Diaphragm Amplitude Research Articles

Diaphragm stimulation elicits phrenic afferent-induced neuromuscular plasticity

We hypothesized that activation of phrenic afferents induces diaphragm motor plasticity. In anesthetized and spontaneously breathing rats we delivered 40 Hz, low threshold (twitch and 1.5X twitch threshold), inspiratory-triggered stimulation to the left hemidiaphragm for 30 min to activate ipsilateral phrenic afferents. Diaphragm amplitude ipsilateral and contralateral to stimulation were increased for 60 min following both currents compared to time controls not receiving stimulation. Diaphragm stimulation was repeated in laminectomy controls or following a unilateral C3-C6 dorsal rhizotomy to eliminate phrenic afferent volleys. Laminectomy controls expressed neuromuscular plasticity post-stimulation. In contrast, ipsilateral and contralateral diaphragm amplitude following dorsal rhizotomy was lower than laminectomy controls and no different than time controls, suggesting diaphragm motor plasticity was not induced post-rhizotomy. Our results indicate that diaphragm stimulation induces a novel form of plasticity in the phrenic motor system which requires phrenic afferent activation. Respiratory motor plasticity elicited by diaphragm stimulation may have value as a therapeutic strategy to improve diaphragm output in neuromuscular conditions.

Novel Simulation for Dosimetry Impact of Diaphragm Respiratory Motion in 4D VMAT for Esophageal Cancer

<h3>Purpose/Objective(s)</h3> Respiratory motion affects the robustness of the dose distribution. For esophageal cancer (EC) near the esophagogastric junction, respiratory motion causes unintentional over- or under- dose distributions for the target. Although four-dimensional computed tomography (4DCT) is useful for robust evaluation, it increases the exposure dose and acquisition time. The objective of the current study is to propose the framework of the virtual 4DCT based robust evaluation method. Moreover, the robust evaluation with the virtual 4DCT was applied to EC patients. <h3>Materials/Methods</h3> We retrospectively evaluated 10 superficial (T1a - T1b) EC patients, had real 4DCT scans (real-4DCT). Target delineation was as follows; GTV: the primary lesion, CTV: GTV + 10mm (horizontal direction (H)), and 30mm (cranial and caudal direction (CC)). PTV: CTV + 8mm (H), and 15mm (CC). Volumetric modulated arc therapy (VMAT) was planned using double arcs which rotated 360° including two 60° lateral avoidance sectors during delivery. The virtual 4DCT defined as simulated 4DCT images (sim-4DCT) was generated with the simulated-organ motion function in commercial treatment planning system. Each sim-4DCT of 10 phases was generated from the end-inhalation CT image (reference image) by moving the diaphragm with mathematical equation proposed by Lujan et al (Med Phys 2003). First, we validated the accumulated CTV dose (D_99%, D_mean and D_1%) of 4D dose distribution in the sim-4DCT by comparing with the real-4DCT. The diaphragm motions (max, min and 60-90% tile of value) in the real 4DCT were obtained from an in-house program and adapted to sim-4DCTs. Then, the robustness of the CTV (D_99%, D_mean and D_1%) was evaluated by moving diaphragm from 5 to 20 mm. The percentage dose difference (ΔDx) between sim 4D-CT and static 3D-CT images which were used for planning was investigated. <h3>Results</h3> The accumulated CTV dose difference between sim-4DCT and real-4DCT was within 1% at 70% tile of the diaphragm motion. The mean CTV value of ΔD_99%, ΔD_mean and ΔD_1%, increased from 0.2% to 2.3%, 0.1% to 0.7 % and 0.1% to 0.6%, respectively, along with an increase in the diaphragm amplitude. For the diaphragm amplitude up to 15 mm, the mean ΔD_99%, ΔD_mean and ΔD_1% of CTV were within 3%. The largest percentage change was ΔD_99%, which was 2.2%. For the diaphragm amplitude of 20 mm, ΔD_99% for one patient was over 5%. The ΔD_99% of CTV for the other patients was within 3.9%. <h3>Conclusion</h3> This study proposed a novel method to evaluate the robust by generating virtual 4DCT. For EC case near the esophagogastric junction, the robust was enough if the diaphragm motion was within the PTV margin. The treatment planning with virtual 4DCT based robust evaluation method could propose an appropriate margin for PTV.

