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Marker-Free Tracking for Motion Artifact Compensation and Deformation Measurements in Optical Mapping Videos of Contracting Hearts
摘要： Optical mapping is a high-resolution fluorescence imaging technique, which provides highly detailed visualizations of the electrophysiological wave phenomena, which trigger the beating of the heart. Recent advancements in optical mapping have demonstrated that the technique can now be performed with moving and contracting hearts and that motion and motion artifacts, once a major limitation, can now be overcome by numerically tracking and stabilizing the heart’s motion. As a result, the optical measurement of electrical activity can be obtained from the moving heart surface in a co-moving frame of reference and motion artifacts can be reduced substantially. The aim of this study is to assess and validate the performance of a 2D marker-free motion tracking algorithm, which tracks motion and non-rigid deformations in video images. Because the tracking algorithm does not require markers to be attached to the tissue, it is necessary to verify that it accurately tracks the displacements of the cardiac tissue surface, which not only contracts and deforms, but also fluoresces and exhibits spatio-temporal physiology-related intensity changes. We used computer simulations to generate synthetic optical mapping videos, which show the contracting and fluorescing ventricular heart surface. The synthetic data reproduces experimental data as closely as possible and shows electrical waves propagating across the deforming tissue surface, as seen during voltage-sensitive imaging. We then tested the motion tracking and motion-stabilization algorithm on the synthetic as well as on experimental data. The motion tracking and motion-stabilization algorithm decreases motion artifacts approximately by 80% and achieves sub-pixel precision when tracking motion of 1–10 pixels (in a video image with 100 by 100 pixels), effectively inhibiting motion such that little residual motion remains after tracking and motion-stabilization. To demonstrate the performance of the algorithm, we present optical maps with a substantial reduction in motion artifacts showing action potential waves propagating across the moving and strongly deforming ventricular heart surface. The tracking algorithm reliably tracks motion if the tissue surface is illuminated homogeneously and shows sufficient contrast or texture which can be tracked or if the contrast is artificially or numerically enhanced. In this study, we also show how a reduction in dissociation-related motion artifacts can be quantified and linked to tracking precision. Our results can be used to advance optical mapping techniques, enabling them to image contracting hearts, with the ultimate goal of studying the mutual coupling of electrical and mechanical phenomena in healthy and diseased hearts.
关键词： computer vision,ventricular fibrillation,motion tracking,cardiac arrhythmias,optical mapping,atrial fibrillation,fluorescence imaging,heart rhythm disorders
更新于2025-09-09 09:28:46
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Stable Mesoporous Silica Nanoparticles Incorporated with MoS2 and AIE for Targeted Fluorescence Imaging and Photothermal Therapy of Cancer Cells
摘要： Theranostics for imaging-guided cancer treatment have obtained great attention in recent years for their outstanding capability of both tumor diagnosis and treatment. Molybdenum disulfide (MoS2) nanosheets revealed excellent photothermal conversion efficiency, which could be used as photothermal agents. However, MoS2 nanosheets would often quench or decrease the emission of fluorescence dyes when they were incorporated with these dyes to construct fluorescence-imaging-guided nanotheranostic systems. In this work, MoS2 nanosheets were embedded into mesoporous silica nanoparticles (MSNs), and Aggregation Induced Emission (AIE) fluorogen PhENH2 was chemically modified on the surface of MSNs, which could demonstrate more stable fluorescence emission compared with other MSNs with physically absorbed luminescent molecules. Moreover, folic acid (FA) was also chemically decorated on the nanoparticles to facilitate their targeted bioimaging and photothermal therapy. As expected, the obtained PhENH2-MoS2-FA MSNs could be efficiently taken up by MDA-MB-231 cells than HepG2 cells, owing to the over-expressed FA receptors on MDA-MB-231 cells. Meanwhile, these MDA-MB-231 cells could be efficiently killed under an 808 nm laser irradiation. These results indicated that the achieved multifunctional MSNs chemically decorated with AIE fluorogens would demonstrate more stable fluorescence for bioimaging-targeted photothermal therapy of MDA-MB-231 cells, which made them promising nanotheranostics for further cancer treatment.
