Towards spatially selective efferent neuromodulation: anatomical and functional organization of cardiac fibres in the porcine cervical vagus nerve.

Spatially selective vagus nerve stimulation (sVNS) offers a promising approach for addressing heart disease with enhanced precision. Despite its therapeutic potential, VNS is limited by off-target effects and the need for time-consuming titration. Our research aimed to determine the spatial organization of cardiac afferent and efferent fibres within the vagus nerve of pigs to achieve targeted neuromodulation. Using trial-and-error sVNS in vivo and ex vivo micro-computed tomography fascicle tracing, we found significant spatial separation between cardiac afferent and cardiac efferent fibres at the mid-cervical level and they were localized on average on opposite sides of the nerve cross-section. This was consistent between both in vivo and ex vivo methods. Specifically, cardiac afferent fibres were located near pulmonary fibres, consistent with findings of cardiopulmonary convergent circuits and, notably, cardiac efferent fascicles were exclusive. These cardiac efferent regions were located in close proximity to the recurrent laryngeal regions. This is consistent with the roughly equitable spread across the nerve of the afferent and efferent fibres. Our study demonstrated that targeted neuromodulation via sVNS could achieve scalable heart rate decreases without eliciting cardiac afferent-related reflexes; this is desirable for reducing sympathetic overactivation associated with heart disease. These findings indicate that understanding the spatial organization of cardiac-related fibres within the vagus nerve can lead to more precise and effective VNS therapy, minimizing off-target effects and potentially mitigating the need for titration. KEY POINTS: Spatially selective vagus nerve stimulation (sVNS) presents a promising approach for addressing chronic heart disease with enhanced precision. Our study reveals significant spatial separation between cardiac afferent and efferent fibres in the vagus nerve, particularly at the mid-cervical level. Utilizing trial-and-error sVNS in vivo and micro-computed tomography fascicle tracing, we demonstrate the potential for targeted neuromodulation, achieving therapeutic effects such as scalable heart rate decrease without stimulating cardiac afferent-related reflexes. This spatial understanding opens avenues for more effective VNS therapy, minimizing off-target effects and potentially eliminating the need for titration, thereby expediting therapeutic outcomes in myocardial infarction and related conditions.

Peritoneal dialysis-associated peritonitis presenting with Ralstonia pickettii infection: A novel series of three cases during the COVID-19 pandemic.

Peritoneal dialysis (PD)-associated peritonitis secondary to Ralstonia infection is very rare. Ralstonia pickettii is an organism that can grow in contaminated saline, water, chlorhexidine, and other medical products used in laboratories and the clinical setting. Infective endocarditis, prosthetic joint, and severe chest infections are previously reported with R. pickettii infection. We report a novel series of three cases diagnosed with PD-associated peritonitis caused by R. pickettii, where the cases appeared consecutively to our unit during a span of 4 weeks. During the COVID-19 pandemic, there were increased uses of non-sterile gloves by clinical staff as a form of personal protective equipment throughout patient interaction and PD exchange, as recommended by local hospital policy for all staff attending to patient care. A multidisciplinary team root cause analysis of our cases suggested non-sterile gloves being the likely source of environmental contamination, leading to PD-associated peritonitis caused by R. pickettii in this scenario.

Imaging of focal seizures with Electrical Impedance Tomography and depth electrodes in real time.

