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Heart rate variability (HRV) is an important metric with a variety of applications in clinical situations such as cardiovascular diseases, diabetes mellitus, and mental health. HRV data can be potentially obtained from electrocardiography and photoplethysmography signals, then computational techniques such as signal filtering and data segmentation are used to process the sampled data for calculating HRV measures. However, uncertainties arising from data acquisition, computational models, and physiological factors can lead to degraded signal quality and affect HRV analysis. Therefore, it is crucial to address these uncertainties and develop advanced models for HRV analysis. Although several reviews of HRV analysis exist, they primarily focus on clinical applications, trends in HRV methods, or specific aspects of uncertainties such as measurement noise. This paper provides a comprehensive review of uncertainties in HRV analysis, quantifies their impacts, and outlines potential solutions. To the best of our knowledge, this is the first study that presents a holistic review of uncertainties in HRV methods and quantifies their impacts on HRV measures from an engineer's perspective. This review is essential for developing robust and reliable models, and could serve as a valuable future reference in the field, particularly for dealing with uncertainties in HRV analysis.

Throughout his career, Dr. Máximo (Max) E. Valentinuzzi worked long and hard for the development of the BME profession locally, regionally, and internationally. His accomplishments were numerous and valuable, including his editorship of the IEEE Pulse special column known as "Retrospectroscope" for more than ten years. A highlight and strength of the magazine over the past decade, this special column was built largely on the efforts and contributions from Dr. Valentinuzzi (Figure 1).

Coronavirus disease 2019 (COVID-19) has emerged as a pandemic with serious clinical manifestations including death. A pandemic at the large-scale like COVID-19 places extraordinary demands on the world's health systems, dramatically devastates vulnerable populations, and critically threatens the global communities in an unprecedented way. While tremendous efforts at the frontline are placed on detecting the virus, providing treatments and developing vaccines, it is also critically important to examine the technologies and systems for tackling disease emergence, arresting its spread and especially the strategy for diseases prevention. The objective of this article is to review enabling technologies and systems with various application scenarios for handling the COVID-19 crisis. The article will focus specifically on 1) wearable devices suitable for monitoring the populations at risk and those in quarantine, both for evaluating the health status of caregivers and management personnel, and for facilitating triage processes for admission to hospitals; 2) unobtrusive sensing systems for detecting the disease and for monitoring patients with relatively mild symptoms whose clinical situation could suddenly worsen in improvised hospitals; and 3) telehealth technologies for the remote monitoring and diagnosis of COVID-19 and related diseases. Finally, further challenges and opportunities for future directions of development are highlighted.

The most commonly used oscillometric upper-arm (UA) blood pressure (BP) monitors are not convenient enough for ambulatory BP monitoring, given the large size of the arm cuff and the compression of UA during the measurement. Finger-worn oscillometric BP devices featuring miniaturized finger cuff have been developed and researched as an alternative solution to the UA-based measurement, yet the reliability of the finger-based measurement is still questioned. To investigate the feasibility of oscillometric BP measurements at the finger position, we performed model-based analysis and experimental validation to explore the underlying issues associated with extending the cuff-based oscillometric approach from UA to other alternative sites. The simulation results revealed that a larger bone-to-tissue volume ratio produced a lower pressure transmission efficiency, which can account for the inter-site measurement discrepancies of mean blood pressure (MBP). We also experimentally compared the oscillometric MBP measurements at UA, middle forearm, wrist, finger proximal phalanx, and finger distal phalanx (FD) of 20 young adults, and each position was matched with a cuff of appropriate size and kept at the same height with the heart. The experimental results demonstrated that FD could be a superior alternative position for oscillometric BP measurement, as it requires the smallest cuff size while providing the most consistent MBP with the UA. Our analysis also suggested that further study is demanded to identify the appropriate oscillometric algorithm for reliable systolic blood pressure and diastolic blood pressure measurements at FD.