Respiratory Response‐Based Intermittent Hypoxia Treatment Leads to Diaphragmatic Long Term Facilitation in Adult Rats

Spinal cord injury (SCI) most commonly occurs at the cervical level and can lead to severe respiratory dysfunction such as paresis of the diaphragm, the primary mammalian inspiratory muscle. Intermittent hypoxia (IH) treatment (tx) can be applied to induce a prolonged increase in breathing motor output, known as long term facilitation (LTF), which is achievable following SCI in humans. However, this does not potentiate following multiple days of tx, indicating a need for optimization of existing IH protocols. Many seminal experiments demonstrating LTF in uninjured animals employ phrenic nerve recordings to measure respiratory response to moderate IH protocols consisting of 3, 5‐minute‐long periods of hypoxia (~11% O2) interspersed with periods of normoxia (~20.9% O2). This tx increases respiratory motor drive, stimulating serotonin (5‐HT) and growth factor‐dependent plasticity within the cervical spinal cord. Importantly, many studies have shown that the pattern and severity of IH dramatically affect LTF expression. Indeed, fundamental literature indicates that the details of 5‐HT‐based or other stimulation protocol are crucial for induction of plasticity across multiple phenomena, species, and preparations. In these studies, real‐time verification of the stimulus’ effect is key. Since LTF is a neuroplastic paradigm which depends on sequelae of effective stimulation of respiratory drive, we constructed an IH protocol which adapts to the animal’s real‐time respiratory response during treatment. We hypothesized that novel, respiratory response‐based (RRB) IH tx would induce a greater degree of diaphragmatic (dia) LTF than would standard fixed duration (FD) tx in uninjured adult rats. To develop RRB treatment, we first derived an initial setpoint from previous EMG/IH experiments in rats which reflected the magnitude of diaEMG amplitude increase expressed during hypoxic exposure. We then utilized this setpoint during each of three IH cycles such that the animal would qualify for progression from hypoxic to normoxic exposure by expressing a sufficiently robust diaEMG amplitude increase with respect to output measured in previous normoxic conditions. To evaluate our hypothesis, we conducted diaphragm EMG recordings in isoflurane‐anesthetized Sprague‐Dawley retired breeder rats before, during, and after three cycles of either moderate RRB or FD tx administered by nose cone. Preliminary data demonstrated that RRB treatment (n=2) resulted in LTF reaching 113.2% and 130.8% of baseline diaphragm amplitude for the two subjects at least 1‐hr. post‐IH. Further elucidation of appropriate hypoxia‐induced diaphragm amplitude setpoints is a necessary next step, followed by completion of greater numbers of both RRB and FD treatments to achieve adequate power for statistical comparison before applying RRB to the rat C2 hemisection injury model to explore the treatment’s utility in restoring breathing motor function once lost.

Acute Diaphragm Stimulation Elicits Phrenic Afferent Induced Neuromuscular Plasticity

Activation of phrenic afferents increases phrenic motor output and induces short‐term plasticity. Here we tested the hypothesis that activation of phrenic afferents via acute diaphragm stimulation induces neuromuscular plasticity within the phrenic motor system. Bilateral EMG activity was recorded from the mid‐costal diaphragm of anesthetized and spontaneously breathing rats. Inspiratory‐triggered stimulation was delivered to the left diaphragm for 30 minutes at twitch threshold (n=7; 0.6 ± 0 mA) or 1.5X twitch threshold (n=7; 1.0 ± 0.12 mA), and output was recorded for 60 minutes post‐stimulation. Arterial blood gas samples revealed that PaCO2 was no different than baseline during or after stimulation (P=0.2204) or across experimental groups (P=0.3534). Diaphragm amplitude ipsilateral and contralateral to stimulation was increased 60 minutes following threshold (P=0.0021 and P=0.0096) and 1.5X threshold (P=0.0003 and P=0.0448) stimulation compared to time controls (n=7). Separate groups of rats received 1.5X threshold stimulation and either a C3‐C6 laminectomy (n=6; 0.8 ± 0.06mA) or a left C3‐C6 dorsal rhizotomy (n=6; 0.7 ± 0.10mA) to prevent afferent input from reaching the spinal cord. Laminectomy controls continued to express neuromuscular plasticity ipsilateral (P=0.0017) and contralateral (P=0.0076) to stimulation compared to time controls. By contrast, following unilateral dorsal rhizotomy, ipsilateral and contralateral diaphragm amplitude 60 minutes post‐stimulation was lower than laminectomy controls (P=0.0107 and P=0.0115) and no different than time controls (P=0.5692 and P=0.4784), suggesting neuromuscular plasticity was not induced. Our results indicate that acute diaphragm stimulation induces a novel form of neuromuscular plasticity which requires activation of phrenic afferents. We hypothesize that phrenic afferent induced neuromuscular plasticity may be valuable as a therapeutic strategy following spinal cord injury.