Intracranial EEG is the current gold standard technique for localizing seizures for surgery, but it can be insensitive to tangential dipole or distant sources. Electrical Impedance Tomography (EIT) offers a novel method to improve coverage and seizure onset localization. The feasibility of EIT has been previously assessed in a computer simulation, which revealed an improved accuracy of seizure detection with EIT compared to intracranial EEG. In this study, slow impedance changes, evoked by cell swelling occurring over seconds, were reconstructed in real time by frequency division multiplexing EIT using depth and subdural electrodes in a swine model of epilepsy. EIT allowed to generate repetitive images of ictal events at similar time course to fMRI but without its significant limitations. EIT was recorded with a system consisting of 32 parallel current sources and 64 voltage recorders. Seizures triggered with intracranial injection of benzylpenicillin (BPN) in five pigs caused a repetitive peak impedance increase of 3.4 ± 1.5 mV and 9.5 ± 3% (N =205 seizures); the impedance signal change was seen already after a single, first seizure. EIT enabled reconstruction of the seizure onset 9 ± 1.5 mm from the BPN cannula and 7.5 ± 1.1 mm from the closest SEEG contact (p<0.05, n =37 focal seizures in three pigs) and it could address problems with sampling error in intracranial EEG. The amplitude of the impedance change correlated with the spread of the seizure on the SEEG (p <<0.001, n =37). The results presented here suggest that combining a parallel EIT system with intracranial EEG monitoring has a potential to improve the diagnostic yield in epileptic patients and become a vital tool in improving our understanding of epilepsy.

In vivo imaging of deep neural activity from the cortical surface during hippocampal epileptiform events in the rat brain using electrical impedance tomography.

Electrical impedance tomography (EIT) is a medical imaging technique which reconstructs images of the internal impedance changes within an object using non-penetrating surface electrodes. To date, EIT has been used to image fast neural impedance changes during somatosensory evoked potentials and epileptiform discharges through the rat cerebral cortex with a resolution of 2 â€‹ms and <300 â€‹µm. However, imaging of neural activity in subcortical structures has never been achieved with this technique. Here, we evaluated the feasibility of using EIT to image epileptiform activity in the rat hippocampus using non-penetrating electrodes implanted on the cortical surface. Hippocampal epileptiform events, comprising repetitive 30-50 â€‹Hz ictal spikes, were induced by electrically stimulating the perforant path of rats anaesthetised with fentanyl-isoflurane. For each of ≥30 seizures, impedance measurements were obtained by applying 100 â€‹µA current at 1.4 â€‹kHz through an independent pair of electrodes on a 54-electrode planar epicortical array and recording boundary voltages on all remaining electrodes. EIT images of averaged ictal spikes were reconstructed using impedance recordings from all seizures in each animal. These revealed a focus of neural activity localised to the dentate gyrus which was spatially and temporally aligned to local field potential (LFP) recordings and could be reconstructed reproducibly in all animals with a localisation accuracy of ≤400 â€‹µm (p â€‹< â€‹0.03125, N â€‹= â€‹5). These findings represent the first experimental evidence of the ability of EIT to image neural activity in subcortical structures from the surface of the cortex with high spatiotemporal resolution and suggest that this method may be used for improving understanding of functional connectivity between cortico-hippocampal networks in both physiological and pathophysiological states.

Social Determinants of Health and Emergency Department Use Among Children With Sickle Cell Disease.

Sickle cell disease (SCD) is associated with disproportionate emergency department (ED) use. This study described the social determinants of health associated with ED visits and hospital admission from the ED among children with SCD using a nationally representative dataset. We analyzed data from 126 children 0 to 17 years of age with SCD included in the 2011 to 2017 rounds of the National Health Interview Survey (mean age, 8 y; 50% female individuals; 74% African American). Study variables were summarized using weighted means and proportions and compared according to ED use and admission by Wald tests. Fifty-two identified children had visited the ED within the last 12 months and 21 were admitted to the hospital after their most recent ED visit. Children living in a single-mother household were more likely to visit the ED (P=0.040), as were younger children (mean age, 6 vs. 9 y; P=0.034), with no evaluated social determinants of health significantly impacting hospital admission from the ED. The lack of association between ED use and either poverty or insurance type may be related to the overall high level of social disadvantage among children with SCD. Our findings demonstrate the need to better characterize specific social factors impacting acute care use among children with SCD.

Self-Abrading Servo Electrode Helmet for Electrical Impedance Tomography.