This study evaluated the new bone formation potential of micro–macro biphasic calcium phosphate (MBCP) and Bio-Oss grafting materials with and without dental pulp-derived mesenchymal stem cells (DPSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in a rabbit calvarial bone defect model. The surface structure of the grafting materials was evaluated using a scanning electron microscope (SEM). The multipotent differentiation characteristics of the DPSCs and BMSCs were assessed. Four circular bone defects were created in the calvarium of 24 rabbits and randomly allocated to eight experimental groups: empty control, MBCP, MBCP+DPSCs, MBCP+BMSCs, Bio-Oss+DPSCs, Bio-Oss+BMSCs, and autogenous bone. A three-dimensional analysis of the new bone formation was performed using micro-computed tomography (micro-CT) and a histological study after 2, 4, and 8 weeks of healing. Homogenously porous structures were observed in both grafting materials. The BMSCs revealed higher osteogenic differentiation capacities, whereas the DPSCs exhibited higher colony-forming units. The micro-CT and histological analysis findings for the new bone formation were consistent. In general, the empty control showed the lowest bone regeneration capacity throughout the experimental period. By contrast, the percentage of new bone formation was the highest in the autogenous bone group after 2 (39.4% ± 4.7%) and 4 weeks (49.7% ± 1.5%) of healing (p &lt, 0.05). MBCP and Bio-Oss could provide osteoconductive support and prevent the collapse of the defect space for new bone formation. In addition, more osteoblastic cells lining the surface of the newly formed bone and bone grafting materials were observed after incorporating the DPSCs and BMSCs. After 8 weeks of healing, the autogenous bone group (54.9% ± 6.1%) showed a higher percentage of new bone formation than the empty control (35.3% ± 0.5%), MBCP (38.3% ± 6.0%), MBCP+DPSC (39.8% ± 5.7%), Bio-Oss (41.3% ± 3.5%), and Bio-Oss+DPSC (42.1% ± 2.7%) groups. Nevertheless, the percentage of new bone formation did not significantly differ between the MBCP+BMSC (47.2% ± 8.3%) and Bio-Oss+BMSC (51.2% ± 9.9%) groups and the autogenous bone group. Our study results demonstrated that autogenous bone is the gold standard. Both the DPSCs and BMSCs enhanced the osteoconductive capacities of MBCP and Bio-Oss. In addition, the efficiency of the BMSCs combined with MBCP and Bio-Oss was comparable to that of the autogenous bone after 8 weeks of healing. These findings provide effective strategies for the improvement of biomaterials and MSC-based bone tissue regeneration.

Objective: To fight the “silent killer” hypertension, continuous blood pressure (BP) monitoring has been one of the most desired functions in wearable electronics. However, current BP measuring principles and protocols either involve a vessel occlusion process with a cuff or require multiple sensing nodes on the body, which makes it difficult to implement them in compact wearable electronics like smartwatches and wristbands with long-term wearability. Methods: In this work, we proposed a highly compact multi-wavelength photoplethysmography (MWPPG) module and a depth-resolved MWPPG approach for continuous monitoring of BP and systemic vascular resistance (SVR). By associating the wavelength-dependent light penetration depth in the skin with skin vasculatures, our method exploited the pulse transit time (PTT) on skin arterioles for tracking SVR ( n = 20). Then, we developed an arteriolar PTT-based method for beat-to-beat BP measurement. The BP estimation accuracy of the proposed arteriolar PTT method was validated against Finometer ( n = 20) and the arterial line ( n = 4). Results: The correlation between arteriolar PTT and SVR was theoretically deduced and experimentally validated on 20 human subjects performing various maneuvers. The proposed arteriolar PTT-based method outperformed the traditional arterial PTT-based method with better BP estimation accuracy and simpler measurement setup, i.e., with a single sensing node. Conclusion: The proposed depth-resolved MWPPG method can provide accurate measurements of SVR and BP, which are traditionally difficult to measure in a noninvasive or continuous fashion. Significance: This MWPPG work provides the wearable healthcare electronics of compact size with a low-cost and physiology-based solution for continuous measurement of BP and SVR.

Cuffless technique holds great promise to measure blood pressure (BP) in an unobtrusive way, improving diagnostics and monitoring of hypertension and its related cardiovascular diseases, and maximizing the independence and participation of individual. Pulse transit time (PTT) has been the most commonly employed techniques for cuffless BP estimation. Many studies have been conducted to explore its feasibility and validate its performance in the clinical settings. However, there is still issues and challenges ahead before its wide application. This review will investigate the understanding and development of the PTT technique in depth, with a focus on the physiological regulation of arterial BP, the relationship between PTT and BP, and the summaries of the PTT-based models for BP estimation.

Cuffless blood pressure monitoring is critical for the prevention and early diagnosis of a wide variety of cardiovascular diseases. However, cuffless blood pressure estimation devices suitable for home healthcare applications still suffer from numerous technological limitations. In this paper, we propose a novel method to continuously estimate blood pressure from the pulse morphology of the photoplethysmographic signals, acquired by a commercial oximeter. We conducted cold-pressor tests for 70 healthy subjects, simultaneously acquiring the photoplethysmograms from the oximeter and the continuous blood pressure from a commercial sphygmomanometer as a reference. The shape of each pulse was extracted, normalized, and regressed with the reference blood pressure using support vector machines. The performance of the regression model for each subject was evaluated using 10-fold cross-validation. Results showed that the predicted values from the regression model were highly correlated with the reference measurements from the commercial device. The mean correlation coefficients were 0.748, 0.754, and 0.775 for systolic, diastolic, and mean blood pressures, respectively. The mean errors were 0.043 mmHg, 0.011 mmHg, and 0.008 mmHg, with standard deviations of 5.001 mmHg, 3.689 mmHg, and 4.140 mmHg for systolic, diastolic, and mean blood pressures, respectively. These results suggest high feasibility of the proposed method to be employed in wearable medical and home healthcare devices.

