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1.
J Neurosci ; 43(34): 5989-5995, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612141

RESUMEN

The brain is a complex system comprising a myriad of interacting neurons, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such interconnected systems, offering a framework for integrating multiscale data and complexity. To date, network methods have significantly advanced functional imaging studies of the human brain and have facilitated the development of control theory-based applications for directing brain activity. Here, we discuss emerging frontiers for network neuroscience in the brain atlas era, addressing the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease. We underscore the importance of fostering interdisciplinary opportunities through workshops, conferences, and funding initiatives, such as supporting students and postdoctoral fellows with interests in both disciplines. By bringing together the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way toward a deeper understanding of the brain and its functions, as well as offering new challenges for network science.


Asunto(s)
Neurociencias , Humanos , Encéfalo , Impulso (Psicología) , Neuronas , Investigadores
2.
Medicina (Kaunas) ; 58(1)2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-35056374

RESUMEN

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Acute exacerbations (AECOPD) are common and often triggered by viral infection. During the COVID-19 pandemic social restrictions, including 'shielding' and 'lockdowns', were mandated. Multiple, worldwide studies report a reduction in AECOPD admissions during this period. This study aims to assess the effect of the pandemic and Lockdown on the rates of admission with AECOPD and severity of hospitalised exacerbations in the North-East of England. Materials and Methods: Data were extracted for patients presenting with a diagnosis of AECOPD or respiratory failure secondary to AECOPD during the 'COVID-19 period' (26/3/20-31/12/20) and a date-matched control period from the year previous. We present descriptive statistics and regression analysis of the effects of the COVID-19 period on the rates of hospital admission. Results: Compared to the matched control period, the COVID-19 period was associated with fewer AECOPD admissions (COVID-19 = 719, control = 1257; rate ratio 0.57, p < 0.001) and shorter length of stay (COVID-19 = 3.9 ± 0.2, control = 4.78 ± 0.2 days; p = 0.002), with similar in-hospital plus 30-day post-discharge mortality. Demographics were similar between periods. Only six patients had a positive COVID-19 PCR test. Conclusion: During the COVID-19 period there was a substantial reduction in AECOPD admissions, but no increase in overall severity of exacerbations or mortality. Rather than fear driving delayed hospital presentation, physical and behavioural measures taken during this period to limit transmission of COVID-19 are likely to have reduced transmission of other respiratory viruses. This has important implications for control of future AECOPD.


Asunto(s)
COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Cuidados Posteriores , Control de Enfermedades Transmisibles , Hospitales , Humanos , Pandemias , Alta del Paciente , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , SARS-CoV-2
3.
Inorg Chem ; 58(23): 15801-15811, 2019 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-31714068

RESUMEN

O2 activation at nonheme iron centers is a common motif in biological systems. While synthetic models have provided numerous insights into the reactivity of high-valent iron-oxo complexes related to biological processes, the majority of these complexes are synthesized using alternative oxidants. This report describes O2 activation by an iron(II)-triflate complex of the imino-functionalized tris(pyrrol-2-ylmethyl)amine ligand framework, H3[N(piCy)3]. Initial reaction conditions result in the formation of a mixture of oxidation products including terminal iron(III)-oxo and iron(III)-hydroxo complexes. The relevance of these species to the O2 activation process is demonstrated through reactivity studies and electrochemical analysis of the iron(III)-oxo complex.

4.
J Acoust Soc Am ; 146(2): EL158, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31472567

RESUMEN

Characterization of ultrasound fields is a routine procedure for both diagnostic and therapeutic ultrasound. Quantitative field mapping with a calibrated hydrophone and multi-axis positioning system can be difficult and time consuming. In this study, the use of acoustic cavitation field mapping as a qualitative surrogate to acoustic pressure field mapping, albeit without acoustic pressure values is demonstrated. This technique allows for fast qualitative mapping of ultrasound fields and thereby functionality of the corresponding transducers, in a matter of seconds. In addition, this technique could be used to rapidly image in vivo acoustic cavitation fields during therapeutic ultrasound applications.


