MACS-W:A modified optical clearing agent for imaging 3D cell cultures

Three-dimensional(3D)cell cultures have contributed to a variety of biological research fields by filling the gap between monolayers and animal models.The modern optical sectioning microscopic methods make it possible to probe the complexity of 3D cell cultures but are limited by the inherent opaqueness.While tissue optical clearing methods have emerged as powerful tools for investigating whole-mount tissues in 3D,they often have limitations,such as being too harsh for fragile 3D cell cultures,requiring complex handling protocols,or inducing tissue deformation with shrinkage or expansion.To address this issue,we proposed a modified optical clearing method for 3D cell cultures,called MACS-W,which is simple,highly efficient,and morphology-preserving.In our evaluation of MACS-W,we found that it exhibits excellent clearing capability in just 10 min,with minimal deformation,and helps drug evaluation on tumor spheroids.In summary,MACS-W is a fast,minimally-deformative and fluorescence compatible clearing method that has the potential to be widely used in the studies of 3D cell cultures.

Multiplexed stimulated emission depletion nanoscopy(mSTED)for 5-color live-cell long-term imaging of organelle interactome

Stimulated emission depletion microscopy(STED)holds great potential in biological science applications,especially in studying nanoscale subcellular structures.However,multi-color STED imaging in live-cell remains challenging due to the limited excitation wavelengths and large amount of laser radiation.Here,we develop a multiplexed live-cell STED method to observe more structures simultaneously with limited photo-bleaching and photo-cytotoxicity.By separating live-cell fluorescent probes with similar spectral properties using phasor analysis,our method enables five-color live-cell STED imaging and reveals long-term interactions between different subcellular structures.The results here provide an avenue for understanding the complex and delicate interactome of subcellular structures in live-cell.

Multimodal imaging in the diagnosis of bone giant cell tumors:A retrospective study

BACKGROUND Giant cell tumor of bone is a locally aggressive and rarely metastasizing tumor,and also a potential malignant tumor that may develop into a primary malignant giant cell tumor.AIM To evaluate the role of multimodal imaging in the diagnosis of giant cell tumors of bone.METHODS The data of 32 patients with giant cell tumor of bone confirmed by core-needle biopsy or surgical pathology at our hospital between March 2018 and March 2023 were retrospectively selected.All the patients with giant cell tumors of the bone were examined by X-ray,computed tomography(CT)and magnetic resonance imaging(MRI),and 7 of them were examined by positron emission tomography(PET)-CT.RESULTS X-ray imaging can provide overall information on giant cell tumor lesions.CT and MRI can reveal the characteristics of the internal structure of the tumor as well as the adjacent relationships of the tumor,and these methods have unique advantages for diagnosing tumors and determining the scope of surgery.PET-CT can detect small lesions and is highly valuable for identifying benign and malignant tumors to aid in the early diagnosis of metastasis.CONCLUSION Multimodal imaging plays an important role in the diagnosis of giant cell tumor of bone and can provide a reference for the treatment of giant cell tumors.

Medical imaging for the diagnosis,recurrence and metastasis evaluation of clear cell sarcoma

Clear cell sarcoma(CCS)of soft tissue is extremely rare,accounting for approximately 1%of all soft tissue tumours.It is very difficult to diagnose CCS based on clinical manifestations.Magnetic resonance imaging(MRI)provides highresolution images of soft tissues and pathological features such as mucus,necrosis,bleeding,and fat through high and low signals on T1 weighted image(T1WI)and T2 weighted image(T2WI).On the other hand,the paramagnetism of melanin in CCS shortens the relaxation time of T1 and T2,and high signal intensity on T1WI and low signal intensity on T2WI can be found.This is different from most other soft tissue sarcomas.At present,the treatment method for CCS is surgical resection.MRI can effectively display the tumour edge,extent of surrounding oedema,and extent of fat involvement,which is highly important for guiding surgical resection and predicting postoperative recurrence.As an invasive sarcoma,CCS has a high risk of metastasis.Regardless of the pathological condition of the resected tumour,MRI or computed tomography(CT)should be performed every 1-2 years to assess recurrence at the primary site and to screen for metastasis in the lungs,liver,and bones.If necessary,PET-CT can be performed to evaluate the overall condition of the patient.

