rates, and relax hardware limitations.

Precisely controlled polydopamine-mediated antibacterial system: mathematical model of polymerization, prediction of antibacterial capacity, and promotion of wound healing.

In this work, the polydopamine (PDA)-mediated antibacterial system is synthesized to carry out antimicrobial activities in vitro and in vivo. First, to precisely control the surface modification of nanodiamonds (NDs), a mathematical kinetics model of PDA deposition is established, and the conditions of synthesis reaction are discussed including influencing factors such as the concentrations of dopamine, reaction time, and the kinetic constant k1, which is a function of several variables associated with the reaction temperature, light irradiance (especially at ultraviolet wavelengths), pH value and concentration of dissolved O2 in the solution. A simulated visualization demonstrates that the deposition thickness of PDA is positively correlated with temperature and light irradiance, and PDA is easier to deposit in an alkaline solution and will be terminated if the dissolved O2 is insufficient. Then, the precisely controlled thickness of PDA can control the growth of AgNPs, rendering the intensity of Raman peaks increased and providing a predictable antibacterial effect against E. coli in vitro. An optimized antibacterial hydrogel containing NDs-PDA/Ag is prepared and characterized by the Fourier transform infrared spectroscopy and field emission scanning electron microscopy. Finally, the antibacterial experiments to promote wound healing in vivo are performed, which are verified by pathological and immunohistochemical-stained sections. This work provides a theoretical basis of predicting the PDA-assisted surface modification of NDs, giving a divinable antibacterial effect, and promoting wounds healing in vivo.

Tumor microenvironment responsive Mn3O4 nanoplatform for in vivo real-time monitoring of drug resistance and photothermal/chemodynamic synergistic therapy of gastric cancer.

BACKGROUND: Postoperative chemotherapy for gastric cancer often causes multidrug resistance (MDR), which has serious consequences for therapeutic effects. Individualized treatment based on accurate monitoring of MDR will greatly improve patient survival. RESULTS: In this article, a self-enhanced Mn3O4 nanoplatform (MPG NPs) was established, which can react with glutathione to produce Mn2+ to enhance T1-weighted magnetic resonance imaging (MRI) and mediate in vivo real-time MDR monitoring. In vitro MRI results showed that MRI signals could be enhanced in the presence of hydrogen peroxide and glutathione and at acidic pH. In vivo MRI results indicated that MPG NPs could specifically target MDR cells, thereby realizing real-time monitoring of MDR in gastric cancer. Furthermore, MPG NPs have good chemodynamic activity, which can convert the endogenous hydrogen peroxide of tumor cells into highly toxic hydroxyl radical through Fenton-like reaction at acidic pH to play the role of chemodynamic therapy. In addition, Mn3O4 can significantly enhance the chemodynamic therapy effect because of its good photothermal conversion effect. Furthermore, in situ photothermal/chemodynamic synergistic therapy obtained remarkable results, the tumors of the mice in the synergistic therapy group gradually became smaller or even disappeared. CONCLUSIONS: MPG NPs have good biocompatibility, providing a good nanoplatform for real-time monitoring and precise diagnosis and treatment of MDR in gastric cancer.

Britanin Exhibits Potential Inhibitory Activity on Human Prostate Cancer Cell Lines Through PI3K/Akt/NF-κB Signaling Pathways.

Britanin, a natural pseudoguaiacane sesquiterpene lactone, has significant antioxidant and anti-inflammatory activity, but little is known about its tumor inhibitory activity and the underlying mechanism. Here, we demonstrated in vitro and in vivo that britanin inhibited the growth of human prostate cancer cell lines (PC-3, PC-3-LUC, and DU-145). Through in vitro study, the results showed that britanin significantly decreased cell proliferation, migration, and motility. The moderate toxicity of britanin was determined with an acute toxicity study. A luciferase-labeled animal tumor xenograft model and bioluminescence imaging were applied, combining with biological validation for assessing the tumor progression. In vivo results demonstrated that britanin inhibited the growth of PC-3-LUC. The interleukin-2 level in mice was upregulated by britanin, which indicated that britanin induced antitumor immune activation. In addition, britanin downregulated the expression of nuclear factor (NF)-κB p105/p50, pp65, IκBα, pIκBα, phosphoinositide 3-kinase, pPI3k, Akt (protein kinase B, PKB), and pAkt proteins and upregulated expression of Bax. We discovered that britanin inhibits the growth of prostate cancer cells both in vitro and in vivo by regulating PI3K/Akt/NF-κB-related proteins and activating immunity. These findings shed light on the development of britanin as a promising agent for prostate cancer therapy.

A photo-triggered conjugation approach for attaching RGD ligands to biodegradable mesoporous silica nanoparticles for the tumor fluorescent imaging.

