Comparison between Speckle Plethysmography and Photoplethysmography during Cold Pressor Test Referenced to Finger Arterial Pressure.

Speckle Plethysmography (SPG) and Photoplethysmography (PPG) are different biophotonics technologies that allow for measurement of haemodynamics. As the difference between SPG and PPG under low perfusion conditions is not fully understood, a Cold Pressor Test (CPT-60 s full hand immersion in ice water), was used to modulate blood pressure and peripheral circulation. A custom-built setup simultaneously derived SPG and PPG from the same video streams at two wavelengths (639 nm and 850 nm). SPG and PPG were measured at the right index finger location before and during the CPT using finger Arterial Pressure (fiAP) as a reference. The effect of the CPT on the Alternating Component amplitude (AC) and Signal-to-Noise Ratio (SNR) of dual-wavelength SPG and PPG signals was analysed across participants. Furthermore, waveform differences between SPG, PPG, and fiAP based on frequency harmonic ratios were analysed for each subject (n = 10). Both PPG and SPG at 850 nm show a significant reduction during the CPT in both AC and SNR. However, SPG showed significantly higher and more stable SNR than PPG in both study phases. Harmonic ratios were found substantially higher in SPG than PPG. Therefore, in low perfusion conditions, SPG seems to offer a more robust pulse wave monitoring with higher harmonic ratios than PPG.

An Implantable Neuromorphic Sensing System Featuring Near-sensor Computation and Send-on-Delta Transmission for Wireless Neural Sensing of Peripheral Nerves.

This paper presents a bio-inspired event-driven neuromorphic sensing system (NSS) capable of performing on-chip feature extraction and "send-on-delta" pulse-based transmission, targeting peripheral-nerve neural recording applications. The proposed NSS employs event-based sampling which, by leveraging the sparse nature of electroneurogram (ENG) signals, achieves a data compression ratio of >125×, while maintaining a low normalized RMS error of 4% after reconstruction. The proposed NSS consists of three sub-circuits. A clockless level-crossing (LC) ADC with background offset calibration has been employed to reduce the data rate, while maintaining a high signal to quantization noise ratio. A fully synthesized spiking neural network (SNN) extracts temporal features of compound action potential signals consumes only 13 µW. An event-driven pulse-based body channel communication (Pulse-BCC) with serialized address-event representation encoding (AER) schemes minimizes transmission energy and form factor. The prototype is fabricated in 40-nm CMOS occupying a 0.32-mm2 active area and consumes in total 28.2 µW and 50 µW power in feature extraction and full diagnosis mode, respectively. The presented NSS also extracts temporal features of compound action potential signals with 10-µs precision.

Camera-Derived Photoplethysmography (rPPG) and Speckle Plethysmography (rSPG): Comparing Reflective and Transmissive Mode at Various Integration Times Using LEDs and Lasers.

Background: Although both speckle plethysmography (SPG) and photoplethysmography (PPG) examine pulsatile changes in the vasculature using opto-electronics, PPG has a long history, whereas SPG is relatively new and less explored. The aim of this study was to compare the effects of integration time and light-source coherence on signal quality and waveform morphology for reflective and transmissive rSPG and rPPG. Methods: (A) Using time-domain multiplexing, we illuminated 10 human index fingers with pulsed lasers versus LEDs (both at 639 and 850 nm), in transmissive versus reflective mode. A synchronized camera (Basler acA2000-340 km, 25 cm distance, 200 fps) captured and demultiplexed four video channels (50 fps/channel) in four stages defined by illumination mode. From all video channels, we derived rPPG and rSPG, and applied a signal quality index (SQI, scale: Good > 0.95; Medium 0.95−0.85; Low 0.85−0.8; Negligible < 0.8); (B) For transmission videos only, we additionally calculated the intensity threshold area (ITA), as the area of the imaging exceeding a certain intensity value and used linear regression analysis to understand unexpected similarities between rPPG and rSPG. Results: All mean SQI-values. Reflective mode: Laser-rSPG > 0.965, LED-rSPG < 0.78, rPPG < 0.845. Transmissive mode: 0.853−0.989 for rSPG and rPPG at all illumination settings. Coherent mode: Reflective rSPG > 0.951, reflective rPPG < 0.740, transmissive rSPG and rPPG 0.990−0.898. Incoherent mode: Reflective all <0.798 and transmissive all 0.92−0.987. Linear regressions revealed similar R2 values of rPPG with rSPG (R2 = 0.99) and ITA (R2 = 0.98); Discussion: Laser-rSPG and LED-rPPG produced different waveforms in reflection, but not in transmission. We created the concept of ITA to investigate this behavior. Conclusions: Reflective Laser-SPG truly originated from coherence. Transmissive Laser-rSPG showed a loss of speckles, accompanied by waveform changes towards rPPG. Diffuse spatial intensity modulation polluted spatial-mode SPG.