Industry 4.0 is spilling out from manufacturing to healthcare. In this article, we provide a brief history and key enabling technologies of Industry 4.0, and its revolution in healthcare—Healthcare 4.0—and its reshaping of the landscape of the entire healthcare value chain. We discuss the shift in the system design paradigm from open, small, and single loop to closed, large, and multiple loops. We provide the example of a Caregiving Home, and discuss emerging research topics and challenges, including healthcare big data, automated medical production, healthcare robotics, and human–robot symbiosis. Relevant papers published in this special section are also presented.

This work developed a four-channel photoplethysmogram (PPG) acquisition system to collect the multi-wavelength PPG signals of red, yellow, green and blue light at the fingertip simultaneously. Eight subjects including 4 females took part in the experiment, and the multi-wavelength PPG signals from their fingertip were recorded. Since different PPG signal carries the blood pulsation information in different depth of the tissue, the time differences between multi-wavelengths was examined to investigate their relationships. The result shows the three time difference between yellow PPG and other PPGs (red PPG, green PPG and blue PPG) are highly correlated with each other (|r| > 0.7).

This work investigates the time difference between epidermal pressure pulse and PPG signal over the radial artery. 8 healthy subjects including 4 females participated in the experiment with their PPG signals and epidermal pressure pulses recorded at wrist simultaneously by a multi-modal pulse sensing patch. The arrival times of two signals are marked by three different characteristic points. The result shows that there is a significant delay between the peaks of epidermal pressure pulse and PPG signal.

Respiratory rate (RR) is an important vital sign which can be difficult to measure accurately and unobtrusively in routine clinical practice. Pulse transit time (PTT), on the other hand, is unobtrusive to collect from electrocardiogram (ECG) and photoplethysmogram (PPG) signals. Using PTT is a novel method to estimate and monitor blood pressure (BP) and RR. This study aimed to estimate continuous RR using PTT with singular spectrum analysis to extract respiratory components. The performance of this method was validated on 17 subjects who carried out spontaneous breathing and controlled deep breathing conditions. Three types of estimated RR parameters (average RR by power spectral density (PSD) (RRPSD), number of breaths (RR#), and instantaneous RR (RRinst)) were compared with the corresponding reference RR. The reference RR was collected using a respiratory belt. Our findings demonstrate that the PTT signal reliably tracked respiratory variation with a root mean square error of 0.84, 1.11, and 0.74 breaths/min for RRPSD, RR#, and RRinst estimations, respectively. Overall, RR estimated by PTT was more accurate than heart/pulse rate interval, QRS area, and PPG amplitude, which were also extracted from ECG and PPG. The results suggest that it may be feasible to use PTT as an estimation of RR and that ECG and PPG may be relied upon for monitoring not only RR but also BP and heart rate. Graphical abstract The Pulse Transit Time (PTT) based Respiratory Rate (RR) estimation with Singular Spectrum Analysis (SSA) provides a superior performance than the method with other respiratory indicators extracted from Electrocardiogram (ECG) or Photoplethysmogram (PPG).

Repairing articular cartilage defects is difficult due to the hypovascular biostructure and poor self-repairing capacity of articular cartilage. Currently, mesenchymal stem cells (MSCs) with excellent differentiation potential are considered as a promising biological approach for cartilage regeneration. The effect, however, remains far from satisfactory for clinical applications owing to the main drawbacks of tracking the retention of cells and a low differentiation efficiency. As known, the nanoparticles with superparamagnetic properties has been used to monitor the MSCs in vivo through magnetic resonance imaging (MRI) in clinical application. In this study, different external and internal bio-conditions were applied to regulate the biological behavior of cells. Here, intracellular MRI contrast agents, superparamagnetic iron oxide nanocrystals (SPIONs), and a hypoxic culture environment were found to exert synergistic effects on gene and protein expression, and the cell viability, cell cycle, apoptosis, reactive oxygen species and the stem cell differentiations were measured. The levels of chondrogenic and migrant markers (including collagen II, collagen X, aggrecan, SOX9, MMPs and CXCR4) increased, triggering directional differentiation and enhancing cell migration to the inflammatory site. Moreover, SPION-labeled hypoxia-preconditioned MSCs were found without reactive oxygen species generation and transplanted into rat models with articular cartilage disorders. Interestingly, MRI and histological identification confirmed that new cartilage-like tissue was regenerated and that defects were repaired, and this method is more efficient for cartilage regeneration than SPION-labeled normoxia MSCs. The synergistic effect of hypoxia-precondition and SPIONs based cellular iron source could improve the cell migration and facilitate chondrogenic differentiation.

The steady increases in cardiovascular disease (CVD) and the continuing spread of coronavirus disease (COVID- 19) remain unprecedented public health crises of international concerns. The multiple crises are causing catastrophic human losses and tremendous health and economic burdens worldwide. This issue explores the CVD crisis in the era of the COVID-19 pandemic. The success of fighting against both deadly diseases will only come from a paradigm shift transforming the current reactive medicine focusing on the last stage of treatment to proactive health focusing on the early prediction, early diagnosis and prevention of diseases. Reports on the emerging field of health engineering, an emerging interdisciplinary field for the implementation of proactive health.

