scholarly journals Real-time optoacoustic tracking of single moving micro-objects in deep tissue-mimicking phantoms

2019 ◽  
Author(s):  
Azaam Aziz ◽  
Mariana Medina-Sánchez ◽  
Jing Claussen ◽  
Oliver G. Schmidt
Keyword(s):  
Real Time ◽  
Biological Tissues ◽  
Optical Methods ◽  
Dynamic Monitoring ◽  
Spatiotemporal Resolution ◽  
Spectral Signatures ◽  
Optoacoustic Tomography ◽  
Molecular Specificity ◽  
Micro Implants

ABSTRACTMedical imaging plays an important role in diagnosis and treatment of multiple diseases. It is a field under continuous development which seeks for improved sensitivity and spatiotemporal resolution to allow the dynamic monitoring of diverse biological processes that occur at the micro- and nanoscale. Emerging technologies for targeted diagnosis and therapy such as nanotherapeutics, micro-implants, catheters and small medical tools also need to be precisely located and monitored while performing their function inside the human body. In this work, we show for the first time the real-time tracking of moving single micro-objects below centimeter thick tissue-mimicking phantoms, using multispectral optoacoustic tomography (MSOT). This technique combines the advantages of ultrasound imaging regarding depth and resolution with the molecular specificity of optical methods, thereby facilitating the discrimination between the spectral signatures of the micro-objects from those of intrinsic tissue molecules. The resulting MSOT signal is further improved in terms of contrast and specificity by coating the micro-objects’ surface with gold nanorods, possessing a unique absorption spectrum, which will allow their discrimination from surrounding biological tissues when translated to in vivo settings.

scholarly journals Dual-Modal In Vivo Fluorescence/Photoacoustic Microscopy Imaging of Inflammation Induced by GFP-Expressing Bacteria

Sensors ◽  
2019 ◽  
Vol 19 (2) ◽  
pp. 238 ◽  
Author(s):  
Yubin Liu ◽  
Lei Fu ◽  
Mengze Xu ◽  
Jun Zheng ◽  
Zhen Yuan
Keyword(s):  
Multimodal Imaging ◽  
Fluorescent Protein ◽  
Biological Tissues ◽  
Photoacoustic Microscopy ◽  
Microscopy Imaging ◽  
Enhanced Sensitivity ◽  
Imaging Results ◽  
Molecular Specificity ◽  
Green Fluorescent

In this study, dual-modal fluorescence and photoacoustic microscopy was performed for noninvasive and functional in vivo imaging of inflammation induced by green fluorescent protein (GFP) transfected bacteria in mice ear. Our imaging results demonstrated that the multimodal imaging technique is able to monitor the tissue immunovascular responses to infections with molecular specificity. Our study also indicated that the combination of photoacoustic and fluorescence microscopy imaging can simultaneously track the biochemical changes including the bacterial distribution and morphological change of blood vessels in the biological tissues with high resolution and enhanced sensitivity. Consequently, the developed method paves a new avenue for improving the understanding of the pathology mechanism of inflammation.

scholarly journals Magnetomicrometry

2021 ◽  
Vol 6 (57) ◽  
pp. eabg0656
Author(s):  
C. R. Taylor ◽  
S. S. Srinivasan ◽  
S. H. Yeon ◽  
M. K. O’Donnell ◽  
T. J. Roberts ◽  
...  
Keyword(s):  
Real Time ◽  
Magnetic Beads ◽  
Control Strategies ◽  
Muscle Length ◽  
Human Movement ◽  
Biological Tissues ◽  
Wearable Robots ◽  
Length Changes ◽  
Portable Sensor

We live in an era of wearable sensing, where our movement through the world can be continuously monitored by devices. Yet, we lack a portable sensor that can continuously monitor muscle, tendon, and bone motion, allowing us to monitor performance, deliver targeted rehabilitation, and provide intuitive, reflexive control over prostheses and exoskeletons. Here, we introduce a sensing modality, magnetomicrometry, that uses the relative positions of implanted magnetic beads to enable wireless tracking of tissue length changes. We demonstrate real-time muscle length tracking in an in vivo turkey model via chronically implanted magnetic beads while investigating accuracy, biocompatibility, and long-term implant stability. We anticipate that this tool will lay the groundwork for volitional control over wearable robots via real-time tracking of muscle lengths and speeds. Further, to inform future biomimetic control strategies, magnetomicrometry may also be used in the in vivo tracking of biological tissues to elucidate biomechanical principles of animal and human movement.