Artefact Detection in Impedance Pneumography Signals: A Machine Learning Approach.

Impedance pneumography has been suggested as an ambulatory technique for the monitoring of respiratory diseases. However, its ambulatory nature makes the recordings more prone to noise sources. It is important that such noisy segments are identified and removed, since they could have a huge impact on the performance of data-driven decision support tools. In this study, we investigated the added value of machine learning algorithms to separate clean from noisy bio-impedance signals. We compared three approaches: a heuristic algorithm, a feature-based classification model (SVM) and a convolutional neural network (CNN). The dataset consists of 47 chronic obstructive pulmonary disease patients who performed an inspiratory threshold loading protocol. During this protocol, their respiration was recorded with a bio-impedance device and a spirometer, which served as a gold standard. Four annotators scored the signals for the presence of artefacts, based on the reference signal. We have shown that the accuracy of both machine learning approaches (SVM: 87.77 ± 2.64% and CNN: 87.20 ± 2.78%) is significantly higher, compared to the heuristic approach (84.69 ± 2.32%). Moreover, no significant differences could be observed between the two machine learning approaches. The feature-based and neural network model obtained a respective AUC of 92.77±2.95% and 92.51±1.74%. These findings show that a data-driven approach could be beneficial for the task of artefact detection in respiratory thoracic bio-impedance signals.

Platform for Analysis and Labeling of Medical Time Series.

Reliable and diverse labeled reference data are essential for the development of high-quality processing algorithms for medical signals, such as electrocardiogram (ECG) and photoplethysmogram (PPG). Here, we present the Platform for Analysis and Labeling of Medical time Series (PALMS) designed in Python. Its graphical user interface (GUI) facilitates three main types of manual annotations-(1) fiducials, e.g., R-peaks of ECG; (2) events with an adjustable duration, e.g., arrhythmic episodes; and (3) signal quality, e.g., data parts corrupted by motion artifacts. All annotations can be attributed to the same signal simultaneously in an ergonomic and user-friendly manner. Configuration for different data and annotation types is straightforward and flexible in order to use a wide range of data sources and to address many different use cases. Above all, configuration of PALMS allows plugging-in existing algorithms to display outcomes of automated processing, such as automatic R-peak detection, and to manually correct them where needed. This enables fast annotation and can be used to further improve algorithms. The GUI is currently complemented by ECG and PPG algorithms that detect characteristic points with high accuracy. The ECG algorithm reached 99% on the MIT/BIH arrhythmia database. The PPG algorithm was validated on two public databases with an F1-score above 98%. The GUI and optional algorithms result in an advanced software tool that allows the creation of diverse reference sets for existing datasets.

Vessel wall and adventitial DCE-MRI parameters demonstrate similar correlations with carotid plaque microvasculature on histology.

