Blood Oxygen Research Articles

Mapping Activity and Functional Organisation of the Motor and Visual Pathways Using ADC-fMRI in the Human Brain.

In contrast to blood-oxygenation level-dependent (BOLD) functional MRI (fMRI), which relies on changes in blood flow and oxygenation levels to infer brain activity, diffusion fMRI (DfMRI) investigates brain dynamics by monitoring alterations in the apparent diffusion coefficient (ADC) of water. These ADC changes may arise from fluctuations in neuronal morphology, providing a distinctive perspective on neural activity. The potential of ADC as an fMRI contrast (ADC-fMRI) lies in its capacity to reveal neural activity independently of neurovascular coupling, thus yielding complementary insights into brain function. To demonstrate the specificity and value of ADC-fMRI, both ADC- and BOLD-fMRI data were collected at 3 T in human subjects during visual stimulation and motor tasks. The first aim of this study was to identify an acquisition design for ADC that minimises BOLD contributions. By examining the timings in responses, we report that ADC 0/1 timeseries (acquired with b values of 0 and 1 ms/ ) exhibit residual vascular contamination, while ADC 0.2/1 timeseries (with b values of 0.2 and 1 ms/ ) show minimal BOLD influence and higher sensitivity to neuromorphological coupling. Second, a general linear model was employed to identify activation clusters for ADC 0.2/1 and BOLD, from which the average ADC and BOLD responses were calculated. The negative ADC response exhibited a significantly reduced delay relative to the task onset and offset as compared to BOLD. This early onset further supports the notion that ADC is sensitive to neuromorphological rather than neurovascular coupling. Remarkably, in the group-level analysis, positive BOLD activation clusters were detected in the visual and motor cortices, while the negative ADC clusters mainly highlighted pathways in white matter connected to the motor cortex. In the averaged individual level analysis, negative ADC activation clusters were also present in the visual cortex. This finding confirmed the reliability of negative ADC as an indicator of brain function, even in regions with lower vascularisation such as white matter. Finally, we established that ADC-fMRI time courses yield the expected functional organisation of the visual system, including both grey and white matter regions of interest. Functional connectivity matrices were used to perform hierarchical clustering of brain regions, where ADC-fMRI successfully reproduced the expected structure of the dorsal and ventral visual pathways. This organisation was not replicated with the b = 0.2 ms/ diffusion-weighted time courses, which can be seen as a proxy for BOLD (via T2-weighting). These findings underscore the robustness of ADC time courses in functional MRI studies, offering complementary insights into BOLD-fMRI regarding brain function and connectivity patterns.

Computational exploration of injection strategies for improving medicine distribution in the liver.

The liver, a vital metabolic organ, is always susceptible to various diseases that ultimately lead to fibrosis, cirrhosis, acute liver failure, chronic liver failure, and even cancer. Optimal and specific medicine delivery in various diseases, hepatectomy, shunt placement, and other surgical interventions to reduce liver damage, transplantation, optimal preservation, and revival of the donated organ all rely on a complete understanding of perfusion and mass transfer in the liver. This study aims to simulate the computational fluid dynamics of perfusion and the temporal-spatial distribution of a medicine in a healthy liver to evaluate the hemodynamic characteristics of flow and medicine transport with the purpose of more effective liver treatment. Patient-specific geometries of parenchyma and hepatic artery, portal vein, and hepatic vein vessels of a healthy liver were segmented and reconstructed from the abdominal computed tomography scan images. Mesh was generated for the comprehensive combined model using unstructured tetrahedral elements. Transient pressure values were applied as boundary conditions at the portal vein and hepatic artery inlets, and pressure outlet boundary condition was assumed at the hepatic vein outlet. Medicine injection was done through the portal vein. The liver parenchyma was assumed to be a porous medium. Finally, computational fluid dynamics (CFD) simulation was performed to investigate blood perfusion, medicine distribution, and saturation time. The velocity parameter values calculated for the hepatic artery, portal vein, and hepatic vein vessels were consistent with the physiological ranges. The mass flow rate was higher in the portal vein than in the hepatic artery, which was consistent with high perfusion through the portal vein. The portal pressure gradient was 8.53mmHg. From a pharmacokinetic viewpoint, medicine distribution in porous tissue was a heterogeneous process. Medicine distribution was higher at end-diastolic pressure than at peak-systolic pressure which showed the influence of hepatic artery flow. The tissue was saturated faster at first 40s and with decreasing porosity, saturation time decreased, and distribution improved. The right lobe included a higher number of vascular terminals due to its larger volume, and the flow rate was higher in this lobe compared to the left lobe. This showed the significant effect of the right lobe on the overall function of the body. Recirculation flow zones along hepatic artery and portal vein branches emphasized the sensitivity of downstream vessels. Rotational flow and potential vortex formation at the hepatic vein outlet may indicate a risk of plaque and clot formation in this region. The heterogeneous distribution of medicine indicated the importance of injection time in treating liver diseases. The percentage of tissue porosity affected the saturation time, so adjusting the medicine dose and injection time could be challenging in treatments.