Respiratory muscle training program supplemented by a cell-phone application in COPD patients with severe airflow limitation

PurposeThe purpose of this study was to implement a respiratory muscle training program through a mobile phone application for COPD patients with severe airflow limitation. MethodsWe conducted an experimental study to determine the efficacy of a six-month mobile phone application. At least three times a week for six months the patients would participate in an online training session. We evaluated the lung volumes, maximal inspiratory and expiratory pressure (MIP/MEP) and diaphragm amplitude. The tests were performed at the beginning and at the end of the study. ResultsThirty-four patients with severe COPD, aged between 44 and 67 years (Mean ± SD, 59.29 ± 6.063), accepted to follow a rehabilitation program based on the use of the Pneumocontrol application. We observed on increased of MEP from the pre-rehabilitation state (83.41 cmH2O) to the post-rehabilitation state (95.03 cmH2O), z = 5.087, p < 0.001. Also, the median MIP significantly increased from the pre-rehabilitation state to the post-rehabilitation state, z = 5.052, p < 0.001. Diaphragmatic distance also increased from 2.81 cm to 3.44 cm, z = 5.069, p < 0.001. ConclusionRespiratory muscle training supplemented through a cell phone-based application can improve respiratory muscle strength and diaphragm mobility.

Consequences of SUR2[A478V] Mutation in Skeletal Muscle of Murine Model of Cantu Syndrome.

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the ABCC9 and KCNJ8 genes, which encode ATP-sensitive K+ (KATP) channel subunits SUR2 and Kir6.1, respectively. Most CS patients have mutations in SUR2, the major component of skeletal muscle KATP, but the consequences of SUR2 GOF in skeletal muscle are unknown. (2) Methods: We performed in vivo and ex vivo characterization of skeletal muscle in heterozygous SUR2[A478V] (SUR2wt/AV) and homozygous SUR2[A478V] (SUR2AV/AV) CS mice. (3) Results: In SUR2wt/AV and SUR2AV/AV mice, forelimb strength and diaphragm amplitude movement were reduced; muscle echodensity was enhanced. KATP channel currents recorded in Flexor digitorum brevis fibers showed reduced MgATP-sensitivity in SUR2wt/AV, dramatically so in SUR2AV/AV mice; IC50 for MgATP inhibition of KATP currents were 1.9 ± 0.5 × 10−5 M in SUR2wt/AV and 8.6 ± 0.4 × 10−6 M in WT mice and was not measurable in SUR2AV/AV. A slight rightward shift of sensitivity to inhibition by glibenclamide was detected in SUR2AV/AV mice. Histopathological and qPCR analysis revealed atrophy of soleus and tibialis anterior muscles and up-regulation of atrogin-1 and MuRF1 mRNA in CS mice. (4) Conclusions: SUR2[A478V] “knock-in” mutation in mice impairs KATP channel modulation by MgATP, markedly so in SUR2AV/AV, with atrophy and non-inflammatory edema in different skeletal muscle phenotypes.

Ultrasonography validation for early alteration of diaphragm echodensity and function in the mdx mouse model of Duchenne muscular dystrophy.