Data augmentation of ultrasound imaging for non-invasive white blood cell in vitro peritoneal dialysis

The limited amount of data in the healthcare domain and the necessity of training samples for increased performance of deep learning models is a recurrent challenge,especially in medical imaging.Newborn Solutions aims to enhance its non-invasive white blood cell counting device,Neosonics,by creating synthetic in vitro ultrasound images to facilitate a more efficient image generation process.This study addresses the data scarcity issue by designing and evaluating a continuous scalar conditional Generative Adversarial Network(GAN)to augment in vitro peritoneal dialysis ultrasound images,increasing both the volume and variability of training samples.The developed GAN architecture incorporates novel design features:varying kernel sizes in the generator’s transposed convolutional layers and a latent intermediate space,projecting noise and condition values for enhanced image resolution and specificity.The experimental results show that the GAN successfully generated diverse images of high visual quality,closely resembling real ultrasound samples.While visual results were promising,the use of GAN-based data augmentation did not consistently improve the performance of an image regressor in distinguishing features specific to varied white blood cell concentrations.Ultimately,while this continuous scalar conditional GAN model made strides in generating realistic images,further work is needed to achieve consistent gains in regression tasks,aiming for robust model generalization.

Guidelines for application of high-content screening in traditional Chinese medicine:concept,equipment,and troubleshooting

High-content screening(HCS)technology combines automated high-speed imaging hardware and single-cell quantitative analysis.It can greatly accelerate data acquisition in cellular fluorescence imaging and is a powerful research technique in traditional Chinese medicine(TCM).An increasing number of laboratories and platforms,including TCM laboratories,have begun utilizing HCS systems.However,this technology is still in its infancy in TCM research and there is a lack of sufficient experience with the associated concepts,instrument configurations,and analysis methods.To improve the understanding of HCS among researchers in the field of TCM,this paper summarizes the concept of HCS,software and hardware configuration,the overall research process,as well as common problems and related solutions of HCS in TCM research based on our team’s previous research experience,providing several research examples and an outlook on future perspectives,aiming to provide a technical guide for HCS in TCM research.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

Magnetic resonance imaging focused on the ferritin heavy chain 1 reporter gene detects neuronal differentiation in stem cells

The neuronal differentiation of mesenchymal stem cells offers a new strategy for the treatment of neurological disorders.Thus,there is a need to identify a noninvasive and sensitive in vivo imaging approach for real-time monitoring of transplanted stem cells.Our previous study confirmed that magnetic resonance imaging,with a focus on the ferritin heavy chain 1 reporter gene,could track the proliferation and differentiation of bone marrow mesenchymal stem cells that had been transduced with lentivirus carrying the ferritin heavy chain 1 reporter gene.However,we could not determine whether or when bone marrow mesenchymal stem cells had undergone neuronal differentiation based on changes in the magnetic resonance imaging signal.To solve this problem,we identified a neuron-specific enolase that can be differentially expressed before and after neuronal differentiation in stem cells.In this study,we successfully constructed a lentivirus carrying the neuron-specific enolase promoter and expressing the ferritin heavy chain 1 reporter gene;we used this lentivirus to transduce bone marrow mesenchymal stem cells.Cellular and animal studies showed that the neuron-specific enolase promoter effectively drove the expression of ferritin heavy chain 1 after neuronal differentiation of bone marrow mesenchymal stem cells;this led to intracellular accumulation of iron and corresponding changes in the magnetic resonance imaging signal.In summary,we established an innovative magnetic resonance imaging approach focused on the induction of reporter gene expression by a neuron-specific promoter.This imaging method can be used to noninvasively and sensitively detect neuronal differentiation in stem cells,which may be useful in stem cell-based therapies.