PURPOSE: To assess parameter agreement of volume transfer coefficient (Ktrans ) between two vascular regions and to study the correlation with microvessel density on histology. The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameter Ktrans is frequently used to study atherosclerotic plaque microvasculature. Ktrans has been reported using different descriptive statistics (mean, median, 75th percentile) either for the whole vessel wall or the adventitia in previous studies. MATERIALS AND METHODS: DCE-MRI parameter agreement was analyzed in 110 symptomatic patients with ≥2 mm carotid plaque that underwent a 3T carotid DCE-MRI examination. Ktrans was estimated in the entire vessel wall and adventitia. Twenty-three patients underwent carotid endarterectomy and were used for comparison with histological quantification of microvessel density of the plaque using CD31 immunohistochemistry. DCE-MRI parameters in the vessel wall regions were compared using Pearson's correlation coefficient, Bland-Altman analysis, and a two-sided paired samples t-test. Correlation of the DCE-MRI parameters with histology was studied using the Pearson's correlation coefficient. RESULTS: Median adventitial Ktrans was 5% higher (P = 0.003) than entire vessel wall Ktrans , with no differences for other descriptive statistics. Vessel wall and adventitial Ktrans showed similar moderately strong correlations with plaque microvessel density on histology (Pearson's ρ: 0.59-0.65 [P < 0.003] and 0.52-0.64 [P < 0.011], respectively). CONCLUSION: The similar moderately strong correlations for vessel wall and adventitial Ktrans with microvessel density on histology suggested that both regions reflected plaque microvessel density. Care should to be taken when comparing absolute values between studies. Future studies incorporating thresholds for risk stratification need to agree upon standardization of DCE-MRI parameters. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1053-1059.

High Spatial Inhomogeneity in the Intima-Media Thickness of the Common Carotid Artery is Associated with a Larger Degree of Stenosis in the Internal Carotid Artery: The PARISK Study.

Purpose Inhomogeneity of arterial wall thickness may be indicative of distal plaques. This study investigates the intra-subject association between relative spatial intima-media thickness (IMT) inhomogeneity of the common carotid artery (CCA) and the degree of stenosis of plaques in the internal carotid artery (ICA). Materials and Methods We included 240 patients with a recent ischemic stroke or transient ischemic attack and mild-to-moderate stenosis in the ipsilateral ICA. IMT inhomogeneity was extracted from B-mode ultrasound recordings. The degree of ICA stenosis was assessed on CT angiography according to the European Carotid Surgery Trial method. Patients were divided into groups with a low (≤ 2 %) and a high (> 2 %) IMT inhomogeneity scaled with respect to the local end-diastolic diameter. Results 182 patients had suitable CT and ultrasound measurements. Relative CCA-IMT inhomogeneity was similar for the symptomatic and asymptomatic side (difference: 0.02 %, p = 0.85). High relative IMT inhomogeneity was associated with a larger IMT (difference: 235 µm, p < 0.001) and larger degree of ICA stenosis (difference: 5 %, p = 0.023) which remained significant (p = 0.016) after adjustment for common risk factors. Conclusion Regardless of common risk factors, high relative CCA-IMT inhomogeneity is associated with a greater degree of ICA stenosis and is therefore indicative of atherosclerotic disease. The predictive value of CCA-IMT inhomogeneity for plaque progression and recurrence of cerebrovascular symptoms will be determined in the follow-up phase of PARISK.

Mechano-electrical coupling as framework for understanding functional remodeling during LBBB and CRT.

It is not understood why, after onset of left bundle-branch block (LBBB), acute worsening of cardiac function is followed by a further gradual deterioration of function, whereas most adverse cardiac events lead to compensatory adaptations. We investigated whether mechano-electrical coupling (MEC) can explain long-term remodeling with LBBB and cardiac resynchronization therapy (CRT). To this purpose, we used an integrative modeling approach relating local ventricular electrophysiology, calcium handling, and excitation-contraction coupling to global cardiovascular mechanics and hemodynamics. Each ventricular wall was composed of multiple mechanically and electrically coupled myocardial segments. MEC was incorporated by allowing adaptation of L-type Ca(2+) current aiming at minimal dispersion of local external work, an approach that we previously applied to replicate T-wave memory in a synchronous heart after a period of asynchronous activation. LBBB instantaneously decreased left-ventricular stroke work and increased end-diastolic volume. During sustained LBBB, MEC reduced intraventricular dispersion of mechanical workload and repolarization. However, MEC-induced reduction in contractility in late-activated regions was larger than the contractility increase in early-activated regions, resulting in further decrease of stroke work and increase of end-diastolic volume. Upon the start of CRT, stroke work increased despite a wider dispersion of mechanical workload. During sustained CRT, MEC-induced reduction in dispersion of workload and repolarization coincided with a further reduction in end-diastolic volume. In conclusion, MEC may represent a useful framework for better understanding the long-term changes in cardiac electrophysiology and contraction following LBBB as well as CRT.