Electrical Impedance Tomography (EIT) is a medical imaging technique which has the potential to reduce time to treatment in acute stroke by rapidly differentiating between ischaemic and haemorrhagic stroke. The potential of these methods has been demonstrated in simulation and phantoms, it has not yet successfully translated to clinical studies, due to high sensitivity to errors in scalp electrode mislocation and poor electrode-skin contact. To overcome these limitations, a novel electrode helmet was designed, bearing 32 independently controlled self-abrading electrodes. The contact impedance was reduced through rotation on an abrasive electrode on the scalp using a combined impedance, rotation and position feedback loop. Potentiometers within each unit measure the electrode tip displacement within 0.1 mm from the rigid helmet body. Characterisation experiments on a large-scale test rig demonstrated that approximately 20 kPa applied pressure and 5 rotations was necessary to achieve the target 5 kΩ contact impedance at 20 Hz. This performance was then replicated in a simplified self-contained unit where spring loaded electrodes are rotated by servo motors. Finally, a 32-channel helmet and controller which sequentially minimised contact impedance and simultaneously located each electrode was built which reduced the electrode application and localisation time to less than five minutes. The results demonstrated the potential of this approach to rapidly apply electrodes in an acute setting, removing a significant barrier for imaging acute stroke with EIT.

Feasibility of imaging epileptic seizure onset with EIT and depth electrodes.

Imaging ictal and interictal activity with Electrical Impedance Tomography (EIT) using intracranial electrode mats has been demonstrated in animal models of epilepsy. In human epilepsy subjects undergoing presurgical evaluation, depth electrodes are often preferred. The purpose of this work was to evaluate the feasibility of using EIT to localise epileptogenic areas with intracranial electrodes in humans. The accuracy of localisation of the ictal onset zone was evaluated in computer simulations using 9M element FEM models derived from three subjects. 5 mm radius perturbations imitating a single seizure onset event were placed in several locations forming two groups: under depth electrode coverage and in the contralateral hemisphere. Simulations were made for impedance changes of 1% expected for neuronal depolarisation over milliseconds and 10% for cell swelling over seconds. Reconstructions were compared with EEG source modelling for a radially orientated dipole with respect to the closest EEG recording contact. The best accuracy of EIT was obtained using all depth and 32 scalp electrodes, greater than the equivalent accuracy with EEG inverse source modelling. The localisation error was 5.2 ±â€¯1.8, 4.3 ±â€¯0 and 46.2 ±â€¯25.8 mm for perturbations within the volume enclosed by depth electrodes and 29.6 ±â€¯38.7, 26.1 ±â€¯36.2, 54.0 ±â€¯26.2 mm for those without (EIT 1%, 10% change, EEG source modelling, n = 15 in 3 subjects, p < 0.01). As EIT was insensitive to source dipole orientation, all 15 perturbations within the volume enclosed by depth electrodes were localised, whereas the standard clinical method of visual inspection of EEG voltages, only localised 8 out of 15 cases. This suggests that adding EIT to SEEG measurements could be beneficial in localising the onset of seizures.

Feasibility of imaging evoked activity throughout the rat brain using electrical impedance tomography.