Secondary rectal linitis plastica caused by prostatic adenocarcinoma-magnetic resonance imaging findings and dissemination pathways:A case report

BACKGROUND Secondary rectal linitis plastica(RLP)from prostatic adenocarcinoma is a rare and poorly understood form of metastatic spread,characterized by a desmoplastic response and concentric rectal wall infiltration with mucosal preservation.This complicates endoscopic diagnosis and can mimic gastrointestinal malignancies.This case series underscores the critical role of magnetic resonance imaging(MRI)in identifying the distinct imaging features of RLP and highlights the importance of considering this condition in the differential diagnosis of patients with a history of prostate cancer.CASE SUMMARY Three patients with secondary RLP due to prostatic adenocarcinoma presented with varied clinical features.The first patient,a 76-year-old man with advanced prostate cancer,had rectal pain and incontinence.MRI showed diffuse prostatic invasion and significant rectal wall thickening with a characteristic"target sign"pattern.The second,a 57-year-old asymptomatic man with elevated prostatespecific antigen levels and a history of prostate cancer exhibited rectoprostatic angle involvement and rectal wall thickening on MRI,with positron emission tomography/computed tomography PSMA confirming the prostatic origin of the metastatic spread.The third patient,an 80-year-old post-radical prostatectomy,presented with refractory constipation.MRI revealed a neoplastic mass infiltrating the rectal wall.In all cases,MRI consistently showed stratified thickening,concentric signal changes,restricted diffusion,and contrast enhancement,which were essential for diagnosing secondary RLP.Biopsies confirmed the prostatic origin of the neoplastic involvement in the rectum.CONCLUSION Recognizing MRI findings of secondary RLP is essential for accurate diagnosis and management in prostate cancer patients.

Observing single cells in whole organs with optical imaging

Cells are the basic unit of human organs that are not fully understood.The revolutionary advancements of optical imaging alowed us to observe single cells in whole organs,revealing the complicated composition of cells with spatial information.Therefore,in this review,we revisit the principles of optical contrast related to those biomolecules and the optical techniques that transform optical contrast into detectable optical signals.Then,we describe optical imaging to achieve threedimensional spatial discrimination for biological tisutes.Due to the milky appearance of tissues,the spatial information burred deep in the whole organ.Fortunately,strategies developed in the last decade could circumvent this issue and lead us into a new era of investigation of the cells with their original spatial information.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study

BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.Linked color imaging(LCI)is a novel image-enhanced endoscopic technique that can distinguish subtle differences in mucosal color.AIM To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions.METHODS In this prospective study,we enrolled 543 patients who underwent white light imaging(WLI),LCI and LCE successively.We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions.Clinicopathological features and color analysis of lesions were assessed.RESULTS In total,43 patients(45 neoplastic lesions)were analyzed.Among them,36 patients(38 neoplastic lesions)were diagnosed with LCI,and 39 patients(41 neoplastic lesions)were diagnosed with LCE.The sensitivity of LCI was similar to that of LCE(83.7%vs 90.7%,P=0.520),whereas the specificity of LCI was greater than that of LCE(92.4%vs 87.0%,P=0.007).The LCI procedure time in the esophageal examination was significantly shorter than that of LCE[42(34,50)s vs 160(130,189)s,P<0.001].The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI.However,the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer.CONCLUSION LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions,and LCI represents a promising screening strategy for general populations.

Simultaneous Morphologies and Luminescence Control of NaYF_(4)∶Yb/Er Nanophosphors by Surfactants for Cancer Cell Imaging

Hydrophilic rare-earth up-conversion nanophosphors(UCNPs)with small sizes and a strong up-conversion luminescence have attracted much interest.Herein the simultaneous control of morphologies and the up-conversion luminescence intensities was reported for NaYF_(4)∶Yb/Er nanophosphors by a facile hydrothermal procedure with different surfactants.With the change of the surfactants from polyvinylpyrrolidone(PVP)to sodium citrate(CIT),edetate disodium(EDTA)or sodium dodecyl benzenesulfonate(SDBS),the morphology of NaYF_(4)∶Yb/Er nanophosphors transformed from nanoparticles with a diameter of about 70.0 nm to hexagonal nanoblocks with a thickness of about 125.0 nm and a length of about 240.0 nm,nanorods with a diameter of about 700.0 nm and a length of about 2.6μm,or nanowires with a diameter of 250.0 nm and a length of about 3.2μm.Simultaneously,their up-conversion luminescence intensity went down gradually under laser irradiation at a wavelength of 980 nm due to the increase of photobleaching.PVP-capped NaYF_(4)∶Yb/Er nanoparticles exhibited the smallest size and the strongest up-conversion luminescence intensity.Biological experiment results revealed that NaYF_(4)∶Yb/Er nanophosphors exhibited a high biocompatibility and could be used as biological labels with a perfect signal-to-noise ratio for cancer cell imaging.