Advancing the Local Pulse Wave Velocity Measurement-Wave Confluence Decomposition Using a Double Gaussian Propagation Model.

Background Pulse wave velocity (PWV) is a marker of arterial stiffness and local measurements could facilitate its widescale clinical use. However, confluence of incident and early reflected waves leads to biased spatiotemporal PWV estimates. Objective We introduce the Double Gaussian Propagation Model (DGPM) to measure local PWV in consideration of wave confluence (PWV[Formula: see text]) and compare it against conventional spatiotemporal PWV (PWV[Formula: see text]), with Bramwell-Hill PWV (PWV[Formula: see text]) and blood pressure (BP) as reference measures. Methods Ten subjects ranging from normotension to hypertension were repeatedly measured at rest and with induced PWV changes. Carotid distension waveforms over a 19 mm wide segment were acquired from ultrasonography, simultaneously with noninvasive continuous BP. Per cardiac cycle, the 8-parameter DGPM (amplitude, centroid, width, and velocity, respectively of forward and backward propagating wave) was fitted to the distension waveforms' systolic foot and dicrotic notch complexes. Corresponding PWV[Formula: see text] was computed from linear fittings of respective feature timings and distances. Regression analyses were conducted with PWV[Formula: see text] and PWV[Formula: see text] as predictors, and various PWV and BP measures as response variables. Results Whereas PWV[Formula: see text] correlations were insignificant, PWV[Formula: see text] estimated the reference PWV[Formula: see text] with a significant reduction in errors (P < 0.001), explained up to 65% PWV[Formula: see text] variability at rest, demonstrated higher intra-method consistency and correlated significantly with all BP measures (P < 0.001). Conclusion The proposed DGPM measures local carotid PWV in consideration of wave confluence, showing significant correlations with Bramwell-Hill PWV and BP at two distinct waveform complexes. Thereby PWV[Formula: see text] outperforms the conventional PWV[Formula: see text] in all investigated respects, potentially enabling PWV assessment in routine clinical practice.

Combined 18F-FDG PET-CT and DCE-MRI to assess inflammation and microvascularization in atherosclerotic plaques.

BACKGROUND AND PURPOSE: Hallmarks of vulnerable atherosclerotic plaques are inflammation that can be assessed with 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography, and increased neovascularization that can be evaluated by dynamic contrast-enhanced-MRI. It remains unclear whether these parameters are correlated or represent independent imaging parameters. This study determines whether there is a correlation between inflammation and neovascularization in atherosclerotic carotid plaques. METHODS: A total of 58 patients with transient ischemic attack or minor stroke in the carotid territory and ipsilateral carotid artery stenosis of 30% to 69% were included. All patients underwent positron emission tomography/computed tomography and dynamic contrast-enhanced-MRI of the carotid plaque. 18Fluorine-fluorodeoxyglucose standard uptake values with target/background ratio were determined. Neovascularization was quantified by the mean (leakage) volume transfer constant Ktrans. Spearman rank correlation coefficients between target/background ratio and Ktrans were calculated. RESULTS: Images suitable for further analysis were obtained in 49 patients. A weak but significant positive correlation between target/background ratio and mean Ktrans (Spearman ρ=0.30 [P=0.035]) and 75th percentile Ktrans (Spearman ρ=0.29 [P=0.041]) was found. CONCLUSIONS: There is a weak but significant positive correlation between inflammation on positron emission tomography/computed tomography and neovascularization as assessed with dynamic contrast-enhanced-MRI. Future studies should investigate which imaging modality has the highest predictive value for recurrent stroke, as these are not interchangeable. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00451529.

