Multimodal Imaging Technology Research Articles

Dual-modal fullerenol probe containing glypican-3 monoclonal antibody for electron paramagnetic resonance/fluorescence imaging

The multi-modal imaging contrast agent has been attracted an increased interest to the tumor detecting and diagnosis in these recent years since the multi-modal imaging technology combines the advantages of several medical imaging modalities. A water-soluble fullerenol probe containing glypican-3 monoclonal antibody (GPC3-mAb) group mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 was synthesized by the incorporation of 5-formyl-1,1,3,3-tetramethylisoindolin-2-yloxyl (FTMIO), naphthalimide (NI) and GPC3-mAb as a tumor-targeting group into fullerenol C60(OH)11. This nanomaterial was further characterized by FTIR, UV, MS, fluorescence, etc., and then its properties including electron paramagnetic resonance (EPR), particle size, electrophoresis, electrochemical assay, cell cytotoxicity, cell uptake and fluorescent imaging of HeLa tumor cells in vitro were also evaluated. Experiment results indicated that mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 had similar fluorescent properties as NI and similar electrochemical and redox properties as 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO). Moreover, mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 possessed low cell cytotoxicity, good fluorescence and good tumor-targeting property. Meanwhile, mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 can be taken up highly by HeLa tumor cells, achieve good green fluorescent imaging in tumor cells and highly enhance the contrast of fluorescent images. Therefore, mAb-GPC3-C60(OH)10-(TMIO)3-(NI)3 can disperse homogeneously in aqueous solution and be used as a potential tumor-targeting dual-modal contrast agent for EPR imaging/fluorescence imaging (EPRI/FI).

Genome-Scale Imaging of the 3D Organization and Transcriptional Activity of Chromatin

The 3D organization of chromatin regulates many genome functions. Our understanding of 3D genome organization requires tools to directly visualize chromatin conformation in its native context. Here we report an imaging technology for visualizing chromatin organization across multiple scales in single cells with high genomic throughput. First we demonstrate multiplexed imaging of hundreds of genomic loci by sequential hybridization, which allows high-resolution conformation tracing of whole chromosomes. Next we report a multiplexed error-robust fluorescence in situ hybridization (MERFISH)-based method for genome-scale chromatin tracing and demonstrate simultaneous imaging of more than 1,000 genomic loci and nascent transcripts of more than 1,000 genes together with landmark nuclear structures. Using this technology, we characterize chromatin domains, compartments, and trans-chromosomal interactions and their relationship to transcription in single cells. We envision broad application of this high-throughput, multi-scale, and multi-modal imaging technology, which provides an integrated view of chromatin organization in its native structural and functional context.

Role of the Imager in Transcatheter Mitral Valve Repair.

To describe the key role of the structural imager/interventional echocardiographer in transcatheter mitral valve therapies, particularly edge-to-edge repair. In addition, we review important recent advances in structural imaging and briefly describe several novel devices for transcatheter mitral valve repair. Structural imagers represent a new subspecialty in cardiology and anesthesiology with specific skillset and training requirements. Their role is particularly important in imaging-based transcatheter interventions such as edge-to-edge mitral valve repair. This therapy has increasingly been used to treat primary (degenerative) mitral regurgitation when surgical risk is prohibitive and has recently been extended to patients with secondary (functional) mitral regurgitation. As novel transcatheter therapies continue to emerge, so do new multimodality imaging technologies. Structural imagers have become an integral part of the heart team. Their role is particularly visible in transcatheter mitral procedures. Rapidly developing transcatheter therapies have helped shape this new subspecialty and spark innovation in imaging technologies.

The Novel DPP-BDT Nanoparticles as Efficient Photoacoustic Imaging and Positron Emission Tomography Agents in Living Mice.