Continuous blood pressure (BP) measurement without a cuff is advantageous for the early detection and prevention of hypertension. The pulse transit time (PTT) method has proven to be promising for continuous cuffless BP measurement. However, the problem of accuracy is one of the most challenging aspects before the large-scale clinical application of this method. Since PTT-based BP estimation relies primarily on the relationship between PTT and BP under certain assumptions, estimation accuracy will be affected by cardiovascular disorders that impair this relationship and by the calibration frequency, which may violate these assumptions. This study sought to examine the impact of heart disease and the calibration interval on the accuracy of PTT-based BP estimation. The accuracy of a PTT-BP algorithm was investigated in 37 healthy subjects and 48 patients with heart disease at different calibration intervals, namely 15 min, 2 weeks, and 1 month after initial calibration. The results showed that the overall accuracy of systolic BP estimation was significantly lower in subjects with heart disease than in healthy subjects, but diastolic BP estimation was more accurate in patients than in healthy subjects. The accuracy of systolic and diastolic BP estimation becomes less reliable with longer calibration intervals. These findings demonstrate that both heart disease and the calibration interval can influence the accuracy of PTT-based BP estimation and should be taken into consideration to improve estimation accuracy.

Noninvasive and real-time cuffless blood pressure (BP) measurement realizes the idea of unobtrusive and continuous BP monitoring which is essential for diagnosis and prevention of cardiovascular diseases associated with hypertension. In this paper, a wearable sensor patch system that integrates flexible piezoresistive sensor (FPS) and epidermal electrocardiogram (ECG) sensors for cuffless BP measurement is presented. By developing parametric models on the FPS sensing mechanism and optimizing operational conditions, a highly stable epidermal pulse monitoring method is established and beat-to-beat BP measurement from the ECG and epidermal pulse signals is demonstrated. In particular, this study highlights the compromise between sensor sensitivity and signal stability. As compared with the current optical-based cuffless BP measurement devices, the sensing patch requires much lower power consumption (3 nW) and is capable of detecting subtle physiological signal variations, e.g., pre and postexercises, thus providing a promising solution for low-power, real-time, and home-based BP monitoring.

Negative emotion has a wide range of pernicious impacts on people, ranging from the failure in real-time task performance to the development of chronic health conditions. An unobtrusive wearable biofeedback system for personalized emotional management has been designed and presented in this paper. The system integrated heart rate variability (HRV) biofeedback to wearable biosensor platform, which could function both as an early stress warning system as well as a visual interface to manipulate subject's affective state. The designed and developed system would help subject to transform the negative emotion state into positive through real-time HRV biofeedback training. The results indicated that the real-time HRV biofeedback is significantly effective in cases of negative emotion. With the aid of the developed biofeedback system, the subhealth subjects could transform heart rhythm from negative emotion to positive emotion-related oscillation mode.

Cardiovascular disease, like hypertension, is one of the top killers of human life and early detection of cardiovascular disease is of great importance. However, traditional medical devices are often bulky and expensive, and unsuitable for home healthcare. In this paper, we proposed an easy and inexpensive technique to estimate continuous blood pressure from the heart sound signals acquired by the microphone of a smartphone. A cold-pressor experiment was performed in 32 healthy subjects, with a smartphone to acquire heart sound signals and with a commercial device to measure continuous blood pressure. The Fourier spectrum of the second heart sound and the blood pressure were regressed using a support vector machine, and the accuracy of the regression was evaluated using 10-fold cross-validation. Statistical analysis showed that the mean correlation coefficients between the predicted values from the regression model and the measured values from the commercial device were 0.707, 0.712, and 0.748 for systolic, diastolic, and mean blood pressure, respectively, and that the mean errors were less than 5 mmHg, with standard deviations less than 8 mmHg. These results suggest that this technique is of potential use for cuffless and continuous blood pressure monitoring and it has promising application in home healthcare services.

The depth and rate of human respiration reveal important and diverse sets of physiological information for evaluating human health. Here, we introduce an ultrathin, skin-integrated respiration sensor based on the thermal convection effect. The device features a filamentary fractal design of the gold heating electrode, a mini sensor (0.6 mm × 0.3 mm × 0.23 mm) with high thermal sensitivity and an ultrasoft encapsulation package to enhance the overall flexibility and biaxial stretchability of the system. Adjusting the input power of the heating electrode, i.e., increasing the temperature difference between the thermal sensor and environment, can further improve the sensitivity of the respiration sensor. The real-time monitoring respiration sensor can competently distinguish various breathing patterns (sitting, frightening, sleeping, meditating, and gasping) through breath rate/depth of detection subjects. In addition, the respiration sensor can effectively capture, in real time, the respiration of a volunteer while exercising, resting, or sleeping for prolonged periods of time. The combination of advanced mechanics, high sensitivity, and good stability make this respiration sensor a great candidate for potential use in real-time monitoring of human health.

