Detection of inspiratory recruitment of atelectasis by automated lung sound analysis as compared to four-dimensional computed tomography in a porcine lung injury model.

BACKGROUND: Cyclic recruitment and de-recruitment of atelectasis (c-R/D) is a contributor to ventilator-induced lung injury (VILI). Bedside detection of this dynamic process could improve ventilator management. This study investigated the potential of automated lung sound analysis to detect c-R/D as compared to four-dimensional computed tomography (4DCT). METHODS: In ten piglets (25 ± 2 kg), acoustic measurements from 34 thoracic piezoelectric sensors (Meditron ASA, Norway) were performed, time synchronized to 4DCT scans, at positive end-expiratory pressures of 0, 5, 10, and 15 cmH2O during mechanical ventilation, before and after induction of c-R/D by surfactant washout. 4DCT was post-processed for within-breath variation in atelectatic volume (Δ atelectasis) as a measure of c-R/D. Sound waveforms were evaluated for: 1) dynamic crackle energy (dCE): filtered crackle sounds (600-700 Hz); 2) fast Fourier transform area (FFT area): spectral content above 500 Hz in frequency and above -70 dB in amplitude in proportion to the total amount of sound above -70 dB amplitude; and 3) dynamic spectral coherence (dSC): variation in acoustical homogeneity over time. Parameters were analyzed for global, nondependent, central, and dependent lung areas. RESULTS: In healthy lungs, negligible values of Δ atelectasis, dCE, and FFT area occurred. In lavage lung injury, the novel dCE parameter showed the best correlation to Δ atelectasis in dependent lung areas (R2 = 0.88) where c-R/D took place. dCE was superior to FFT area analysis for each lung region examined. The analysis of dSC could predict the lung regions where c-R/D originated. CONCLUSIONS: c-R/D is associated with the occurrence of fine crackle sounds as demonstrated by dCE analysis. Standardized computer-assisted analysis of dCE and dSC seems to be a promising method for depicting c-R/D.

Influence of inspiration to expiration ratio on cyclic recruitment and derecruitment of atelectasis in a saline lavage model of acute respiratory distress syndrome.

OBJECTIVE: Cyclic recruitment and derecruitment of atelectasis can occur during mechanical ventilation, especially in injured lungs. Experimentally, cyclic recruitment and derecruitment can be quantified by respiration-dependent changes in PaO2 (ΔPaO2), reflecting the varying intrapulmonary shunt fraction within the respiratory cycle. This study investigated the effect of inspiration to expiration ratio upon ΔPaO2 and Horowitz index. DESIGN: Prospective randomized study. SETTING: Laboratory investigation. SUBJECTS: Piglets, average weight 30 ± 2 kg. INTERVENTIONS: At respiratory rate 6 breaths/min, end-inspiratory pressure (Pendinsp) 40 cm H2O, positive end-expiratory pressure 5 cm H2O, and FIO2 1.0, measurements were performed at randomly set inspiration to expiration ratios during baseline healthy and mild surfactant depletion injury. Lung damage was titrated by repetitive surfactant washout to induce maximal cyclic recruitment and derecruitment as measured by multifrequency phase fluorimetry. Regional ventilation distribution was evaluated by electrical impedance tomography. Step changes in airway pressure from 5 to 40 cm H2O and vice versa were performed after lavage to calculate PO2-based recruitment and derecruitment time constants (TAU). MEASUREMENTS AND MAIN RESULTS: In baseline healthy, cyclic recruitment and derecruitment could not be provoked, whereas in model acute respiratory distress syndrome, the highest ΔPaO2 were routinely detected at an inspiration to expiration ratio of 1:4 (range, 52-277 torr [6.9-36.9 kPa]). Shorter expiration time reduced cyclic recruitment and derecruitment significantly (158 ± 85 torr [21.1 ± 11.3 kPa] [inspiration to expiration ratio, 1:4]; 25 ± 12 torr [3.3 ± 1.6 kPa] [inspiration to expiration ratio, 4:1]; p < 0.0001), whereas the PaO2/FIO2 ratio increased (267 ± 50 [inspiration to expiration ratio, 1:4]; 424 ± 53 [inspiration to expiration ratio, 4:1]; p < 0.0001). Correspondingly, regional ventilation redistributed toward dependent lung regions (p < 0.0001). Recruitment was much faster (TAU: fast 1.6 s [78%]; slow 9.2 s) than derecruitment (TAU: fast 3.1 s [87%]; slow 17.7 s) (p = 0.0078). CONCLUSIONS: Inverse ratio ventilation minimizes cyclic recruitment and derecruitment of atelectasis in an experimental model of surfactant-depleted pigs. Time constants for recruitment and derecruitment, and regional ventilation distribution, reflect these findings and highlight the time dependency of cyclic recruitment and derecruitment.