Asunto(s)
Ultrasonografía/métodos , Medios de Contraste , Microburbujas , Transductores , Ondas Ultrasónicas , Ultrasonografía/instrumentación
5.
J Am Chem Soc ; 140(6): 2093-2104, 2018 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-29369622

RESUMEN

Redox active polymers (RAPs) are electrochemically versatile materials that find key applications in energy storage, sensing, and surface modification. In spite of the ubiquity of RAP-modified electrodes, a critical knowledge gap exists in the understanding of the electrochemistry of soluble RAPs and their relation to polyelectrolyte dynamics. Here, we explore for the first time the intersection between polyelectrolyte behavior and the electrochemical response that highly soluble and highly substituted RAPs with viologen, ferrocene, and nitrostyrene moieties elicit at electrodes. This comprehensive study of RAP electrolytes over several orders of magnitude in concentration and ionic strength reveals distinct signatures consistent with surface confined, colloidal, and bulk-like electrochemical behavior. These differences emerge across polyelectrolyte packing regimes and are strongly modulated by changes in RAP coil size and electrostatic interactions with the electrode. We found that, unlike monomer motifs, simple changes in the ionic strength caused variations over 1 order of magnitude in the current measured at the electrode. In addition, the thermodynamics of adsorbed RAP films were also affected, giving rise to standard reduction potential shifts leading to redox kinetic effects as a result of the mediating nature of the RAP film in equilibrium with the solution. Full electrochemical characterization via transient and steady-state techniques, including the use of ultramicroelectrodes and the rotating disk electrode, were correlated to dynamic light scattering, ellipsometry, and viscometric analysis. These methods helped elucidate the relationship between electrochemical behavior and RAP coil size, film thickness, and polyelectrolyte packing regime. This study underscores the role of electrostatics in modulating the reactivity of redox polyelectrolytes.

6.
BMC Cancer ; 18(1): 1284, 2018 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-30577821

RESUMEN

BACKGROUND: Cisplatin has been widely used for the treatment of cancer and its antitumour activity is attributed to its capacity to form DNA adducts, predominantly at guanine residues, which impede cellular processes such as DNA replication and transcription. However, there are associated toxicity and drug resistance issues which plague its use. This has prompted the development and screening of a range of chemotherapeutic drug analogues towards improved efficacy. The biological properties of three novel platinum-based compounds consisting of varying cis-configured ligand groups, as well as a commercially supplied compound, were characterised in this study to determine their potential as anticancer agents. METHODS: The linear amplification reaction was employed, in conjunction with capillary electrophoresis, to quantify the sequence specificity of DNA adducts induced by these compounds using a DNA template containing telomeric repeat sequences. Additionally, the DNA interstrand cross-linking and unwinding efficiency of these compounds were assessed through the application of denaturing and native agarose gel electrophoresis techniques, respectively. Their cytotoxicity was determined in HeLa cells using a colorimetric cell viability assay. RESULTS: All three novel platinum-based compounds were found to induce DNA adduct formation at the tandem telomeric repeat sequences. The sequence specificity profile at these sites was characterised and these were distinct from that of cisplatin. Two of these compounds with the enantiomeric 1,2-diaminocyclopentane ligand (SS and RR-DACP) were found to induce a greater degree of DNA unwinding than cisplatin, but exhibited marginally lower DNA cross-linking efficiencies. Furthermore, the RR-isomer was more cytotoxic in HeLa cells than cisplatin. CONCLUSIONS: The biological characteristics of these compounds were assessed relative to cisplatin, and a variation in the sequence specificity and a greater capacity to induce DNA unwinding was observed. These compounds warrant further investigations towards developing more efficient chemotherapeutic drugs.