Dobutamine-induced alterations in internal carotid artery blood flow and cerebral blood flow in healthy adults.

Dobutamine, a sympathomimetic agent, is widely used clinically, influencing cardiac output, heart rate (HR), and blood pressure (BP), which may impact cerebral blood flow (CBF), critical for brain metabolism. However, the effects of dobutamine on CBF and internal carotid artery (ICA) blood flow remain unclear, with contradictory reported in both clinical and animal studies. It is necessary to investigate the effects of dobutamine on cervical and cerebral hemodynamics. This study aimed to evaluate the effects of dobutamine infusion on ICA blood flow and CBF, explore their relationship, and identify factors influencing CBF to facilitate timely monitoring in clinical practice. Forty-eight healthy volunteers underwent physiological assessment, ICA ultrasound, and brain magnetic resonance imaging (MRI) data before and after the administration of dobutamine. Paired t and Wilcoxon signed-rank tests were used to analyze changes, while logistic regression explored associations between hemodynamic factors and CBF. Dobutamine infusion significantly increased HR, respiration rate, systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure, while blood oxygen remained stable. Compared with those in the resting state, the peak systolic velocity (Vs), resistance index, pulsatility index, and systolic/diastolic ratio (S/D) increased, whereas end-diastolic velocity (Vd) decreased. ICA diameter and mean velocity showed no significant changes. CBF significantly decreased in the anterior and middle cerebral arteries. Logistic regression identified SBP, DBP, and S/D difference as key factors associated with CBF reduction. Dobutamine altered ICA hemodynamics and reduced CBF in anterior and middle cerebral arteries. Real-time ICA ultrasound monitoring provides valuable guidance during clinical use.

Time-Varying Spatial Propagation of Brain Networks in fMRI Data.

Spontaneous neural activity coherently relays information across the brain. Several efforts have been made to understand how spontaneous neural activity evolves at the macro-scale level as measured by resting-state functional magnetic resonance imaging (rsfMRI). Previous studies observe the global patterns and flow of information in rsfMRI using methods such as sliding window or temporal lags. However, to our knowledge, no studies have examined spatial propagation patterns evolving with time across multiple overlapping 4D networks. Here, we propose a novel approach to study how dynamic states of the brain networks spatially propagate and evaluate whether these propagating states contain information relevant to mental illness. We implement a lagged windowed correlation approach to capture voxel-wise network-specific spatial propagation patterns in dynamic states. Results show systematic spatial state changes over time, which we confirmed are replicable across multiple scan sessions using human connectome project data. We observe networks varying in propagation speed; for example, the default mode network (DMN) propagates slowly and remains positively correlated with blood oxygenation level-dependent (BOLD) signal for 6-8 s, whereas the visual network propagates much quicker. We also show that summaries of network-specific propagative patterns are linked to schizophrenia. More specifically, we find significant group differences in multiple dynamic parameters between patients with schizophrenia and controls within four large-scale networks: default mode, temporal lobe, subcortical, and visual network. Individuals with schizophrenia spend more time in certain propagating states. In summary, this study introduces a promising general approach to exploring the spatial propagation in dynamic states of brain networks and their associated complexity and reveals novel insights into the neurobiology of schizophrenia.