Electrical Impedance Tomography (EIT) is an emerging technique which has been used to image evoked activity during whisker displacement in the cortex of an anaesthetised rat with a spatiotemporal resolution of 200 µm and 2 ms. The aim of this work was to extend EIT to image not only from the cortex but also from deeper structures active in somatosensory processing, specifically the ventral posterolateral (VPL) nucleus of the thalamus. The direct response in the cortex and VPL following 2 Hz forepaw stimulation were quantified using a 57-channel epicortical electrode array and a 16-channel depth electrode. Impedance changes of -0.16 ±â€¯0.08% at 12.9 ±â€¯1.4 ms and -0.41 ±â€¯0.14% at 8.8±1.9 ms were recorded from the cortex and VPL respectively. For imaging purposes, two 57-channel epicortical electrode arrays were used with one placed on each hemisphere of the rat brain. Despite using parameters optimised toward measuring thalamic activity and undertaking extensive averaging, reconstructed activity was constrained to the cortical somatosensory forepaw region and no significant activity at a depth greater than 1.6 mm below the surface of the cortex could be reconstructed. An evaluation of the depth sensitivity of EIT was investigated in simulations using estimates of the conductivity change and noise levels derived from experiments. These indicate that EIT imaging with epicortical electrodes is limited to activity occurring 2.5 mm below the surface of the cortex. This depth includes the hippocampus and so EIT has the potential to image activity, such as epilepsy, originating from this structure. To image deeper activity, however, alternative methods such as the additional implementation of depth electrodes will be required to gain the necessary depth resolution.

A Versatile and Reproducible Multi-Frequency Electrical Impedance Tomography System.

A highly versatile Electrical Impedance Tomography (EIT) system, nicknamed the ScouseTom, has been developed. The system allows control over current amplitude, frequency, number of electrodes, injection protocol and data processing. Current is injected using a Keithley 6221 current source, and voltages are recorded with a 24-bit EEG system with minimum bandwidth of 3.2 kHz. Custom PCBs interface with a PC to control the measurement process, electrode addressing and triggering of external stimuli. The performance of the system was characterised using resistor phantoms to represent human scalp recordings, with an SNR of 77.5 dB, stable across a four hour recording and 20 Hz to 20 kHz. In studies of both haeomorrhage using scalp electrodes, and evoked activity using epicortical electrode mats in rats, it was possible to reconstruct images matching established literature at known areas of onset. Data collected using scalp electrode in humans matched known tissue impedance spectra and was stable over frequency. The experimental procedure is software controlled and is readily adaptable to new paradigms. Where possible, commercial or open-source components were used, to minimise the complexity in reproduction. The hardware designs and software for the system have been released under an open source licence, encouraging contributions and allowing for rapid replication.

Characterisation and imaging of cortical impedance changes during interictal and ictal activity in the anaesthetised rat.

Epilepsy affects approximately 50 million people worldwide, and 20-30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30-contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12ms prior to the IISs, followed by a steep rise in impedance within ~120ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future improve the localisation of seizure foci in the clinical setting.

Imaging fast electrical activity in the brain with electrical impedance tomography.

Imaging of neuronal depolarization in the brain is a major goal in neuroscience, but no technique currently exists that could image neural activity over milliseconds throughout the whole brain. Electrical impedance tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of impedance changes with non-invasive surface electrodes. We report EIT imaging of impedance changes in rat somatosensory cerebral cortex with a resolution of 2ms and <200µm during evoked potentials using epicortical arrays with 30 electrodes. Images were validated with local field potential recordings and current source-sink density analysis. Our results demonstrate that EIT can image neural activity in a volume 7×5×2mm in somatosensory cerebral cortex with reduced invasiveness, greater resolution and imaging volume than other methods. Modeling indicates similar resolutions are feasible throughout the entire brain so this technique, uniquely, has the potential to image functional connectivity of cortical and subcortical structures.

Noise-based correction for electrical impedance tomography.

