Role of molecular imaging in prognosis,diagnosis,and treatment of gastrointestinal cancers:An update on new therapeutic methods

One of the leading causes of cancer-related death is gastrointestinal cancer,which has a significant morbidity and mortality rate.Although preoperative risk assessment is essential for directing patient care,its biological behavior cannot be accurately predicted by conventional imaging investigations.Potential pathophysiological information in anatomical imaging that cannot be visually identified can now be converted into high-dimensional quantitative image features thanks to the developing discipline of molecular imaging.In order to enable molecular tissue profile in vivo,molecular imaging has most recently been utilized to phenotype the expression of single receptors and targets of biological therapy.It is expected that molecular imaging will become increasingly important in the near future,driven by the expanding range of biological therapies for cancer.With this live molecular fingerprinting,molecular imaging can be utilized to drive expression-tailored customized therapy.The technical aspects of molecular imaging are first briefly discussed in this review,followed by an examination of the most recent research on the diagnosis,prognosis,and potential future clinical methods of molecular imaging for GI tract malignancies.

THE DETECTION OF THE BOUNDARY OF IMAGE OF WOODANATOMICAL STRUCTURE MOLECULAR

Basing on a lot of examinations, according to the fundamental inage processing theories and methods, getting touch with the property of wood anatomical structure image,we put forward the optimum method and theory which are suitable for the binary processing of the wood anatomical structure image. After the wood image has been processed binary, with the help of computer vision technology, the boundary of wood anatomical structure molecular binary image was sought This kind of theory and method lay a solid foundaion on the collection of feature and the pottern recognition and other high level processing of wood anatomical structure molecular image.

Coverless Information Hiding Based on the Molecular Structure Images of Material

The traditional information hiding methods embed the secret information by modifying the carrier,which will inevitably leave traces of modification on the carrier.In this way,it is hard to resist the detection of steganalysis algorithm.To address this problem,the concept of coverless information hiding was proposed.Coverless information hiding can effectively resist steganalysis algorithm,since it uses unmodified natural stego-carriers to represent and convey confidential information.However,the state-of-the-arts method has a low hidden capacity,which makes it less appealing.Because the pixel values of different regions of the molecular structure images of material(MSIM)are usually different,this paper proposes a novel coverless information hiding method based on MSIM,which utilizes the average value of sub-image’s pixels to represent the secret information,according to the mapping between pixel value intervals and secret information.In addition,we employ a pseudo-random label sequence that is used to determine the position of sub-images to improve the security of the method.And the histogram of the Bag of words model(BOW)is used to determine the number of subimages in the image that convey secret information.Moreover,to improve the retrieval efficiency,we built a multi-level inverted index structure.Furthermore,the proposed method can also be used for other natural images.Compared with the state-of-the-arts,experimental results and analysis manifest that our method has better performance in anti-steganalysis,security and capacity.

Advancements of molecular imaging and radiomics in pancreatic carcinoma

Despite the recent progress of medical technology in the diagnosis and treatment of tumors,pancreatic carcinoma remains one of the most malignant tumors,with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation.This paper focuses on the research progress of magnetic resonance imaging,nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma.We also briefly described the achievements of our team in this field,to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

An environmentally sensitive zinc-selective two-photon NIR fluorescent turn-on probe and zinc sensing in stroke

A two-photon near infrared(NIR)fluorescence turn-on sensor with high selectivity and sensitivity for Zn^(2+)detection has been developed.This sensor exhibits a large Stokes'shift(-300 nm)and can be excited from 900 to 1000 nm,with an emission wavelength of-785 nm,making it ideal for imaging in biological tissues.The sensor's high selectivity for Zn^(2+)over other structurally similar cations,such as Cd^(2+),makes it a promising tool for monitoring zinc ion levels in biological systems.Given the high concentration of zinc in thrombi,this sensor could provide a useful tool for in vivo thrombus imaging.

Epileptic brain network mechanisms and neuroimaging techniques for the brain network

Epilepsy can be defined as a dysfunction of the brain network,and each type of epilepsy involves different brain-network changes that are implicated diffe rently in the control and propagation of interictal or ictal discharges.Gaining more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical practice.An increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tra ctography,diffusion kurtosis imaging-based fiber tractography,fiber ball imagingbased tra ctography,electroencephalography,functional magnetic resonance imaging,magnetoencephalography,positron emission tomography,molecular imaging,and functional ultrasound imaging have been extensively used to delineate epileptic networks.In this review,we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy,and extensively analyze the imaging mechanisms,advantages,limitations,and clinical application ranges of each technique.A greater focus on emerging advanced technologies,new data analysis software,a combination of multiple techniques,and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