Measuring the effects of motion corruption in fetal fMRI.

Irregular and unpredictable fetal movement is the most common cause of artifacts in in utero functional magnetic resonance imaging (fMRI), affecting analysis and limiting our understanding of early functional brain development. The accurate detection of corrupted functional connectivity (FC) resulting from motion artifacts or preprocessing, instead of neural activity, is a prerequisite for reliable and valid analysis of FC and early brain development. Approaches to address this problem in adult data are of limited utility in fetal fMRI. In this study, we evaluate a novel technique for robust computational assessment of motion artifacts, and the quantitative comparison of regression models for artifact removal in fetal FC analysis. It exploits the association between dynamic FC and non-stationarity of fetal movement, to detect residual noise. To validate our motion artifact detection technique in detail, we used a parametric generative model for neural events and fMRI blood oxygenation level-dependent (BOLD) signal. We conducted a systematic evaluation of 11 commonly used regression models in a sample of 70 fetuses with gestational age of 19-39 weeks. Results demonstrate that the proposed method has better accuracy in identifying corrupted FC compared to methods designed for adults. The technique, suggests that censoring, global signal regression and anatomical component-based regression models are the most effective models for compensating motion. The benchmarking technique, and the generative model for realistic fetal fMRI BOLD enables investigators conducting in utero fMRI analysis to effectively quantify the impact of fetal motion and evaluate alternative regression strategies for mitigating this impact. The code is publicly available at: https://github.com/cirmuw/fetalfMRIproc.

Interictal epileptiform discharge-related BOLD responses in the default mode network and subcortical regions.

To examine the blood oxygen level-dependent (BOLD) responses in the default mode network (DMN) and subcortical regions in relation to epileptic events in scalp EEG and intracranial EEG (iEEG). We retrospectively compared BOLD responses in the DMN and subcortical regions to interictal epileptiform discharge (IED) characteristics of the scalp and iEEG in consecutive patients with focal epilepsy. All voxels were used as the denominator to assess the positive and negative BOLD ratios in each region, and the percentage of voxels with significant activation or deactivation was assessed. Seventy-one EEG-fMRI studies were included. The widespread IED group showed a higher negative BOLD ratio in the DMN than did the focal IED group. Spike and ripple spreads in iEEG positively correlated with a positive BOLD ratio in the DMN and subcortical regions and a negative BOLD ratio in the DMN. Fast ripple spread showed no correlation with the BOLD ratio in any region. IEDs affect local regions, as well as distant neocortical (DMN) and subcortical regions, depending on their localization and characteristics. Our findings showed both positive and negative IED-related BOLD responses in subcortical regions and new evidence of network dysfunction related to focal epileptic activity.

Incorporating an Elevated Perfusion Index in the Right Hand Enhanced Screening Sensitivity for Critical Aortic Arch Obstruction in Newborn Infants.

Newborn infants with critical aortic arch obstruction are often undiagnosed at discharge, despite screening. This study investigated if adding the perfusion index improved early detection. We retrospectively studied 38 newborn infants with critical aortic arch obstruction, who were routinely screened in 2014-2019 by 13 Swedish hospitals using pulse oximetry and the perfusion index. They were identified through surgery records and national mortality databases. The controls were 512 healthy newborn infants from one hospital. Optimal perfusion index cut-offs were determined using frequency distribution analysis. The groups had similar median gestational ages and birth weight. No infants with critical aortic arch obstruction were diagnosed just because of a positive perfusion index result. However, the right-hand perfusion index was significantly higher in the cases than in controls (p < 0.001). A perfusion index of > 3%, or positive pulse oximetry or positive physical examination, yielded 76% sensitivity and 85% specificity, with an area under the receiver operating characteristic curve of 0.81 (range 0.73-0.89, p < 0.0001). Pulse oximetry and just neonatal physical examinations had a lower sensitivity (45%, p = 0.009). A high perfusion index in the right hand enhanced critical aortic arch obstruction screening and repeated measurements should be explored to minimise false positives.

