Respiratory rate estimation from multi-channel signals using auto-regulated adaptive extended Kalman filter

Background: Respiration rate (RR) is a major cause for false alarms in intensive care units (ICU) and is primarily impaired by the artifact prone signals from skin-attached electrodes. Catheter-integrated esophageal electrodes are an alternative source for multi-channel physiological signals from multiple organs such as the heart and the diaphragm. Nonlinear estimation and sensor fusion are promising techniques for extracting the respiratory activity from such multi-component signals, however, pathologic breathing patterns with rapid RR changes typically observed in patient populations such as premature infants, pose significant challenges. Methods: We developed an auto-regulated adaptive extended Kalman filter (AA-EKF), which iteratively adapts the system model and the noise parameters based on the respiratory pattern. AA-EKF was tested on neonatal esophageal observations (NEO), and also on simulated multi-components signals created using waveforms in CapnoBase and ETNA databases. Results: AA-EKF derived RR (RRAA-EKF) from NEO had lower median (inter-quartile range) error of 0.1 (10.6) breaths per minute (bpm) compared to contemporary neonatal ICU monitors (RRNICU): −3.8 (15.7) bpm (p <0.001). RRAA-EKF error of −0.2 (3.2) bpm was achieved for ETNA wave forms and a bias (95% LOA) of 0.1 (−5.6, 5.9) in breath count. Mean absolute error (MAE) of RRAA-EKF with Capnobase waveforms, as median (inter-quartile range), at 0.3 (0.2) bpm was comparable to the literature reported values. Discussion: The auto-regulated approach allows RR estimation on a broad set of clinical data without requiring extensive patient specific adjustments. Causality and fast response times of EKF based algorithms makes the AA-EKF suitable for bedside monitoring in the ICU setting

Multichannel esophageal signals to monitor respiratory rate in preterm infants

Background Apnea of prematurity cannot be reliably measured with current monitoring techniques. Instead, indirect parameters such as oxygen desaturation or bradycardia are captured. We propose a Kalman filter-based detection of respiration activity and hence apnea using multichannel esophageal signals in neonatal intensive care unit patients. Methods We performed a single-center observational study with moderately preterm infants. Commercially available nasogastric feeding tubes containing multiple electrodes were used to capture signals with customized software. Multichannel esophageal raw signals were manually annotated, processed using extended Kalman filter, and compared with standard monitoring data including chest impedance to measure respiration activity. Results Out of a total of 405.4 h captured signals in 13 infants, 100 episodes of drop in oxygen saturation or heart rate were examined. Median (interquartile range) difference in respiratory rate was 0.04 (−2.45 to 1.48)/min between esophageal measurements annotated manually and with Kalman filter and −3.51 (−7.05 to −1.33)/min when compared to standard monitoring, suggesting an underestimation of respiratory rate when using the latter. Conclusions Kalman filter-based estimation of respiratory activity using multichannel esophageal signals is safe and feasible and results in respiratory rate closer to visual annotation than that derived from chest impedance of standard monitoring

Multichannel Esophageal Heart Rate Monitoring of Preterm Infants

Objective: Autonomic dysregulation in preterm infants requires continuous monitoring of vital signs such as heart rate over days to months. Unfortunately, common surface electrodes are prone to electrocardiography (ECG) signal artifacts and cause serious skin irritations during long-term use. In contrast, esophageal ECG is known to be very sensitive due to the proximity of electrodes and heart and insensitive to external influences. This study addresses if multichannel esophageal ECG qualifies for heart rate monitoring in preterm infants. Methods: We recorded esophageal leads with a multi-electrode gastric feeding tube in a clinical study with 13 neonates and compared the heartbeat detection performance with standard surface leads. A computationally simple and versatile ECG wave detection algorithm was used. Results: Multichannel esophageal ECG manifested heartbeat sensitivity and positive predictive value >98.5% and significant less false negative (FN) ECG waves as compared to surface ECG due to site-typical electrode motion artifacts. False positive bradycardia as indicated with >13 consecutive FN ECG waves was equally expectable in esophageal and surface channels. No adverse events were reported for the multi-electrode gastric feeding tube. Conclusion: Heart rate monitoring of preterm infants with multiple esophageal electrodes is considered as feasible and reliable. Less signal artifacts will improve the detection of bradycardia, which is crucial for immediate interventions, and reduce alarm fatigue. Significance: Due to the possibility to integrate the multichannel ECG into a gastric feeding tube and meanwhile omit harmful skin electrodes, the presented system has great potential to facilitate future intensive care of preterm infants

Functional and Structural Network Recovery after Mild Traumatic Brain Injury: A 1-Year Longitudinal Study

Brain connectivity after mild traumatic brain injury (mTBI) has not been investigated longitudinally with respect to both functional and structural networks together within the same patients, crucial to capture the multifaceted neuropathology of the injury and to comprehensively monitor the course of recovery and compensatory reorganizations at macro-level. We performed a prospective study with 49 mTBI patients at an average of 5 days and 1 year post-injury and 49 healthy controls. Neuropsychological assessments as well as resting-state functional and diffusion-weighted magnetic resonance imaging were obtained. Functional and structural connectome analyses were performed using network-based statistics. They included a cross-sectional group comparison and a longitudinal analysis with the factors group and time. The latter tracked the subnetworks altered at the early phase and, in addition, included a whole-brain group × time interaction analysis. Finally, we explored associations between the evolution of connectivity and changes in cognitive performance. The early phase of mTBI was characterized by a functional hypoconnectivity in a subnetwork with a large overlap of regions involved within the classical default mode network. In addition, structural hyperconnectivity in a subnetwork including central hub areas such as the cingulate cortex was found. The impaired functional and structural subnetworks were strongly correlated and revealed a large anatomical overlap. One year after trauma and compared to healthy controls we observed a partial normalization of both subnetworks along with a considerable compensation of functional and structural connectivity subsequent to the acute phase. Connectivity changes over time were correlated with improvements in working memory, divided attention, and verbal recall. Neuroplasticity-induced recovery or compensatory processes following mTBI differ between brain regions with respect to their time course and are not fully completed 1 year after trauma