BackgroundMolecular imaging is of great benefit to early disease diagnosis and timely treatment. One of the most striking innovations is the development of multimodal molecular imaging technology, which integrates two or more imaging modalities, largely in view of making the best of the advantages of each modality while overcoming their respective shortcomings. Hence, engineering a versatile and easily prepared nanomaterial with integrating multimodal molecular imaging function holds great promise, but is still a great challenge.Materials and MethodsWe firstly designed and synthesized a BDT-DPP conjugated polymer and then noncovalent self-assembly with phospholipid-polyethylene glycol endowed BDT-DPP with water solubility and biocompatibility. Followed by [Cu] labeling, the acquired multifunctional nanoparticles (NPs) were studied in detail for the photophysical property. The cytotoxicity and biocompatibility of DPP-BDT NPs were examined through MTT assay and H&E stained analysis. In addition, we investigated the accumulation of the NPs in HepG2 tumor models by positron emission tomography (PET) and photoacoustic (PA) dual-mode imaging.Results and DiscussionThe DPP-BDT NPs exhibited excellent optical stability, strong near-infrared (NIR) light absorption as well as fine biocompatibility. After tail vein injection into the living mice, the PA signals in the neoplastic tissues were gradually increased and reached to the maximum at the 4-h post-injection, which was consistent with the PET analysis. Such strong PA and PET signals were attributed to the efficient NPs accumulation resulting from the enhanced permeability and retention (EPR) effect.ConclusionThe biocompatible DPP-BDT NPs demonstrated to be strong NIR absorption property and PAI sensitivity. Besides, these novel DPP-BDT NPs can act not only as a PA imaging contrast agent but also as an imaging agent for PET.

Metal‐organic framework‐based cancer theranostic nanoplatforms

AbstractThe rapid development of imaging technologies provides a visual diagnostic tool for scientists and surgeons to comprehensively and accurately understand the pathogenesis and pathological processes of complicated diseases, especially cancer. Theranostic platforms integrating various imaging technologies and treatment strategies for the diagnosis and treatment of cancer have been extensively studied. Notably, metal‐organic frameworks (MOFs) – an emerging porous organic‐inorganic hybrid material composed of metal ions/ion clusters as nodes and organic ligands as linkers bridged by coordination bonds – have been widely used as intelligent carriers for cancer theranostics in recent years due to their fascinating properties, including facile synthesis, diverse compositions, high surface areas and porosities, tailorable sizes, multiple physicochemical properties, easy surface functionalization, and good biocompatibility. This review summarizes the recent advanced developments and achievements of MOFs as smart theranostic platforms for effective cancer diagnosis and treatment guided by monomodal imaging technologies, including optical imaging, magnetic resonance imaging, computed tomography imaging, positron emission tomography imaging, and photoacoustic imaging, and multimodal imaging technologies. Moreover, the development prospects and critical challenges of MOFs for cancer theranostics are also addressed.

Biomedical image analysis challenges should be considered as an academic exercise, not an instrument that will move the field forward in a real, practical way.

The biomedical imaging community has witnessed innovative algorithmic developments in quantitative imaging biomarkers taking advantage of modern multimodality imaging technologies. These developments encompass a wide methodological portfolio including but not limited to image registration, segmentation, classification, and prediction. Despite the enormous progress in technical developments, including rigorous peer-review preceding publication in the scientific literature, extensive testing, and feedback from users of the associated open-source software tools, validation of these advanced image analysis tools prior to their deployment in the clinic is still one of the main challenges faced by developers and end-users.

Integrating photoacoustic microscopy, optical coherence tomography, OCT angiography, and fluorescence microscopy for multimodal imaging.

We have developed a multimodal imaging system, which integrated optical resolution photoacoustic microscopy, optical coherence tomography, optical coherence tomography angiography, and confocal fluorescence microscopy in one platform. The system is able to image complementary features of a biological sample by combining different contrast mechanisms. We achieved fast imaging and large field of view by combining optical scanning with mechanical scanning, similar to our previous publication. We have demonstrated the capability of the multimodal imaging system by imaging a mouse ear in vivo. Impact statement Photoacoustic microscopy-based multimodal imaging technology can provide high-resolution complementary information for biological tissues in vivo. It will potentially bring significant impact on the research and diagnosis of diseases by providing combined structural and functional information.

Multimodal intravascular imaging technology for characterization of atherosclerosis.