Evaluation of the Effectiveness of the Separate Anesthesia Induction Rooms on Multidisciplinary Work Flow in Operating Rooms.

Introduction: Operating suites are multidisciplinary units par excellence, and mostly they are the most expensive units in hospitals. Interdisciplinary workflow and efficiency are therefore crucial, which is influenced by floor plans varying from hospital to hospital. Most operating rooms are equipped with adjacent induction rooms, allowing preparation and anesthesia induction of the next patient, while the previous patient is still in the operating room. Parallelizing the working steps is thought to improve turn-over time, thus increasing throughput, number of cases and finally revenue. However, this assumption has never been challenged. Methods: We analyzed workflow during regular working hours in an operating suite equipped with a mixture of operating rooms (OR) with next door induction rooms and operating rooms without induction rooms. This allows a direct comparison of both structural elements for efficiency using utilization data over a 24-months period. Both settings were used for gynecological operations. Results: Key result is that induction rooms do not improve perioperative workflow including turn-over time. Instead, ORs without adjacent induction rooms have a significantly shorter turn-over time and OR occupancy duration per case, although surgical time and staffing were similar. Discussion: Adjacent induction rooms require extra space, funding, and high maintenance costs, but they do not speed up peri-operative processes. Modern anesthetic techniques allow for fast induction of and emergence from anesthesia. Induction rooms adjacent to the OR are no longer needed if general anesthesia without extended monitoring is used for the majority of cases.

Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model.

INTRODUCTION: Cyclic alveolar recruitment/derecruitment (R/D) is an important mechanism of ventilator-associated lung injury. In experimental models this process can be measured with high temporal resolution by detection of respiratory-dependent oscillations of the paO2 (ΔpaO2). A previous study showed that end-expiratory collapse can be prevented by an increased respiratory rate in saline-lavaged rabbits. The current study compares the effects of increased positive end-expiratory pressure (PEEP) versus an individually titrated respiratory rate (RRind) on intra-tidal amplitude of Δ paO2 and on average paO2 in saline-lavaged pigs. METHODS: Acute lung injury was induced by bronchoalveolar lavage in 16 anaesthetized pigs. R/D was induced and measured by a fast-responding intra-aortic probe measuring paO2. Ventilatory interventions (RRind (n=8) versus extrinsic PEEP (n=8)) were applied for 30 minutes to reduce Δ paO2. Haemodynamics, spirometry and Δ paO2 were monitored and the Ventilation/Perfusion distributions were assessed by multiple inert gas elimination. The main endpoints average and Δ paO2 following the interventions were analysed by Mann-Whitney-U-Test and Bonferroni's correction. The secondary parameters were tested in an explorative manner. RESULTS: Both interventions reduced Δ paO2. In the RRind group, ΔpaO2 was significantly smaller (P<0.001). The average paO2 continuously decreased following RRind and was significantly higher in the PEEP group (P<0.001). A sustained difference of the ventilation/perfusion distribution and shunt fractions confirms these findings. The RRind application required less vasopressor administration. CONCLUSIONS: Different recruitment kinetics were found compared to previous small animal models and these differences were primarily determined by kinetics of end-expiratory collapse. In this porcine model, respiratory rate and increased PEEP were both effective in reducing the amplitude of paO2 oscillations. In contrast to a recent study in a small animal model, however, increased respiratory rate did not maintain end-expiratory recruitment and ultimately resulted in reduced average paO2 and increased shunt fraction.

Quantitative molecular bioluminescence tomography.

SIGNIFICANCE: Bioluminescence imaging and tomography (BLT) are used to study biologically relevant activity, typically within a mouse model. A major limitation is that the underlying optical properties of the volume are unknown, leading to the use of a "best" estimate approach often compromising quantitative accuracy. AIM: An optimization algorithm is presented that localizes the spatial distribution of bioluminescence by simultaneously recovering the optical properties and location of bioluminescence source from the same set of surface measurements. APPROACH: Measured data, using implanted self-illuminating sources as well as an orthotopic glioblastoma mouse model, are employed to recover three-dimensional spatial distribution of the bioluminescence source using a multi-parameter optimization algorithm. RESULTS: The proposed algorithm is able to recover the size and location of the bioluminescence source while accounting for tissue attenuation. Localization accuracies of <1 mm are obtained in all cases, which is similar if not better than current "gold standard" methods that predict optical properties using a different imaging modality. CONCLUSIONS: Application of this approach, using in-vivo experimental data has shown that quantitative BLT is possible without the need for any prior knowledge about optical parameters, paving the way toward quantitative molecular imaging of exogenous and indigenous biological tumor functionality.