Asunto(s)
Aductos de ADN/efectos de los fármacos , ADN/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Compuestos Organoplatinos/química , Cisplatino/análogos & derivados , Cisplatino/química , Cisplatino/uso terapéutico , Reactivos de Enlaces Cruzados , ADN/química , Daño del ADN/efectos de los fármacos , Células HeLa , Humanos , Conformación de Ácido Nucleico/efectos de los fármacos , Compuestos Organoplatinos/uso terapéutico , Platino (Metal)/química , Platino (Metal)/uso terapéutico , Estereoisomerismo
7.
Emerg Med J ; 35(9): 532-537, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29794121

RESUMEN

INTRODUCTION: Prehospital emergency anaesthesia (PHEA or 'prehospital rapid sequence intubation') is a high-risk procedure. Standard operating procedures (SOPs) and checklists within healthcare systems have been demonstrated to reduce human error and improve patient safety. We aimed to describe the current practice of PHEA in the UK, determine the use of checklists for PHEA and describe the content, format and layout of any such checklists currently used in the UK. METHOD: A survey of UK prehospital teams was conducted to establish the incidence and conduct of PHEA practice. Results were grouped into systems delivering a high volume of PHEA per year (>50 PHEAs) and low volume (≤50 PHEAs per annum). Standard and 'crash' (immediate) induction checklists were reviewed for length, content and layout. RESULTS: 59 UK physician-led prehospital services were identified of which 43 (74%) participated. Thirty services (70%) provide PHEA and perform approximately 1629 PHEAs annually. Ten 'high volume' services deliver 84% of PHEAs per year with PHEA being performed on a median of 11% of active missions. The most common indication for PHEA was trauma. 25 of the 30 services (83%) used a PHEA checklist prior to induction of anaesthesia and 24 (80%) had an SOP for the procedure. 19 (76%) of the 'standard' checklists and 5 (50%) of the 'crash' induction checklists used were analysed. On average, standard checklists contained 169 (range: 52-286) words and 41 (range: 28-70) individual checks. The style and language complexity varied significantly between different checklists. CONCLUSION: PHEA is now performed commonly in the UK. The use of checklists for PHEA is relatively common among prehospital systems delivering this intervention. Care must be taken to limit checklist length and to use simple, unambiguous language in order to maximise the safety of this high-risk intervention.


Asunto(s)
Anestesia/métodos , Servicios Médicos de Urgencia/métodos , Anestesia/normas , Anestesiología , Lista de Verificación/métodos , Servicios Médicos de Urgencia/tendencias , Humanos , Intubación Intratraqueal/métodos , Intubación Intratraqueal/normas , Estándares de Referencia , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Reino Unido
8.
Acc Chem Res ; 49(11): 2649-2657, 2016 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-27673336

RESUMEN

It is an exciting time for exploring the synergism between the chemical and dimensional properties of redox nanomaterials for addressing the manifold performance demands faced by energy storage technologies. The call for widespread adoption of alternative energy sources requires the combination of emerging chemical concepts with redesigned battery formats. Our groups are interested in the development and implementation of a new strategy for nonaqueous flow batteries (NRFBs) for grid energy storage. Our motivation is to solve major challenges in NRFBs, such as the lack of membranes that simultaneously allow fast ion transport while minimizing redox active species crossover between anolyte (negative electrolyte) and catholyte (positive electrolyte) compartments. This pervasive crossover leads to deleterious capacity fade and materials underutilization. In this Account, we highlight redox active polymers (RAPs) and related polymer colloids as soluble nanoscopic energy storing units that enable the simple but powerful size-exclusion concept for NRFBs. Crossover of the redox component is suppressed by matching high molecular weight RAPs with simple and inexpensive nanoporous commercial separators. In contrast to the vast literature on the redox chemistry of electrode-confined polymer films, studies on the electrochemistry of solubilized RAPs are incipient. This is due in part to challenges in finding suitable solvents that enable systematic studies on high polymers. Here, viologen-, ferrocene- and nitrostyrene-based polymers in various formats exhibit properties that make amenable their electrochemical exploration as solution-phase redox couples. A main finding is that RAP solutions store energy efficiently and reversibly while offering chemical modularity and size versatility. Beyond the practicality toward their use in NRFBs, the fundamental electrochemistry exhibited by RAPs is fascinating, showing clear distinctions in behavior from that of small molecules. Whereas RAPs conveniently translate the redox properties of small molecules into a nanostructure, they give rise to charge transfer mechanisms and electrolyte interactions that elicit distinct electrochemical responses. To understand how the electrochemical characteristics of RAPs depend on molecular features, including redox moiety, macromolecular size, and backbone structure, a range of techniques has been employed by our groups, including voltammetry at macro- and microelectrodes, rotating disk electrode voltammetry, bulk electrolysis, and scanning electrochemical microscopy. RAPs rely on three-dimensional charge transfer within their inner bulk, which is an efficient process and allows quantitative electrolysis of particles of up to ∼800 nm in radius. Interestingly, we find that interactions between neighboring pendants create unique opportunities for fine-tuning their electrochemical reactivity. Furthermore, RAP interrogation toward the single particle limit promises to shed light on fundamental charge storage mechanisms.