Comparing Remote Speckle Plethysmography and Finger-Clip Photoplethysmography with Non-Invasive Finger Arterial Pressure Pulse Waves, Regarding Morphology and Arrival Time.

OBJECTIVE: The goal was to compare Speckle plethysmography (SPG) and Photoplethysmography (PPG) with non-invasive finger Arterial Pressure (fiAP) regarding Pulse Wave Morphology (PWM) and Pulse Arrival Time (PAT). METHODS: Healthy volunteers (n = 8) were connected to a Non-Invasive Blood Pressure (NIBP) monitor providing fiAP pulse wave and PPG from a clinical transmission-mode SpO2 finger clip. Biopac recorded 3-lead ECG. A camera placed at a 25 cm distance recorded a video stream (100 fps) of a finger illuminated by a laser diode at 639 nm. A chest belt (Polar) monitored respiration. All signals were recorded simultaneously during episodes of spontaneous breathing and paced breathing. ANALYSIS: Post-processing was performed in Matlab to obtain SPG and analyze the SPG, PPG and fiAP mean absolute deviations (MADs) on PWM, plus PAT modulation. RESULTS: Across 2599 beats, the average fiAP MAD with PPG was 0.17 (0-1) and with SPG 0.09 (0-1). PAT derived from ECG-fiAP correlated as follows: 0.65 for ECG-SPG and 0.67 for ECG-PPG. CONCLUSION: Compared to the clinical NIBP monitor fiAP reference, PWM from an experimental camera-derived non-contact reflective-mode SPG setup resembled fiAP significantly better than PPG from a simultaneously recorded clinical transmission-mode finger clip. For PAT values, no significant difference was found between ECG-SPG and ECG-PPG compared to ECG-fiAP.

Pulse Arrival Time Segmentation Into Cardiac and Vascular Intervals - Implications for Pulse Wave Velocity and Blood Pressure Estimation.

OBJECTIVE: This study demonstrates a novel method for pulse arrival time (PAT) segmentation into cardiac isovolumic contraction (IVC) and vascular pulse transit time to approximate central pulse wave velocity (PWV). METHODS: 10 subjects (38 ± 10 years, 121 ± 12 mmHg SBP) ranging from normotension to hypertension were repeatedly measured at rest and with induced changes in blood pressure (BP), and thus PWV. ECG was recorded simultaneously with ultrasound-based carotid distension waveforms, a photoplethysmography-based peripheral waveform, noninvasive continuous and intermittent cuff BP. Central PAT was segmented into cardiac and vascular time intervals using a fiducial point in the carotid distension waveform that reflects the IVC onset. Central and peripheral PWVs were computed from (segmented) intervals and estimated arterial path lengths. Correlations with Bramwell-Hill PWV, systolic and diastolic BP (SBP/DBP) were analyzed by linear regression. RESULTS: Central PWV explained more than twice the variability (R2) in Bramwell-Hill PWV compared to peripheral PWV (0.56 vs. 0.27). SBP estimated from central PWV undercuts the IEEE mean absolute deviation threshold of 5 mmHg, significantly lower than peripheral PWV or PAT (4.2 vs. 7.1 vs. 10.1 mmHg). CONCLUSION: Cardiac IVC onset signaled in carotid distension waveforms enables PAT segmentation to obtain unbiased vascular pulse transit time. Corresponding PWV estimates provide the basis for single-site assessment of central arterial stiffness, confirmed by significant correlations with Bramwell-Hill PWV and SBP. SIGNIFICANCE: In a small-scale cohort, we present proof-of-concept for a novel method to estimate central PWV and BP, bearing potential to improve the practicality of cardiovascular risk assessment in clinical routines.

Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice.

