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2021 ◽  
Author(s):  
Tyler Hornsby

<div>Frequency compounding is an ultrasound imaging technique used to reduce artifacts and improve signal-to-noise-ratio (SNR). In this work a new nonlinear frequency compounding (NLFC) method was introduced, and its application in B-mode imaging and noninvasive thermometry was investigated. NLFC input frequencies were optimized to maximize speckle-signal-to-noise-ratio (SSNR) in a tissue mimicking phantom, and the method was then used to produce maps of the temperature sensitive change in backscattered energy of acoustic harmonics (<i>h</i>CBE) during heating of ex vivo porcine tissue with a focused ultrasound transducer. A <i>h</i>CBE-to-temperature calibration was also performed and temperature maps produced. Lastly, a comparative study of the NLFC and previously used nonlinear single frequency (NLSF) method was completed. By using the NLFC method it was concluded that SSNR of B-mode and backscattered energy images, SNR of <i>h</i>CBE maps, and temperature map agreement with a theoretical COMSOL based model were improved over the previously used NLSF method.</div>


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Eric B. Miller ◽  
Sarah J. Karlen ◽  
Kaitryn E. Ronning ◽  
Marie E. Burns

Abstract Background The ability to track individual immune cells within the central nervous system has revolutionized our understanding of the roles that microglia and monocytes play in synaptic maintenance, plasticity, and neurodegenerative diseases. However, distinguishing between similar subpopulations of mobile immune cells over time during episodes of neuronal death and tissue remodeling has proven to be challenging. Methods We recombineered a photoconvertible fluorescent protein (Dendra2; D2) downstream of the Cx3cr1 promoter commonly used to drive expression of fluorescent markers in microglia and monocytes. Like the popular Cx3cr1–GFP line (Cx3cr1+/GFP), naïve microglia in Cx3cr1–Dendra2 mice (Cx3cr1+/D2) fluoresce green and can be noninvasively imaged in vivo throughout the CNS. In addition, individual D2-expressing cells can be photoconverted, resulting in red fluorescence, and tracked unambiguously within a field of green non-photoconverted cells for several days in vivo. Results Dendra2-expressing retinal microglia were noninvasively photoconverted in both ex vivo and in vivo conditions. Local in vivo D2 photoconversion was sufficiently robust to quantify cell subpopulations by flow cytometry, and the protein was stable enough to survive tissue processing for immunohistochemistry. Simultaneous in vivo fluorescence imaging of Dendra2 and light scattering measurements (Optical Coherence Tomography, OCT) were used to assess responses of individual microglial cells to localized neuronal damage and to identify the infiltration of monocytes from the vasculature in response to large scale neurodegeneration. Conclusions The ability to noninvasively and unambiguously track D2-expressing microglia and monocytes in vivo through space and time makes the Cx3cr1–Dendra2 mouse model a powerful new tool for disentangling the roles of distinct immune cell subpopulations in neuroinflammation.


2021 ◽  
Author(s):  
Tyler Hornsby

<div>Frequency compounding is an ultrasound imaging technique used to reduce artifacts and improve signal-to-noise-ratio (SNR). In this work a new nonlinear frequency compounding (NLFC) method was introduced, and its application in B-mode imaging and noninvasive thermometry was investigated. NLFC input frequencies were optimized to maximize speckle-signal-to-noise-ratio (SSNR) in a tissue mimicking phantom, and the method was then used to produce maps of the temperature sensitive change in backscattered energy of acoustic harmonics (<i>h</i>CBE) during heating of ex vivo porcine tissue with a focused ultrasound transducer. A <i>h</i>CBE-to-temperature calibration was also performed and temperature maps produced. Lastly, a comparative study of the NLFC and previously used nonlinear single frequency (NLSF) method was completed. By using the NLFC method it was concluded that SSNR of B-mode and backscattered energy images, SNR of <i>h</i>CBE maps, and temperature map agreement with a theoretical COMSOL based model were improved over the previously used NLSF method.</div>


2021 ◽  
Vol 8 ◽  
Author(s):  
Claire Conway ◽  
Farhad R. Nezami ◽  
Campbell Rogers ◽  
Adam Groothuis ◽  
James C. Squire ◽  
...  

Recent concern for local drug delivery and withdrawal of the first Food and Drug Administration-approved bioresorbable scaffold emphasizes the need to optimize the relationships between stent design and drug release with imposed arterial injury and observed pharmacodynamics. In this study, we examine the hypothesis that vascular injury is predictable from stent design and that the expanding force of stent deployment results in increased circumferential stress in the arterial tissue, which may explain acute injury poststent deployment. Using both numerical simulations and ex vivo experiments on three different stent designs (slotted tube, corrugated ring, and delta wing), arterial injury due to device deployment was examined. Furthermore, using numerical simulations, the consequence of changing stent strut radial thickness on arterial wall shear stress and arterial circumferential stress distributions was examined. Regions with predicted arterial circumferential stress exceeding a threshold of 49.5 kPa compared favorably with observed ex vivo endothelial denudation for the three considered stent designs. In addition, increasing strut thickness was predicted to result in more areas of denudation and larger areas exposed to low wall shear stress. We conclude that the acute arterial injury, observed immediately following stent expansion, is caused by high circumferential hoop stresses in the interstrut region, and denuded area profiles are dependent on unit cell geometric features. Such findings when coupled with where drugs move might explain the drug–device interactions.