The mdx mouse model of Duchenne muscular dystrophy is characterized by functional and structural alterations of the diaphragm since early stages of pathology, closely resembling patients’ condition. In recent years, ultrasonography has been proposed as a useful longitudinal non-invasive technique to assess mdx diaphragm dysfunction and evaluate drug efficacy over time. To date, only a few preclinical studies have been conducted. Therefore, an independent validation of this method by different laboratories is needed to increase results reliability and reduce biases. Here, we performed diaphragm ultrasonography in 3- and 6-month-old mdx mice, the preferred age-window for pharmacology studies. The alteration of diaphragm function over time was measured as diaphragm ultrasound movement amplitude. At the same time points, a first-time assessment of diaphragm echodensity was performed, as an experimental index of progressive loss of contractile tissue. A parallel evaluation of other in vivo and ex vivo dystrophy-relevant readouts was carried out. Both 3- and 6-month-old mdx mice showed a significant decrease in diaphragm amplitude compared to wild type (wt) mice. This index was well-correlated either with in vivo running performance or ex vivo isometric tetanic force of isolated diaphragm. In addition, diaphragms from 6-month-old dystrophic mice were also highly susceptible to eccentric contraction ex vivo. Importantly, we disclosed an age-dependent increase in echodensity in mdx mice not observed in wt animals, which was independent from abdominal wall thickness. This was accompanied by a notable increase of pro-fibrotic TGF-β1 levels in the mdx diaphragm and of non-muscle tissue amount in diaphragm sections stained by hematoxylin & eosin. Our findings corroborate the usefulness of diaphragm ultrasonography in preclinical drug studies as a powerful tool to monitor mdx pathology progression since early stages.

McSART: an iterative model-based, motion-compensated SART algorithm for CBCT reconstruction

4D cone beam computed tomography (CBCT) images of the thorax and abdomen can have reduced quality due to the limited number of projections per respiratory bin used in gated image reconstruction. In this work, we present a new algorithm to reconstruct high quality CBCT images by simultaneously reconstructing images and generating an associated respiratory motion model. This is done by updating model parameters to compensate for motion during the iterative image reconstruction process. CBCT image acquisition was simulated using the digital eXternal CArdiac Torso (XCAT) phantom, simulating breathing motion using four patient breathing traces. 4DCBCT images were reconstructed using the simultaneous algebraic reconstruction technique (SART), and compared to the proposed motion-compensated SART (McSART) algorithm. McSART used a motion model that describes tissue position as a function of diaphragm amplitude and velocity. The McSART algorithm alternately updated the motion model and image reconstruction, increasing the number of projections used for image reconstruction with every iteration. The model was able to interpolate and extrapolate deformations according to the magnitude of the surrogate signal. Without noise, the final iteration McSART images had HU errors at 31%, 34%, and 44% of their SART-reconstructed counterparts compared to ground truth XCAT images, with corresponding root-mean-square (RMS) motion model errors of 0.75 mm, 1.08 mm, and 1.17 mm respectively. With added image noise, McSART’s HU error was 31% of the SART-reconstructed 4DCBCT error, with a 1.43 mm RMS motion model error. Qualitatively, blurring and streaking artifacts were reduced in all the reconstructed images compared to 3D or SART-reconstructed 4DCBCT. The output of the algorithm was a high quality reference image and a corresponding motion model, that could be used to deform the reference image to any other point in a breathing cycle.

A retrospective 4D-MRI based on 2D diaphragm profiles for lung cancer patients.

4D-MRI, compared to 4D-CT, provides better soft-tissue contrast for target delineation. However, motion artefacts are often observed due to residual breathing variations. This study is to present a retrospective 4D-MRI reconstruction method based on 2D diaphragm profiles to improve the quality of 4D-MR images in the presence of significant breathing variations. The proposed 4D-MRI reconstruction method utilized diaphragm profiles (2D cine images on a single sagittal plan at the peak diaphragm) in conjunction with 4D-MR scans (2D-cine images on multiple pre-determined coronal planes along the anterior-posterior direction over a volume of interest). The diaphragm profile images were exploited to sort the 4D-MR scans by matching respiratory amplitude of diaphragm on the 4D-MR scans to the diaphragm profiles. To evaluate reconstructed 4D-MR images (ten 3D-MR images), sagittal images on ten 3D-MR images under free breathing (FB) and respiratory guidance (GB) were compared with diaphragm profile images (reference) from 13 healthy volunteers. Forty-four 4D-MR scan datasets were successfully reconstructed without distinct respiratory-related motion artefacts even with the presence of breathing variation. The differences in diaphragm profiles between the reference and corresponding reconstructed images in the mean of root mean square were similar between FB (3.5mm) and GB (3.0mm), confirming that the 4D-MRI reconstruction method was effective even with significant breathing variation. The diaphragm profiles were utilized to reconstruct 4D-MR images with spatial reliability and a fixed scan time under FB and GB. Our method can provide reliable 4D information of thoracic and abdominal regions for MRI-guided radiotherapy.