The Recovery Room: Transition from a Sleepy Postoperative Unit to a Vibrant and Cost-Effective Multipurpose Perioperative Care Unit.

The anesthesiologist, who traditionally was solely responsible for the intra- and postoperative care of patients, has undergone a transformation over the last decades and has emerged as a specialist for perioperative medicine. This includes preoperative assessment, preoperative stabilization of emergent cases, pre- or postoperative initiation of regional blocks, postoperative recovery and if needed postoperative intensive care outside the intensive care unit. A traditional recovery room, designated to take care of patients emerging from anesthesia only, no longer matches the modern anesthesiologist's demands. However, a traditional recovery room can easily be transformed into a vibrant multi-purpose perioperative care unit. Especially in smaller hospitals, this serves to match the anesthesiologist's demands without the financial burden of separate units for each task. On the contrary, it allows to transform the recovery room from a mandatory, but costly postoperative unit into a highly productive and demanding perioperative unit, allowing for extra revenues without corresponding costs. Worldwide, operating rooms are linked to an adjacent recovery room allowing patients to emerge from anesthesia until they fulfill the criteria to be transferred either to the regular ward or, in case of outpatient surgery, to be discharged home. Running these recovery rooms, however, is expensive due to the required technical equipment and the monthly costs of highly qualified anesthesia personnel. Despite these financial burdens, such recovery rooms are still mandatory to ensure full recovery after anesthesia and surgery. In most countries, there is no (full) reimbursement for providing recovery rooms, turning them into fiscally deficient units in most hospitals. However, recovery rooms can be further developed allowing hospitals to improve their caseloads, reduce turnover times in the operating room, and even help to manage a shortage of beds in the intensive care unit. In this paper, we describe the potential transformation from a traditional recovery room to a multi-purpose perioperative high-tech unit.

Simultaneous diffuse optical and bioluminescence tomography to account for signal attenuation to improve source localization.

Photonics based pre-clinical imaging is an extensively used technique to allow for the study of biologically relevant activity typically within a small-mouse model. Namely, bioluminescent tomography (BLT) attempts to tomographically reconstruct the 3-dimensional spatial light distribution of luminophores within a small animal given surface light measurements and known underlying optical parameters. Often it is the case where these optical parameters are unknown leading to the use of a 'best' guess approach or to direct measurements using either a multi-modal or dedicated system. Using these conventional approaches can lead to both inaccurate results and extending periods of imaging time. This work introduces the development of an algorithm that is used to accurately localize the spatial light distribution from a bioluminescence source within a subject by simultaneously reconstructing both the underlying optical properties and source spatial distribution and intensity from the same set of surface measurements. Through its application in 2- and 3-dimensional, homogeneous and heterogenous numerical models, it is demonstrated that the proposed algorithm is capable of replicating results as compared to 'gold' standard where the absolute optical properties are known. Additionally, the algorithm has been applied to experimental data using a tissue mimicking block phantom, recovering a spatial light distribution that has a localization error of ∼1.53 mm, which is better than previously published results without the need of assumptions regarding the underlying optical properties or source distribution.

Applications of compressive sensing in spatial frequency domain imaging.

SIGNIFICANCE: Spatial frequency domain imaging (SFDI) is an imaging modality that projects spatially modulated light patterns to determine optical property maps for absorption and reduced scattering of biological tissue via a pixel-by-pixel data acquisition and analysis procedure. Compressive sensing (CS) is a signal processing methodology which aims to reproduce the original signal with a reduced number of measurements, addressing the pixel-wise nature of SFDI. These methodologies have been combined for complex heterogenous data in both the image detection and data analysis stage in a compressive sensing SFDI (cs-SFDI) approach, showing reduction in both the data acquisition and overall computational time. AIM: Application of CS in SFDI data acquisition and image reconstruction significantly improves data collection and image recovery time without loss of quantitative accuracy. APPROACH: cs-SFDI has been applied to an increased heterogenic sample from the AppSFDI data set (back of the hand), highlighting the increased number of CS measurements required as compared to simple phantoms to accurately obtain optical property maps. A novel application of CS to the parameter recovery stage of image analysis has also been developed and validated. RESULTS: Dimensionality reduction has been demonstrated using the increased heterogenic sample at both the acquisition and analysis stages. A data reduction of 30% for the cs-SFDI and up to 80% for the parameter recover was achieved as compared to traditional SFDI, while maintaining an error of <10 % for the recovered optical property maps. CONCLUSION: The application of data reduction through CS demonstrates additional capabilities for multi- and hyperspectral SFDI, providing advanced optical and physiological property maps.