9.
J Am Chem Soc ; 138(40): 13230-13237, 2016 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-27629363

RESUMEN

Versatile and readily available battery materials compatible with a range of electrode configurations and cell designs are desirable for renewable energy storage. Here we report a promising class of materials based on redox active colloids (RACs) that are inherently modular in their design and overcome challenges faced by small-molecule organic materials for battery applications, such as crossover and chemical/morphological stability. RACs are cross-linked polymer spheres, synthesized with uniform diameters between 80 and 800 nm, and exhibit reversible redox activity as single particles, as monolayer films, and in the form of flowable dispersions. Viologen-based RACs display reversible cycling, accessing up to 99% of their capacity and 99 ± 1% Coulombic efficiency over 50 cycles by bulk electrolysis owing to efficient, long-distance intraparticle charge transfer. Ferrocene-based RACs paired with viologen-based RACs cycled efficiently in a nonaqueous redox flow battery employing a simple size-selective separator, thus demonstrating a possible application that benefits from their colloidal dimensions. The unprecedented versatility in RAC synthetic and electrochemical design opens new avenues for energy storage.

10.
Analyst ; 141(12): 3842-50, 2016 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-27064026

RESUMEN

Elucidating the impact of interactions between the electrolyte and electroactive species in redox active polymers is key to designing better-performing electrodes for electrochemical energy storage and conversion. Here, we present on the improvement of the electrochemical activity of poly(para-nitrostyrene) (PNS) in solution and as a film by exploiting the ionic interactions between reduced PNS and K(+), which showed increased reactivity when compared to tetrabutylammonium (TBA(+))- and Li(+)-containing electrolytes. While cyclic voltammetry enabled the study of the effects of cations on the electrochemical reversibility and the reduction potential of PNS, scanning electrochemical microscopy (SECM) provided new tools to probe the ionic and redox reactivity of this system. Using an ion-sensitive Hg SECM tip allowed to probe the ingress of ions into PNS redox active films, while surface interrogation SECM (SI-SECM) measured the specific kinetics of PNS and a solution phase mediator in the presence of the tested electrolytes. SI-SECM measurements illustrated that the interrogation kinetics of PNS in the presence of K(+) compared to TBA(+) and Li(+) are greatly enhanced under the same surface concentration of adsorbed radical anion, exhibiting up to a 40-fold change in redox kinetics. We foresee using this new application of SECM methods for elucidating optimal interactions that enhance polymer reactivity for applications in redox flow batteries.

11.
J Med Entomol ; 53(1): 152-6, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26545717

RESUMEN

Nit combing and removal of head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae), eggs is a task made more difficult because "nit combs" vary in efficiency. There is currently no evidence that the binding of the eggshell to the hair can be loosened chemically and few hair treatments improve the slip of the louse eggs along the hair. Ultrasound, applied through the teeth of a nit comb, may facilitate the flow of fluids into the gap between the hair shaft and the tube of fixative holding louse eggs in place to improve lubrication. Ultrasound alone had little effect to initiate sliding, requiring a force of 121.5 ± 23.8 millinewtons (mN) compared with 125.8 ± 18.0 mN without ultrasound, but once the egg started to move it made the process easier. In the presence of a conditioner-like creamy lotion, ultrasound reduced the Peak force required to start movement to 24.3 ± 8.8 mN from 50.4 ± 13.0 mN without ultrasound. In contrast, some head louse treatments made removal of eggs more difficult, requiring approximately twice the Peak force to initiate movement compared with dry hair in the absence of ultrasound. However, following application of ultrasound, the forces required to initiate movement increased for an essential oil product, remained the same for isopropyl myristate and cyclomethicone, and halved for 4% dimeticone lotion. Fixing the nit comb at an estimated angle of 16.5° to the direction of pull gave an optimum effect to improve the removal process when a suitable lubricant was used.