In vivo pharmacokinetic features and biodistribution of star and rod shaped gold nanoparticles by multispectral optoacoustic tomography

RSC Advances ◽  
2015 ◽  
Vol 5 (10) ◽  
pp. 7529-7538 ◽  
Author(s):  
Jing Wang ◽  
Yadian Xie ◽  
Liming Wang ◽  
Jinglong Tang ◽  
Jiayang Li ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Real Time ◽  
Real Time Monitoring ◽  
Monitoring Method ◽  
Optoacoustic Tomography

Multispectral optoacoustic tomography (MSOT) provides a real-time monitoring method to evaluate gold nanoparticles' pharmacokinetics and biodistribution.

scholarly journals Visualizing ATP Dynamics in Live Mice

2020 ◽  
Author(s):  
Norimichi Koitabashi ◽  
Riki Ogasawara ◽  
Ryuto Yasui ◽  
Yuki Sugiura ◽  
Hinako Matsuda ◽  
...  
Keyword(s):  
Mouse Model ◽  
Real Time ◽  
Biological Activities ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Spatiotemporal Resolution ◽  
Physiological Mechanisms ◽  
Multiple Organs ◽  
Atp Levels

ABSTRACTAnalysis of the dynamics of adenosine triphosphate (ATP) is vital to quantitatively define the actual roles of ATP in biological activities. Here, we applied a genetically encoded Förster resonance energy transfer biosensor “GO-ATeam” and created a transgenic mouse model that allows systemic ATP levels to be quantitatively, sensitively, noninvasively, and spatiotemporally measured under physiological and pathological conditions. We used this model to readily conduct intravital imaging of ATP dynamics under three different conditions: during exercise, in all organs and cells; during myocardial infarction progression; and in response to the application of cardiotoxic drugs. These findings provide compelling evidence that the GO-ATeam mouse model is a powerful tool to investigate the multifarious functions of cellular ATP in vivo with unprecedented spatiotemporal resolution in real-time. This will inform predictions of molecular and morphological responses to perturbations of ATP levels, as well as the elucidation of physiological mechanisms that control ATP homeostasis.One Sentence SummaryIntravital real-time imaging of ATP dynamics in multiple organs using GO-ATeam mice, can be used to quantitatively, sensitively, noninvasively, and spatiotemporally measure systemic ATP levels and provide a platform for preclinical pharmacological studies.

scholarly journals Differential Responses of Transplanted Stem Cells to Diseased Environment Unveiled by a Molecular NIR-II Cell Tracker

Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Hao Chen ◽  
Huaxiao Yang ◽  
Chen Zhang ◽  
Si Chen ◽  
Xin Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Single Cell ◽  
Real Time ◽  
Stem Cell Therapy ◽  
Cellular Migration ◽  
Cell Cluster ◽  
Spatiotemporal Resolution

Stem cell therapy holds high promises in regenerative medicine. The major challenge of clinical translation is to precisely and quantitatively evaluate the in vivo cell distribution, migration, and engraftment, which cannot be easily achieved by current techniques. To address this issue, for the first time, we have developed a molecular cell tracker with a strong fluorescence signal in the second near-infrared (NIR-II) window (1,000-1,700 nm) for real-time monitoring of in vivo cell behaviors in both healthy and diseased animal models. The NIR-II tracker (CelTrac1000) has shown complete cell labeling with low cytotoxicity and profound long-term tracking ability for 30 days in high spatiotemporal resolution for semiquantification of the biodistribution of transplanted stem cells. Taking advantage of the unique merits of CelTrac1000, the responses of transplanted stem cells to different diseased environments have been discriminated and unveiled. Furthermore, we also demonstrate CelTrac1000 as a universal and effective technique for ultrafast real-time tracking of the cellular migration and distribution in a 100 μm single-cell cluster spatial resolution, along with the lung contraction and heart beating. As such, this NIR-II tracker will shift the optical cell tracking into a single-cell cluster and millisecond temporal resolution for better evaluating and understanding stem cell therapy, affording optimal doses and efficacy.

scholarly journals Genetically-encoded fluorescent biosensor for rapid detection of protein expression

2020 ◽  
Author(s):  
Matthew G Eason ◽  
Antonia T Pandelieva ◽  
Marc M Mayer ◽  
Safwat T Khan ◽  
Hernan G Garcia ◽  
...  
Keyword(s):  
Protein Expression ◽  
Real Time ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Live Cells ◽  
Spatiotemporal Resolution ◽  
E Coli ◽  
Fluorescent Biosensor ◽  
Green Fluorescent

Fluorescent proteins are widely used as fusion tags to detect protein expression in vivo. To become fluorescent, these proteins must undergo chromophore maturation, a slow process with a half-time of 5 to >30 min, which causes delays in real-time detection of protein expression. Here, we engineer a genetically-encoded fluorescent biosensor to enable detection of protein expression within seconds in live cells. This sensor for transiently-expressed proteins (STEP) is based on a fully matured but dim green fluorescent protein in which pre-existing fluorescence increases 11-fold in vivo following the specific and rapid binding of a protein tag (Kd 120 nM, kon 1.7 x 10^5 M-1s-1). In live E. coli cells, our STEP biosensor enables detection of protein expression twice as fast as the use of standard fluorescent protein fusions. Our biosensor opens the door to the real-time study of short-timescale processes in research model animals with high spatiotemporal resolution.