Vagal and spinal pulmonary afferents contribute to respiratory variability and gender‐specific response to mechanical challenge

Respiratory variability is important in order to respond to internal and external perturbations. While vagal afferents have been shown to be important for feedback during breathing, the influence of spinal afferents has not been as well described. We hypothesized that disruption of vagal and spinal afferents reduces respiratory variability during eupnea and alters respiratory response during thoracic mechanical restriction (banding). We measured costal diaphragm and thyroarytenoid electromyography (EMG) activity in sodium pentobarbital anesthetized spontaneously breathing male and female Sprague Dawley rats. We conducted three sets of experiments to elucidate contributions of vagal, and spinal afferents: A) inhalation of 10% nebulized lidocaine to attenuate pulmonary vagal afferents B) bilateral injections of 10% lidocaine into the pleural space to attenuate thoracic afferent feedback; C) bilateral tracheal vagotomy caudal to the larynx. Solutions of 10% lidocaine were mixed with saline and 2% Evans Blue dye to confirm the distribution of lidocaine following nebulization and injection. Additionally, banding was performed before and after each experimental protocol. Banding significantly increased costal diaphragm amplitude which was further increased with each intervention, however there was a gender specific increase in thyroarytenoid activity with only ~50% of males demonstrating this phenomenon. Both lidocaine protocols demonstrated features of vagotomy including reduction of each eupneic phase duration coefficient of variance as well as alterations in EMG amplitude. These results demonstrate gender‐specific effects of the respiratory system to challenges, and provide preliminary evidence of the importance of non‐vagal pulmonary feedback. Moreover, this present study could have broad clinical implications in disorders such as spinal cord injury.Support or Funding InformationThis work was supported by NIH grants HL 111215, HL 103415 and OT20D001983, the Craig F. Neilson Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, and the Commonwealth of Kentucky Challenge for Excellence.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Piezoelectric Resonance Pump Based on a Flexible Support.

Small volume changes are important factors that restrict the improvement of the performance of a piezoelectric diaphragm pump. In order to increase the volume change of the pump chamber, a square piezoelectric vibrator with a flexible support is proposed in this paper and used as the driving unit of the pump. The pump chamber diaphragm was separated from the driving unit, and the resonance principle was used to amplify the amplitude of the pump diaphragm. After analyzing the working principle of the piezoelectric resonance pump and establishing the motion differential equation of the vibration system, prototypes with different structural parameters were made and tested. The results show that the piezoelectric resonance pump resonated at 236 Hz when pumping air. When the peak-to-peak voltage of the driving power was 220 V, the amplitude of the diaphragm reached a maximum value of 0.43933 mm, and the volume change of the pump was correspondingly improved. When the pump chamber height was 0.25 mm, the output flow rate of pumping water reached a maximum value of 213.5 mL/min. When the chamber height was 0.15 mm, the output pressure reached a maximum value of 85.2 kPa.

Heat Transfer Performance of a Synthetic Jet at Various Driving Frequencies and Diaphragm Amplitude