Heartbeats based random binary sequences (RBSs) are the backbone for several security aspects in wireless body sensor networks (WBSNs). However, current heartbeats based methods require a lot of processing time (∼25–30 s) to generate 128-bit RBSs in real-time healthcare applications. In order to improve time efficiency, a biometric RBSs generation technique using interpulse intervals (IPIs) of heartbeats is developed in this study. The proposed technique incorporates a finite monotonic increasing sequences generation mechanism of IPIs and a cyclic block encoding procedure that extracts a high number of entropic bits from each IPI. To validate the proposed technique, 89 ECG recordings including 25 healthy individuals in a laboratory environment, 20 from MIT-BIH Arrhythmia Database, and 44 cardiac patients from the clinical environment are considered. By applying the proposed technique on the ECG signals, at most 16 random bits can be extracted from each heartbeat to generate 128-bit RBSs via concatenation of eight consecutive IPIs. And the randomness and distinctiveness of generated 128-bit RBSs are measured based on the National Institute of Standards and Technology statistical tests and hamming distance, respectively. From the experimental results, the generated 128-bit RBSs from both healthy subjects and patients can potentially be used as keys for encryption or entity identifiers to secure WBSNs. Moreover, the proposed approach is examined to be up to four times faster than the existing heartbeat-based RBSs generation schemes. Therefore, the developed technique necessitates less processing time (0–8 s) in real-time health monitoring scenarios to construct 128-bit RBSs in comparisons with current methods.

Discusses the benefits of mobile health(mHealth) technologies. These technologies empower patients to be more involved in their own care, give healthcare consumers greater access to providers, and vice versa, and allow for better personalized, precise, pervasive, and preventive medicine, in more effective and less costlyways.At the cutting edge of health engineering, the field of emerging mHealth promises a new era of highly individualized treatment of disease and preventive medicine, bringing the health convergence to reality.

This study evaluated the association between carotid intima-media thickness (IMT) and 24 h ambulatory blood pressure variability (BPV) in 150 subjects. The subjects were divided into different age groups and gender groups. We found that for the subjects aged less than 45 years, 24 h and daytime diastolic BPV were associated with the increased IMT (r = 0.525, P = 0.018; r = 0.507, P = 0.022). For the middle aged people (46–55 years), daytime (r = 0.377, P = 0.014) and 24 h systolic BPV (r = 0.366, P = 0.017) were more related to the increases in IMT than 24 h diastolic BPV (r = 0.320, P = 0.039). However, no association between carotid IMT and BPV was found in the elderly (>55 years). In addition, the relationships between carotid IMT and BPV were more obvious in males than females. 24 h systolic BPV (P = 0.008) is the independent factor to evaluate the increased carotid IMT for males, but not for females. The findings in our study indicated that age and sex had influences on progression of carotid IMT. We conclude that the relationship between carotid IMT and ambulatory BPV can be modified by age and sex, thus, the regression model using BPV to evaluate the arteriosclerotic progression should take age and sex into account.

An automated framework for detecting lumen and media-adventitia borders in intravascular ultrasound images was developed on the basis of an adaptive region-growing method and an unsupervised clustering method. To demonstrate the capability of the framework, linear regression, Bland-Altman analysis and distance analysis were used to quantitatively investigate the correlation, agreement and spatial distance, respectively, between our detected borders and manually traced borders in 337 intravascular ultrasound images in vivo acquired from six patients. The results of these investigations revealed good correlation (r = 0.99), good agreement (>96.82% of results within the 95% confidence interval) and small average distance errors (lumen border: 0.08 mm, media-adventitia border: 0.10 mm) between the borders generated by the automated framework and the manual tracing method. The proposed framework was found to be effective in detecting lumen and media-adventitia borders in intravascular ultrasound images, indicating its potential for use in routine studies of vascular disease.

Current markers for heart failure (HF) diagnosis and prognosis are mainly for the evaluation of cardiac functions. Since previous studies have reported that HF patients demonstrated abnormal vascular responses to external stimuli, it is speculated that vascular tone, a measure of activation level of vascular wall, may be able to reflect these abnormalities to assist HF detection. Nevertheless, vascular tone is difficult to be objectively quantified using existing tools. In this study, a vascular tone index was estimated from noninvasive blood pressure and pulse transit time measurements using system identification technique. This method was evaluated in 35 subjects (10 healthy, 13 with HF risk factors and 12 HF patients) in a regular maximal exercise test. It was found that the vascular tone index significantly increased by 24.4 ± 26.6% (p