Use of Radioiodinated Peptide Arg-Arg-Leu Targeted to Neovascularization as well as Tumor Cells in Molecular Tumor Imaging

Objective： To explore a tumor peptide imaging agent Arginine-Arginine-Leucine （Tyr-Cys-Gly-Gly-Arg-Arg- Leu-Gly-Gly-Cys, tripeptide RRL [tRRL]） that targeted to tumor cells and tumor-derived endothelial cells （TDECs） and primarily investigate the possible relationship between tRRL and vascular endothelial growth factor receptor 2 （VEGFR-2）. Methods： The tRRL sequence motif was identified as a tumor molecular marker specifically binding to TDECs. Tyrosine was conjugated to the amino terminal of RRL （Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys） for labeling with radionuclide iodine-131 （1311-tRRL）. The uptake ability and molecular binding of tRRL to tumor cells and angiogenic endothelium were studied using flow cytometry and radioactivity counter in vitro. Whether VEGFR-2 is the binging site of tRRL was investigated. Biodistribution and single-photon emission computed tomography （SPECT） imaging of 131-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice. Results： In vitro cellular uptake experiments revealed that tRRL could not only adhere to tumor angiogenic endothelial cells but also largely accumulate in malignant tumor cells. VEGFR-2, which is highly expressed on TDECs, was probably not the solely binding ligand for tRRL targeted to tumor angiogenic endothelium, 131-tRRL mainly accumulated in tumors in vivo, not other organs at 24 h after injection. SPECT imaging with 131-tRRL clearly visualized tumors in nude mice, especially at 24 h. Conclusion： Radioiodinated tRRL offers a noninvasive of tumors targeted to neovascularization, and may be a carrier. nuclear imaging method for functional molecular imaging promising candidate for tumor radioimmunotherapeutic carrier,

Diffusion magnetic resonance imaging: A molecular imaging tool caught between hope, hype and the real world of “personalized oncology”

"Personalized oncology" is a multi-disciplinary science, which requires inputs from various streams for optimal patient management. Humongous progress in the treatment modalities available and the increasing need to provide functional information in addition to the morphological data; has led to leaping progress in the field of imaging. Magnetic resonance imaging has undergone tremendous progress with various newer MR techniques providing vital functional information and is becoming the cornerstone of "radiomics/radiogenomics". Diffusionweighted imaging is one such technique which capitalizes on the tendency of water protons to diffuse randomly in a given system. This technique has revolutionized oncological imaging, by giving vital qualitative and quantitative information regarding tumor biology which helps in detection, characterization and post treatment surveillance of the lesions and challenging the notion that "one size fits all". It has been applied at various sites with different clinical experience. We hereby present a brief review of this novel functional imaging tool, with its application in "personalized oncology".

Tumor Molecular Imaging with Nanoparticles

Molecular imaging(MI)can provide not only structural images using traditional imaging techniques but also functional and molecular information using many newly emerging imaging techniques.Over the past decade,the utilization of nanotechnology in MI has exhibited many significant advantages and provided new opportunities for the imaging of living subjects.It is expected that multimodality nanoparticles(NPs)can lead to precise assessment of tumor biology and the tumor microenvironment.This review addresses topics related to engineered NPs and summarizes the recent applications of these nanoconstructs in cancer optical imaging,ultrasound,photoacoustic imaging,magnetic resonance imaging(MRI),and radionuclide imaging.Key challenges involved in the translation of NPs to the clinic are discussed.

Recent progress in the molecular imaging of therapeutic monoclonal antibodies

Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in need.It is equally critical to acquire sufficient knowledge of their molecular structure and biological functions to ensure the efficacy and safety by incorporating new detection approaches since new challenges like individual differences and resistance are presented.Conventional techniques for determining antibody disposition including plasma drug concentration measurements using LC-MS or ELISA,and tissue distribution using immunohistochemistry and immunofluorescence are now complemented with molecular imaging modalities like positron emission tomography and near-infrared fluorescence imaging to obtain more dynamic information,while methods for characterization of antibody’s interaction with the target antigen as well as visualization of its cellular and intercellular behavior are still under development.Recent progress in detecting therapeutic antibodies,in particular,the development of methods suitable for illustrating the molecular dynamics,is described here.

Preclinical and clinical applications of specific molecular imaging for HER2-positive breast cancer

Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.

Noninvasive in vivo cell tracking using molecular imaging:A useful tool for developing mesenchymal stem cell-based cancer treatment

Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body.Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes,understanding pathophysiological mechanisms of diseases,and evaluating the kinetics/dynamics of cell therapies.In particular,mesenchymal stem cells(MSCs)have shown promise in recent years as drug carriers for cancer treatment.They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells,and to optimize therapy.The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition,and the exact interactions between MSCs and specific cancer microenvironments are not clear.In this review,a multitude of labeling approaches,imaging modalities,and the merits/demerits of each strategy are outlined.In addition,specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided.Finally,present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.

Construction and Identification of the Adenoviral Vector with Dual Reporter Gene for Multimodality Molecular Imaging

Summary： In this study, the recombinant adenovirus （Ad） vector containing dual reporter gene [i.e. human transferrin receptor gene （TFRC） and firefly luciferase reporter gene] was constructed to provide a novel experimental tool for magnetic resonance （MR） and bioluminescence dual-modality molecular imaging. The cDNA of TFRC was amplified by polymerase chain reaction （PCR） and cloned into the multiple cloning site of pShuttle-CMV-CMV-Luciferase vector. After identification by Sfi I digestion and sequencing, pShuttle-TFRC-Luciferase vector and the adenoviral backbone vector （pAdeno） were subjected to homologous recombination. The correct recombinant plasmid was then transfected into 293 packaging cells to produce adenoviral particles and confirmed by PCR. After infection of human colo- rectal cancer LOVO cells with Ad-TFRC-Luciferase, the expressions of transferrin receptor （TfR） and luciferase protein were detected respectively by Western blotting and bioluminescence imaging in vitro. The results showed that TFRC gene was successfully inserted into the adenoviral shuttle vector carrying luciferase gene. DNA sequence analysis indicated that the TFRC gene sequence in the shuttle plasmid was exactly the same as that reported in GenBank. The recombinant plasmid was identified correct by restriction digestion. Ad-TFRC-Luciferase recombinant adenovirns was constructed successfully, and the virus titer was 1.6x10^10 pfu/mL. Forty-eight h after dual reporter gene transfection, the expressions of TfR and luciferase protein were increased significantly （P〈0.01）. It was concluded that the recombinant adenovirus vector with dual reporter gene was successfully established, which may be used for in vivo tracing target cells in multimodality imaging.

IMAGING RNA IN LIVING CELLS WITH MOLECULAR BEACONS:CURRENT PERSPECTIVES AND CHALLENGES

There is a growing realization that cell-to-cell variations in gene expression have importantbiological consequences underlying phenotype diversity and cell fate. Although analytical toolsfor measuring gene expression, such as DNA microarrays, reverse-transcriptase PCR and in situhybridization have been widely utilized to discover the role of genetic variations in governingcellular behavior, these methods are performed in cell lysates and/or on fixed cells, and thereforelack the ability to provide comprehensive spatial-dynamic information on gene expression. Thishas invoked the recent development of molecular imaging strategies capable of illuminatingthe distribution and dynamics of RNA molecules in living cells. In this review, we describe aclass of molecular imaging probes known as molecular beacons (MBs), which have increasinglybecome the probe of choice for imaging RNA in living cells. In addition, we present the majorchallenges that can limit the ability of MBs to provide accurate measurements of RNA, anddiscuss efforts that have been made to overcome these challenges. It is envisioned that withcontinued refinement of the MB design, MBs will eventually become an indispensable tool foranalyzing gene expression in biology and medicine.

Optical Molecular Imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity

Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging(CLI), and optical imageguided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.

DEVELOPMENT OF NEEDLE-BASED MICROENDOSCOPY FOR FLUORESCENCE MOLECULAR IMAGING OF BREAST TUMOR MODELS

Fluorescence molecular imaging enables the visualization of basic molecular processes such as gene expression,enzyme activity,and disease-specific molecular interactions in vivo using targeted contrast agents,and therefore,is being developed for early detection and in situ characterization of breast cancers.Recent advances in developing near-infrared fluorescent imaging contrast agents have enabled the specific labeling of human breast cancer cells in mouse model systems.In synergy with contrast agent development,this paper describes a needle-based fluorescence molecular imaging device that has the strong potential to be translated into clinical breast biopsy procedures.This microendoscopy probe is based on a gradient-index(GRIN)lens interfaced with a laser scanning microscope.Specifications of the imaging performance,including the field-of-view,transverse resolution,and focus tracking characteristics were calibrated.Orthotopic MDA-MB-231 breast cancer xenografts stably expressing the tdTomato red fluorescent protein(RFP)were used to detect the tumor cells in this tumor model as a proof of principle study.With further development,this technology,in conjunction with the development of clinically applicable,injectable fluorescent molecular imaging agents,promises to perform fluorescence molecular imaging of breast cancers in vivo for breast biopsy guidance.

Molecular Structure of Feeds in Relation to Nutrient Utilization and Availability in Animals： A Novel Approach

The invention and development of new research concepts, novel methodologies, and novel bioanalytical techniques are essential in advancing the animal sciences, which include feed and nutrition science. This article introduces a novel approach that shows the potential of advanced synchrotron-based bioanalytical technology for studying the effects of molecular structural changes in feeds induced by various treatments （e.g., genetic modification, gene silencing, heat-related feed processing, biofuel processing） in relation to nutrient digestion and absorption in animals. Advanced techniques based on synchrotron radiation （e.g., synchrotron radiation infrared microspectroscopy （SR-IMS） and synchrotron radiation X-ray techniques） have been developed as a fast, noninvasive, bioanalytical technology that, unlike traditional wet chemistry methods, does not damage or destroy the inherent molecular structure of the feed. The cutting-edge and advanced research tool of synchrotron light （which is a million times brighter than sunlight） can be used to explore the inherent structure of biological tissue at cellular and molecular levels at ultra-high spatial resolutions. In conclusion, the use of recently developed bioanalytical techniques based on synchrotron radiation along with common research techniques is leading to dramatic advances in animal feed and nutritional research.

Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related mortality.HCC-targeted magnetic resonance imaging(MRI)is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers,such as alpha-fetoprotein(AFP)or glypican-3(GPC3),with iron oxide nanoparticles.However,in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative(T2)contrast agents,which might weaken their future clinical applications due to tumor heterogeneity and negative MRI contrast.Ultra-small superparamagnetic iron oxide(USPIO)nanoparticles(approximately 5 nm)are potential optimal positive(T1)contrast agents.We previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in vitro.AIM To validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage HCC.METHODS The single-and double-antibody-conjugated 5-nm USPIO probes,including antiAFP-USPIO(UA),anti-GPC3-USPIO(UG),and anti-AFP-USPIO-anti-GPC3(UAG),were synthesized.T1-and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse model.Following intravenous injection of U,UA,UG,and UAG probes,T1-and T2-weighted images were obtained at 12,12,and 32 h post-injection.At the end of scanning,mice were euthanized,and a histologic analysis was performed on tumor samples.RESULTS T1-and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection,with the T1-and T2-weighted signals increasing by 46.7%and decreasing by 11.1%,respectively,relative to pre-injection levels.Additionally,T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-,2.64-,and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO,anti-AFP-USPIO,and nontargeted USPIO probes,respectively.Comparison of U-,UA-,UG-,and UAG-treated tumor sections revealed that UAG-treated mice exhibited increased stained regions compared to those observed in UG-or UA-treated mice.CONCLUSION The bi-specific T1-positive contrast-enhanced MRI probe(UAG)for HCC demonstrated increased specificity and sensitivity to diagnose early-stage HCC irrespective of tumor size and/or heterogeneity.

Role of molecular imaging in the management of patients affected by inflammatory bowel disease:State-of-the-art

AIM To present the current state-of-the art of molecular imaging in the management of patients affected by inflammatory bowel disease(IBD).METHODS A systematic review of the literature was performed in order to find important original articles on the role of molecular imaging in the management of patients affected by IBD. The search was updated until February 2016 and limited to articles in English.RESULTS Fifty-five original articles were included in this review, highlighting the role of single photon emission tomography and positron emission tomography. CONCLUSION To date, molecular imaging represents a useful tool to detect active disease in IBD. However, the available data need to be validated in prospective multicenter studies on larger patient samples.

MINIMIZING EXCITATION LIGHT LEAKAGE AND MAXIMIZING MEASUREMENT SENSITIVITY FOR MOLECULAR IMAGING WITH NEAR-INFRARED FLUORESCENCE

Near-infraredfluorescence(NIRF)imaging involves the separation of weakfluorescence signals from backscattered excitation light.The measurement sensitivity of current NIRF imaging systems is limited by the excitation light leakage through rejectionfilters.In this contribution,the authors demonstrate that the excitation light leakage can be suppressed upon using appropriatefilter combination and permutations.The excitation light leakage and measurement sensitivity were assessed and compared in this study by computing the transmission ratios of excitation to emission light collected and the signal-to-noise ratios in well-controlled phantom studies with differentfilter combinations and permutations.Using appropriatefilter combinations and permutations,we observe as much as two orders of magnitude reduction in the transmission ratio and higher signal-to-noise ratio.