The miniaturization of electronic devices with high-speed processing components is aggravating the heat generation of devices/systems. Space constraint has become a major issue in electronic cooling as these system can no longer accommodate a fan and liquid piping. Synthetic jets are an alternative solution because of their low operating cost and low space requirement. In this work, we fabricated a synthetic jet and analyzed its amplitude motion at different frequencies to measure the enhancement of heat transfer. ANSYS FLUENT $$^{{\textregistered }}$$ 15 was used to identify the vortex formation related to the fluid velocity profile during the ejection and suction phases to substantiate heat transfer performance. The amplitude was determined by conducting laser Doppler experiments for each frequency applied. The experimental results were validated against numerical prediction using an appropriate turbulent model and a structured meshing grade. The conformity between the numerical and experimental results was found to be < 5%. The maximum velocity was observed at 500 Hz driving frequency, which agreed with the result that the resonance frequency at 500 Hz had the highest amplitude and sweep volume. A large vortex formation was also recorded during the ejection phase at 500 Hz, resulting in the maximum temperature drop and a higher heat transfer coefficient (h) than the nonresonance frequency. The synthetic jet operating at the resonance frequency produced the maximum amplitude, fluid velocity, and large vortex formation proportional to h.

Impact of chronic exposure to the pesticide chlorpyrifos on respiratory parameters and sleep apnea in juvenile and adult rats.

The widely used organophosphorus pesticide chlorpyrifos (CPF) is often detected in food. CPF inhibits acetylcholinesterase and can modify muscle contractility and respiratory patterns. We studied the effects of chronic exposure to CPF on respiratory parameters and diaphragm contractility in 21- and 60-days old rats. Pregnant rats were exposed to oral CPF (1 or 5 mg/ kg /day: CPF-1 or CPF-5 groups vs vehicle: controls) from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle) thereafter. Two developmental time points were studied: weaning (day 21) and adulthood (day 60). Whole-body plethysmography was used to score breathing patterns and apnea index during sleep. Then, diaphragm strips were dissected for the assessment of contractility and acetylcholinesterase activity. Results showed that the sleep apnea index was higher in CPF-exposed rats than in controls. In adult rats, the expiratory time and tidal volume were higher in CPF-exposed animals than in controls. At both ages, the diaphragm’s amplitude of contraction and fatigability index were higher in the CPF-5 group, due to lower acetylcholinesterase activity. We conclude that chronic exposure to CPF is associated with higher sleep apnea index and diaphragm contractility, and modifies respiratory patterns in sleeping juvenile and adult rats.

Validation of ultrasonography for non-invasive assessment of diaphragm function in muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe, degenerative muscle disease that is commonly studied using the mdx mouse. The mdx diaphragm muscle closely mimics the pathophysiological changes in DMD muscles. mdx diaphragm force is commonly assessed ex vivo, precluding time course studies. Here we used ultrasonography to evaluate time-dependent changes in diaphragm function in vivo, by measuring diaphragm movement amplitude. In mdx mice, diaphragm amplitude decreased with age and values were much lower than for wild-type mice. Importantly, diaphragm amplitude strongly correlated with ex vivo specific force values. Micro-dystrophin administration increased mdx diaphragm amplitude by 26% after 4weeks. Diaphragm amplitude correlated positively with ex vivo force values and negatively with diaphragm fibrosis, a major cause of DMD muscle weakness. These studies validate diaphragm ultrasonography as a reliable technique for assessing time-dependent changes in mdx diaphragm function in vivo. This technique will be valuable for testing potential therapies for DMD. Duchenne muscular dystrophy (DMD) is a severe, degenerative muscle disease caused by dystrophin mutations. The mdx mouse is a widely used animal model of DMD. The mdx diaphragm muscle most closely recapitulates key features of DMD muscles, including progressive fibrosis and considerable force loss. Diaphragm function in mdx mice is commonly evaluated by specific force measurements ex vivo. While useful, this method only measures force from a small muscle sample at one time point. Therefore, accurate assessment of diaphragm function in vivo would provide an important advance to study the time course of functional decline and treatment benefits. Here, we evaluated an ultrasonography technique for measuring time-dependent changes of diaphragm function in mdx mice. Diaphragm movement amplitude values for mdx mice were considerably lower than those for wild-type, decreased from 8 to 18months of age, and correlated strongly with ex vivo specific force. We then investigated the time course of diaphragm amplitude changes following administration of an adeno-associated viral vector expressing Flag-micro-dystrophin (AAV-μDys) to young adult mdx mice. Diaphragm amplitude peaked 4weeks after AAV-μDys administration, and was 26% greater than control mdx mice at this time. This value decreased slightly to 21% above mdx controls after 12weeks of treatment. Importantly, diaphragm amplitude again correlated strongly with ex vivo specific force. Also, diaphragm amplitude and specific force negatively correlated with fibrosis levels in the muscle. Together, our results validate diaphragm ultrasonography as a reliable technique for assessing time-dependent changes in dystrophic diaphragm function in vivo, and for evaluating potential therapies for DMD.