BACKGROUND: Smoothelins are actin-binding proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. Their expression is strongly associated with the contractile phenotype of smooth muscle cells. Analysis of mice lacking both smoothelins (Smtn-A/B(-/-) mice) previously revealed a critical role for smoothelin-A in intestinal smooth muscle contraction. Here, we report on the generation and cardiovascular phenotype of mice lacking only smoothelin-B (Smtn-B(-/-)). METHODS AND RESULTS: Myograph studies revealed that the contractile capacity of the saphenous and femoral arteries was strongly reduced in Smtn-B(-/-) mice, regardless of the contractile agonist used to trigger contraction. Arteries from Smtn-A/B(-/-) compound mutant mice exhibited a similar contractile deficit. Smtn-B(-/-) arteries had a normal architecture and expressed normal levels of other smooth muscle cell-specific genes, including smooth muscle myosin heavy chain, alpha-smooth muscle actin, and smooth muscle-calponin. Decreased contractility of Smtn-B(-/-) arteries was paradoxically accompanied by increased mean arterial pressure (20 mm Hg) and concomitant cardiac hypertrophy despite normal parasympathetic and sympathetic tone in Smtn-B(-/-) mice. Magnetic resonance imaging experiments revealed that cardiac function was not changed, whereas distension of the proximal aorta during the cardiac cycle was increased in Smtn-B(-/-) mice. However, isobaric pulse wave velocity and pulse pressure measurements indicated normal aortic distensibility. CONCLUSIONS: Collectively, our results identify smoothelins as key determinants of arterial smooth muscle contractility and cardiovascular performance. Studies on mutations in the Smtn gene or alterations in smoothelin levels in connection to hypertension in humans are warranted.

Confluence of incident and reflected waves interferes with systolic foot detection of the carotid artery distension waveform.

OBJECTIVES: Local pulse wave velocity, a direct measure of arterial stiffness, can be measured using the systolic foot of the pressure waveform as the time reference point. The accuracy and precision of systolic foot identification, which may be disturbed by early wave reflections, heavily affects pulse wave transit time measurements. We investigated within subjects the existence of early wave reflections and their interference with systolic foot identification. METHODS: Fourteen ultrasound-derived distension waveforms, spaced over 16.4 mm, were simultaneously recorded in the CCA 3 cm proximal of the bifurcation of 12 young subjects. The second derivatives of the distension waveforms were calculated to identify the systolic foot and an inflection point preceding systolic peak distension. Pulse wave transit time was calculated as the time difference between the most proximal and most distal time-point, using either the systolic foot or the inflection point. The time to reflection (DeltaTSF_IP) was defined as the time difference between the systolic foot and the inflection point. RESULTS: Both transit times (TT SF and TT IP) could be determined with good intrasubject precision: 0.7 and 1.4 ms, respectively. The systolic foot is running forward, TT SF = 3.1 +/- 0.9 ms, whereas the inflection point appears to run backward, TT IP = -3.9 +/- 1.4 ms. DeltaTSF_IP was 44.3 +/- 8.8 ms. CONCLUSION: Despite the good intrasubject reproducibility, confluence of incident and reflected waves disturbs identification and discrimination of the systolic foot and the inflection point, resulting in biased estimates. Therefore both points are unsuitable for local pulse transit time measurements in the common carotid artery.

Perfluorohexane-loaded macrophages as a novel ultrasound contrast agent: a feasibility study.

PURPOSE: We investigated in vitro the potential of macrophages to act as targeted vehicle for ultrasound molecular imaging. PROCEDURES: Murine bone marrow-derived macrophages (BMM), incubated for 3 h with different concentrations of perfluorohexane (PFH) emulsions, were monitored by microscopy, flow cytometry, and ultrasound. Effects of PFH loading on BMM adhesion molecule (PSGL-1, VLA-4, Mac-1, LFA-1) expression were analyzed by flow cytometry. Static adhesion of PFH loaded BMM to unstimulated and TNF-alpha stimulated b.End5 endothelial cells was assessed by microscopy. RESULTS: Incubation of BMM with PFH emulsions resulted in dose-dependent uptake and increased echogenicity (max. 17 dB). Flow cytometry analyses revealed no down-regulation related to PFH loading of BMM adhesion molecule expression. Endothelial adhesion remained functional, even after 24 h, although PFH loading dose-dependently attenuated static adhesion. CONCLUSION: PFH loaded BMM may potentially serve as ultrasound contrast agent for noninvasive detection of atherogenic hotspots in arteries.