IN SITU IMAGING OF BREAST CANCER CELLS USING GREEN SEMICONDUCTOR QUANTUM DOTS

The breast cancer is the most common cause of cancer death in women. To establish an early stage in situ imaging of breast cancer cells, green quantum dots （QDs） are used as a fluorescent signal generator. The QDs based imaging of breast cancer cells involves anti-HER2/neu antibody for labeling the over expressed HER2 on the surface of breast cancer cells. The complete assay involves breast cancer cells, biotin labeled antibody and streptavidin conjugated QDs. The breast cancer cells are grown in culture plates and exposed to the biotin labeled antibodies, and then exposed to streptavidin labeled QDs to utilize the strong and stable biotin-streptavidin interaction. Fluorescent images of the complete assay for breast cancer cells are evaluated on a microscope with a UV light source. Results show that the breast cancer cells in the complete assay are used as fluorescent cells with brighter signals compared with those labeled by the organic dye using similar parameters and the same number of cells.

Application of Image Fusion Methods to Cell Imaging Processing

Aim To fuse the fluorescence image and transmission image of a cell into a single image containing more information than any of the individual image. Methods Image fusion technology was applied to biological cell imaging processing. It could match the images and improve the confidence and spatial resolution of the images. Using two algorithms, double thresholds algorithm and denoising algorithm based on wavelet transform,the fluorescence image and transmission image of a Cell were merged into a composite image. Results and Conclusion The position of fluorescence and the structure of cell can be displyed in the composite image. The signal-to-noise ratio of the exultant image is improved to a large extent. The algorithms are not only useful to investigate the fluorescence and transmission images, but also suitable to observing two or more fluoascent label proes in a single cell.

Imaging findings of inflammatory pseudotumor-like follicular dendritic cell tumors of the liver:Two case reports and literature review

BACKGROUND Inflammatory pseudotumor-like follicular dendritic cell(IPT-like FDC)tumors of the liver is an uncommon tumor with extremely low incidence.To date,the radiologic findings of this tumor in multiphase computed tomography(CT)and magnetic resonance imaging(MRI)imaging have not been described.CASE SUMMARY Patient 1 is a 31-year-old Chinese female,whose complaining incidentally coincided with the finding of multiple liver masses.In the local hospital,an abdominal enhanced CT found two hypo-dense solid lesions,with heterogeneous sustained hypoenhancement,in the upper segment of the liver’s right posterior lobe.In our hospital,enhanced magnetic resonance imaging(MRI)with hepatocyte-specific contrast agents showed a similar enhanced pattern of lesions with patchy hyperintensity in the hepatobiliary phase(HBP).The patient underwent surgery and recovered well.The final pathology confirmed an IPTlike FDC tumor.No recurrence was found on the regular re-examination.Patient 2 is a 48-year-old Chinese male admitted to our hospital for a huge unexpected hepatic lesion.A dynamic enhanced abdominal CT revealed a huge heterogeneous enhanced solid tumor in the right lobe of the liver with a size of 100 mm×80 mm,which showed a heterogeneous sustained hypoenhancement.In addition,enlarged lymph nodes were found in the hilum of the liver.This patient underwent a hepatic lobectomy and lymph node dissection.The final pathology confirmed an IPT-like FDC tumor.No recurrence was found upon regular re-examination.CONCLUSION When a hepatic tumor shows heterogeneous sustained hypoenhancement with a patchy enhancement during HBP,an IPT-like FDC tumor should be considered in the differential diagnosis.

