scholarly journals In vivo preclinical verification of a multimodal diffuse reflectance and correlation spectroscopy system for sensing tissue perfusion

Author(s):  
Julia M. Pakela ◽  
Seung Yup Lee ◽  
Taylor L. Hedrick ◽  
Karthik Vishwanath ◽  
Michael C. Helton ◽  
...  
2019 ◽  
Vol 9 (15) ◽  
pp. 3047 ◽  
Author(s):  
Karthik Vishwanath ◽  
Sara Zanfardino

Diffuse correlation spectroscopy (DCS) has widely been used as a non-invasive optical technique to measure tissue perfusion in vivo. DCS measurements are quantified to yield information about moving scatterers using photon diffusion theory and are therefore obtained at long source-detector separations (SDS). However, short SDS DCS could be used for measuring perfusion in small animal models or endoscopically in clinical studies. Here, we investigate the errors in analytically retrieved flow coefficients from simulated and experimental data acquired at short SDS. Monte Carlo (MC) simulations of photon correlation transport was programmed to simulate DCS measurements and used to (a) examine the accuracy and validity of theoretical analyses, and (b) model experimental measurements made on phantoms at short SDS. Experiments consisted of measurements from a series of optical phantoms containing an embedded flow channel. Both the fluid flow rate and depth of the flow channel from the liquid surface were varied. Inputs to MC simulations required to model experiments were obtained from corrected theoretical analyses. Results show that the widely used theoretical DCS model is robust for quantifying relative changes in flow. We also show that retrieved flow coefficients at short SDS can be scaled to retrieve absolute values via MC simulations.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 770
Author(s):  
Patrick M. Perrigue ◽  
Richard A. Murray ◽  
Angelika Mielcarek ◽  
Agata Henschke ◽  
Sergio E. Moya

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.


2019 ◽  
Vol 9 (11) ◽  
pp. 2366 ◽  
Author(s):  
Laura Di Sieno ◽  
Alberto Dalla Mora ◽  
Alessandro Torricelli ◽  
Lorenzo Spinelli ◽  
Rebecca Re ◽  
...  

In this paper, a time-domain fast gated near-infrared spectroscopy system is presented. The system is composed of a fiber-based laser providing two pulsed sources and two fast gated detectors. The system is characterized on phantoms and was tested in vivo, showing how the gating approach can improve the contrast and contrast-to-noise-ratio for detection of absorption perturbation inside a diffusive medium, regardless of source-detector separation.


2000 ◽  
Vol 113 (22) ◽  
pp. 3921-3930 ◽  
Author(s):  
R.H. Kohler ◽  
P. Schwille ◽  
W.W. Webb ◽  
M.R. Hanson

Dynamic tubular projections emanate from plastids in certain cells of vascular plants and are especially prevalent in non-photosynthetic cells. Tubules sometimes connect two or more different plastids and can extend over long distances within a cell, observations that suggest that the tubules may function in distribution of molecules within, to and from plastids. In a new application of two-photon excitation (2PE) fluorescence correlation spectroscopy (FCS), we separated diffusion of fluorescent molecules from active transport in vivo. We quantified the velocities of diffusion versus active transport of green fluorescent protein (GFP) within plastid tubules and in the cytosol in vivo. GFP moves by 3-dimensional (3-D) diffusion both in the cytosol and plastid tubules, but diffusion in tubules is about 50 times and 100 times slower than in the cytosol and an aqueous solution, respectively. Unexpectedly larger GFP units within plastid tubules exhibited active transport with a velocity of about 0.12 microm/second. Active transport might play an important role in the long-distance distribution of large numbers of molecules within the highly viscous stroma of plastid tubules.


Author(s):  
Gleb S. Budylin ◽  
Denis A. Davydov ◽  
Nadezhda V. Zlobina ◽  
Alexey V. Baev ◽  
Vyacheslav G. Artyushenko ◽  
...  

2018 ◽  
Vol 3 (5) ◽  
pp. 349-355 ◽  
Author(s):  
Gerrit C. Langhout ◽  
Koert F.D. Kuhlmann ◽  
Pim Schreuder ◽  
Torre Bydlon ◽  
Ludi E. Smeele ◽  
...  

2018 ◽  
Author(s):  
Sandra B. Lemke ◽  
Thomas Weidemann ◽  
Anna-Lena Cost ◽  
Carsten Grashoff ◽  
Frank Schnorrer

Cells in a developing organism are subjected to particular mechanical forces, which shape tissues and instruct cell fate decisions. How these forces are sensed and transmitted at the molecular level is thus an important question, which has mainly been investigated in cultured cells in vitro. Here, we elucidate how mechanical forces are transmitted in an intact organism. We studied Drosophila muscle attachment sites, which experience high mechanical forces during development and require integrin-mediated adhesion for stable attachment to tendons. Hence, we quantified molecular forces across the essential integrin-binding protein Talin, which links integrin to the actin cytoskeleton. Generating flies expressing three FRET-based Talin tension sensors reporting different force levels between 1 and 11 pN enabled us to quantify physiologically-relevant, molecular forces. By measuring primary Drosophila muscle cells, we demonstrate that Drosophila Talin experiences mechanical forces in cell culture that are similar to those previously reported for Talin in mammalian cell lines. However, in vivo force measurements at developing flight muscle attachment sites revealed that average forces across Talin are comparatively low and decrease even further while attachments mature and tissue-level tension increases. Concomitantly, Talin concentration at attachment sites increases five-fold as quantified by fluorescence correlation spectroscopy, suggesting that only few Talin molecules are mechanically engaged at any given time. We therefore propose that high tissue forces are shared amongst a large excess of adhesion molecules of which less than 15% are experiencing detectable forces at the same time. Our findings define an important new concept of how cells can adapt to changes in tissue mechanics to prevent mechanical failure in vivo.


OSA Continuum ◽  
2019 ◽  
Vol 2 (3) ◽  
pp. 905 ◽  
Author(s):  
Peter Naglič ◽  
Luka Vidovič ◽  
Matija Milanič ◽  
Lise L. Randeberg ◽  
Boris Majaron

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