Objective.Noisy measurements frequently cause noisy and inaccurate images in impedance imaging. No post-processing technique exists to calculate the propagation of measurement noise and use this to suppress noise in the image. The objectives of this work were (1) to develop a post-processing method for noise-based correction (NBC) in impedance tomography, (2) to test whether NBC improves image quality in electrical impedance tomography (EIT), (3) to determine whether it is preferable to use correlated or uncorrelated noise for NBC, (4) to test whether NBC works within vivodata and (5) to test whether NBC is stable across model and perturbation geometries.Approach.EIT was performedin silicoin a 2D homogeneous circular domain and an anatomically realistic, heterogeneous 3D human head domain for four perturbations and 25 noise levels in each case. This was validated by performing EIT for four perturbations in a circular, saline tank in 2D as well as a human head-shaped saline tank with a realistic skull-like layer in 3D. Images were assessed on the error in the weighted spatial variance (WSV) with respect to the true, target image. The effect of NBC was also tested forin vivoEIT data of lung ventilation in a human thorax and cortical activity in a rat brain.Main results.On visual inspection, NBC maintained or increased image quality for all perturbations and noise levels in 2D and 3D, both experimentally andin silico. Analysis of the WSV showed that NBC significantly improved the WSV in nearly all cases. When the WSV was inferior with NBC, this was either visually imperceptible or a transformation between noisy reconstructions. Forin vivodata, NBC improved image quality in all cases and preserved the expected shape of the reconstructed perturbation.Significance.In practice, uncorrelated NBC performed better than correlated NBC and is recommended as a general-use post-processing technique in EIT.

Anatomical and functional organization of cardiac fibers in the porcine cervical vagus nerve allows spatially selective efferent neuromodulation.

Cardiac disease progression reflects the dynamic interaction between adversely remodeled neurohumoral control systems and an abnormal cardiac substrate. Vagal nerve stimulation (VNS) is an attractive neuromodulatory option to dampen this dynamic interaction; however, it is limited by off-target effects. Spatially-selective VNS (sVNS) offers a promising solution to induce cardioprotection while mitigating off-target effects by specifically targeting pre-ganglionic parasympathetic efferent cardiac fibers. This approach also has the potential to enhance therapeutic outcomes by eliminating time-consuming titration required for optimal VNS. Recent studies have demonstrated the independent modulation of breathing rate, heart rate, and laryngeal contraction through sVNS. However, the spatial organization of afferent and efferent cardiac-related fibers within the vagus nerve remains unexplored. By using trial-and-error sVNS in vivo in combination with ex vivo micro-computed tomography fascicle tracing, we show the significant spatial separation of cardiac afferent and efferent fibers (179±55° SD microCT, p<0.05 and 200±137° SD, p<0.05 sVNS - degrees of separation across a cross-section of nerve) at the mid-cervical level. We also show that cardiac afferent fibers are located in proximity to pulmonary fibers consistent with recent findings of cardiopulmonary convergent neurons and circuits. We demonstrate the ability of sVNS to selectively elicit desired scalable heart rate decrease without stimulating afferent-related reflexes. By elucidating the spatial organization of cardiac-related fibers within the vagus nerve, our findings pave the way for more targeted neuromodulation, thereby reducing off-target effects and eliminating the need for titration. This, in turn, will enhance the precision and efficacy of VNS therapy in treating cardiac pathology, allowing for improved therapeutic efficacy.

Non-invasive imaging of neural activity with magnetic detection electrical impedance tomography (MDEIT): a modelling study.

Objectives.(1) Develop a computational pipeline for three-dimensional fast neural magnetic detection electrical impedance tomography (MDEIT), (2) determine whether constant current or constant voltage is preferable for MDEIT, (3) perform reconstructions of simulated neural activity in a human head model with realistic noise and compare MDEIT to EIT and (4) perform a two-dimensional study in a saline tank for MDEIT with optically pumped magnetometers (OPMs) and compare reconstruction algorithms.Approach.Forward modelling and image reconstruction were performed with a realistic model of a human head in three dimensions and at three noise levels for four perturbations representing neural activity. Images were compared using the error in the position and size of the reconstructed perturbations. Two-dimensional MDEIT was performed in a saline tank with a resistive perturbation and one OPM. Six reconstruction algorithms were compared using the error in the position and size of the reconstructed perturbations.Main results.A computational pipeline was developed in COMSOL Multiphysics, reducing the Jacobian calculation time from months to days. MDEIT reconstructed images with a lower reconstruction error than EIT with a mean difference of 7.0%, 5.5% and 11% for three noise cases representing current noise, reduced current source noise and reduced current source and magnetometer noise. A rank analysis concluded that the MDEIT Jacobian was less rank-deficient than the EIT Jacobian. Reconstructions of a phantom in a saline tank had a best reconstruction error of 13%, achieved using 0th-order Tikhonov regularisation with simulated noise-based correction.Significance.This study demonstrated that three-dimensional MDEIT for neural imaging is feasible and that MDEIT reconstructed superior images to EIT, which can be explained by the lesser rank deficiency of the MDEIT Jacobian. Reconstructions of a perturbation in a saline tank demonstrated a proof of principle for two-dimensional MDEIT with OPMs and identified the best reconstruction algorithm.

