scholarly journals Real-time detection of circulating tumor cells in living animals using functionalized large gold nanorods

2018 ◽  
Author(s):  
Rebecca Dutta ◽  
Orly Liba ◽  
Elliott D SoRelle ◽  
Yonatan Winetraub ◽  
Vishnu Ramani ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Tumor Cells ◽  
Gold Nanorods ◽  
Cell Tracking ◽  
Speckle Noise ◽  
Speckle Reduction ◽  
Exciting Opportunity ◽  
Contrast Enhanced ◽  
The Individual

Optical coherence tomography (OCT) with significant speckle reduction can be used with highly-scattering contrast agents for noninvasive, contrast-enhanced imaging of living tissue at the cellular scale. The advantages of reduced speckle noise and improved targeted contrast can be harnessed to track objects as small as 2 μm in vivo, with the potential for cell tracking and counting in living subjects. Here we demonstrate the use of Large Gold Nanorods (LGNRs) as contrast agents for detecting individual micron-sized polystyrene beads and single myeloma cells in blood circulation using speckle modulating-OCT (SM-OCT). This is the first time that OCT has been used to image at the individual cell scale in vivo. This technical capability presents an exciting opportunity for the dynamic detection and quantification of tumor cells circulating in living subjects.

Non-radioactive imaging strategies for in vivo immune cell tracking

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Łukasz Kiraga ◽  
Paulina Kucharzewska ◽  
Damian Strzemecki ◽  
Tomasz P. Rygiel ◽  
Magdalena Król
Keyword(s):  
Diagnostic Imaging ◽  
Contrast Agents ◽  
Cell Tracking ◽  
Immune Cell ◽  
Imaging Techniques ◽  
Diagnostic Technique ◽  
Cell Labeling ◽  
X Ray Imaging ◽  
Disease Study

Abstract In vivo tracking of administered cells chosen for specific disease treatment may be conducted by diagnostic imaging techniques preceded by cell labeling with special contrast agents. The most commonly used agents are those with radioactive properties, however their use in research is often impossible. This review paper focuses on the essential aspect of cell tracking with the exclusion of radioisotope tracers, therefore we compare application of different types of non-radioactive contrast agents (cell tracers), methods of cell labeling and application of various techniques for cell tracking, which are commonly used in preclinical or clinical studies. We discuss diagnostic imaging methods belonging to three groups: (1) Contrast-enhanced X-ray imaging, (2) Magnetic resonance imaging, and (3) Optical imaging. In addition, we present some interesting data from our own research on tracking immune cell with the use of discussed methods. Finally, we introduce an algorithm which may be useful for researchers planning leukocyte targeting studies, which may help to choose the appropriate cell type, contrast agent and diagnostic technique for particular disease study.

Polymeric/Inorganic Multifunctional Nanoparticles for Simultaneous Drug Delivery and Visualization

2010 ◽  
Vol 1257 ◽  
Author(s):  
Andrea Fornara ◽  
Alberto Recalenda ◽  
Jian Qin ◽  
Abhilash Sugunan ◽  
Fei Ye ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluorescence Microscopy ◽  
Contrast Agents ◽  
Gold Nanorods ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Multifunctional Nanoparticles ◽  
Cytotoxicity Studies

AbstractNanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.

scholarly journals Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
John R. Eisenbrey ◽  
Anush Sridharan ◽  
Ji-Bin Liu ◽  
Flemming Forsberg
Keyword(s):  
Contrast Agents ◽  
Tumor Imaging ◽  
Three Dimensional ◽  
Ultrasound Contrast Agents ◽  
Surrounding Tissue ◽  
Contrast Enhanced Ultrasound ◽  
Ultrasound Contrast ◽  
Contrast Enhanced ◽  
Subharmonic Response

Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imagingin vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging.

scholarly journals Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures

2012 ◽  
Vol 303 (1) ◽  
pp. H126-H132 ◽  
Author(s):  
Jaydev K. Dave ◽  
Valgerdur G. Halldorsdottir ◽  
John R. Eisenbrey ◽  
Joel S. Raichlen ◽  
Ji-Bin Liu ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Contrast Agents ◽  
Acoustic Emissions ◽  
Right Heart Catheterization ◽  
Ultrasound Contrast Agents ◽  
Heart Catheterization ◽  
Ultrasound Contrast ◽  
Individual Calibration ◽  
The Individual

Right heart catheterization is often required to monitor intra-cardiac pressures in a number of disease states. Ultrasound contrast agents can produce pressure modulated subharmonic emissions that may be used to estimate right ventricular (RV) pressures. A technique based on subharmonic acoustic emissions from ultrasound contrast agents to track RV pressures noninvasively has been developed and its clinical potential evaluated. The subharmonic signals were obtained from the aorta, RV, and right atrium (RA) of five anesthetized closed-chest mongrel dogs using a SonixRP ultrasound scanner and PA4-2 phased array. Simultaneous pressure measurements were obtained using a 5-French solid state micromanometer tipped catheter. Initially, aortic subharmonic signals and systemic blood pressures were used to obtain a calibration factor in units of millimeters of mercury per decibel. This factor was combined with RA pressures (that can be obtained noninvasively) and the acoustic data from the RV to obtain RV pressure values. The individual calibration factors ranged from −2.0 to −4.0 mmHg/dB. The subharmonic signals tracked transient changes in the RV pressures within an error of 0.6 mmHg. Relative to the catheter pressures, the mean errors in estimating RV peak systolic and minimum diastolic pressures, and RV relaxation [isovolumic negative derivative of change in pressure over time (−dP/d t)] by use of the subharmonic signals, were −2.3 mmHg, −0.8 mmHg, and 2.9 mmHg/s, respectively. Overall, acoustic estimates of RV peak systolic and minimum diastolic pressures and RV relaxation were within 3.4 mmHg, 1.8 mmHg, and 5.9 mmHg/s, respectively, of the measured pressures. This pilot study demonstrates that subharmonic emissions from ultrasound contrast agents have the potential to noninvasively track in vivo RV pressures with errors below 3.5 mmHg.