Fabrication and characterization of MEMS piezoelectric synthetic jet actuators with bulk-micromachined PZT thick film

In this paper, we have developed a fabrication process for micro synthetic jet actuators (SJA) by bonding a high-quality Pb (Zr,Ti) O3 (PZT) ceramic wafer to a silicon wafer using epoxy resin at low temperature (<150 °C). The bulk-PZT was lapped and polished to be PZT thick film by chemical mechanical polishing (CMP) method, and patterned by wet-etching method. The cavity and orifice of SJA were formed by inductive coupled plasma etching (ICP) method. A MEMS piezoelectric SJA was then completed and characterized, including the performance of the PZT thick film. While the dimension of bonded PZT thick film is about 6,000 × 6,000 × 100 μm, and the dimension of Si membrane is about 1,000 × 1,000 × 20 μm. The experimental results show that the maximum center amplitude of PZT-Si diaphragm is 15.05 μm at Vp-p of 90 V and the resonant frequency of 5 kHz, and the maximum jet velocity is higher than 11 m/s. This novel process has great potential to fabricate MEMS piezoelectric synthetic jet actuators.

Diaphragm motion and lung function prediction in patients operated for lung cancer – a pilot study on 27 patients

BackgroundThe influence of the diaphragm motion to the accuracy of postoperative lung function prediction after the lung resction is still debatable.MethodsProspective study that included 27 patients who underwent a lung resection for cancer. Diaphragm movements were assessed radiographically and by ultrasonography before the operation and postoperatively, with the lung fully expanded. The relationship between the diaphragm movements and differences between ppo FEV1 and measured postoperative FEV1, was analysed by expressing diaphragm movements as preoperative diaphragm amplitudes, preoperative-postoperative amplitude differences or in relation to fixed intrathoracic distances.ResultsThe mean difference between preoperative and postoperative diaphragm amplitudes of the diseased side was 2.42 ± 1.25 cm and 2.11 ± 2.04 cm when measured radiographically and by ultra sound respectively (p > 0.05). A significant positive correlation was found for the entire group only between the patients’ height and the differences ppo FEV1 - actual FEV1: the prediction was more unprecise in taller patients. With the cut-off value of 550 ml for differences between ppo FEV1 and actual FEV1, a significant inverse correlation was found only if the preoperative ipsilateral diaphragm amplitude was presented as a percentage of the preoperative apex-base distance in inspiration. For right-sided tumours, the greater the difference between preoperative and postoperative ipsilateral diaphragm amplitudes, the greater discrepancy between predicted and actual postoperative FEV1. For left-sided tumours, inverse correlation existed if the preoperative diaphragm amplitude was presented as a percentage of the preoperative distance apex-base.ConclusionDiaphragm movements influence the accuracy of the postoperative lung function prediction.

THE EFFECTS OF GASTRIN-RELEASING PEPTIDE MICROINJECTIONS INTO THE PRE-BOTZINGER COMPLEX ON THE RESPIRATORY PARAMETERS OF RATS

In the article, the results of investigation of the respiratory effects of gastrinreleasing peptide microjections into the pre-Botzinger complex are presented. It was found that microinjections of neuropeptide induced an increase in respiratory rate, tidal volume, amplitude of diaphragm and external intercostal muscles bursting activity. The statistically significant respiratory responses observed when 10^-5 M of GRP was used, while 10^-8 M of GRP appeared to be sub-threshold and didn’t alter the breathing pattern and activity of inspiratory muscles. The suggested mechanisms of action of GRP at the level of pre-Botzinger complex are discussed.