Comparative study on artificial intelligence systems for detecting early esophageal squamous cell carcinoma between narrow-band and white-light imaging

BACKGROUND Non-magnifying endoscopy with narrow-band imaging(NM-NBI)has been frequently used in routine screening of esophagus squamous cell carcinoma(ESCC).The performance of NBI for screening of early ESCC is,however,significantly affected by operator experience.Artificial intelligence may be a unique approach to compensate for the lack of operator experience.AIM To construct a computer-aided detection(CAD)system for application in NMNBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging(WLI).METHODS A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions(Zhongshan Hospital of Fudan University,Xuhui Hospital,and Kiang Wu Hospital)as the training dataset,and 316 pairs of images,each pair including images obtained by WLI and NBI(same part),were collected for validation.Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems.The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity,specificity,accuracy,positive predictive value,and negative predictive value.RESULTS The area under receiver operating characteristic curve for CAD-NBI was 0.9761.For the validation dataset,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of CAD-NBI were 91.0%,96.7%,94.3%,95.3%,and 93.6%,respectively,while those of CAD-WLI were 98.5%,83.1%,89.5%,80.8%,and 98.7%,respectively.CAD-NBI showed superior accuracy and specificity than CAD-WLI(P=0.028 and P≤0.001,respectively),while CAD-WLI had higher sensitivity than CAD-NBI(P=0.006).By using both CAD-WLI and CAD-NBI,the endoscopists could improve their diagnostic efficacy to the highest level,with accuracy,sensitivity,and specificity of 94.9%,92.4%,and 96.7%,respectively.CONCLUSION The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI.Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI.

Serial imaging of human embryonic stem-cell engraftment and teratoma formation in live mouse models

Two new types of lentiviral vectors expressing a reporter transgene encoding either firefly luciferase （fLuc） for bioluminescence imaging or the HSV1 thymidine kinase （HSV1-TK） for radiopharmaceutical-based imaging were constructed to monitor human embryonic stem cell （hESC） engraftment and proliferation in live mice after trans- plantation. The constitutive expression of either transgene did not alter the properties of hESCs in the culture. We next monitored the formation of teratomas in SCID mice to test （1） whether the gene-modified hESCs maintain their developmental pluripotency, and （2） whether sustained reporter gene expression allows noninvasive, whole-body imaging of hESC derivatives in a live mouse model. We observed teratoma formation from both types of gene-modified cells as well as wild-type hESCs 2-4 months after inoculation. Using an optical imaging system, bioluminescence from the fLuc-transduced hESCs was easily detected in mice bearing teratomas long before palpable tumors could be detected. To develop a noninvasive imaging method more readily translatable to the clinic, we also utilized HSV1-TK and its specific substrate, 1-（2＇-deoxy-2＇-fluoro-β-D-arabinofuranosyl）-5-[^125I]iodouracil（[^125I]FIAU）, as a reporter/ probe pair. After systemic administration, [^125I]FIAU is phosphorylated only by the transgene-encoded HSV1-TK enzyme and retained within transduced （and transplanted） cells, allowing sensitive and quantitative imaging by single-photon emission computed tomography. Noninvasive imaging methods such as these may enable us to monitor the presence and distribution of transplanted human stem cells repetitively within live recipients over a long term through the expression of a reporter gene.

In vivo tracking of human adipose-derived stem cells labeled with ferumoxytol in rats with middle cerebral artery occlusion by magnetic resonance imaging

Ferumoxytol, an iron replacement product, is a new type of superparamagnetic iron oxide ap- proved by the US Food and Drug Administration. Herein, we assessed the feasibility of tracking transplanted human adipose-derived stem cells labeled with ferumoxytol in middle cerebral artery occlusion-injured rats by 3.0 T MRI in vivo. 1 × 104 human adipose-derived stem cells labeled with ferumoxytol-heparin-protamine were transplanted into the brains of rats with middle cerebral artery occlusion. Neurologic impairment was scored at 1, 7, 14, and 28 days after transplantation. T2-weighted imaging and enhanced susceptibility-weighted angiography were used to observe transplanted cells. Results of imaging tests were compared with results of Prussian blue staining. The modified neurologic impairment scores were significantly lower in rats transplanted with cells at all time points except I day post-transplantation compared with rats without transplantation. Regions with hypointense signals on T2-weighted and enhanced susceptibility-weighted angiography images corresponded with areas stained by Prussian blue, suggesting the presence of superparamagnetic iron oxide particles within the engrafted cells. Enhanced susceptibility-weighted angiography image exhibited better sensitivity and contrast in tracing ferumoxytol-heparin-protamine-labeled human adipose-derived stem ceils compared with T2-weighted imaging in routine MRI.