White noise’s effect on premature infants’ physiological parameters during peripheral intravenous catheter insertion

BackgroundEarly and continuous exposure to painful stimuli in premature infants leads to short-and long-term complications. Listening to white noise is an accessible and inexpensive non-invasive method that can be used as a safe nursing intervention in hospitals. This study aimed to assess white noise’s effect on premature Infants’ physiological parameters during peripheral intravenous catheter insertion.MethodsThe present experimental study was conducted on 40 premature Infants. From 5 min before Indwelling catheters to 10 min after, white noise was played through headphones to infants at a controlled volume in the test group. Using a monitor, physiological parameters were recorded from 10 min before to 30 min after the Indwelling catheter. Statistical analysis was done through the SPSS version 27 software program.ResultsRegarding respiratory rate, there was no statistically significant difference between the two groups in the first, second, and sixth stages (p < 0.05). However, in the third, fourth, and fifth stages, RR in the control group was significantly higher than the test group (p ≤ 0.05). In terms of mean arterial blood pressure, there was no statistically significant difference between the two groups in any of the stages (p < 0.05). In terms of heart rate, there was no statistically significant difference between the two groups in the first, second, and sixth stages (p < 0.05). However, in the third, fourth, and fifth stages, HR in the control group was significantly higher than the test group (p ≤ 0.05). Regarding oxygen saturation percentage, there was no statistically significant difference between the two groups in the first, second, third, and sixth stages (p < 0.05). In contrast, in the fourth and fifth stages, the oxygen saturation percentage in the test group was significantly higher than in the control group (p < 0.05).ConclusionsAlthough in both groups the painful procedure led to an increase in physiological variables (respiratory rate, heart rate, mean arterial blood pressure) and a decrease in blood oxygen saturation, in the test group these variables approached their initial state more quickly within half an hour after exposure to white noise. This confirms that the effect of white noise on the improvement of physiological variables is gradual.Clinical trial numberNot applicable.

HUC-MSCs Prevent Acute High-Altitude Injury through Apoe/Pdgf-b/p-Erk1/2 Axis in Mice.

The hypobaric hypoxic atmosphere can cause adverse reactions or sickness. The purpose of this study was to explore the preventive effect and mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) on acute pathological injury in mice exposed to high-altitude. We pretreated C57BL/6 mice with hUC-MSCs via the tail vein injection, and then the mice were subjected to hypobaric hypoxic conditions for five days. The effects of hUC-MSCs on the pathological injury of lung, heart, brain were assessed by biochemical analysis, histopathological testing, quantitative real-time polymerase chain reaction (qPCR), and western blot (WB). Further, transcriptome sequencing was used to screen for the potential therapeutic targets of hUC-MSCs in acute pathological injury, the identified signaling axis was characterized using Apoe-/- mice, qPCR and WB. hUC-MSCs administration notably prevented and relieved gastrointestinal symptoms and inflammation of lung and heart, increased blood oxygen saturation and serum superoxide dismutase (SOD) level, decreased serum malondialdehyde (MDA) level, rescued lung tissue injury and myocardial mitochondrial disorder, elevated nissl bodies number in brain tissue and reduced the degree of pulmonary and cerebral edema. Furthermore, hUC-MSCs pretreatment reversed the down-regulated Apoe and up-regulated Pdgf-b and p-Erk1/2 in the lung of hypobaric hypoxic mice. Thus, hUC-MSCs protected against acute pathological injury caused by hypobaric hypoxic condition via the Apoe/Pdgf-b/p-Erk1/2 axis, and the identified pathway was confirmed by the negative results of Apoe-/- mice. hUC-MSCs possess the preventive effect on acute pathological injury caused by hypobaric hypoxia environment at high-altitude.