Heat transfer enhancement in micro-channel with multiple synthetic jets

A three-dimensional computational model has been developed to investigate the effect of multiple synthetic jets interaction with cross-flow in micro-channel on the cooling of microchip. Studies were performed with the use of two micro jets being in-phase and 180° out-of-phase at two different operating frequencies and a fixed diaphragm amplitude. The addition of one synthetic jet was shown to achieve greater mixing of flow in the micro-channel than those with single synthetic jet. Greater heat transfer enhancement was achieved with double synthetic jets. Results showed that greater cooling enhancement could be achieved with the out-of-phase flow configuration at oscillating frequency of 560Hz compared with the in-phase flow configuration. However, the effect of the actuation phase at a frequency of 1120Hz was found to be insignificant. With double synthetic jet actuators operating out-of-phase, a mere 0.1K reduction was achieved in maximum silicon temperature compared with in-phase flow jets. The greater the mixing of flow in the micro-channel in either in-phase or out-of-phase flow configuration due to higher jets Reynolds number resulted in the constraint in further cooling enhancement despite having different phases of the flow configuration.

SU‐E‐J‐119: Development of Voxel‐by‐Voxel Respiratory Lung Motion Simulation Model

Purpose: 1. To justify the respiratory induced lung tumor motion is correlated to volume change in lung 2.To show that such motion is a hysteresis type of motion, i.e. the inspiration and expiration paths the tumor follows are different. Methods: The model equation was generated based on the data obtained from the axial displacement versus volume plot of the lung by Verschakelen et al (1989). The time variation of the lung volume change was introduced using linear and non‐linear functions. After comparison with literature (Lu et al, 2006), we verified the non‐linear time variation is more reliable. The lung motion amplitude as a function of time was then plotted and fitted with sinusoidal function. The dynamic 3D lung motion was simulated as a function of time based on the model equation. Two independent simulations were performed and compared: 1. Independent tumor motion amplitude and lung volume change. 2. Lung tumor motion dependent on the lung volume change. Results: 1.The model function generated from the fitting curve is periodic function with even power. This agrees with the periodic nature of respiration induced lung motion and also with the fact that longer time is spent at the end of exhalation than at the end of inhalation, which is proven by other researchers too. 2.Based on the simulated dynamic lung motion, we observe that the lung tumor motion is well correlated to the lung volume change. Conclusions: Clinically, chest wall as well as diaphragm amplitude measurements are used to provide lung motion gating window. In this study, we observe that respiration induced motion of the lung tumor is correlated to the lung volume change, and this can give a good prediction of: 1. The 3D location of the lung tumor. 2. Density change of the lung.

Diaphragm long-term facilitation following acute intermittent hypoxia during wakefulness and sleep

Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). Here, we tested four hypotheses in unanesthetized, spontaneously breathing rats using radiotelemetry for EEG and diaphragm electromyography (Dia EMG) activity: 1) AIH induces LTF in Dia EMG activity; 2) diaphragm LTF (Dia LTF) is more robust during sleep vs. wakefulness; 3) AIH (or repetitive AIH) disrupts natural sleep-wake architecture; and 4) preconditioning with daily AIH (dAIH) for 7 days enhances Dia LTF. Sleep-wake states and Dia EMG were monitored before (60 min), during, and after (60 min) AIH (10, 5-min hypoxic episodes, 5-min normoxic intervals; n = 9), time control (continuous normoxia, n = 8), and AIH following dAIH preconditioning for 7 days (n = 7). Dia EMG activities during quiet wakefulness (QW), rapid eye movement (REM), and non-REM (NREM) sleep were analyzed and normalized to pre-AIH values in the same state. During NREM sleep, diaphragm amplitude (25.1 ± 4.6%), frequency (16.4 ± 4.7%), and minute diaphragm activity (amplitude × frequency; 45.2 ± 6.6%) increased above baseline 0-60 min post-AIH (all P < 0.05). This Dia LTF was less robust during QW and insignificant during REM sleep. dAIH preconditioning had no effect on LTF (P > 0.05). We conclude that 1) AIH induces Dia LTF during NREM sleep and wakefulness; 2) Dia LTF is greater in NREM sleep vs. QW and is abolished during REM sleep; 3) AIH and repetitive AIH disrupt natural sleep patterns; and 4) Dia LTF is unaffected by dAIH. The capacity for plasticity in spinal pump muscles during sleep and wakefulness suggests an important role in the neural control of breathing.