Systolic Time Interval Estimation Using Continuous Wave Radar With On-Body Antennas.

The estimation of systolic time intervals (STIs) is done using continuous wave (CW) radar at 2.45 GHz with an on-body antenna. MOTIVATION: In the state of the art, typically bioimpedance, heart sounds and/or ultrasound are used to measure STIs. All three methods suffer from insufficient accuracy of STI estimation due to various reasons. CW radar is investigated for its ability to overcome the deficiencies in the state of the art. METHODS: Ten healthy male subjects aged 25-45 were asked to lie down at a 30 incline. Recordings of 60 s were taken without breathing and with paced breathing. Heart sounds, electrocardiogram, respiration, and impedance cardiogram were measured simultaneously as reference. The radar antennas were placed at two positions on the chest. The antennas were placed directly on the body as well as with cotton textile in between. The beat to beat STIs have been determined from the reference signals as well as CW radar signals. RESULTS: The results indicate that CW radar can be used to estimate STIs in ambulatory monitoring. SIGNIFICANCE: The results pave way to a potentially more compact method of estimating STIs, which can be integrated into a wearable device.

Carotid artery pulse wave time characteristics to quantify ventriculoarterial responses to orthostatic challenge.

Central blood pressure waveforms contain specific features related to cardiac and arterial function. We investigated posture-related changes in ventriculoarterial hemodynamics by means of carotid artery (CA) pulse wave analysis. ECG, brachial cuff pressure, and common CA diameter waveforms (by M-mode ultrasound) were obtained in 21 healthy volunteers (19-30 yr of age, 10 men and 11 women) in supine and sitting positions. Pulse wave analysis was based on a timing extraction algorithm that automatically detects acceleration maxima in the second derivative of the CA pulse waveform. The algorithm enabled determination of isovolumic contraction period (ICP) and ejection period (EP): ICP=43+/-8 (SD) ms (4-ms precision), and EP=302+/-16 (SD) ms (5-ms precision). Compared with the supine position, in the sitting position diastolic blood pressure (DBP) increased by 7+/-4 mmHg (P<0.001) and R-R interval decreased by 49+/-82 ms (P=0.013), reflecting normal baroreflex response, whereas EP decreased to 267+/-19 ms (P<0.001). Shortening of EP was significantly correlated to earlier arrival of the lower body peripheral reflection wave (r2=0.46, P<0.001). ICP increased by 7+/-7 ms (P<0.001), the ICP-to-EP ratio increased from 14+/-3% (supine) to 19+/-3% (P<0.001) and the DBP-to-ICP ratio decreased by 7% (P=0.023). These results suggest that orthostasis decreases left ventricular output as a result of arterial wave reflections and, presumably, reduced cardiac preload. We conclude that CA ultrasound and pulse wave analysis enable noninvasive quantification of ventriculoarterial responses to changes in posture.

Measurement of local pulse wave velocity: effects of signal processing on precision.

Pulse wave velocity (PWV) provides information about the mechanical properties of the vessel: the stiffer the artery is, the higher the PWV will be. PWV measured over a short arterial segment facilitates direct characterization of local wall properties corrected for prevailing pressure without the necessity of measuring pulse pressure locally. Current methods for local PWV assessment have a poor precision, but it can be improved by applying linear regression to a characteristic time-point in distension waveforms as recorded simultaneously by multiple M-line ultrasounds. We investigated the precision of this method in a phantom scaled according to realistic in vivo conditions. Special attention was paid to the identification of the foot of the wave, using the maximum of the second derivative, the intersecting tangent and the 20% threshold method. Before foot detection, the distension waveforms were subjected to preprocessing with various filters. The precision of the maximum of the second derivative had a coefficient of variation (CV) of 0.45% and 10.45% for an eighth and second order low pass filter, respectively. The intersecting tangent and the threshold method were less sensitive to filtering; the CVs were 0.66% and 0.68% for the high order filter and 2.36% and 1.43% for the low order filter, respectively. We conclude that foot detection by a threshold of 20% or by the tangent method are more suitable to identify the foot of the wave to measure local PWV. Both methods are less sensitive to (phase) noise than the maximum of the second derivative method and exhibit good precision with a CV of less than 1%.