Perfusion index monitoring and its correlation with outcome in neonates undergoing surgery

Background: The perfusion index (PI) has been found to be a reliable indicator of peripheral perfusion and can be used to monitor perfusion in neonates undergoing surgical procedures. To study correlation of perfusion index with the need for post op mechanical ventilation, ICU care and inotropic support in neonates undergoing surgery. Methods: Eighty neonates posted for surgery were enrolled after taking proper written informed consent from the parents. HR, BP and SPO2 and PI were recorded at 3 minutes interval for the first 30 minutes of surgery, followed by every 5 minutes till the end of procedure. Neonates requiring admission in the Department of Pediatrics were shifted to the Neonatal ICU or ward. Post-operative vitals were monitored initially every 30 minutes for first 24 hours followed by 2 hourly. Results: There was a statistically significant association between PI and need for post-op mechanical ventilation (MV). Duration of post-operative MV based on PI showed no significant difference. A lower PI was strongly correlated with an increased likelihood of requiring ICU-level care post-operatively, but not the duration of ICU stay. There was a potential association between PI and the requirement for inotropic support. Mortality rate was higher in patients with low PI, but not statistically significant. Conclusions: Low PI in neonates is associated with poor outcome in terms of need for ICU stay, need of postoperative mechanical ventilation and inotropic support.

Noninvasive Detection of Chorioretinal Hypoxia via Poly(lactic‐co‐glycolic acid) Nanoparticles Embedded with Purely Organic Phosphors

Ischemia‐induced hypoxia is a critical complication in retinal diseases, leading to significant vision impairment and blindness due to disrupted blood flow and oxygen delivery. Currently, there is no effective method to assess oxygen levels in extravascular retinal tissue. Traditional hypoxia detection methods, such as oxygen‐sensitive microelectrodes, magnetic resonance imaging, and retinal oximetry, have limitations including invasiveness, low spatial resolution, and lack of real‐time monitoring. Herein, a noninvasive hypoxia detection method is proposed by utilizing lipid‐polymer nanoparticles (NPs) with purely organic room‐temperature phosphorescence materials for real‐time detection with high spatial and temporal resolution. To enhance biocompatibility and efficacy, NPs were fabricated using biodegradable poly(lactic‐co‐glycolic acid) (PLGA) and SeCO as a phosphor. PLGA degrades into nontoxic by‐products, while the excitation wavelength of SeCO at 393 nm minimizes damage from short wavelengths and enhances tissue penetration. Furthermore, the NPs’ size is optimized to improve cellular uptake and reduce bodily accumulation, as smaller NPs are preferred for biocompatibility. Herein, synthesis, characterization, and evaluation of these PLGA‐based phosphorescent NPs in rabbit models of retinal vein occlusion and choroidal vascular occlusion are involved. This approach represents a significant advancement in noninvasive biomedical imaging, improving the diagnosis and management of ischemic retinal diseases.

Ultra high density imaging arrays in diffuse optical tomography for human brain mapping improve image quality and decoding performance

Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing (~ 13 mm) than sparse fNIRS (~ 30 mm) and therefore provide higher image quality, with spatial resolution ~ 1/2 that of fMRI, when using the several source-detector distances (13–40 mm) afforded by the HD-DOT grid. Herein, simulations indicated reducing inter-optode spacing to 6.5 mm, creating a higher-density grid with more source-detector distances, would further improve image quality and noise-resolution tradeoff, with diminishing returns below 6.5 mm. We then constructed an ultra-high-density DOT system (6.5-mm spacing) with 140 dB dynamic range that imaged stimulus-evoked activations with 30–50% higher spatial resolution and repeatable multi-focal activity with excellent agreement with participant-matched fMRI. Further, this system decoded visual stimulus position with 19–35% lower error than previous HD-DOT, throughout occipital cortex.

