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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Head orientation should be considered in ultrasound studies on carotid artery distensibility.

INTRODUCTION: During ultrasound distensibility assessment of the carotid artery, the patient's head is usually rotated sideward and slightly upward to optimize visibility of the carotid segment. Head rotation may affect vessel length and thus the longitudinal strain of the arterial segment. Because the longitudinal and circumferential mechanical behaviour of an artery are intrinsically related, head rotation may influence circumferential mechanics and thereby measured distensibility. METHODS: In 12 apparently healthy volunteers (age 22 ±â€Š3 years, mean ±â€ŠSD, 6 men/6 women), we investigated whether head rotation led to a change in absolute and relative distension of the common carotid artery (CCA) by performing ultrasound examinations with the head in two orientations. Additionally, CCA length was measured in both orientations with MRI to assess whether indeed a change in length occurred because of head rotation. Rotation-induced longitudinal strain was calculated from these lengths. RESULTS: We found a significant decrease of 0.054 mm (6.8%, P = 0.001) and 0.007 (5.6%, P = 0.019) in absolute and relative distension with head rotation, respectively. MRI measurements showed a significant rotation-induced longitudinal strain of 1.7 ±â€Š2.3% (P = 0.032). CONCLUSION: We conclude that consistent head rotation during a CCA ultrasound assessment causes a significant and clinically relevant bias in carotid artery distension measurements. The impact of unstandardized use of head rotation in studies with carotid distensibility as an outcome measure can therefore not be neglected; thus, standardization is highly recommendable.

Standard B-Mode Ultrasound Measures Local Carotid Artery Characteristics as Reliably as Radiofrequency Phase Tracking in Symptomatic Carotid Artery Patients.

Local arterial stiffness can be assessed with high accuracy and precision by measuring arterial distension on the basis of phase tracking of radiofrequency ultrasound signals acquired at a high frame rate. However, in clinical practice, B-mode ultrasound registrations are made at a low frame rate (20-50 Hz). We compared the accuracy and intra-subject precision of edge tracking and phase tracking distension in symptomatic carotid artery patients. B-mode ultrasound recordings (40 mm, 37 fps) and radiofrequency recordings (31 lines covering 29 mm, 300 fps) were acquired from the left common carotid artery of 30 patients (aged 45-88 y) with recent cerebrovascular events. To extract the distension, semi-automatic echo edge and phase tracking algorithms were applied to B-mode and radiofrequency recordings, respectively. Both methods exhibited a similar intra-subject precision for distension (standard deviation = 44 µm and 47 µm, p = 0.66) and mean distension (difference: -6 ± 69 µm, p = 0.67). Intra-subject distension inhomogeneity tends to be larger for edge tracking (difference: 15 ± 35 µm, p = 0.04). Standard B-mode scanners are suitable for measuring local artery characteristics in symptomatic carotid artery patients with good precision and accuracy.

Pressure-dependence of arterial stiffness: potential clinical implications.

BACKGROUND: Arterial stiffness measures such as pulse wave velocity (PWV) have a known dependence on actual blood pressure, requiring consideration in cardiovascular risk assessment and management. Given the impact of ageing on arterial wall structure, the pressure-dependence of PWV may vary with age. METHODS: Using a noninvasive model-based approach, combining carotid artery echo-tracking and tonometry waveforms, we obtained pressure-area curves in 23 hypertensive patients at baseline and after 3 months of antihypertensive treatment. We predicted the follow-up PWV decrease using modelled baseline curves and follow-up pressures. In addition, on the basis of these curves, we estimated PWV values for two age groups (mean ages 41 and 64 years) at predefined hypertensive (160/90 mmHg) and normotensive (120/80 mmHg) pressure ranges. RESULTS: Follow-up measurements showed a near 1 m/s decrease in carotid PWV when compared with baseline, which fully agreed with our model-prediction given the roughly 10 mmHg decrease in diastolic pressure. The stiffness-blood pressure-age pattern was in close agreement with corresponding data from the 'Reference Values for Arterial Stiffness' study, linking the physical and empirical bases of our findings. CONCLUSION: Our study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements.

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.

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.

Mechano-electrical feedback explains T-wave morphology and optimizes cardiac pump function: insight from a multi-scale model.

In the ECG, T- and R-wave are concordant during normal sinus rhythm (SR), but discordant after a period of ventricular pacing (VP). Experiments showed that the latter phenomenon, called T-wave memory, is mediated by a mechanical stimulus. By means of a mathematical model, we investigated the hypothesis that slow acting mechano-electrical feedback (MEF) explains T-wave memory. In our model, electromechanical behavior of the left ventricle (LV) was simulated using a series of mechanically and electrically coupled segments. Each segment comprised ionic membrane currents, calcium handling, and excitation-contraction coupling. MEF was incorporated by locally adjusting conductivity of L-type calcium current (g(CaL)) to local external work. In our set-up, g(CaL) could vary up to 25%, 50%, 100% or unlimited amount around its default value. Four consecutive simulations were performed: normal SR (with MEF), acute VP, sustained VP (with MEF), and acutely restored SR. MEF led to T-wave concordance in normal SR and to discordant T-waves acutely after restoring SR. Simulated ECGs with a maximum of 25-50% adaptation closely resembled those during T-wave memory experiments in vivo and also provided the best compromise between optimal systolic and diastolic function. In conclusion, these simulation results indicate that slow acting MEF in the LV can explain a) the relatively small differences in systolic shortening and mechanical work during SR, b) the small dispersion in repolarization time, c) the concordant T-wave during SR, and d) T-wave memory. The physiological distribution in electrophysiological properties, reflected by the concordant T-wave, may serve to optimize cardiac pump function.