Clinical relevance of fluorodeoxyglucose positron emission tomography/computed tomography and magnifying endoscopy with narrow band imaging in decision-making regarding the treatment strategy for esophageal squamous cell carcinoma

BACKGROUND Recent advances in endoscopic technology,especially magnifying endoscopy with narrow band imaging(ME-NBI)enable us to detect superficial esophageal squamous cell carcinoma(ESCC),but determining the appropriate method of resection,endoscopic resection(ER)vs surgical resection,is often challenging.Recently,several studies have reported that 18F-fluorodeoxyglucose positron emission tomography(FDG-PET)is a useful indicator for decision-making regarding treatment for superficial ESCC.Although,there are not enough reports on association between FDG-PET uptake and clinicopathological characteristics of superficial ESCC.And,there are not enough reports on evaluating the usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.This study evaluated clinical relevance of FDG-PET and ME-NBI in decision-making regarding the treatment strategy for ESCC.AIM To investigate the association between FDG uptake and the clinicopathological characteristics of superficial ESCC and its usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.METHODS A database of all patients with superficial ESCC who had undergone both MENBI and FDG-PET for pre-treatment staging at Aichi Cancer Center Hospital between January 2008 and November 2018 was retrospectively analyzed.FDG uptake was defined positive or negative whether the primary lesion was visualized or could be distinguished from the background,or not.The invasion depth of ESCC was classified according to the Japan Esophageal Society.Primary endpoint is to evaluate the association between FDG uptake and clinicopathological characteristics of superficial ESCC.Secondary endpoint is to investigate the efficacy of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.RESULTS A total of 82 lesions in 82 patients were included.FDG-PET showed positive uptake in 29(35.4%)lesions.Univariate analysis showed that uptake of FDG-PET had significant correlations with circumferential extension(P=0.014),pathological depth of tumor invasion(P<0.001),infiltrative growth pattern(P<0.001),histological grade(P=0.002),vascular invasion(P=0.001),and lymphatic invasion(P<0.001).On multivariate analysis,only depth of tumor invasion was independently correlated with FDG-PET/computed tomography visibility(P=0.018).The sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and accuracy of Type B2 in ME-NBI for the invasion depth of T1a muscularis mucosae and T1b upper submucosal layer were 68.4%/79.4%/50.0%/89.3%/76.8%,respectively,and those of Type B3 for the depth of T1b middle and deeper submucosal layers(SM2 and SM3)were 46.7%/100%/100%/89.3%/90.2%,respectively.On the other hand,those of FDGPET for SM2 and SM3 were 93.3%/77.6%/48.2%/98.1%/80.5%,respectively,whereas,if the combination of positive FDG uptake and type B2 and B3 was defined as an indicator for radical esophagectomy or definitive chemoradiotherapy,the sensitivity,specificity,PPV,NPV,and accuracy were 78.3%/91.5%/78.3%/91.5%/87.8%,respectively.CONCLUSION FDG uptake was correlated with the invasion depth of superficial ESCC.Combined use of FDG-PET and ME-NBI,especially with the microvascular findings of Type B2 and B3,is useful to determine whether ER is indicated for the lesion.

Ultra-sensitive Nanoprobe Modified with Tumor Cell Membrane for UCL/MRI/PET Multimodality Precise Imaging of Triple-Negative Breast Cancer

Triple-negative breast cancer(TNBC)is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed,and human epidermal growth factor receptor 2 is not amplified or overexpressed either,which make the clinical diagnosis and treatment very challenging.Molecular imaging can provide an effective way to diagnose TNBC.Upconversion nanoparticles(UCNPs),are a promising new generation of molecular imaging probes.However,UCNPs still need to be improved for tumor-targeting ability and biocompatibility.This study describes a novel probe based on cancer cell membrane-coated upconversion nanoparticles(CCm-UCNPs),owing to the low immunogenicity and homologous-targeting ability of cancer cell membranes,and modified multifunctional UCNPs.This probe exhibits excellent performance in breast cancer molecular classification and TNBC diagnosis through UCL/MRI/PET tri-modality imaging in vivo.By using this probe,MDA-MB-231 was successfully differentiated between MCF-7 tumor models in vivo.Based on the tumor imaging and molecular classification results,the probe is also expected to be modified for drug delivery in the future,contributing to the treatment of TNBC.The combination of nanoparticles with biomimetic cell membranes has the potential for multiple clinical applications.