Single pixel hyperspectral bioluminescence tomography based on compressive sensing.

Photonics based imaging is a widely utilised technique for the study of biological functions within pre-clinical studies. Specifically, bioluminescence imaging is a sensitive non-invasive and non-contact optical imaging technique that is able to detect distributed (biologically informative) visible and near-infrared activated light sources within tissue, providing information about tissue function. Compressive sensing (CS) is a method of signal processing that works on the basis that a signal or image can be compressed without important information being lost. This work describes the development of a CS based hyperspectral Bioluminescence imaging system that is used to collect compressed fluence data from the external surface of an animal model, due to an internal source, providing lower acquisition times, higher spectral content and potentially better tomographic source localisation. The work demonstrates that hyperspectral surface fluence images of both block and mouse shaped phantom due to internal light sources could be obtained at 30% of the time and measurements it would take to collect the data using conventional raster scanning methods. Using hyperspectral data, tomographic reconstruction of internal light sources can be carried out using any desired number of wavelengths and spectral bandwidth. Reconstructed images of internal light sources using four wavelengths as obtained through CS are presented showing a localisation error of ∼3 mm. Additionally, tomographic images of dual-colored sources demonstrating multi-wavelength light sources being recovered are presented further highlighting the benefits of the hyperspectral system for utilising multi-colored biomarker applications.

Melatonin receptors mediate improvements of liver function but not of hepatic perfusion and integrity after hemorrhagic shock in rats.

OBJECTIVE: Melatonin has been demonstrated to attenuate organ damage in models of ischemia and reperfusion. Melatonin treatment before hemorrhagic shock has been shown to improve liver function and hepatic perfusion. Proposed mechanisms of the pineal hormone involve direct inactivation of reactive oxygen species and induction of antioxidative enzymes. However, recent evidence suggests a strong influence of melatonin receptor activation for these effects. Specific protection of organ function by melatonin after hemorrhage has not been investigated yet. In this study, we evaluated whether melatonin therapy after hemorrhagic shock improves liver function and hepatic perfusion, with emphasis on melatonin receptor activation. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats, 200-300 g (n = 10 per group). INTERVENTIONS: Animals underwent hemorrhagic shock (mean arterial pressure, 35 +/- 5 mm Hg for 90 mins) and were resuscitated with shed blood and Ringer's solution. At the end of shock, animals were treated with either melatonin (10 mg/kg, intravenously), melatonin receptor antagonist luzindole (2.5 mg/kg, intravenously) plus melatonin (10 mg/kg, intravenously), luzindole alone (2.5 mg/kg, intravenously), or vehicle. MEASUREMENTS AND MAIN RESULTS: After 2 hrs of reperfusion, either liver function was assessed by plasma disappearance rate of indocyanine green or intravital microscopy of the liver was performed for evaluation of hepatic perfusion, hepatocellular redox state, and hepatic integrity. Compared with vehicle controls, melatonin therapy after hemorrhagic shock significantly improved plasma disappearance rate of indocyanine green, hepatic redox state, hepatocellular injury, and hepatic perfusion index. Coadministration of luzindole completely abolished the protective effect with respect to liver function only, and improvements regarding hepatic redox state, perfusion, and integrity were comparable with melatonin treatment alone. CONCLUSIONS: Melatonin therapy after hemorrhagic shock improves liver function, hepatic perfusion, redox state, and hepatic integrity. With respect to liver function, beneficial effects of the pineal hormone seem to be dependent on melatonin receptor activation.

Melatonin pretreatment improves liver function and hepatic perfusion after hemorrhagic shock.

Exogenous administration of pineal hormone melatonin (MEL) has been demonstrated to attenuate organ damage in models of I/R and inflammation by antioxidative effects. However, specific organ-protective effects of MEL with respect to hemorrhagic shock have not been investigated yet. In the present study, we evaluated the role of MEL pretreatment for hepatic perfusion, redox state, and function after hemorrhage and resuscitation, with emphasis on MEL receptor activation. In a model of hemorrhagic shock (MAP 35 +/- 5 mmHg for 90 min) and reperfusion (2 h), we measured nicotinamide adenine dinucleotide phosphate (reduced form; NADPH) autofluorescence, hepatic microcirculation, and hepatocellular injury by intravital microscopy, as well as plasma disappearance rate of indocyanine green (PDRICG) as a sensitive maker of liver function in rat. Pretreatment with 10 mg kg(-1) MEL (i.v.) 15 min before induction of hemorrhage resulted in a significantly improved PDR(ICG) compared with controls (MEL/shock, 15.02% min(-1) +/- 2.9 SD vs. vehicle/shock, 6.18 +/- 4.6 SD; P = 0.001). Intravital microscopy after reperfusion revealed an improved hepatic perfusion index, redox state, and reduced hepatocellular injury in pretreated animals compared with the vehicle group. Melatonin receptor antagonist luzindole (LZN; 2.5 mg kg(-1)) almost completely abolished the protective effects of MEL pretreatment with respect to liver function (MEL + LZN/shock PDR(ICG), 7.31% min(-1) +/- 3.4 SD). Beneficial effects regarding hepatic perfusion, redox state, and cellular injury were not influenced by LZN, indicating that they may depend on antioxidative effects of MEL. However, liver function after hemorrhage is effectively maintained by MEL pretreatment via receptor-dependent pathways.