Thoracoscopic minimally invasive surgery for the treatment of flail chest with multiple rib fractures

To investigate the clinical efficacy of thoracoscopic minimally invasive surgery with nickel-titanium shape memory alloy wrap bone plate versus rib periosteal internal fixation in patients with multiple rib fractures (MRF) and flail chest. A retrospective analysis was performed on 100 patients with MRF and flail chest treated with thoracoscopic minimally invasive surgery and internal fixation with rib fracture preservation between January 2019 and December 2022, including 54 males and 46 females, aged from 20 to 65 years old, with an average age of (38.0±18.0)years old. The duration of the disease ranged from 8 to 21 days. According to the different surgical methods, the patients were divided into control group and study group, with 50 patients in each group. The control group consisted of 23 males and 27 females, with an average age of (38.35±18.05) years old, who underwent rib preservation periosteal internal fixation. In the study group, there were 31 males and 19 females, with an average age of (38.15±17.99) years old, treated with thoracoscopic nickel-titanium shape memory alloy circumferential bone plate. The pulmonary function indices, electrocardiographic monitoring indices, pain severity, levels of inflammatory factors, complications, rehabilitation indices, and therapeutic efficacy were compared between the two groups before and after treatment. All patients were followed up for 6 months. After 3 days of treatment, the heart rate of both groups was (102.43±13.74) beats per minute vs (86.26±8.06) beats per minute, respiratory rate (28.45±3.40) breaths per minute vs (22.05±2.85) breaths per minute, blood oxygen saturation (89.68±3.66)% vs (98.46±4.84)%, rest pain (3.5±0.5) points vs (2.6±0.6) points, movement pain (3.6±0.5) points vs (2.5±0.5) points, and these differences were statistically significant(P<0.05). The levels of Interleukin-6 (IL-6) (102.30±17.00) pg·ml-1 vs (85.68±21.20) pg·ml-1 and tumor necrosis factor-alpha (TNF-α)(33.44±4.85) pg·ml-1 vs (18.14±4.28) pg·ml-1 in both groups exhibited an increase post-treatment, while the C-reactive protein (CRP) (75.51±10.54) mg·L-1 vs (60.75±9.84) mg·L-1 demonstrated a decrease compared to pre-treatment levels. Furthermore, the study group displayed significantly lower levels than the control group (P<0.05). After 10 days of treatment, the peak expiratory flow rate (3.31±0.52) L·s-1 vs (5.69±0.74) L·s-1, forced expiratory volume (1.46±0.29) L vs (2.06±0.38) L, and forced vital capacity (2.68±0.95) L vs (4.26±1.05) L of both groups exhibited significant improvements compared to pre-treatment levels. Moreover, the study group demonstrated significantly higher values than the control group (P<0.05). The incidence of postoperative complications in the study group was significantly lower compared to the control group (6 cases vs 14 cases, P<0.05). Additionally, the duration of bone callus formation(9.50±1.40) days and fracture healing (72.20±8.32) days in the study group was significantly shorter compared to the control group(11.35±2.15) days, (93.70±9.90) days (P<0.001). Compared with traditional rib-preserving internal fixation, patients with MRF and flail chest treated with minimally invasive internal fixation with thoracoscopic nickel-titanium shape memory alloy surround bone plate have better therapeutic effect, because of less surgical trauma, less pain and inflammatory reaction, fewer postoperative pulmonary complications, faster and better recovery of lung function, and thus promote the recovery of patients.

Detachable Top Electrode-Organic Photodetector for Repeated Nondestructive Evaluation of Device Performance and Surface Analysis of the Active Layer.

Organic photodetectors (OPDs) are key devices for monitoring vital signs, such as heart rate and blood oxygen level. For realizing the long-term measurement of biosignals, stable operation is essential. To improve the stability of OPDs, it is important to analyze each layer to understand the degradation mechanism. We developed detachable top electrode (DTE)-OPDs to enable both surface analysis of the active layer and device characterization to be performed nondestructively and repeatedly within a single device. The substrate of the top electrode is a 2 μm thick elastomer sheet reinforced with polyurethane nanofibers. The DTE-OPDs showed a Dsh* of 1.4 × 1012 Jones by attaching the top electrodes to the bottom stack without external pressure. The DTE-OPDs showed no degradation after 1000 attaching/detaching cycles of the top electrodes. Using the DTE-OPDs, we successfully observed the relationship between dark current increase and oxidization of the active layer.