Asunto(s)
Infestaciones por Piojos/terapia , Pediculus , Dermatosis del Cuero Cabelludo/terapia , Terapia por Ultrasonido , Animales , Óvulo
12.
Analyst ; 140(10): 3630-41, 2015 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-25869990

RESUMEN

To operate an ion-sensitive field-effect transistor (ISFETs) it is necessary to set the electrolyte potential using a reference electrode. Conventional reference electrodes are bulky, fragile, and too big for applications where the electrolyte volume is small. Several researchers have proposed tackling this issue using a solid-state planar micro-reference electrode or a reference field-effect transistor. However, these approaches are limited by poor robustness, high cost, or complex integration with other microfabrication processes. Here we report a simple method to create robust on-chip quasi-reference electrodes by electrodepositing polypyrrole on micro-patterned metal leads. The electrodes were fabricated through the polymerization of pyrrole on patterned metals with a cyclic voltammetry process. Open circuit potential measurements were performed to characterize the polypyrrole electrode performance, demonstrating good stability (±1 mV), low drift (∼1 mV h(-1)), and reduced pH response (5 mV per pH). In addition, the polypyrrole deposition was repeated in microelectrodes made of different metals to test compatibility with standard complementary metal-oxide-semiconductor (CMOS) processes. Our results suggest that nickel, a metal commonly used in semiconductor foundries for silicide formation, is a good candidate to form the polypyrrole quasi-reference electrodes. Finally, the polypyrrole microelectrodes were used to operate foundry fabricated ISFETs. These experiments demonstrated that transistors biased with polypyrrole electrodes have pH sensitivity and resolution comparable to ones that are biased with standard reference electrodes. Therefore, the simple fabrication, high compatibility, and robust electrical performance make polypyrrole an ideal choice for the fabrication of outstanding microreference electrodes that enable robust and sensitive operation of multiple ISFET sensors on a chip.


Asunto(s)
Dispositivos Laboratorio en un Chip , Metales/química , Polímeros/química , Pirroles/química , Transistores Electrónicos , Concentración de Iones de Hidrógeno , Microelectrodos
13.
PeerJ ; 11: e16001, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37701830

RESUMEN

Following school closures and changes in contact behavior of children and adults a reduced head louse prevalence has been reported from across the globe. In parallel, sales of treatments were observed to fall, partly because of supply problems of some products following the pandemic, but this did not appear to result in more cases of infestation. Surveys of schools in and around Cambridge, UK, found that infestation rates were significantly reduced particularly in city schools compared with similar surveys conducted before the COVID-19 pandemic. Contrary to expectation the number of cases in schools has only risen slowly since schools returned to normal full time working in 2022-2023.


Asunto(s)
COVID-19 , Infestaciones por Piojos , Pediculus , Adulto , Niño , Animales , Humanos , Pandemias/prevención & control , Prevalencia , COVID-19/epidemiología , Infestaciones por Piojos/epidemiología , Reino Unido/epidemiología
14.
Mol Oncol ; 17(10): 1947-1949, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37766480

RESUMEN

A breakthrough study from Du et al. has developed a wearable, ultrasound imaging patch for standardized and reproducible breast tissue imaging. The technology utilizes a honeycomb patch design to facilitate guided movement of the ultrasound array, enabling comprehensive, multiangle breast imaging. The system was validated in vitro and in vivo with a single human subject and has the potential for early-stage breast cancer detection. This study addressed the current limitations of wearable ultrasound technologies, including imaging over large, curvilinear organs and integration of superior piezoelectric materials for high-performance ultrasound arrays. The transition of ultrasound from the bedside to portable and wearable devices will pave the way for integration with big data collection, such as artificial intelligence (AI)-based diagnosis and personalized ultrasonographic profile generation, for rapid and objective measurements. This advancement is especially important in the context of breast cancer, where early diagnosis and assessment of medical therapy responses are paramount to patient care.