Fluorescent probes conjugated to peptide or antibody directing groups, which exhibit high signal to background ratios, have been widely used to image tumors and monitor their growth. A photo-triggered cycloaddition reaction between the arginine-glycine-aspartic acid -N-ɛ-acryllysine (RGD-Acrk) peptides and the tetrazole compounds bound to the surface of biodegradable mesoporous silica nanoparticles (bMSN) has been used to construct a fluorescent nanoprobe (bMSN@T2-RGD-Acrk), which showed fluorescent emission at 550 nm and could selectively image the 4T1 cells and breast cancer. This means that the bMSN@T2-RGD-Acrk nanoprobe made by photo-triggered conjugation approach is a promising fluorescent imaging agent for visualizing tumors. Thus, the photo-triggered one-spot reaction can give a stable crosslinker in a biocompatible manner for bioconjugation with nanoparticles and produce a fluorescent group that is suitable for imaging in vivo.

Expression and Distribution of the Auxin Response Factors in Sorghum bicolor During Development and Temperature Stress.

Auxin response factor (ARF) is a transcription factor that can specifically bind to the promoter of auxin-responsive genes in plants and plays an important regulatory role in plant growth and development. The previous studies have predicted 25 ARF genes in Sorghum bicolor (SbARFs) and indicated that SbARFs play complex roles in salt and drought stresses. In this study, we reclassified and analyzed the structures of ARFs in three plants, including sorghum, rice, and Arabidopsis. Phylogenetic analyses categorized 73 ARF into five classes. By studying the characterization of the structures, it was found that SbARFs from the same evolutionary branches showed similar motif patterns. Furthermore, the expression patterns of SbARF genes during development and temperature stress were investigated in sorghum. Quantitative transcription-quantitative polymerase chain reaction (qRT-PCR) results suggested that they had different expression patterns in vegetative and reproductive organs at various developmental stages. High and low-temperature treatments and qRT-PCR demonstrated some of them changed dramatically along with the increase of treatment time. Additionally, in situ hybridization results displayed that SbARF genes were accumulated in vascular tissues under temperature stress. These findings provide evidence that SbARFs may play important roles in sorghum vegetative development, reproductive development, and auxin response to temperature stress.

Gamma rays excited radioluminescence tomographic imaging.

BACKGROUND: Radionuclide-excited luminescence imaging is an optical radionuclide imaging strategy to reveal the distributions of radioluminescent nanophosphors (RLNPs) inside small animals, which uses radioluminescence emitted from RLNPs when excited by high energy rays such as gamma rays generated during the decay of radiotracers used in clinical nuclear medicine imaging. Currently, there is no report of tomographic imaging based on radioluminescence. METHODS: In this paper, we proposed a gamma rays excited radioluminescence tomography (GRLT) to reveal three-dimensional distributions of RLNPs inside a small animal using radioluminescence through image reconstruction from surface measurements of radioluminescent photons using an inverse algorithm. The diffusion equation was employed to model propagations of radioluminescent photons in biological tissues with highly scattering and low absorption characteristics. RESULTS: Phantom and artificial source-implanted mouse model experiments were employed to test the feasibility of GRLT, and the results demonstrated that the ability of GRLT to reveal the distribution of RLNPs such as Gd2O2S:Tb using the radioluminescent signals when excited by gamma rays produced from 99mTc. CONCLUSIONS: With the emerging of targeted RLNPs, GRLT can provide new possibilities for in vivo and noninvasive examination of biological processes at cellular levels. Especially, combining with Cerenkov luminescence imaging, GRLT can achieve dual molecular information of RLNPs and nuclides using single optical imaging technology.

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles.

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.

Preparation of Biocompatible Near-Infrared Fluorescent Nanoparticles for Cellular Imaging.

This study presents a novel and simple method to prepare a new biocompatible near-infrared (NIR) IR-780 nanoparticles (NPs) by modifying a bio-inspired silification approach. The solubility of as-prepared IR-780 NPs was greatly increased and the fluorescence intensity was dramatically enhanced by 5­7 fold compared to free IR-780 dye. Also, an exceptionally small size of 28 nm and the colloidal stability of the IR-780 NPs were sufficient to realize the desired permeability and retention effect (EPR). Furthermore, the in vitro cell viability assays indicated that the IR-780 NPs were highly safe even at the highest concentration of 1.0 mg/mL. The in vitro studies using MDA-231 breast cancer cells showed that the IR-780 NPs were successfully uptaken by the cancer cells and located at the cytoplasm of the cells. The results suggest that the IR-780 NPs may be a promising fluorescence imaging agent for clinical application.

In Vivo Dual-Modality Fluorescence and Magnetic Resonance Imaging-Guided Lymph Node Mapping with Good Biocompatibility Manganese Oxide Nanoparticles.