An animal model of severe acute respiratory distress syndrome for translational research

BackgroundDespite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.ResultsIn this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.ConclusionsThis modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Correlation of zero echo time functional MRI with neuronal activity in rats.

Zero echo time (zero-TE) pulse sequences provide a quiet and artifact-free alternative to conventional functional magnetic resonance imaging (fMRI) pulse sequences. The fast readouts (<1 ms) utilized in zero-TE fMRI produce an image contrast with negligible contributions from blood oxygenation level-dependent (BOLD) mechanisms, yet the zero-TE contrast is highly sensitive to brain function. However, the precise relationship between the zero-TE contrast and neuronal activity has not been determined. Therefore, we aimed to derive a function to model the temporal dynamics of the zero-TE fMRI signal in response to neuronal activity. Furthermore, we examined the correlation of zero-TE fMRI with neuronal activity across stimulation frequencies. To these ends, we performed simultaneous electrophysiological recordings and zero-TE fMRI in rats subjected to whisker stimulation. The presented impulse response function provides a basis for the statistical modeling of neuronal activity-induced changes in the zero-TE fMRI signal. The temporal characteristics of the zero-TE fMRI response were found to be consistent with the previously postulated non-BOLD hemodynamic origin of the functional contrast. The zero-TE fMRI signal was well predicted by electrophysiological recordings, although systematic stimulation-dependent residuals were also observed, suggesting nonlinearities in neurovascular coupling. We conclude that zero-TE fMRI provides a robust proxy for neuronal activity.

Pulse oximetry at two sensor placement sites in conscious foals

BackgroundPulse oximetry has not been thoroughly evaluated for assessment of oxygenation in conscious foals. Compared with invasive arterial blood sampling, it is a painless and non-invasive method for real-time monitoring of blood oxygen saturation. The aim of this prospective clinical study was to evaluate the usability, validity, and reliability of pulse oximetry at two measuring sites (lip and caudal abdominal skin fold) for blood oxygen saturation measurement in conscious foals with and without respiratory compromise. Thirty-two foals under one month of age were used. Nineteen foals had normal respiratory and cardiovascular function, and 13 had pneumonia. Pulse oximetry with a transmittance sensor was performed in triplicate on each foal’s lip (n = 196 measurements) and/or skin fold (n = 338 measurements), and arterial blood sample was collected. The oxygen saturation values measured by pulse oximetry from the lip and skin fold were compared with each other (n = 58 measurement pairs) and with the calculated arterial oxygen saturation based on arterial blood samples (n = 93 measurement pairs). Furthermore, repeatability of the pulse oximetry measurements was assessed.ResultsMeasured blood oxygen saturation was clearly associated with the calculated saturation, but on average (± SD) it was 1.8 (± 3.3) percentage units higher from the lip and 5.7 (± 4.3) percentage units higher from the skin fold than the calculated saturation. In concurrent lip and skin fold measurements within a foal, the skin fold measurements were 2.4 (± 2.4) percentage units higher than the lip measurements. The repeatability of three pulse oximetry saturation measurement results was moderate to good and significantly improved when the measurement furthest from the middle-measured value was excluded. The most deviating measurement was often obtained first. Pulse oximetry in general was well tolerated and easy to perform, but as expected in conscious foals, movement and contact problems generated occasional technical difficulties in some individuals.ConclusionsIn conscious foals, pulse oximetry with a transmittance sensor attached to the lip (but not to the skin fold) is a clinically applicable and valid method for arterial blood oxygen saturation determination. Several measurements should be obtained and outliers discarded to obtain a reliable result.