2021 ◽  
Author(s):  
Wen-Wen Zhang ◽  
Rong-Pei Zhang ◽  
Ya-Jun Liu ◽  
Zi-Fang He ◽  
Si Zhang ◽  
...  

Abstract Purpose: To investigate the role of distilled water (DW) in isolated human lens epithelial cells (LECs) viability and lysis ex vivo.Methods: After immersion in DW or balanced salt solution (BSS) for 1-, 2-, and 3-minutes, respectively, the cell viability of LECs was quantitatively evaluated. In addition, the capsule samples soaked in DW or BSS for 1-, 2-, and 3-minutes were combined with rinse for 1 minute to analyze the difference of LECs shedding percentage in each subgroup. The histopathological changes of the samples after treating were observed.Results: The percentage of LECs shed in DW immersion combined with rinse was significantly higher than in DW immersion alone (p all <0.001). In the subgroup soaked in DW for 3 minutes, the death number, mortality, and the percentage of cell shedding of LECs was the most (p all <0.001). The histopathological changes showed that the cell destruction in the DW subgroup for 1-, 2-, and 3-minutes, and the transmission electron microscope results showed that the cells were partially detached from the capsule in the DW 3 minutes subgroup.Conclusions: Soaking in the DW can cause LECs death, and DW immersion combined with rinse was an effective method to remove LECs. The histopathology changes of treated DW suggested cellular necrosis was one type of LECs death mechanism.


Author(s):  
Mari C. Mañas-Torres ◽  
Cristina Gila-Vilchez ◽  
Francisco J. Vazquez-Perez ◽  
Pavel Kuzhir ◽  
David Momier ◽  
...  

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Lorna B. Jarvis ◽  
Daniel B. Rainbow ◽  
Valerie Coppard ◽  
Sarah K. Howlett ◽  
Zoya Georgieva ◽  
...  

AbstractThe adoptive transfer of regulatory T-cells (Tregs) is a promising therapeutic approach in transplantation and autoimmunity. However, because large cell numbers are needed to achieve a therapeutic effect, in vitro expansion is required. By comparing their function, phenotype and transcriptomic profile against ex vivo Tregs, we demonstrate that expanded human Tregs switch their metabolism to aerobic glycolysis and show enhanced suppressive function through hypoxia-inducible factor 1-alpha (HIF1A) driven acquisition of CD73 expression. In conjunction with CD39, CD73 expression enables expanded Tregs to convert ATP to immunosuppressive adenosine. We conclude that for maximum therapeutic benefit, Treg expansion protocols should be optimised for CD39/CD73 co-expression.


Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5155
Author(s):  
Luca Digiacomo ◽  
Erica Quagliarini ◽  
Vincenzo La Vaccara ◽  
Alessandro Coppola ◽  
Roberto Coppola ◽  
...  

Pancreatic Ductal Adeno Carcinoma (PDAC) is one of the most lethal malignancies worldwide, and the development of sensitive and specific technologies for its early diagnosis is vital to reduce morbidity and mortality rates. In this proof-of-concept study, we demonstrate the diagnostic ability of magnetic levitation (MagLev) to detect PDAC by using levitation of graphene oxide (GO) nanoparticles (NPs) decorated by a biomolecular corona of human plasma proteins collected from PDAC and non-oncological patients (NOP). Levitation profiles of corona-coated GO NPs injected in a MagLev device filled with a paramagnetic solution of dysprosium(III) nitrate hydrate in water enables to distinguish PDAC patients from NOP with 80% specificity, 100% sensitivity, and global classification accuracy of 90%. Our findings indicate that Maglev could be a robust and instrumental tool for the early detection of PDAC and other cancers.


Author(s):  
Eissa Alfadil ◽  
Frank Bradke ◽  
Sebastian Dupraz

2021 ◽  
Vol 4 (4) ◽  
pp. 74
Author(s):  
Molly Yao ◽  
Samayita Ganguly ◽  
Jane Hae Soo Shin ◽  
Tamer Elbayoumi

Homeostasis of vascular tone is intricately and delicately maintained systemically and locally, by autonomic nerves and hormones in the blood and by intimal vasoactive substances, respectively. The balance can be acutely or chronically interrupted secondary to many alterations, especially under pathological conditions. Excessive matricellular glycoprotein thrombospondin 1 (TSP1) levels in circulation have been found to play an important role in ischemia-reperfusion injuries of different organs, by acutely suppressing vasorelaxation and chronically remodeling vascular bed. Our laboratory has been interested in identifying new drug moieties, which can selectively and effectively counteract TSP1-induced vascular dysfunction, in order to address associated clinical complications. Preliminary studies using computational docking and molecular models revealed potential drug candidates for further evaluation via vascular functional bioassay to prove the antagonism using an ex vivo vascular model. Herein, we described an efficient screening method for the identification of active drug candidates, by adapting a multiwire myograph system to perform a protocol with different treatments, in the presence of pathological levels of TSP1. We discussed the promising pharmacological evaluation results and suggested suitable modification for versatile applications. We also described the necessity of pre-determination of optimal resting tension to obtain the maximal response, if the experimental test model is different from those with determined optimal resting tension.


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