Heart rate lowering treatment leads to a reduction in vulnerable plaque features in atherosclerotic rabbits.

OBJECTIVE: To investigate the effect of a heart rate (HR) lowering agent (Ivabradine) on features of atherosclerotic plaque vulnerability with magnetic resonance imaging (MRI), ultrasound imaging, and histology. APPROACH AND RESULTS: Atherosclerosis was induced in the abdominal aorta of 19 rabbits. Nine rabbits were treated with Ivabradine (17 mg/kg/day) during the entire study period. At week 14, imaging was performed. Plaque size was quantified on contrast-enhanced T1-weighted MR images. Microvascular flow, density, and permeability was studied with dynamic contrast-enhanced MRI. Plaque biomechanics was studied by measuring the aortic distension with ultrasound. After, animals were sacrificed and histology was performed. HR was reduced by 16% (p = 0.026) in Ivabradine-treated animals. No differences in absolute and relative vessel wall beat-to-beat distension were found, but due to the reduction in HR, the frequency of the biomechanical load on the plaque was reduced. Plaque size (MR and histology) was similar between groups. Although microvessel density (histology) was similar between groups, AUC and Ktrans, indicative for plaque microvasculature flow, density, and permeability, were decreased by 24% (p = 0.029) and 32% (p = 0.037), respectively. Macrophage content (relative RAM11 positive area) was reduced by 44% (p<0.001) on histology in Ivabradine-treated animals. CONCLUSIONS: HR lowering treatment with Ivabradine in an atherosclerotic rabbit model is associated with a reduction in vulnerable plaque features. The current study suggests that HR reduction may be beneficial for inducing or maintaining a more stable plaque phenotype.

The systolic-diastolic difference in carotid stiffness is increased in type 2 diabetes: The Maastricht Study.

OBJECTIVE: In type 2 diabetes (T2D), increased arterial stiffening results from accelerated arterial wall matrix remodeling. The associated structural alterations modify the pressure dependency of arterial stiffness, which can be quantified by the systolic-diastolic difference in carotid pulse wave velocity (δPWV). We evaluated the association between T2D and δPWV as marker for matrix remodeling and whether δPWV may contain additional information beyond carotid stiffness (cPWV). METHODS: In 746 individuals from The Maastricht Study, 415 with normal glucose metabolism; 126 with prediabetes; and 205 with T2D, carotid pulse wave velocity (cPWV) and δPWV were determined by ultrasonography and tonometry. Multiple linear regression analyses were used to investigate associations of glucose metabolism status (with normal glucose metabolism as reference) with cPWV and δPWV, adjusting for age, sex, mean arterial pressure, prior cardiovascular disease, estimated glomerular filtration rate and smoking, and δPWV or cPWV as appropriate. RESULTS: After adjustment for age, sex, mean arterial pressure, prior cardiovascular disease, estimated glomerular filtration rate and smoking, T2D was associated with greater cPWV [ß (95% confidence interval) 0.376 (0.119; 0.632)] and δPWV [0.301 (0.013; 0.589)]. After additional adjustment for δPWV or cPWV, associations of T2D with cPWV and δPWV were attenuated [0.294 (0.048; 0.539) and 0.173 (-0.103; 0.449), respectively]. Prediabetes was not associated with either cPWV or δPWV. CONCLUSION: The systolic-diastolic difference in carotid stiffness is increased in T2D, but not prediabetes. Importantly, the association was not abolished by carotid stiffness, which suggests that systolic-diastolic difference in carotid stiffness carries additional information regarding arterial matrix remodeling.