scholarly journals Real-time single-cell characterization of the eukaryotic transcription cycle reveals correlations between RNA initiation, elongation, and cleavage

2021 ◽  
Vol 17 (5) ◽  
pp. e1008999
Author(s):  
Jonathan Liu ◽  
Donald Hansen ◽  
Elizabeth Eck ◽  
Yang Joon Kim ◽  
Meghan Turner ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Single Cell ◽  
Real Time ◽  
Fruit Fly ◽  
Effective Parameters ◽  
Spatiotemporal Resolution ◽  
Eukaryotic Transcription ◽  
Nascent Rna ◽  
Transcription Cycle

The eukaryotic transcription cycle consists of three main steps: initiation, elongation, and cleavage of the nascent RNA transcript. Although each of these steps can be regulated as well as coupled with each other, their in vivo dissection has remained challenging because available experimental readouts lack sufficient spatiotemporal resolution to separate the contributions from each of these steps. Here, we describe a novel application of Bayesian inference techniques to simultaneously infer the effective parameters of the transcription cycle in real time and at the single-cell level using a two-color MS2/PP7 reporter gene and the developing fruit fly embryo as a case study. Our method enables detailed investigations into cell-to-cell variability in transcription-cycle parameters as well as single-cell correlations between these parameters. These measurements, combined with theoretical modeling, suggest a substantial variability in the elongation rate of individual RNA polymerase molecules. We further illustrate the power of this technique by uncovering a novel mechanistic connection between RNA polymerase density and nascent RNA cleavage efficiency. Thus, our approach makes it possible to shed light on the regulatory mechanisms in play during each step of the transcription cycle in individual, living cells at high spatiotemporal resolution.

scholarly journals Red Light Optogenetics in Neuroscience

2022 ◽  
Vol 15 ◽  
Author(s):  
Kimmo Lehtinen ◽  
Miriam S. Nokia ◽  
Heikki Takala
Keyword(s):  
Red Light ◽  
Long Term Potentiation ◽  
Biological Tissues ◽  
Infrared Light ◽  
Cellular Functions ◽  
Spatiotemporal Resolution ◽  
New Developments ◽  
Term Potentiation

Optogenetics, a field concentrating on controlling cellular functions by means of light-activated proteins, has shown tremendous potential in neuroscience. It possesses superior spatiotemporal resolution compared to the surgical, electrical, and pharmacological methods traditionally used in studying brain function. A multitude of optogenetic tools for neuroscience have been created that, for example, enable the control of action potential generation via light-activated ion channels. Other optogenetic proteins have been used in the brain, for example, to control long-term potentiation or to ablate specific subtypes of neurons. In in vivo applications, however, the majority of optogenetic tools are operated with blue, green, or yellow light, which all have limited penetration in biological tissues compared to red light and especially infrared light. This difference is significant, especially considering the size of the rodent brain, a major research model in neuroscience. Our review will focus on the utilization of red light-operated optogenetic tools in neuroscience. We first outline the advantages of red light for in vivo studies. Then we provide a brief overview of the red light-activated optogenetic proteins and systems with a focus on new developments in the field. Finally, we will highlight different tools and applications, which further facilitate the use of red light optogenetics in neuroscience.

scholarly journals Characterization of a Fiber Bundle-Based Real-Time Ultrasound/Photoacoustic Imaging System and Its In Vivo Functional Imaging Applications

Micromachines ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 820
Author(s):  
He Leng ◽  
Yuhling Wang ◽  
De-Fu Jhang ◽  
Tsung-Sheng Chu ◽  
Chia-Hui Tsao ◽  
...  
Keyword(s):  
User Interface ◽  
Real Time ◽  
In Vivo Imaging ◽  
Fiber Bundle ◽  
Imaging System ◽  
Structural Information ◽  
Photoacoustic Imaging ◽  
Numerical Aperture ◽  
Biological Tissues

Photoacoustic (PA) imaging is an attractive technology for imaging biological tissues because it can capture both functional and structural information with satisfactory spatial resolution. Current commercially available PA imaging systems are limited by their bulky size or inflexible user interface. We present a new handheld real-time ultrasound/photoacoustic imaging system (HARP) consisting of a detachable, high-numerical-aperture (NA) fiber bundle-based illumination system integrated with an array-based ultrasound (US) transducer and a data acquisition platform. In this system, different PA probes can be used for different imaging applications by switching the transducers and the corresponding jackets to combine the fiber pads and transducer into a single probe. The intuitive user interface is a completely programmable MATLAB-based platform. In vitro phantom experiments were conducted to test the imaging performance of the developed PA system. Furthermore, we demonstrated (1) in vivo brain vasculature imaging, (2) in vivo imaging of real-time stimulus-evoked cortical hemodynamic changes during forepaw electrical stimulation, and (3) in vivo imaging of real-time cerebral pharmacokinetics in rats using the developed PA system. The overall purpose of this design concept for a customizable US/PA imaging system is to help overcome the diverse challenges faced by medical researchers performing both preclinical and clinical PA studies.

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