24-h blood pressure (BP) has significant prognostic value for cardiovascular risk screening, but the present BP devices are mainly cuff-based, which are unsuitable for long-term BP measurement, especially during nighttime. In this paper, we developed an armband wearable pulse transit time (PTT) system for 24-h cuff-less BP measurement and evaluated it in an unattended out-of-laboratory setting. Ten healthy young subjects participated in this ambulatory study, where PTT was measured at 30-min interval by this wearable system and the reference BP was measured by a standard oscillometric ambulatory BP monitor. Due to the misalignment of BP and PTT on their recording time caused by the different measurement principles of the two BP devices, a new estimation method has been proposed: transients in PTT were removed from the raw data by defined criteria, and then evenly interpolated, low-pass filtered, and resampled to synchronize at the time when BP was recorded. The results show that with the proposed method, the correlation between PTT and systolic BP (SBP) during nighttime with dynamic range of 21.8 ± 14.2 mmHg has improved from −0.50 ± 0.24 to −0.62 ± 0.20 $(p , and the difference between the estimated and reference SBP has improved from 0.7 ± 10.7 to 2.8 ± 8.2 mmHg with root mean square error reduced from 10.7 to 8.7 mmHg. In addition, the correlation between a very low frequency component of SBP and PTT obtained from the proposed method during nighttime is −0.80 ± 0.10 and the difference is 2.4 ± 5.7 mmHg for a dynamic BP range of 13.5 ± 8.0 mmHg. It is therefore concluded from this study that the proposed wearable system has great potential to be used for overnight SBP monitoring, especially to measure the averaged SBP over a long period.

In this work, we present a multi-wavelength (MW) PPG method exploiting the wavelength dependence of light penetration in skin tissue to provide depth resolution of skin blood pulsation. The MW PPG system requires two to three light sources in different wavelengths and extracts the arterial blood pulsation through a multi-wavelength multi-layer light-skin interaction model, which removes the capillary pulsation (determined from the short-wavelength PPG signal) from the long-wavelength PPG signal using absorption weighting factors that are quasi-analytically calibrated. The extracted pulsations are used to calculate blood pressure (BP) through pulse transit time (PTT), and the results are compared with those obtained from the single wavelength PPG method. The comparative study is clinically performed on 20 subjects including 10 patients diagnosed with cardiovascular diseases and 10 healthy subjects. The result demonstrates that the MW PPG method significantly improves the measurement accuracy of systolic BP (SBP), reducing the mean absolute difference between the reference and the estimated SBP values from 5.7 mmHg (for single-wavelength PPG) to 2.9 mmHg (for three-wavelength PPG).

Accurate and ambulatory measurement of blood pressure (BP) is essential for efficient diagnosis, management and prevention of cardiovascular diseases (CVDs). However, traditional cuff-based BP measurement methods provide only intermittent BP readings and can cause discomfort with the occlusive cuff. Although pulse transit time (PTT) method is promising for cuffless and continuous BP measurement, its pervasive use is restricted by its limited accuracy and requirement of placing sensors on multiple body sites. To tackle these issues, we propose a novel dual-modality arterial pulse monitoring system for continuous blood pressure measurement, which simultaneously records the pressure and photoplethysmography (PPG) signals of radial artery. The obtained signals can be used to generate a pressure-volume curve, from which the elasticity index (EI) and viscosity index (VI) can be extracted. Experiments were carried out among 7 healthy subjects with their PPG, ECG, arterial pressure wave and reference BP collected to examine the effectiveness of the proposed indexes. The results of this study demonstrate that a linear regression model combining EI and VI has significantly higher BP tracking correlation coefficient as compared to the PTT method. This suggests that the proposed system and method can potentially be used for convenient and continuous blood pressure estimation with higher accuracy.

Pulse transit time (PTT) has attracted much interest for cuffless blood pressure (BP) measurement. However, its limited accuracy is one of the main problems preventing its widespread acceptance. Arterial BP oscillates mainly at high frequency (HF) because of respiratory activity, and at low frequency (LF) because of vasomotor tone. Prior studies suggested that PTT can track BP variation in HF range, but was inadequate to follow the LF variation, which is probably the main reason for its unsatisfactory accuracy. This paper presents a new indicator, the photoplethysmogram intensity ratio (PIR), which can be affected by changes in the arterial diameter, and, thus, trace the LF variation of BP. Spectral analysis of BP, PTT, PIR, and respiratory signal confirmed that PTT was related to BP in HF at the respiratory frequency, while PIR was associated with BP in LF range. We, therefore, develop a novel BP estimation algorithm by using both PTT and PIR. The proposed algorithm was validated on 27 healthy subjects with continuous Finapres BP as reference. The results showed that the mean ± standard deviation (SD) for the estimated systolic, diastolic, and mean BP with the proposed method against reference were $-0.37 \pm 5.21$ , $-0.08 \pm 4.06$ , $-0.18 \pm 4.13$ mmHg, and mean absolute difference (MAD) were 4.09, 3.18, 3.18 mmHg, respectively. Furthermore, the proposed method outperformed the two most cited PTT algorithms for about 2 mmHg in SD and MAD. These results demonstrated that the proposed BP model using PIR and PTT can estimate continuous BP with improved accuracy.

