Photoacoustic imaging for microcirculation Mirg, Shubham; Turner, Kevin L.; Chen, Haoyang ...
Microcirculation (New York, N.Y. 1994),
October 2022, Letnik:
29, Številka:
6-7
Journal Article
Recenzirano
Odprti dostop
Microcirculation facilitates the blood‐tissue exchange of nutrients and regulates blood perfusion. It is, therefore, essential in maintaining tissue health. Aberrations in microcirculation are ...potentially indicative of underlying cardiovascular and metabolic pathologies. Thus, quantitative information about it is of great clinical relevance. Photoacoustic imaging (PAI) is a capable technique that relies on the generation of imaging contrast via the absorption of light and can image at micron‐scale resolution. PAI is especially desirable to map microvasculature as hemoglobin strongly absorbs light and can generate a photoacoustic signal. This paper reviews the current state of the art for imaging microvascular networks using photoacoustic imaging. We further describe how quantitative information about blood dynamics such as the total hemoglobin concentration, oxygen saturation, and blood flow rate is obtained using PAI. We also discuss its importance in understanding key pathophysiological processes in neurovascular, cardiovascular, ophthalmic, and cancer research fields. We then discuss the current challenges and limitations of PAI and the approaches that can help overcome these limitations. Finally, we provide the reader with an overview of future trends in the field of PAI for imaging microcirculation.
Infection with virulent strains of classical swine fever virus (CSFV) results in an acute haemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopenia and ...immunosuppression, whereas for less virulent isolates infection can become chronic. In view of the haemorrhagic pathology of the disease, the effects of the virus on vascular endothelial cells was studied by using relative quantitative PCR and ELISA. Following infection, there was an initial and short-lived increase in the transcript levels of the proinflammatory cytokines interleukins 1, 6 and 8 at 3 h followed by a second more sustained increase 24 h post-infection. Transcription levels for the coagulation factor, tissue factor and vascular endothelial cell growth factor involved in endothelial cell permeability were also increased. Increases in these factors correlated with activation of the transcription factor NF-kappaB. Interestingly, the virus produced a chronic infection of endothelial cells and infected cells were unable to produce type I interferon. Infected cells were also protected from apoptosis induced by synthetic ouble-stranded RNA. These results demonstrate that, in common with the related pestivirus bovine viral diarrhoea virus, CSFV can actively block anti-viral and apoptotic responses and this may contribute to virus persistence. They also point to a central role for infection of vascular endothelial cells during the pathogenesis of the disease, where a proinflammatory and procoagulant endothelium induced by the virus may disrupt the haemostatic balance and lead to the coagulation and thrombosis seen in acute disease.
Over 20 species of asteroids were devastated by a sea star wasting disease (SSWD) epizootic, linked to a densovirus, from Mexico to Alaska in 2013 and 2014. For Pisaster ochraceus from the San Juan ...Islands, South Puget Sound and Washington outer coast, time-series monitoring showed rapid disease spread, high mortality rates in 2014, and continuing levels of wasting in the survivors in 2015. Peak prevalence of disease at 16 sites ranged to 100%, with an overall mean of 61%. Analysis of longitudinal data showed disease risk was correlated with both size and temperature and resulted in shifts in population size structure; adult populations fell to one quarter of pre-outbreak abundances. In laboratory experiments, time between development of disease signs and death was influenced by temperature in adults but not juveniles and adult mortality was 18% higher in the 19°C treatment compared to the lower temperature treatments. While larger ochre stars developed disease signs sooner than juveniles, diseased juveniles died more quickly than diseased adults. Unusual 2–3°C warm temperature anomalies were coincident with the summer 2014 mortalities. We suggest these warm waters could have increased the disease progression and mortality rates of SSWD in Washington State.
We present multipoint observations of earthward moving dipolarization fronts and energetic particle injections from NASAs Magnetospheric Multiscale mission with a focus on electron acceleration. From ...a case study during a substorm on 02 August 2015, we find that electrons are only accelerated over a finite energy range, from a lower energy threshold at approx. 7-9 keV up to an upper energy cutoff in the hundreds of keV range. At energies lower than the threshold energy, electron fluxes decrease, potentially due to precipitation by strong parallel electrostatic wavefields or initial sources in the lobes. Electrons at energies higher than the threshold are accelerated cumulatively by a series of impulsive magnetic dipolarization events. This case demonstrates how the upper energy cutoff increases, in this case from approx. 130 keV to >500 keV, with each depolarization/injection during sustained activity. We also present a simple model accounting for these energy limits that reveals that electron energization is dominated by betatron acceleration.
Hot Flow Anomalies (HFAs) are transients observed at planetary bow shocks, formed by the shock interaction with a convected interplanetary current sheet. The primary interpretation relies on ...reflected ions channeled upstream along the current sheet. The short duration of HFAs has made direct observations of this process difficult. We employ high resolution measurements by NASA's Magnetospheric Multiscale Mission to probe the ion microphysics within a HFA. Magnetospheric Multiscale Mission data reveal a smoothly varying internal density and pressure, which increase toward the trailing edge of the HFA, sweeping up particles trapped within the current sheet. We find remnants of reflected or other backstreaming ions traveling along the current sheet, but most of these are not fast enough to out‐run the incident current sheet convection. Despite the high level of internal turbulence, incident and backstreaming ions appear to couple gyro‐kinetically in a coherent manner.
Plain Language Summary
Shock waves in space are responsible for energizing particles and diverting supersonic flows around planets and other obstacles. Explosive events known as Hot Flow Anomalies (HFAs) arise when a rapid change in the interplanetary magnetic field arrives at the bow shock formed by, for example, the supersonic solar wind plasma flow from the Sun impinging on the Earth's magnetic environment. HFAs are known to produce impacts all the way to ground level, but the physics responsible for their formation occur too rapidly to be resolved by previous satellite missions. This paper employs NASA's fleet of four Magnetospheric Multiscale satellites to reveal for the first time clear, discreet populations of ions that interact coherently to produce the extreme heating and deflection.