A combined cuff electrode array for organ-specific selective stimulation of vagus nerve enabled by Electrical Impedance Tomography.

Previously developed spatially-selective Vagus Nerve Stimulation (sVNS) allows the targeting of specific nerve fascicles through current steering in a multi-electrode nerve cuff but relies on a trial-and-error strategy to identify the relative orientation between electrodes and fascicles. Fast Neural Electrical Impedance Tomography (FN-EIT) has been recently used for imaging neural traffic in the vagus nerves of pigs in a cross-correlation study with sVNS and MicroCT fascicle tracking. FN-EIT has the potential for allowing targeted sVNS; however, up to now, stimulation and imaging have been performed with separate electrode arrays. In this study, different options were evaluated in-silico to integrate EIT and stimulation into a single electrode array without affecting spatial selectivity. The original pig vagus EIT electrode array geometry was compared with a geometry integrating sVNS and EIT electrodes, and with direct use of sVNS electrodes for EIT imaging. Modelling results indicated that both new designs could achieve image quality similar to the original electrode geometry in all tested markers (e.g., co-localisation error <100 µm). The sVNS array was considered to be the simplest due to the lower number of electrodes. Experimental results from testing evoked EIT imaging of recurrent laryngeal activity using electrodes from the sVNS cuff returned a signal-to-noise ratio similar to our previous study (3.9 ± 2.4 vs. 4.1 ± 1.5, N = 4 nerves from 3 pigs) and a lower co-localisation error (≈14% nerve diameter vs. ≈25%, N = 2 nerves from 2 pigs). Performing FN-EIT and sVNS on the same nerve cuff will facilitate translation to humans, simplify surgery and enable targeted neuromodulation strategies.

Organotopic organization of the porcine mid-cervical vagus nerve.

Introduction: Despite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function. Methods and results: We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization. Discussion: Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N = 4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fiber-containing fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders, and more.

Simplifying the hardware requirements for fast neural EIT of peripheral nerves.

Objective. The main objective of this study was to assess the feasibility of lowering the hardware requirements for fast neural electrical impedance tomography (EIT) in order to support the distribution of this technique. Specifically, the feasibility of replacing the commercial modules present in the existing high-end setup with compact and cheap customized circuitry was assessed.Approach. Nerve EIT imaging was performed on rat sciatic nerves with both our standard ScouseTom setup and a customized version in which commercial benchtop current sources were replaced by custom circuitry. Electrophysiological data and images collected in the same experimental conditions with the two setups were compared. Data from the customized setup was subject to a down-sampling analysis to simulate the use of a recording module with lower specifications.Main results. Compound action potentials (573 ± 287µV and 487 ± 279µV,p=0.28) and impedance changes (36 ± 14µV and 31 ± 16µV,p=0.49) did not differ significantly when measured using commercial high-end current sources or our custom circuitry, respectively. Images reconstructed from both setups showed neglibile (<1voxel, i.e. 40µm) difference in peak location and a high degree of correlation (R2 = 0.97). When down-sampling from 24 to 16 bits ADC resolution and from 100 to 50 KHz sampling frequency, signal-to-noise ratio showed acceptable decrease (<-20%), and no meaningful image quality loss was detected (peak location difference <1voxel, pixel-by-pixel correlationR2 = 0.99).Significance: The technology developed for this study greatly reduces the cost and size of a fast neural EIT setup without impacting quality and thus promotes the adoption of this technique by the neuroscience research community.