Asunto(s)
Neoplasias de la Mama , Dispositivos Electrónicos Vestibles , Humanos , Femenino , Inteligencia Artificial , Diagnóstico por Imagen , Ultrasonografía , Neoplasias de la Mama/diagnóstico por imagen
15.
mBio ; : e0254723, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37962347

RESUMEN

IMPORTANCE: Malaria is a devastating disease that has claimed many lives, especially children <5 years of age in Sub-Saharan Africa, as documented in World Malaria Reports by WHO. Even though vector control and chemoprevention tools have helped with elimination efforts in some, if not all, endemic areas, these efforts have been hampered by serious issues (including drug and insecticide resistance and disruption to social cohesion caused by the COVID-19 pandemic). Development of an effective malaria vaccine is the alternative preventative tool in the fight against malaria. Vaccines save millions of lives each year and have helped in elimination and/or eradication of global diseases. Development of a highly efficacious malaria vaccine that will ensure long-lasting protective immunity will be a "game-changing" prevention strategy to finally eradicate the disease. Such a vaccine will need to counteract the significant obstacles that have been hampering subunit vaccine development to date, including antigenic polymorphism, sub-optimal immunogenicity, and waning vaccine efficacy.

16.
ArXiv ; 2023 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-37214134

RESUMEN

The brain is a complex system comprising a myriad of interacting elements, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such intricate systems, offering a framework for integrating multiscale data and complexity. Here, we discuss the application of network science in the study of the brain, addressing topics such as network models and metrics, the connectome, and the role of dynamics in neural networks. We explore the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease, and discuss the potential for collaboration between network science and neuroscience communities. We underscore the importance of fostering interdisciplinary opportunities through funding initiatives, workshops, and conferences, as well as supporting students and postdoctoral fellows with interests in both disciplines. By uniting the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way towards a deeper understanding of the brain and its functions.

17.
J Acoust Soc Am ; 132(1): 544-53, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22779500

RESUMEN

Previously, passive cavitation imaging has been described in the context of continuous-wave high-intensity focused ultrasound thermal ablation. However, the technique has potential use as a feedback mechanism for pulsed-wave therapies, such as ultrasound-mediated drug delivery. In this paper, results of experiments and simulations are reported to demonstrate the feasibility of passive cavitation imaging using pulsed ultrasound insonations and how the images depend on pulsed ultrasound parameters. The passive cavitation images were formed from channel data that was beamformed in the frequency domain. Experiments were performed in an invitro flow phantom with an experimental echo contrast agent, echogenic liposomes, as cavitation nuclei. It was found that the pulse duration and envelope have minimal impact on the image resolution achieved. The passive cavitation image amplitude scales linearly with the cavitation emission energy. Cavitation images for both stable and inertial cavitation can be obtained from the same received data set.


Asunto(s)
Hígado/fisiología , Ultrasonido/métodos , Animales , Masculino , Fantasmas de Imagen , Conejos , Dispersión de Radiación , Espectrografía del Sonido , Transductores de Presión
18.
Ultrasound Med Biol ; 48(5): 743-759, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35125244

RESUMEN

Ultrasound localization microscopy (ULM) is an emerging, super-resolution imaging technique for detailed mapping of the microvascular structure and flow velocity via subwavelength localization and tracking of microbubbles. Because microbubbles rely on blood flow for movement throughout the vascular space, acquisition times can be long in the smallest, low-flow microvessels. In addition, detection of microbubbles in low-flow regions can be difficult because of minimal separation of microbubble signal from tissue. Nanoscale, phase-change contrast agents (PCCAs) have emerged as a switchable, intermittent or persisting contrast agent for ULM via acoustic droplet vaporization (ADV). Here, the focus is on characterizing the spatiotemporal contrast properties of less volatile perfluoropentane (PFP) PCCAs. The results indicate that at physiological temperature, nanoscale PFP PCCAs with diameters less than 100 nm disappear within microseconds after ADV with high-frequency ultrasound (16 MHz, 5- to 6-MPa peak negative pressure) and that nanoscale PFP PCCAs have an inherent deactivation mechanism via immediate recondensation after ADV. This "blinking" on-and-off contrast signal allowed separation of flow in an in vitro flow phantom, regardless of flow conditions, although with a need for some replenishment at very low flow conditions to maintain count rate. This blinking behavior allows for rapid spatial mapping in areas of low or no flow with ULM, but limits velocity tracking because there is no stable bubble formation with nanoscale PFP PCCAs.