A highly efficient enzyme-based screen printed electrode (SPE) was obtained by using covalent attachment between 1-pyrenebutanoic acid, succinimidyl ester (PASE) adsorbing on the graphene oxide (GO) sheets and amines of tyrosinase-protected gold nanoparticles (Tyr-Au). Herein, the bi-functional molecule PASE was assembled onto GO sheets. Subsequently, the Tyr-Au was immobilized on the PASE-GO sheets forming a biocompatible nanocomposite, which was further coated onto the working electrode surface of the SPE. The characterization of obtained nanocomposite and modified SPE surface was investigated by atomic force microscopy (AFM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Attributing to the synergistic effect of GO-Au integration and the good biocompatibility of the hybrid-material, the fabricated disposable biosensor (Tyr-Au/PASE-GO/SPE) exhibited a rapid amperometric response (less than 6s) with a high sensitivity and good storage stability for monitoring catechol. This method shows a good linearity in the range from 8.3×10(-8) to 2.3×10(-5) M for catechol with a squared correlation coefficient of 0.9980, a quantitation limit of 8.2×10(-8) M (S/N=10) and a detection limit of 2.4×10(-8) M (S/N=3). The Michaelis-Menten constant was measured to be 0.027 mM. This disposable tyrosinase biosensor could offer a great potential for rapid, cost-effective and on-field analysis of phenolic compounds.

This paper reports a novel contactless monitoring method to record photoplethysmogram (PPG) on a mattress for the continuous measurement of heart rate (HR). PPGs were obtained from subjects' fingers and backs with and without making a direct contact between the PPG sensor and their skin when they rested in a supine position on the mattress. Electrocardiograms (ECGs) were measured from the subjects' limbs for reference. Clear PPG waveforms were obtained from the subjects' backs. Beat-to-beat HR derived from contactless PPG measurement was comparable to those measured from contact PPG and ECG measurements. Thus we found that contactless PPG could be captured from the subjects' backs and it was sufficient to provide accurate HR measurements. This contactless monitoring of PPG has the potential to reduce obstruction in sleep and provide clinical evaluation in sleep study.

To overcome the cytotoxicity of the chemical reagents used to fix bioprostheses, genipin, a naturally occurring crosslinking agent, was used to fix biological tissues in present study. We prepared the biological vascular scaffolds through cell extraction and fixing the porcine thoracic arteries with 1% (by w/v) genipin solution for 3 days, and then examined their mechanical properties and microstructures; glutaraldehyde- and epoxy-fixed counterparts were used as controls. HUVECs were seeded on the type I collagen-coated surface of different modified acellular vascular tissues (fixed with different crosslinking agents), and the growths of HUVECs on the specimens were demonstrated by means of MTT test, the secretion of PGI2 and vWF by HUVECs on the various specimens was also measured. Finally, HUVECs were seeded on the luminal surface of acellular biological vascular scaffolds (

This article discusses some of the unique demographic and epidemiological changes that China faces. As China is still a developing country, most of its people cannot afford expensive healthcare solutions. Especially in the poor rural areas, healthcare service is a luxury for some people. Therefore, this article summarizes several key strategies to reduce medical expenditures at the national level and proposes to develop a new information system in the form of a personal, home, community, and hospital (PHCH) four-layered architecture. Using the management of blood pressure (BP) as an example, we have shown that innovative technologies in wearable medical devices and body area networks (BANs) can be developed to collect information for this new system to overcome geographic and financial constraints and to provide a low-cost and effective solution to manage chronic health problems.

Terahertz technology is continually evolving and much progress has been made in recent years. Many new applications are being discovered and new ways to implement terahertz imaging investigated. In this review, we limit our discussion to biomedical applications of terahertz imaging such as cancer detection, genetic sensing and molecular spectroscopy. Our discussion of the development of new terahertz techniques is also focused on those that may accelerate the progress of terahertz imaging and spectroscopy in biomedicine.

Pulse transit time (PTT) has been widely used for noninvasive examination of the arterial viscoelastic properties, such as elasticity, compliance, and stiffness of the vessel walls. PTT is usually determined as the time interval between the peak of the electrocardiogram R wave and the foot of the photoplethysmogram (PPG). However, it was observed that the PPG is affected by the applied contact force between the photoplethysmographic sensor and the measurement site, e.g., finger. In this study, the nonlinear biomechanical properties of the finger arterial wall were considered when investigating the changes in PTT with varying contact force. Emphasis was placed on the changes in the shape of the arterial wall pressure-volume curve. The simulation results indicated that at positive transmural pressure, PTT increased with the applied contact force, reaching the maximum at zero transmural pressure and remaining at a constant level at negative transmural pressure. The theoretical analysis was further verified by the experiments carried out on thirty young subjects and six elderly subjects using twelve discrete levels of contact force.