Overcoming temporal dispersion for measurement of activity-related impedance changes in unmyelinated nerves.

Objective.Fast neural electrical impedance tomography is an imaging technique that has been successful in visualising electrically evoked activity of myelinated fibres in peripheral nerves by measurement of the impedance changes (dZ) accompanying excitation. However, imaging of unmyelinated fibres is challenging due to temporal dispersion (TP) which occurs due to variability in conduction velocities of the fibres and leads to a decrease of the signal below the noise with distance from the stimulus. To overcome TP and allow electrical impedance tomography imaging in unmyelinated nerves, a new experimental and signal processing paradigm is required allowing dZ measurement further from the site of stimulation than compound neural activity is visible. The development of such a paradigm was the main objective of this study.Approach.A finite element-based statistical model of TP in porcine subdiaphragmatic nerve was developed and experimentally validatedex-vivo. Two paradigms for nerve stimulation and processing of the resulting data-continuous stimulation and trains of stimuli, were implemented; the optimal paradigm for recording dispersed dZ in unmyelinated nerves was determined.Main results.While continuous stimulation and coherent spikes averaging led to higher signal-to-noise ratios (SNRs) at close distances from the stimulus, stimulation by trains was more consistent across distances and allowed dZ measurement at up to 15 cm from the stimulus (SNR = 1.8 ± 0.8) if averaged for 30 min.Significance.The study develops a method that for the first time allows measurement of dZ in unmyelinated nerves in simulation and experiment, at the distances where compound action potentials are fully dispersed.

Fluoroscopic angiography in the gross anatomy dissection laboratory: visualizing the aortic arch and its branches in a cadaver.

We present fluoroscopic images of the aortic arch and its branches obtained in a first year medical gross anatomy teaching laboratory after an aberrant right subclavian artery was discovered during dissection. The aortic arch and its branches in the cadaver were filled with contrast medium in molten agar. After the agar solidified, a portable fluoroscope was used to obtain radiographic images. These post-mortem images were then compared with computed tomography images obtained while the individual was living. The embryology, prevalence, and clinical findings of this arterial variation are reviewed, and the importance of recognizing the presence of an aberrant right subclavian artery before performing various procedures is discussed. This exercise gave students the unique opportunity to compare the three-dimensional anatomy seen in the dissection laboratory with the two-dimensional presentation of that same anatomy in the radiographic images that they will see in clinical practice.

Selective Vagus Nerve Stimulation as a Therapeutic Approach for the Treatment of ARDS: A Rationale for Neuro-Immunomodulation in COVID-19 Disease.

Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury. It is induced by sepsis, aspiration, and pneumonia, including that caused by SARS coronavirus and human influenza viruses. The main pathophysiological mechanism of ARDS is a systemic inflammatory response. Vagus nerve stimulation (VNS) can limit cytokine production in the spleen and thereby dampen any systemic inflammation and inflammation-induced tissue damage in the lungs and other organs. However, the effects of increased parasympathetic outflow to the lungs when non-selective VNS is applied may result in bronchoconstriction, increased mucus secretion and enhance local pulmonary inflammatory activity; this may outweigh the beneficial systemic anti-inflammatory action of VNS. Organ/function-specific therapy can be achieved by imaging of localized fascicle activity within the vagus nerve and selective stimulation of identified organ-specific fascicles. This may be able to provide selective neuromodulation of different pathways within the vagus nerve and offer a novel means to improve outcome in ARDS. This has motivated this review in which we discuss the mechanisms of anti-inflammatory effects of VNS, progress in selective VNS techniques, and a possible application for ARDS.