Key Points
MMS observations reveal distinct ion velocity‐space populations within a Hot Flow Anomaly (HFA)
The HFA interior varies smoothly in density with a swept‐up pressure excess toward the trailing edge
The HFA interior displays coherent kinematic coupling between antisunward and sunward backstreaming ions
Using observations from NASA's Van Allen Probes, we study the role of sudden particle enhancements at low L shells (SPELLS) as a source of inner radiation belt electrons. SPELLS events are ...characterized by electron intensity enhancements of approximately an order of magnitude or more in less than 1 day at L < 3. During quiet and average geomagnetic conditions, the phase space density radial distributions for fixed first and second adiabatic invariants are peaked at 2 < L < 3 for electrons ranging in energy from ~50 keV to ~1 MeV, indicating that slow inward radial diffusion is not the dominant source of inner belt electrons under quiet/average conditions. During SPELLS events, the evolution of electron distributions reveals an enhancement of phase space density that can exceed 3 orders of magnitude in the slot region and continues into the inner radiation belt, which is evidence that these events are an important—and potentially dominant—source of inner belt electrons. Electron fluxes from September 2012 through February 2016 reveal that SPELLS occur frequently (~2.5/month at 200 keV), but the number of observed events decreases exponentially with increasing electron energy for ≥100 keV. After SPELLS events, the slot region reforms due to slow energy‐dependent decay over several day time scales, consistent with losses due to interactions with plasmaspheric hiss. Combined, these results indicate that the peaked phase space density distributions in the inner electron radiation belt result from an “on/off,” geomagnetic‐activity‐dependent source from higher radial distances.
Key Points
Phase space density distributions of tens to hundreds of keV electrons in the inner belt are peaked in L* during quiet and average conditions
Sudden flux enhancements during active conditions are the dominant source of hundreds of keV electrons in the inner belt
The occurrence of sudden flux enhancements at low L is strongly dependent on energy
The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain (BF) cholinergic neurons during pathological aging have remained elusive. Here we employed an adeno‐associated ...viral vector‐based RNA interference (AAV‐RNAi) strategy to suppress the expression of tropomyosin‐related kinase A (trkA) receptors by cholinergic neurons in the nucleus basalis of Meynert/substantia innominata (nMB/SI) of adult and aged rats. Suppression of trkA receptor expression impaired attentional performance selectively in aged rats. Performance correlated with trkA levels in the nMB/SI. trkA knockdown neither affected nMB/SI cholinergic cell counts nor the decrease in cholinergic cell size observed in aged rats. However, trkA suppression augmented an age‐related decrease in the density of cortical cholinergic processes and attenuated the capacity of cholinergic neurons to release acetylcholine (ACh). The capacity of cortical synapses to release ACh in vivo was also lower in aged/trkA‐AAV‐infused rats than in aged or young controls, and it correlated with their attentional performance. Furthermore, age‐related increases in cortical proNGF and p75 receptor levels interacted with the vector‐induced loss of trkA receptors to shift NGF signaling toward p75‐mediated suppression of the cholinergic phenotype, thereby attenuating cholinergic function and impairing attentional performance. These effects model the abnormal trophic regulation of cholinergic neurons and cognitive impairments in patients with early Alzheimer's disease. This rat model is useful for identifying the mechanisms rendering aging cholinergic neurons vulnerable as well as for studying the neuropathological mechanisms that are triggered by disrupted trophic signaling.
The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain (BF) cholinergic neurons during pathological aging have remained elusive. Here we employed an adeno‐associated viral vector‐based RNA interference (AAV‐RNAi) strategy to suppress the expression of trkA receptors by cholinergic neurons in the nucleus basalis of Meynert/substantia innominata (nMB/SI) of adult and aged rats. This study provides novel evidence that reduced trkA receptors is not sufficient to trigger cholinergic dysfunction. Rather, aging interacts with disrupted trkA signaling to escalate the vulnerability of BF cholinergic neurons and the manifestation of age‐related attentional impairments.
Significance: Functional brain imaging in awake animal models is a popular and powerful technique that allows the investigation of neurovascular coupling (NVC) under physiological conditions. ...However, ubiquitous facial and body motions (fidgeting) are prime drivers of spontaneous fluctuations in neural and hemodynamic signals. During periods without movement, animals can rapidly transition into sleep, and the hemodynamic signals tied to arousal state changes can be several times larger than sensory-evoked responses. Given the outsized influence of facial and body motions and arousal signals in neural and hemodynamic signals, it is imperative to detect and monitor these events in experiments with un-anesthetized animals.
Aim: To cover the importance of monitoring behavioral state in imaging experiments using un-anesthetized rodents, and describe how to incorporate detailed behavioral and physiological measurements in imaging experiments.
Approach: We review the effects of movements and sleep-related signals (heart rate, respiration rate, electromyography, intracranial pressure, whisking, and other body movements) on brain hemodynamics and electrophysiological signals, with a focus on head-fixed experimental setup. We summarize the measurement methods currently used in animal models for detection of those behaviors and arousal changes. We then provide a guide on how to incorporate this measurements with functional brain imaging and electrophysiology measurements.
Results: We provide a how-to guide on monitoring and interpreting a variety of physiological signals and their applications to NVC experiments in awake behaving mice.
Conclusion: This guide facilitates the application of neuroimaging in awake animal models and provides neuroscientists with a standard approach for monitoring behavior and other associated physiological parameters in head-fixed animals.
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