Towards personalized mapping through lumbosacral spinal cord task fMRI

Abstract The lumbosacral spinal cord contains neural circuits crucial for locomotion, organized into rostrocaudal levels with distinct somatosensory and motor neuron pools that project to and from the muscles of the lower limbs. However, the specific spinal levels that innervate each muscle and the locations of neuron pools vary significantly between individuals, presenting challenges for targeted therapies and neurosurgical interventions aimed at restoring locomotion. Non-invasive approaches to functionally map the segmental distribution of muscle innervation—or projectome—are therefore essential. Here, we developed a pipeline dedicated to record blood oxygenation level dependent (BOLD) signals in the lumbosacral spinal cord using functional magnetic resonance imaging (fMRI). We assessed spinal activity across different conditions targeting the extensor/flexor muscles of the right leg (ankle, knee, and hip) in 12 healthy participants. To enhance clinical relevance, we included not only active movements but also two conditions that did not rely on participants’ performance: passive stretches and muscle-specific tendon vibration, which activates proprioceptive afferents of the vibrated muscle. BOLD activity patterns were primarily located on the side ipsilateral to the movement, stretch, or vibration, both at the group and participant levels, indicating the BOLD activity being associated with the projectome. The fMRI-derived rostrocaudal BOLD activity patterns exhibited mixed alignment with expected innervation maps from invasive studies, varying by muscle and condition. While some muscles and conditions matched well across studies, others did not. Significant variability among individual participants underscores the need for personalized mapping of projections for targeted therapies and neurosurgical interventions. To support the interpretation of BOLD activity patterns, we developed a decision tree-based framework that combines reconstruction of neural structures from high-resolution anatomical MRI datasets and muscle-specific fMRI activity to produce personalized projectomes. Our findings provide a valuable proof-of-concept for the potential of fMRI to map the lumbosacral spinal cord’s functional organization, while shedding light on challenges associated with this endeavor.

Exploring the Molecular Interplay Between Oxygen Transport, Cellular Oxygen Sensing, and Mitochondrial Respiration.

Significance: The mitochondria play a key role in maintaining oxygen homeostasis under normal oxygen tension (normoxia) and during oxygen deprivation (hypoxia). This is a critical balancing act between the oxygen content of the blood, the tissue oxygen sensing mechanisms, and the mitochondria, which ultimately consume most oxygen for energy production. Recent Advances: We describe the well-defined role of the mitochondria in oxygen metabolism with a special focus on the impact on blood physiology and pathophysiology. Critical Issues: Fundamental questions remain regarding the impact of mitochondrial responses to changes in overall blood oxygen content under normoxic and hypoxic states and in the case of impaired oxygen sensing in various cardiovascular and pulmonary complications including blood disorders involving hemolysis and hemoglobin toxicity, ischemia reperfusion, and even in COVID-19 disease. Future Directions: Understanding the nature of the crosstalk among normal homeostatic pathways, oxygen carrying by hemoglobin, utilization of oxygen by the mitochondrial respiratory chain machinery, and oxygen sensing by hypoxia-inducible factor proteins, may provide a target for future therapeutic interventions. Antioxid. Redox Signal. 00, 000-000.

Effect of Low-Level Laser Acupuncture and Microcurrent Electrical Stimulation on Gag Reflex in Children During Dental Impression: A Randomized Controlled Clinical Trial.

Dental impressions are crucial in pediatric dentistry, but exaggerated gagging can obstruct this process. Various methods have been proposed to manage the gag reflex (GR). This study aimed to evaluate and compare the effectiveness of laser acupuncture and electroacupuncture in controlling children's GR. A three-armed randomized controlled trial was conducted with 63 patients aged 6-9, with excessive GR, scheduled for dental impressions. Participants were assigned to one of three groups: low-level laser (n = 21), microcurrent stimulation with a Meridian pen (n = 21), and a control group with a deactivated pen (n = 21). Gag preventive index (GPI) was taken, and dental anxiety was assessed using the Facial Image Scale (FIS), pulse rate (PR), and blood oxygen saturation (SaO2). Significance was set at p < 0.05. All interventions influenced GPI scores. The Meridian pen and laser groups achieved better GPI scores (p < 0.001) than the control group. FIS scores between the Meridian pen and laser groups were comparable, differing significantly from the control group (p < 0.001). The Meridian pen and laser groups showed greater reductions in PR (p < 0.001) and higher SaO2 post-intervention (p < 0.001). The Meridian pen and laser outperformed the control group, demonstrating effectiveness in enhancing physiological and subjective measures. ClinicalTrials.gov identifier: NCT06422286.