Multifunctional manganese oxide nanoparticles (NPs) with impressive enhanced T1 contrast ability show great promise in biomedical diagnosis. Herein, we developed a dual-modality imaging agent system based on polyethylene glycol (PEG)-coated manganese oxide NPs conjugated with organic dye (Cy7.5), which functions as a fluorescence imaging (FI) agent as well as a magnetic resonance imaging (MRI) imaging agent. The formed Mn3O4@PEG-Cy7.5 NPs with the size of ~10 nm exhibit good colloidal stability in different physiological media. Serial FI and MRI studies that non-invasively assessed the bio-distribution pattern and the feasibility for in vivo dual-modality imaging-guided lymph node mapping have been investigated. In addition, histological and biochemical analyses exhibited low toxicity even at a dose of 20 mg/kg in vivo. Since Mn3O4@PEG-Cy7.5 NPs exhibited desirable properties as imaging agents and good biocompatibility, this work offers a robust, safe, and accurate diagnostic platform based on manganese oxide NPs for tumor metastasis diagnosis.

Intrinsically Zirconium-89 Labeled Gd2 O2 S:Eu Nanoprobes for In Vivo Positron Emission Tomography and Gamma-Ray-Induced Radioluminescence Imaging.

The engineering of a novel dual-modality imaging probe is reported here by intrinsically labeling zirconium-89 ((89) Zr, a positron emission radioisotope with a half-life of 78.4 h) to PEGylated Gd2 O2 S:Eu nanophorphors, forming [(89) Zr]Gd2 O2 S:Eu@PEG for in vivo positron emission tomography/radioluminescence lymph node mapping.

Contrastive Disentanglement for Quantitative Ultrasound Muscle Atrophy Evaluation.

OBJECTIVE: Muscle atrophy reduces the quality of life and increases morbidity and mortality from other diseases. The development of non-invasive muscle atrophy evaluation method is of great practical value. The lack of gold standard for pathological grading usually allows only the duration of weightlessness as a criterion for the degree of atrophy. However, the adaptive reductive remodeling of muscle physiology and structure shows a trend of nonlinear changes in time. Consequently, using weightlessness time as a benchmark for the degree of atrophy is inaccurate. METHODS: This paper proposes a new ultrasound imaging-based method for quantifying muscle atrophy that utilizes weakly supervised information between multiple data partitions with controlled variance components, overcoming the limitations of using the weightlessness time as a criterion. We introduce a group-supervised contrastive disentanglement network (GCDNet) to disentangle the individual variances, muscle growth and atrophy components of ultrasound images, and quantify the degree of atrophy using the disentangled atrophy component. RESULTS: The feasibility of GCDNet is validated by the separability, independence, and representativeness of the disentangled components. To simplify the application of GCDNet, a muscle atrophy scoring network requiring no reference images is developed by distilling the GCDNet's knowledge of muscle atrophy quantization. The strength of the proposed methodology allows us, for the first time to our knowledge, to study the muscle growth attribute during hind-limb unloading and the spatial distribution of muscle atrophy.

Exploring Radiomics Features Based on H&E Images as Potential Biomarkers for Evaluating Muscle Atrophy: A Preliminary Study.

Radiomics features have been widely used as novel biomarkers in the diagnosis of various diseases, but whether radiomics features derived from hematoxylin and eosin (H&E) images can evaluate muscle atrophy has not been studied. Therefore, this study aims to establish a new biomarker based on H&E images using radiomics methods to quantitatively analyze H&E images, which is crucial for improving the accuracy of muscle atrophy assessment. Firstly, a weightless muscle atrophy model was established by laying macaques in bed, and H&E images of the shank muscle fibers of the control and bed rest (BR) macaques were collected. Muscle fibers were accurately segmented by designing a semi-supervised segmentation framework based on contrastive learning. Then, 77 radiomics features were extracted from the segmented muscle fibers, and a stable subset of features was selected through the LASSO method. Finally, the correlation between radiomics features and muscle atrophy was analyzed using a support vector machine (SVM) classifier. The semi-supervised segmentation results show that the proposed method had an average Spearman's and intra-class correlation coefficient (ICC) of 88% and 86% compared to manually extracted features, respectively. Radiomics analysis showed that the AUC of the muscle atrophy evaluation model based on H&E images was 96.87%. For individual features, GLSZM_SZE outperformed other features in terms of AUC (91.5%) and ACC (84.4%). In summary, the feature extraction based on the semi-supervised segmentation method is feasible and reliable for subsequent radiomics research. Texture features have greater advantages in evaluating muscle atrophy compared to other features. This study provides important biomarkers for accurate diagnosis of muscle atrophy.