Connectomic and surface-based morphometric correlates of acute mild traumatic brain injury

Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork suggests that mTBI can be conceptualized as a dysconnection syndrome. It remains unclear whether reduced WM integrity is the trigger for changes in cortical surface area or whether tissue deformations are the direct result of mechanical forces acting on the brain. The findings suggest that rapid identification of high-risk patients with the use of clinical scales should be assessed acutely as part of the mTBI protocol

Prefrontal cortical thickening after mild traumatic brain injury: a 1-year MRI study

OBJECTIVE: To evaluate group-by-time interactions between gray matter morphology of healthy controls and that of patients with mild traumatic brain injury (mTBI) as they transitioned from acute to chronic stages and to relate these findings to long-term cognitive alterations to identify distinct recovery trajectories between good (GO) and poor outcome (PO). METHODS: High-resolution T1-weighted MR images were acquired in 49 mTBI patients within 7 days and 1 year post-injury and at equivalent times in 49 healthy controls. Using linear mixed-effects models, we performed mass-univariate analyses and associated the results of the interaction with changes in cognitive performance. Morphological alterations indexed by increased or decreased cortical thickness have been expected mainly in frontal, parietal and temporal brain regions. RESULTS: A significant interaction was found in cortical thickness, spatially restricted to bilateral structures of the prefrontal cortex showing thickening in mTBI and normal developmental thinning in controls. A discrete thickness increase that can interpreted as the absence of cortical thinning typically seen in the healthy population was associated with cognitive recovery in the GO subgroup, but the exaggerated cortical thickening in the PO patients was linked to worsening cognitive performance. CONCLUSIONS: Thickness of the prefrontal cortex is subject to structural alterations during the first year after mTBI. Beside beneficial neuroplasticity, a prolonged state of neuroinflammation for symptomatic patients (maladaptive neuroplasticity) cannot be excluded. If the underlying cellular processes responsible for cortical thickening following mTBI have been determined, brain stimulation or even pharmacological intervention targeting the prefrontal cortex might promote endogenous neural restoration

Longitudinal study of a NoGo-P3 event-related potential component following mild traumatic brain injury in adults

BACKGROUND: Event-related potentials have repeatedly revealed electrophysiological markers of cognitive dysfunction associated with Mild Traumatic Brain Injury (MTBI) and may represent a sensitive tool to guide cognitive rehabilitative interventions. We previously found patients with symptomatic MTBI characterized by smaller P300 (or P3) wave amplitudes in a NoGo-P3 subcomponent in the acute phase of the injury. The goal of this longitudinal study was to investigate whether this early NoGo-P3 subcomponent differs over time in symptomatic MTBI patients and healthy controls. METHODS: We included adults with a diagnosis of MTBI and individually matched healthy controls tested at 1 week, 3 months, and 1 year after the MTBI. Symptoms were assessed by the Rivermead Post-Concussion Symptoms Questionnaire. NoGo-P3 was collected by using a cued Go/NoGo task and the relevant subcomponent was extracted by independent component analysis. RESULTS: Among 53 adults with a diagnosis of MTBI and 53 controls, we included 35 with symptomatic MTBI and 35 matched healthy controls (18 females each group; mean age 34.06±13.15 and 34.26±12.98 years). Amplitudes for the early NoGo-P3 subcomponent were lower for symptomatic MTBI patients than controls (P<0.05) at 1 week post-injury. Furthermore, mixed ANOVA revealed a significant time by group interaction (P<0.05), so the effect of time differed for symptomatic MTBI patients and healthy controls. The amplitudes for MTBI patients normalized from 1 week to 3 months post-injury and were comparable to those of controls from 3 months to 1 year post-injury. However, amplitudes for 3 MTBI patients with particularly severe complaints 1 year post-injury did not normalize and were lower than those for the remaining MTBI sample (P<0.05). CONCLUSIONS: Selected event-related potentials can be used as a sensitive and objective tool to illustrate the cognitive consequences of and recovery after MTBI

Altered cognitive processes in the acute phase of mTBI: an analysis of independent components of event-related potentials

Mild traumatic brain injuries (mTBI) generate acute disruptions of brain function and a subset of patients shows persisting cognitive, affective, and somatic symptoms. Deficits in the executive function domain are among the more frequent cognitive impairments reported by mTBI patients. By means of independent component analysis, event-related potential components from a visual cued go/nogo task, namely contingent negative variation (CNV) and NoGo-P3, were decomposed into distinct independent components that have been shown to be associated with the executive processes of energization, monitoring, and task setting. A group of symptomatic mTBI patients was compared with a group of controls matched for sex, age, and education. Patients showed reduced amplitudes in the late CNV as well as in the early NoGo-P3 subcomponents. Whereas the decreased CNVlate component indicates an impaired ability to generate representations of stimulus-response associations and to energize the maintenance of response patterns, the reduced P3NOGOearly component suggests a deficient ability to invest attentional effort in the initiation of response patterns in mTBI patients. Besides indicating the effects of mTBI on cognitive brain processing, the results may open up the possibility for assessing individual mTBI profiles and facilitate personalized rehabilitative measures