Asunto(s)
Fluorocarburos , Microscopía , Medios de Contraste/química , Fluorocarburos/química , Microburbujas , Ultrasonografía/métodos
19.
Artículo en Inglés | MEDLINE | ID: mdl-35020595

RESUMEN

Elevated intraocular pressure (IOP) is the most prevalent risk factor for initiation and progression of neurodegeneration in glaucoma. Ocular hypertension results from increased resistance to aqueous fluid outflow caused by reduced porosity and increased stiffness of tissues of the outflow pathway. Acoustic activation and resulting bioeffects of the perfluorocarbon (PFC) nanodroplets (NDs) introduced into the anterior chamber (AC) of the eye could potentially represent a treatment for glaucoma by increasing permeability in the aqueous outflow track. To evaluate the potential of NDs to enter the outflow track, 100-nm diameter perfluoropentane (PFP) NDs with a lipid shell were injected into the AC of ex vivo pig eyes and in vivo rat eyes. The NDs were activated and imaged with 18- and 28-MHz linear arrays to assess their location and diffusion. NDs in the AC could also be visualized using optical coherence tomography (OCT). Because of their higher density with respect to aqueous humor, some NDs settled into the iridocorneal angle where they entered the outflow pathway. After acoustic activation of the NDs at the highest acoustic pressure, small gas bubbles were observed in the AC. After two days, no acoustic activation events were visible in the AC of the rats and their eyes showed no evidence of inflammation.


Asunto(s)
Fluorocarburos , Glaucoma , Animales , Humor Acuoso/metabolismo , Glaucoma/diagnóstico por imagen , Glaucoma/metabolismo , Presión Intraocular , Ratas , Porcinos , Ultrasonografía
20.
J Control Release ; 337: 458-471, 2021 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-34324895

RESUMEN

Focused ultrasound (FUS) in combination with systemically injected microbubbles can be used to non-invasively open the blood-brain barrier (BBB) in targeted regions for a variety of therapeutic applications. Over the past two decades, preclinical research into the safety and efficacy of FUS-induced BBB opening has proven this technique to be transient and efficacious, propelling FUS-induced BBB opening into several clinical trials in recent years. However, as clinical trials further progress, the neuroinflammatory response to FUS-induced BBB opening needs to be better understood. In this study, we provide further insight into the relationship of microbubble cavitation and the resulting innate immune response to FUS-induced BBB opening. By keeping ultrasound parameters fixed (i.e. frequency, pressure, pulse length, etc.), three groups of mice were sonicated using a real-time cavitation controller until a target cavitation dose was reached (1 x 107 V2•s, 5 x 107 V2•s, 1 x 108 V2•s). The change in relative gene expression of the mouse inflammatory cytokines and receptors were evaluated at three different time-points (6 h, 24 h, and 72 h) after FUS. At both 6 and 24 h time-points, significant changes in relative gene expression of inflammatory cytokines and receptors were observed across all cavitation groups. However, the degree of changes in relative expression levels and the number of genes with significant changes in expression varied across the cavitation groups. Groups with a higher cavitation dose exhibited both greater changes in relative expression levels and greater number of significant changes. By 72 h post-opening, the gene expression levels returned to baseline in all cavitation dose groups, signifying a transient inflammatory response to FUS-induced BBB opening at the targeted cavitation dose levels. Furthermore, the real-time cavitation controller was able to produce consistent and significantly different BBB permeability enhancement volumes across the three different cavitation dose groups. These results indicate that cavitation monitoring and controlling during FUS-induced BBB opening can be used to potentially modulate or limit the degree of neuroinflammation, further emphasizing the importance of implementing cavitation controllers as FUS-induced BBB opening is translated into the clinic.


Asunto(s)
Barrera Hematoencefálica , Inflamación , Sonicación/métodos , Animales , Sistemas de Liberación de Medicamentos , Imagen por Resonancia Magnética , Ratones , Microburbujas , Permeabilidad , Sonicación/efectos adversos
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