Early detection of vulnerable plaques is the critical step in the prevention of acute coronary events. Morphology, composition, and mechanical property of a coronary artery have been demonstrated to be the key characteristics for the identification of vulnerable plaques. Several intravascular multimodal imaging technologies providing co-registered simultaneous images have been developed and applied in clinical studies to improve the characterization of atherosclerosis. In this paper, the authors review the present system and probe designs of representative intravascular multimodal techniques. In addition, the scientific innovations, potential limitations, and future directions of these technologies are also discussed.

Multimodality Imaging Training for General and Advanced Cardiology Fellowships

With the growth in multimodality imaging technology, there is heightened interest in advanced imaging training within the cardiology fellow community. The ideal training models for multimodality imaging remain to be determined and there are uncertainties about the manpower needs for cardiologists with advanced multimodality imaging expertise. This commentary discusses several areas pertaining to training of cardiology fellows in multimodality imaging.

SP-0700 The future of margins in the era of new (multi-modality) imaging technology

SP-0700 The future of margins in the era of new (multi-modality) imaging technology

Cost-effectiveness of targeted thrombolytic therapy for stroke patients using multi-modal CT compared to usual practice.

IntroductionThe use of multimodal computed tomography imaging (MMCT) in routine clinical assessment of stroke patients improves the identification of patients with large regions of salvageable brain tissue, lower risk for haemorrhagic transformation, or a large vessel occlusion requiring endovascular therapy.AimTo evaluate the cost-effectiveness of using MMCT compared to usual practice for determining eligibility for reperfusion therapy with alteplase using real world data from the International Stroke Perfusion Imaging Registry (INSPIRE).MethodsWe performed a cost-utility analysis. Mean costs and quality-adjusted life years (QALYs) per patient for two alternative screening protocols were calculated. Protocol 1 represented usual practice, while Protocol 2 reflected treatment targeting using multimodal imaging. Cost-effectiveness was assessed using the net-benefit framework.ResultsProtocol 1 had a total mean per patient cost of $2,013 USD and 0.148 QALYs. Protocol 2 had a total mean per patient cost of $1,519 USD and 0.153 QALYs. For a range of willingness-to-pay values, representing implicit thresholds of cost-effectiveness, the lower bound of the incremental net monetary benefit statistic was consistently greater than zero, indicating that MMCT is cost- effective compared to usual practice. The results were most sensitive to variation in the mean number of alteplase vials administered.ConclusionIn a healthcare setting where multimodal imaging technologies are available and reimbursed, their use in screening patients presenting with acute stroke to determine eligibility for alteplase treatment is cost-effective given a range of willingness-to-pay thresholds and warrants consideration as an alternative to routine practice.

Ultrasound Technology for Molecular Imaging: From Contrast Agents to Multimodal Imaging.

Ultrasound (US) takes advantage of ultrasound contrast agents (UCAs) to further increase the sensitivity and specificity of monitoring at the cellular level, which has had a considerable effect on the modern molecular imaging field. Gas-filled microbubbles (MBs) as UCAs in the bloodstream generate resonant volumetric oscillations in response to rapid variations in acoustic pressure, which are related to both the acoustic parameters of applied ultrasound and the physicochemical properties of the contrast agents. Nanoscale UCAs have been developed and have attracted much attention due to their utility in detecting extravascular lesions. Ultrasound molecular assessment is achieved by binding disease-specific ligands to the surface of UCAs, which have been designed to target tissue biomarkers in the area of interest, such as blood vessels, inflammation, or thrombosis. Additionally, the development of multimodal imaging technology is conducive for integration of the advantages of various imaging techniques to acquire additional diagnostic information. In this review paper, the present status and the critical issues for developing ultrasound contrast agents and multimodal imaging applications are described. Conventional MB UCAs are first introduced, including their research material, diagnostic applications, and intrinsic limitations. Then, recent progress in developing targeted UCAs and phase-inversion contrast agents for diagnostic purposes is discussed. Finally, we review the present status and the critical issues for developing ultrasound-based multimodal imaging applications and summarize the existing challenges and future prospects.