Assessment of regional ventilation distribution: comparison of vibration response imaging (VRI) with electrical impedance tomography (EIT).

BACKGROUND: Vibration response imaging (VRI) is a bedside technology to monitor ventilation by detecting lung sound vibrations. It is currently unknown whether VRI is able to accurately monitor the local distribution of ventilation within the lungs. We therefore compared VRI to electrical impedance tomography (EIT), an established technique used for the assessment of regional ventilation. METHODOLOGY/PRINCIPAL FINDINGS: Simultaneous EIT and VRI measurements were performed in the healthy and injured lungs (ALI; induced by saline lavage) at different PEEP levels (0, 5, 10, 15 mbar) in nine piglets. Vibration energy amplitude (VEA) by VRI, and amplitudes of relative impedance changes (rel.ΔZ) by EIT, were evaluated in seven regions of interest (ROIs). To assess the distribution of tidal volume (VT) by VRI and EIT, absolute values were normalized to the VT obtained by simultaneous spirometry measurements. Redistribution of ventilation by ALI and PEEP was detected by VRI and EIT. The linear correlation between pooled VT by VEA and rel.ΔZ was R(2) = 0.96. Bland-Altman analysis showed a bias of -1.07±24.71 ml and limits of agreement of -49.05 to +47.36 ml. Within the different ROIs, correlations of VT-distribution by EIT and VRI ranged between R(2) values of 0.29 and 0.96. ALI and PEEP did not alter the agreement of VT between VRI and EIT. CONCLUSIONS/SIGNIFICANCE: Measurements of regional ventilation distribution by VRI are comparable to those obtained by EIT.

TIP peptide inhalation in oleic acid-induced experimental lung injury: a post-hoc comparison.

BACKGROUND: The lectin-like domain of TNF-α mimicked by an inhaled TIP peptide represents a novel approach to attenuate a pulmonary edema in respiratory failure, which is on the threshold to clinical application. In extension to a previously published study, which reported an improved pulmonary function following TIP peptide inhalation in a porcine model of lavage-induced lung injury, a post-hoc comparison to additional experiments was conducted. This analysis addresses the hypothesis that oleic acid injection-induced capillary leakage and alveolar necrosis blunts the previously reported beneficial effects of TIP peptide inhalation in a porcine model. FINDINGS: Following animal care committee approval lung injury was induced by oleic acid injection in six pigs with a setting strictly according to a previously published protocol that was used for lung-lavaged pigs. Ventilation/perfusion-distribution by multiple inert gas elimination, parameters of gas exchange and pulmonary edema were assessed as surrogates of the pulmonary function. A significantly improved ventilation/perfusion-distribution following TIP inhalation was recognized only in the bronchoalveolar lavage model but not following oleic acid injection. The time course after oleic acid injection yielded no comparable impact of the TIP peptide on gas exchange and edema formation. CONCLUSIONS: Reported beneficial effects of the TIP peptide on gas exchange and pulmonary edema were not reproducible in the oleic acid injection model. This analysis assumes that sustained alveolar epithelial necrosis as induced by oleic acid injection may inhibit the TIP-induced edema resolution. Regarding the on-going clinical development of the TIP peptide this approach should hardly be effective in states of severe alveolar epithelial damage.

An offline auditory P300 brain-computer interface using principal and independent component analysis techniques for functional electrical stimulation application.

A brain-computer interface (BCI) provides technology that allows communication and control for people who are unable to interact with their environment. A P300 BCI exploits the fact that external or internal stimuli may provide a recognition response in the brain's electrical activity which may be recorded by an electroencephalogram (EEG) to act as a control signal. Additionally an auditory BCI does not require the user to avert their visual attention away from the task at hand and is thus more practical in a real environment than other visual stimulus BCIs.