Engineering has been playing an important role in serving and advancing healthcare. The term “Healthcare Engineering” has been used by professional societies, universities, scientific authors, and the healthcare industry for decades. However, the definition of “Healthcare Engineering” remains ambiguous. The purpose of this position paper is to present a definition of Healthcare Engineering as an academic discipline, an area of research, a field of specialty, and a profession. Healthcare Engineering is defined in terms of what it is, who performs it, where it is performed, and how it is performed, including its purpose, scope, topics, synergy, education/training, contributions, and prospects. Published version

Pulse transit time (PTT), which refers to the time it takes a pulse wave to travel between two arterial sites is a promising index for cuff-less blood pressure (BP) estimation, as well as non-invasive assessment of arterial functions. However, it has not been investigated whether PTTs measured from ECG and different wavelength PPG are equally affected by the arterial status. Furthermore, comparison between the changes of different PTTs can provide enlightenment on the hardware implementation of the PTT-based BP estimation method. This work mainly studied the changes of PTTs calculated from electrocardiogram (ECG) and multi-wavelength photoplethysmogram (PPG) after exerting cuff pressure on the upper arm. A four-channel PPG acquisition system was developed to collect the multi-wavelength PPG signals of red, yellow, green and blue light at the fingertip simultaneously. Ten subjects participated in the experiment and their PTTs measured from different PPG and ECG signals before and after exerting cuff pressure were compared. This study found that within one minute after the four-minute cuff inflation and deflation process, the PTT measured from ECG and yellow PPG experienced a significant increase (p;0.05) while the PTT from ECG and blue PPG had no statistical difference (p0.9) compared with that before exerting cuff pressure. This indicates that PTTs calculated from different wavelength PPG have different recoverability from smooth muscle relaxation. Another interesting finding is that the PTT calculated from ECG and yellow PPG had a strong correlation (|r|0.7) with the time difference between yellow PPG and other PPG signals, which implies the potential of the time difference between yellow PPG and other PPGs as a complementary to PTT-based model for blood pressure estimation.

Objective We sought to evaluate the accuracy of quantitative three-dimensional (3D) CT angiography (CTA) for the assessment of coronary luminal stenosis using digital subtraction angiography (DSA) as the standard of reference. Method Twenty-three patients with 54 lesions were referred for CTA followed by DSA. The CTA scans were performed with 256-slice spiral CT. 3D CTA were reconstructed from two-dimensional CTA imaging sequences in order to extract the following quantitative indices: minimal lumen diameter, percent diameter stenosis (%DS), minimal lumen area, and percent area stenosis (%AS). Correlation and limits of agreement were calculated using Pearson correlation and Bland–Altman analysis, respectively. The diagnostic performance and the diagnostic concordance of 3D CTA-derived anatomic parameters (%DS, %AS) for the detection of severe coronary arterial stenosis (as assessed by DSA) were presented as sensitivity, specificity, diagnostic accuracy, and Kappa statistics. Of which vessels with %DS >50% or with %AS >75% were identified as severe coronary arterial lesions. Result The correlations of the anatomic parameters between 3D CTA and DSA were significant (r = 0.51–0.74, P

Heart rate variability is a useful clinical tool for autonomic function assessment and cardiovascular disease diagnosis. To investigate the dynamic changes of sympathetic and parasympathetic activities during the cold pressor test, we used a time-varying autoregressive model for the time-frequency analysis of heart rate variability in 101 healthy subjects. We found that there were two sympathetic peaks (or two parasympathetic valleys) when the abrupt changes of temperature (ACT) occurred at the beginning and the end of the cold stimulus and that the sympathetic and parasympathetic activities returned to normal in about the last 2 min of the cold stimulus. These findings suggested that the ACT rather than the low temperature was the major cause of the sympathetic excitation and parasympathetic withdrawal. We also found that the onsets of the sympathetic peaks were 4–26 s prior to the ACT and the returns to normal were 54–57 s after the ACT, which could be interpreted as the feedforward and adaptation of the autonomic regulation process in the human body, respectively. These results might be helpful for understanding the regulatory mechanisms of the autonomic system and its effects on the cardiovascular system.

The movement of the common carotid artery (CCA) vessel wall has been well accepted as one important indicator of atherosclerosis, but it is still one challenge to estimate the motion of vessel wall from ultrasound images. In this paper, a robust H ∞ filter was incorporated with block matching (BM) method to estimate the motion of carotid arterial wall. The performance of our method was compared with the standard BM method, Kalman filter, and manual traced method respectively on carotid artery ultrasound images from 50 subjects. Our results showed that the proposed method has a small estimation error (96 μm for the longitudinal motion and 46 μm for the radial motion), and good agreement (94.03% results fall within 95% confidence interval for the longitudinal motion and 95.53% for the radial motion) with the manual traced method. These results demonstrated the effectiveness of our method in the motion estimation of carotid wall in ultrasound images.