Role of cardiac imaging and three-dimensional printing in percutaneous appendage closure

Atrial fibrillation is the most frequent cardiac arrhythmia, affecting up to 13% of people aged>80 years, and is responsible for 15-20% of all ischaemic strokes. Left atrial appendage occlusion devices have been developed as an alternative approach to reduce the risk of stroke in patients for whom oral anticoagulation is contraindicated. The procedure can be technically demanding, and obtaining a complete left atrial appendage occlusion can be challenging. These observations have emphasized the importance of preprocedural planning, to optimize the accuracy and safety of the procedure. In this setting, a multimodality imaging approach, including three-dimensional imaging, is often used for preoperative assessment and procedural guidance. These imaging modalities, including transoesophageal echocardiography and multislice computed tomography, allow acquisition of a three-dimensional dataset that improves understanding of the cardiac anatomy; dedicated postprocessing software integrated into the clinical workflow can be used to generate a stereolithography file, which can be printed in a rubber-like material, seeking to replicate the myocardial tissue characteristics and mechanical properties of the left atrial appendage wall. The role of multimodality imaging and 3D printing technology offers a new field for implantation simulation, which may have a major impact on physician training and technique optimization.

The first experience of using of ultrasound with multimodal imaging technology for the diagnosis of pancreatic insulinoma

The first experience of using of ultrasound with multimodal imaging technology for the diagnosis of pancreatic insulinoma

Linking imaging to omics utilizing image-guided tissue extraction

Phenotypic heterogeneity is commonly observed in diseased tissue, specifically in tumors. Multimodal imaging technologies can reveal tissue heterogeneity noninvasively in vivo, enabling imaging-based profiling of receptors, metabolism, morphology, or function on a macroscopic scale. In contrast, in vitro multiomics, immunohistochemistry, or histology techniques accurately characterize these heterogeneities in the cellular and subcellular scales in a more comprehensive but ex vivo manner. The complementary in vivo and ex vivo information would provide an enormous potential to better characterize a disease. However, this requires spatially accurate coregistration of these data by image-driven sampling as well as fast sample-preparation methods. Here, a unique image-guided milling machine and workflow for precise extraction of tissue samples from small laboratory animals or excised organs has been developed and evaluated. The samples can be delineated on tomographic images as volumes of interest and can be extracted with a spatial accuracy better than 0.25 mm. The samples remain cooled throughout the procedure to ensure metabolic stability, a precondition for accurate in vitro analysis.

Multimodal imaging technology by integrated scanning electron, force, and microwave microscopy and its application to study microscaled capacitors

Extracting simultaneously multimodal nanoscale specimen information, by an integrated microscopy technology, is in the focus of this report. The combination of multiple imaging techniques allows for obtaining complementary and often unique datasets of samples under test. An instrumental setup operating under high-vacuum conditions inside the chamber of a scanning electron microscope (SEM), as a platform fusing various microscopy methods, techniques and processes, illustrates the potential of such multimodal technology. An atomic force microscope based on a compact optical interferometer performs imaging of surface topographies and a scanning microwave microscope records electromagnetic properties in the microwave frequency domain at the same time and spot. An open-source software framework, tailored for vision-based automation by nanorobotics, controls the instrument. The setup allows for simultaneously observing the region-of-interest with SEM resolution, while imaging and characterizing with evanescent microwaves and atomic forces. To validate the approach an analysis of microscale capacitors is included.

Diagnosis and treatment guideline for myopic choroidal neovascularization due to pathologic myopia.

Pathologic myopia is a leading cause of visual impairment. Development of myopic choroidal neovascularization (CNV) is one of the most common complications that leads to central vision loss in patients with pathologic myopia. If left untreated, it can cause scarring with expanding macular atrophy leading to irreversible visual loss in a period as short as 5 years. Advancements in multimodal imaging technology have furthered our understanding of the condition; however, further studies are necessary to extend its utility in the diagnosis of myopic CNV. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has become the standard-of-care and the recommended first-line treatment option for myopic CNV. Long-term studies have demonstrated that early treatment of confirmed myopic CNV cases with an intravitreal anti-VEGF agent is useful to avoid late-stage complications. This strategy has also been shown to achieve visual outcome improvements for up to 4 years and visual stabilization up to 6 years. This review article provides an overview of the current knowledge on myopic CNV and discusses recent updates in the diagnosis and management of the condition. Furthermore, treatment recommendations are provided based on the authors' expert opinions.