scholarly journals Speckle-modulating optical coherence tomography in living mice and humans

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Orly Liba ◽  
Matthew D. Lew ◽  
Elliott D. SoRelle ◽  
Rebecca Dutta ◽  
Debasish Sen ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Speckle Noise ◽  
Coherent Detection ◽  
Speckle Reduction ◽  
Optical Coherence ◽  
Coherent Noise ◽  
Speckle Patterns ◽  
Reduction Methods ◽  
Diagnostic Capabilities

Abstract Optical coherence tomography (OCT) is a powerful biomedical imaging technology that relies on the coherent detection of backscattered light to image tissue morphology in vivo. As a consequence, OCT is susceptible to coherent noise (speckle noise), which imposes significant limitations on its diagnostic capabilities. Here we show speckle-modulating OCT (SM-OCT), a method based purely on light manipulation that virtually eliminates speckle noise originating from a sample. SM-OCT accomplishes this by creating and averaging an unlimited number of scans with uncorrelated speckle patterns without compromising spatial resolution. Using SM-OCT, we reveal small structures in the tissues of living animals, such as the inner stromal structure of a live mouse cornea, the fine structures inside the mouse pinna, and sweat ducts and Meissner’s corpuscle in the human fingertip skin—features that are otherwise obscured by speckle noise when using conventional OCT or OCT with current state of the art speckle reduction methods.

scholarly journals Fluorine-19 Mri Contrast Agents for Cell Tracking and Lung Imaging

2015 ◽  
Vol 8s1 ◽  
pp. MRI.S23559 ◽  
Author(s):  
Matthew S. Fox ◽  
Jeffrey M. Gaudet ◽  
Paula J. Foster
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Contrast Agents ◽  
Cell Tracking ◽  
Cellular Therapy ◽  
Medical Intervention ◽  
Mri Contrast Agents ◽  
Lung Imaging ◽  
Resonance Imaging

Fluorine-19 (19F)-based contrast agents for magnetic resonance imaging stand to revolutionize imaging-based research and clinical trials in several fields of medical intervention. First, their use in characterizing in vivo cell behavior may help bring cellular therapy closer to clinical acceptance. Second, their use in lung imaging provides novel noninvasive interrogation of the ventilated airspaces without the need for complicated, hard-to-distribute hardware. This article reviews the current state of 19F-based cell tracking and lung imaging using magnetic resonance imaging and describes the link between the methods across these fields and how they may mutually benefit from solutions to mutual problems encountered when imaging 19F-containing compounds, as well as hardware and software advancements.

scholarly journals Iron Oxide as an Mri Contrast Agent for Cell Tracking: Supplementary Issue

2015 ◽  
Vol 8s1 ◽  
pp. MRI.S23557 ◽  
Author(s):  
Daniel J. Korchinski ◽  
May Taha ◽  
Runze Yang ◽  
Nabeela Nathoo ◽  
Jeff F. Dunn
Keyword(s):  
Iron Oxide ◽  
Contrast Agents ◽  
Cell Tracking ◽  
Ex Vivo ◽  
Cerebral Aneurysms ◽  
Cell Types ◽  
Mri Contrast Agent ◽  
Mri Contrast ◽  
Different Cell Types

Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation.

scholarly journals A Safe Harbor-Targeted CRISPR/Cas9 Homology Independent Targeted Integration (HITI) System for Multi-Modality Reporter Gene-Based Cell Tracking

2020 ◽  
Author(s):  
John J Kelly ◽  
Moe Saee-Marand ◽  
Nivin N Nyström ◽  
Yuanxin Chen ◽  
Melissa M Evans ◽  
...  
Keyword(s):  
Reporter Gene ◽  
Cell Tracking ◽  
Integration Site ◽  
Reporter Genes ◽  
Safe Harbor ◽  
Enhanced Mri ◽  
Contrast Enhanced ◽  
Targeted Integration ◽  
Contrast Enhanced Mri

AbstractImaging reporter genes can provide valuable, longitudinal information on the biodistribution, growth and survival of engineered cells in preclinical models and patients. A translational bottleneck to using reporter genes in patients is the necessity to engineer cells with randomly-integrating vectors. CRISPR/Cas9 targeted knock-in of reporter genes at a genomic safe harbor locus such as adeno-associated virus integration site 1 (AAVS1) may overcome these safety concerns. Here, we built Homology Independent Targeted Integration (HITI) CRISPR/Cas9 minicircle donors for precise AAVS1-targeted simultaneous knock-in of fluorescence, bioluminescence, and MRI (Oatp1a1) reporter genes. Our results showed greater knock-in efficiency at the AAVS1 site using HITI vectors compared to homology-directed repair donor vectors. Characterization of select HITI clones demonstrated functional fluorescence and bioluminescence reporter activity as well as significantly increased Oatp1a1-mediated uptake of the clinically-approved MRI agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. As few as 106 Oatp1a1-expressing cells in a 50 µl subcutaneous injection could be detected in vivo with contrast-enhanced MRI. Contrast-enhanced MRI also improved the conspicuity of both sub-cutaneous and metastatic Oatp1a1-expressing tumours prior to them being palpable or even readily visible on pre-contrast images. Our work demonstrates the first CRISPR/Cas9 HITI system for knock-in of large DNA donor constructs at a safe harbor locus, enabling multi-modal longitudinal in vivo imaging of cells. This work lays the foundation for safer, non-viral reporter gene tracking of multiple cell types.

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