关键词： Photothermal Therapy,Molybdenum Disulfide,Targeted Fluorescence Imaging,Aggregation Induction Emission,Stability
更新于2025-09-09 09:28:46
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[IEEE 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) - Honolulu, HI, USA (2018.7.18-2018.7.21)] 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) - In vitro Measurement of Release Kinetics of Temperature Sensitive Liposomes with a Fluorescence Imaging System
摘要： Temperature sensitive liposomes (TSL) are a promising type of nanoparticles for localized drug delivery. TSL typically release the contained drug at mild hyperthermic temperatures (40-42 oC). Combined with localized hyperthermia, this allows for local drug delivery. In vitro characterization of TSL involves measurements of drug release at varying temperatures, but current methods are inadequate due to low temporal resolution of ~8 – 10 seconds. We present a novel method for measuring the drug release with sub-second temporal resolution. In the proposed system, the TSL entrapping the fluorescent drug (Doxorubicin) are pumped through a capillary tube. The tube is rapidly heated to a desired temperature via Peltier element. Since fluorescence increases as drug is released from TSL, drug release kinetics can be measured via fluorescent imaging. By fitting exponential models, we calculated the time constants of drug release at temperatures of 39.5, 40.5 and 41.5?C were about 6.09, 2.06 and 1.03 seconds, respectively. Our initial tests show that the developed system can measure TSL release at subsecond resolution, and thus allow adequate in vitro evaluation of TSL formulations.
关键词： drug delivery,Peltier element,Temperature sensitive liposomes,fluorescence imaging,capillary tube
更新于2025-09-09 09:28:46
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Comparative Study of Tissue Distribution of Chlorin e6 Complexes with Amphiphilic Polymers in Mice with Cervical Carcinoma
摘要： Many photosensitizers, including chlorins, are highly hydrophobic, which makes intravenous administration problematic and affects their delivery to the tumor and uptake in the cells. Moreover, self-aggregation of the photosensitizer in aqueous solution reduces fluorescence quantum yield, triplet state, and singlet oxygen generation, and consequently diminishes photosensitizing activity. To address these issues, it was proposed to use biocompatible water-soluble polymers. However, animal studies of the photosensitizer-polymer systems are still very limited. In this work, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and pluronic F108 were used for dissolution of chlorin e6 (Ce6). Dynamics of accumulation of the formulations in a mouse cervical carcinoma and clearance from normal tissue, drug plasma concentrations and tissue distribution after intravenous injection were investigated. Ce6 alone and clinically used photosensitizer Photoditazine served as a control. The results showed that none of the polymers significantly changed fluorescence kinetics in the tumor. Concentration of the Ce6 formulated with polymers in the tumor tissue was comparable with Photoditazine, but uptake in the skin was less. At the same time, tumor-to-skin ratios of the Ce6-polymer complexes were similar to free Ce6. We concluded that the use of the polymeric formulation is reasonable for fluorescence diagnosis and PDT of cancer.
关键词： Chemical extraction,Amphiphilic polymer,Mouse cervical carcinoma,Photosensitizer,Chlorin e6,PDT,Fluorescence imaging in vivo
更新于2025-09-09 09:28:46
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Rapid detection of papillary thyroid carcinoma by fluorescence imaging using a γ-glutamyltranspeptidase-specific probe: a pilot study
摘要： Background: Nodular lesions of the thyroid gland, including papillary thyroid carcinoma (PTC), may be difficult to diagnose by imaging, such as in ultrasonic echo testing, or by needle biopsy. Definitive diagnosis is made by pathological examination but takes several days. A more rapid and simple method to clarify whether thyroid nodular lesions are benign or malignant is needed. Fluorescence imaging with γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) uses γ-glutamyltranspeptidase (GGT), a cell-surface enzyme, to hydrolyze the γ-glutamyl peptide and transfer the γ-glutamyl group. GGT is overexpressed in several cancers, such as breast, lung, and liver cancers. This imaging method is rapid and useful for detecting such cancers. In this study, we tried to develop a rapid fluorescence detection method for clinical samples of thyroid cancer, especially papillary carcinoma. Methods: Fluorescence imaging with gGlu-HMRG was performed to detect PTC using 23 surgically resected clinical samples. A portable imaging device conveniently captured white-light images and fluorescence images with blue excitation light. Hematoxylin-eosin (HE) staining was used to evaluate which fluorescent regions coincided with cancer, and immunohistochemical examination was used to detect GGT expression. Results: All 16 PTC samples exhibited fluorescence after topical application of gGlu-HMRG, whereas the normal sections of each sample showed no fluorescence. HE staining revealed that each fluorescent region corresponded to a region with carcinoma. The PTC samples also exhibited GGT expression, as confirmed by immunohistochemistry. Conclusions: All PTC samples were detected by fluorescence imaging with gGlu-HMRG. Thus, fluorescence imaging with gGlu-HMRG is a rapid, simple, and powerful detection tool for PTC.
关键词： Thyroid cancer,γ-glutamyl hydroxymethyl rhodamine green,γ-glutamyltranspeptidase,Papillary thyroid carcinoma,Fluorescence imaging
更新于2025-09-09 09:28:46
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Ultrasound-Switchable Fluorescence Imaging via an EMCCD Camera and a Z-Scan Method
摘要： The spatial resolution of the conventional fluorescence imaging in centimeter-deep tissue is limited due to high light scattering. Ultrasound-switchable fluorescence (USF) imaging was recently developed to achieve high resolution in deep tissue. However, previous frequency-domain USF systems adopted a fiber bundle to collect the emitted fluorescence photons, which led to a few limitations, such as, first, low photon-collection efficiency; second, low efficiency for scanning a sample with an uneven surface; third, low imaging speed, because of the adoption of a raster scan and the long wait time for the tissue to cool down before starting the data acquisition at the next location. In this study, we proposed a camera-based USF imaging system to overcome these limitations. Thanks to the spatial information provided by the camera, a new scan method, Z-scan, was developed, and the imaging speed was improved four times over the raster scan. The USF imaging using the Z-scan for tissue samples was realized. The results were validated by a commercial micro-CT system.
关键词： deep-tissue fluorescence imaging,Ultrasound-switchable fluorescence,biomedical imaging
更新于2025-09-04 15:30:14
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Rembrandt's <i>An Old Man in Military Costume</i> : Combining hyperspectral and MA-XRF imaging to understand how two paintings were painted on a single panel
摘要： Over the past several decades the painting An Old Man in Military Costume by Rembrandt Harmensz van Rijn (ca. 1630–31; J. Paul Getty Museum, 78.PB.246) has been the subject of a number of investigations carried out in order to better visualize a second painting beneath the surface figure. The underlying image – the head and shoulders of a man wearing a cloak – is oriented 180 degrees from the upper image and appears to be fairly complete. Scanning macro x-ray fluorescence (XRF) spectroscopy reveals the face is painted with lead white and a mercury-(likely vermilion), and the cloak is painted with a copper-containing pigment. Following the revelation and digital color reconstruction of the underlying figure, a number of questions still remained. Here, through the use of infrared reflectance imaging spectroscopy (i.e., hyperspectral imaging) and macro-XRF imaging spectroscopy, together with cross-sections taken from targeted areas, the sequence of painting in both compositions was explored. Of particular interest was the discovery of evidence of multiple attempts to situate the lower figure, and the subsequent application of a blocking-out layer over the lower figure before the artist rotated the panel and executed the upper figure. In addition, examination of the placement of the two images on the panel adds to our understanding of the subtle complexities of Rembrandt’s working process.
关键词： re-use of painting supports,Early Rembrandt,infrared reflectance imaging spectroscopy,X-ray fluorescence imaging spectroscopy
更新于2025-09-04 15:30:14
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Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide
摘要： Resection of breast carcinoma with adequate margins reduces the risk of local recurrence and reoperation. Tozuleristide (BLZ-100) is an investigational peptide-fluorophore agent that may aid in intraoperative tumor detection and margin assessment. In this study, fluorescence imaging was conducted ex vivo on gross breast pathology specimens. Objectives.—To determine the potential of tozuleristide to detect breast carcinoma in fresh pathology specimens and the feasibility of fluorescence-guided intraoperative pathology assessment of surgical margins. Design.—Twenty-three patients received an intravenous bolus dose of 6 or 12 mg of tozuleristide at least 1 hour before surgery. Fifteen lumpectomy and 12 mastectomy specimens were evaluated for fluorescence by the site’s clinical pathology staff using the SIRIS, an investigational near-infrared imaging device. The breast tissue was then processed per usual procedures. Fluorescent patterns were correlated with the corresponding hematoxylin-eosin–stained sections. Clinical pathology reports were used to correlate fluorescent signal to grade, histotype, prognostic marker status, and margin measurements. Results.—Tozuleristide fluorescence was readily observed in invasive and in situ breast carcinoma specimens. Most invasive carcinomas were bright and focal, whereas in situ lesions demonstrated a less intense, more diffuse pattern. Tozuleristide was detected in ductal and lobular carcinomas with a similar fluorescent pattern. Fluorescence was detected in high- and low-grade lesions, and molecular marker/hormone receptor status did not affect signal. Fluorescence could be used to identify the relationship of carcinoma to margins intraoperatively. Conclusions.—Tumor targeting with tozuleristide allowed visual real-time distinction between pathologically confirmed breast carcinoma and normal tissue.
关键词： tozuleristide,breast carcinoma,fluorescence imaging,intraoperative pathology assessment,surgical margins
更新于2025-09-04 15:30:14
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Cancellation of Bessel beam side lobes for high-contrast light sheet microscopy
摘要： An ideal illumination for light sheet fluorescence microscopy entails both a localized and a propagation invariant optical field. Bessel beams and Airy beams satisfy these conditions, but their non-diffracting feature comes at the cost of the presence of high-energy side lobes that notably degrade the imaging contrast and induce photobleaching. Here, we demonstrate the use of a light droplet illumination whose side lobes are suppressed by interfering Bessel beams of specific k-vectors. Our droplet illumination readily achieves more than 50% extinction of the light distributed across the Bessel side lobes, providing a more efficient energy localization without loss in transverse resolution. In a standard light sheet fluorescence microscope, we demonstrate a two-fold contrast enhancement imaging micron-scale fluorescent beads. Results pave the way to new opportunities for rapid and deep in vivo observations of large-scale biological systems.
关键词： light sheet microscopy,Bessel beams,fluorescence imaging,droplet illumination,Airy beams
更新于2025-09-04 15:30:14
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<i>In vivo</i> Imaging-Guided Nanoplatform for Tumor Targeting Delivery and Combined Chemo-, Gene- and Photothermal Therapy
摘要： Currently, a large number of anti-tumor drug delivery systems have been widely used in cancer therapy. However, due to the molecular complexity and multidrug resistance of tumors, monotherapies remain suboptimal. Thus, this study aimed to develop a multifunctional theranostic nanoplatform for effective cancer therapy. Methods: Folic acid-modified silver sulfide@mesoporous silica core-shell nanoparticle was first modified with desthiobiotin (db) on the surface, then doxorubicin (DOX) was loaded into pore. Avidin was employed as "gatekeeper" to prevent leakage of DOX via desthiobiotin-avidin interaction. Db-modified survivin antisense oligonucleotide (db-DNA) which could inhibit survivin expression was then grafted on avidin at the outer layer of nanoparticle. DOX release and db-DNA dissociation were simultaneously triggered by overexpressing biotin in cancer cells, then combining PTT from Ag2S QD to inhibit tumor growth. Results: This nanoprobe had satisfactory stability and photothermal conversion efficiency up to 33.86% which was suitable for PTT. Due to the good targeting ability and fluorescent anti-bleaching, its signal still existed at the tumor site after tail vein injection of probe into HeLa tumor-bearing nude mice for 48 h. In vitro and in vivo antitumor experiments both demonstrated that drug, gene and photothermal synergistic therapy significantly enhanced antitumor efficacy with minimal systemic toxicity. Conclusion: Our findings demonstrate that this novel nanoplatform for targeted image-guided treatment of tumor and tactfully integrated chemotherapy, photothermal therapy (PTT) and gene therapy might provide an insight for cancer theranostics.
关键词： mesoporous silica,photothermal therapy,fluorescence imaging,gene therapy,drug delivery system
更新于2025-09-04 15:30:14