Multimodality molecular imaging: Paving the way for personalized medicine

Early diagnosis and therapy increasingly operate at the cellular, molecular or even at the genetic level. As diagnostic techniques transition from the systems to the molecular level, the role of multimodality molecular imaging becomes increasingly important. Positron emission tomography (PET), x-ray CT and MRI are powerful techniques for in vivo imaging. The inability of PET to provide anatomical information is a major limitation of standalone PET systems. Combining PET and CT proved to be clinically relevant and successfully reduced this limitation by providing the anatomical information required for localization of metabolic abnormalities. However, this technology still lacks the excellent soft-tissue contrast provided by MRI. Standalone MRI systems reveal structure and function, but cannot provide insight into the physiology and/or the pathology at the molecular level. The combination of PET and MRI, enabling truly simultaneous acquisition, bridges the gap between molecular and systems diagnosis. MRI and PET offer richly complementary functionality and sensitivity; fusion into a combined system offering simultaneous acquisition will capitalize the strengths of each, providing a hybrid technology that is greatly superior to the sum of its parts.
 This talk also reflects the tremendous increase in interest in quantitative molecular imaging using PET as both clinical and research imaging modality in the past decade. It offers a brief overview of the entire range of quantitative PET imaging from basic principles to various steps required for obtaining quantitatively accurate data from dedicated standalone PET and combined PET/CT and PET/MR systems including algorithms used to correct for physical degrading factors and to quantify tracer uptake and volume for radiation therapy treatment planning. Future opportunities and the challenges facing the adoption of multimodality imaging technologies and their role in biomedical research will also be addressed.

Clinical evaluation of whole-body oncologic PET with time-of-flight and point-spread function for the hybrid PET/MR system

PurposeHybrid positron emission tomography/magnetic resonance (PET/MR) imaging is a new multimodality imaging technology that can provide structural and functional information simultaneously. The aim of this study was to investigate the effects of the time-of-flight (TOF) and point-spread function (PSF) on small lesions observed in PET/MR images from clinical patient image sets. Materials and methodsThis study evaluated 54 small lesions in 14 patients who had undergone 18F-fluorodeoxyglucose (FDG) PET/MR. Lesions up to 30mm in diameter were included. The PET data were reconstructed with a baseline ordered-subsets expectation-maximization (OSEM) algorithm, OSEM+PSF, OSEM+TOF and OSEM+TOF+PSF. PET image quality and small lesions were visually evaluated and scored by a 3-point scale. A quantitative analysis was then performed using the mean and maximum standardized uptake value (SUV) of the small lesions (SUVmean and SUVmax). The lesions were divided into two groups according to the long-axis diameter and the location respectively and evaluated with each reconstruction algorithm. We also evaluated the background signal by analyzing the SUVliver. ResultsOSEM+TOF+PSF provided the highest value and OSEM+TOF or PSF showed a higher value than OSEM for the visual assessment and quantitative analysis. The combination of TOF and PSF increased the SUVmean by 26.6% and the SUVmax by 30.0%. The SUVliverwas not influenced by PSF or TOF. For the OSEM+TOF+PSF model, the change in SUVmean and SUVmax for lesions <10mm in diameter was 31.9% and 35.8%, and 24.5% and 27.6% for lesions 10–30mm in diameter, respectively. The abdominal lesions obtained the higher SUV than those of chest on the images with TOF and/or PSF. ConclusionApplication of TOF and PSF significantly increased the SUV of small lesions in hybrid PET/MR images, potentially improving small lesion detectability.

Effects of meal and incretins in the regulation of splanchnic blood flow.

ObjectiveMeal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions.DesignA non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed.MethodsEffects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively.ResultsIngestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1.ConclusionTogether, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow.