Cuffless Blood Pressure Estimation

The blood pressure is an important factor in the diagnosis and evaluation of several diseases, such as acute myocardial infarction and stroke. This way, continuous monitorization of this parameter is crucial to a correct health evaluation. The current methods, like the oscillometric method, have some major drawbacks, that can influence the output values or even make the measurements impossible. One example is the high frequency evaluation of the blood pressure, in the standard used methods the process of measuring can take up to 3 minutes, and a waiting time is necessary between consecutive measurements. This dissertation presents two different cuffless solution to solve those problems. One based on physical models of the human body, and the other using machine learning techniques. In the first solution seven models that correlate pulse transit time and blood pressure, deducted by different authors, were tested to evaluate which one performed better. The testes were performed in a custom dataset acquired at Fraunhofer AICOS and in clinical environment, with two different devices (low cost device and medical grade device). The results indicate that pulse transit time can be used to track blood pressure, the developed device/method was evaluated as grade A based in the Standard IEEE 1708-2014. The second solution it’s a proof of concept using a public database and three different machine learning methods (Random Forest, Neural Network and AdaBoost). Two sets of features are calculated from the ECG and PPG signals, one using TSFEL (spectral, frequency and time domain features) and a total of 15 custom features. The proposed method outperforms the methods presented in bibliography with mean absolute error of 3.6 mmHg and 2.0 mmHg to systolic and diastolic blood pressure respectively

Estimating pulse wave velocity using mobile phone sensors

Pulse wave velocity has been recognised as an important physiological phenomenon in the human body, and its measurement can aid in the diagnosis and treatment of chronic diseases. It is the gold standard for arterial stiffness measurements, and it also shares a positive relationship with blood pressure and heart rate. There exist several methods and devices via which it can be measured. However, commercially available devices are more geared towards working health professionals and hospital settings, requiring a significant monetary investment and specialised training to operate correctly. Furthermore, most of these devices are not portable and thus generally not feasible for private home use by the common individual. Given its usefulness as an indicator of certain physiological functions, it is expected that having a more portable, affordable, and simple to use solution would present many benefits to both end users and healthcare professionals alike. This study investigated and developed a working model for a new approach to pulse wave velocity measurement, based on existing methods, but making use of novel equipment. The proposed approach made use of a mobile phone video camera and audio input in conjunction with a Doppler ultrasound probe. The underlying principle is that of a two-point measurement system utilising photoplethysmography and electrocardiogram signals, an existing method commonly found in many studies. Data was collected using the mobile phone sensors and processed and analysed on a computer. A custom program was developed in MATLAB that computed pulse wave velocity given the audio and video signals and a measurement of the distance between the two data acquisition sites. Results were compared to the findings of previous studies in the field, and showed similar trends. As the power of mobile smartphones grows, there exists potential for the work and methods presented here to be fully developed into a standalone mobile application, which would bring forth real benefits of portability and cost-effectiveness to the prospective user base

Effects of Hormone Replacement Therapy on Systemic Arterial Properties in Post-Menopausal Women

ABSTRACTEFFECTS OF HORMONE REPLACEMENT THERAPY ON SYSTEMIC ARTERIAL PROPERTIES IN POST-MENOPAUSAL WOMENEric Alps Chen, B.S.University of Pittsburgh, 2002Vascular stiffness properties contribute significantly to the arterial system hydraulic load. There is evidence that vascular stiffness plays a role in cardiovascular remodeling and may be an independent cardiovascular risk factor. Menopause accelerates age-associated increase in arterial stiffness and estrogen administration, which has vasodilating properties, can potentially mitigate this post-menopausal increase in stiffness. The present study examined the effects of chronic hormone replacement therapy (HRT) on systemic arterial mechanical properties in 35 post-menopausal women, divided into two groups: those receiving no HRT (Control, n = 25) and those receiving HRT (HRT-all, n = 10). The HRT-all group consisted of two subgroups: estrogen alone (HRT-E, n = 5) and a combination of estrogen and progesterone (HRT-EP, n = 5). Noninvasive data were collected serially at five times: once at the baseline during the first visit and during four subsequent visits after the initiation of the study at 19±1, 108±5, 193±4, and 388±8 days, respectively. Heart rate (HR), stroke volume (SV), and cardiac output (CO) did not change significantly in the control group throughout the study. This was also true for both HRT groups, except for a small decrease in HR at Visits 3 and 4 for the HRT-E group and an increase in CO at Visit 3 in the HRT-EP group. Mean arterial pressure decreased over time in control and both HRT groups, reaching statistical significance at later times (fifth visit). Systemic vascular resistance did not change significantly in control and both HRT groups. Global arterial compliance (AC) was unchanged for the control group but tended to increase in the HRT-all group, although no statistical significance was reached. In contrast, the subgroup analysis revealed that AC increased for the HRT-E subgroup, reaching statistical significance at the fifth visit. Similarly, significant decrements in pulse wave velocity (PWV), an index of regional vascular stiffness, were observed only for the HRT-E group. In conclusion, AC increased (vascular stiffness decreased) in subjects receiving chronic estrogen therapy only. The inclusion of progesterone seems to counteract the estrogen-mediated decrease in vascular stiffness, indicating that the vascular stiffness-associated cardio-protective effects of HRT, if any, may be limited to estrogen administration alone

Wearable estimation of central aortic blood pressure.

Arterial hypertension affects a third of the world's population and is a significant risk factor for cardiovascular disease. Blood pressure (BP) is one of the most relevant parameters used for monitoring of possible hypertension states in patients at risk of cardiovascular disease. Hence, there exists a need for new monitoring solutions, which allow to increase the frequency between BP assessments, but also allow to reduce the level of occlusion in the attempts. Moens-Korteweg equation is among the main principles to estimate BP by dispensing of any inflatable cuff. This principle might lead to an indirect estimation of BP by measuring the time it takes the pressure pulse to propagate between two pre-established vascular points, accordingly the pulse transit time (PTT) method. This thesis proposes a wearable PTT-based method to estimate central aortic BP (CABP) and, the main milestones of this work included: proof of concept of the proposed method (pilot work), the development of a wearable device (including two stages of validation), the proposition of a miniaturized version (integrated circuit) of the analog front-end of the wearable hardware, and, the development of a novel PTT-based model (PTTBM, i.e., the mathematical relationship between measured variables and estimated BP) suitable for the proposed wearable methodology to estimate BP. The main contributions found at each milestone are presented. One of the contributions of this thesis is the use of the PTT-principle for estimating CABP instead of the peripheral BP (PBP) (as typically used in the literature). The pilot work showed the feasibility of CABP estimation from the PTT principle by using electrocardiogram (ECG) and ballistocardiogram (BCG) recordings from off-the-shelf equipment. Results showed that CABP was more correlated with the proposed methodology in comparison to all PBP variables assessed; confirming our hypothesis that the CABP is the most suitable parameter to collate through the time elapsed from ECG R-wave to the BCG J-wave. That is, considered featured time (RJ-interval) includes the time of a pulse pressure propagating at an aortic district. Bland-Altman plots showed an almost zero mean error (\u\ < 0.02mmHg) and bounded standard deviation o < 5mmHg for all systolic and mean central BP readings. Pilot work provided a landmark in order to develop a compact device that allows the integration of wireless blood pressure monitoring into a wearable system. Another contribution of this thesis is the proposition of a wearable device for PTT-computing by also including design considerations for the signal conditioning chains for ECG and BCG signals. The proposed design procedure takes care of minimizing the impact of spurious delays between physiological signals, which eventually degrade the PTT computation. Further, such a procedure could be suitable for any PTT-acquisition. Filtering with low and controlled delay is required for this biomedical application, and proposed conditioning chains provide less than 2ms group-delay, showing the effectiveness of the proposed approach. In order to provide the methodology with higher autonomy and integration, a highly miniaturized implementation of the filtering approach was also proposed. It includes the design of proposed architectures in CMOS technology to implement the particular low-delay filtering at reduced bandwidth featuring ultra-low-power characteristics. Results show that less than 2ms delay for the ECG QRS-complex can be achieved with a total current consumption of IDD = 2:1nA at VDD = 1:2V of power supply. Such development meant another significant contribution of this work in the conception of highly autonomous wearable devices for PTT acquisition. The first stage of validations on the wearable CABP estimation showed that, when considering data from one volunteer, results achieved with off-the-shelf equipment could be replicated by using a proposed wearable device, and the method could be further validated by using the wearable version. Additionally, CABP estimation from the proposed wearable device could be feasible by using three feature times (FTs) as CABP surrogates; that is, RI, RJ, and IJ intervals (from ECG and BCG wearable recordings). The first validation of the method also showed that CABP could be accurately predicted by the proposed methodology when in the order of daily calibrations are performed. The second stage of validations involved a study with a group of volunteers, and new alternatives were explored (twentyseven: nine PTTBMs along the three FTs) for the CABP estimation. We found that CABP could be accurately estimated (inside AAMI requirements) through the presented methodology by using four of the explored alternatives, whereas the RI interval, an FT lacking any PTT assessment, emerged as the best surrogate for the CABP estimation. Hence, a principle different from the traditional PTT-based method arises as a more advantageous method for the CABP estimation in the light of evidence reported in this validation, and, to our knowledge, this is the first time that CABP has been successfully estimated from a wearable device. The final significant contribution of this thesis meant the last chain-link in the process to achieve an utterly original method to estimate CABP. A novel PTTBM to estimate CABP is proposed, which uses a ow-driven two-element Windkesel network constructed from FTs extracted from the wearable recordings. When classic PTTBMs are applied, the fitting of parameters often leads to values without a physiological basis. Opposite to that in the proposed PTTBM, the parameters have a clear physiological meaning, and the parameter fitting led to values that are consistent with this meaning and more stable throughout calibrations. In conclusion, this thesis introduces a novel device that exploits an alternative and indirect method for CABP estimation. Variants of the principle used, accordingly, PTT method, have been previously explored to estimate PBP but not for central aortic BP. Additionally, the device was designed to be wearable; that is, it is attached to the clothes, causing low discomfort for the user during the measurement, thus, allowing continuous and ambulatory monitoring of aortic pressure. The developed wearable system, validated in a series of volunteers, showed promising results towards the continuous CABP monitoring.Se estima que casi un tercio de la población adulta mundial sufre de algún grado de hipertensión, siendo esto un factor de riesgo significativo para la enfermedad cardiovascular. La presión arterial (PA) es el parámetro utilizado para evaluar estos posibles estados de hipertensión; actualmente existe una necesidad de generación de nuevas tecnologías que permitan aumentar la frecuencia entre medidas de PA, pero al mismo tiempo de reducir el nivel de oclusión de éstas (técnicas aceptadas están mayoritariamente basadas en la oclusión y son de acceso limitado). El modelo Moens-Korteweg podría proveer los argumentos para la creación de nuevas técnicas para estimar la PA prescindiendo de cualquier brazalete inflable. Más específicamente, podría obtenerse una estimación indirecta de la PA a través de la medición del tiempo que tarda el pulso de presión en propagarse entre dos puntos vasculares predefinidos, método conocido como tiempo de tránsito del pulso (PTT). En la presente tesis se desarrolló un dispositivo vestible que explota este método alternativo e indirecto para la estimación de la PA pero a nivel central, es decir, busca estimar la PA en la aorta (CABP), la principal arteria de la red vascular. Para ello, los principales desarrollos de este trabajo incluyeron : prueba de concepto del método propuesto basado en PTT para estimar CABP, el desarrollo de un dispositivo vestible (incluyendo dos etapas de validaciones para la estimación de la PA), la propuesta de un circuito integrado para el hardware vestible y el desarrollo de un nuevo modelo para la estimación de la PA (PTTBM, es decir, la relación matemática que vincula las variables medidas con el hardware diseñado y la estimación de la PA). A continuación se presentan las principales contribuciones resultantes de cada frente de trabajo. Una de las contribuciones de esta tesis es el uso del principio PTT para estimar CABP en lugar de la BP periférica (PBP) (como se usa típicamente en la literatura). La prueba de concepto mostró la viabilidad de la estimación de CABP a partir del principio PTT mediante la adquisición de señales electrocardiograma (ECG) y balistocardiograma (BCG) utilizando equipos comerciales. Los resultados mostraron que CABP estaba más correlacionado con la metodología propuesta en comparación con todas las variables de PBP evaluadas; confirmando nuestra hipótesis de que la CABP sería la variable más adecuada para estimar a partir del tiempo transcurrido desde la onda R del ECG hasta la onda J del BCG. Es decir, el tiempo considerado (intervalo RJ) incluye un tiempo de propagación del pulso de presión a través de un segmento aórtico. Las gráficas de Bland-Altman mostraron un error medio casi nulo (\u\ < 0.02mmHg) y una precisión o < 5mmHg para las variables de presión sistólica y media centrales. La prueba de concepto proporcionó un hito para desarrollar un dispositivo vestible apuntando a la monitorización inalámbrica de la presión arterial en un sistema imperceptible para el usuario. Otra contribución de esta tesis es la propuesta de este dispositivo vestible para la adquisición de la PTT. El desarrollo incluye consideraciones de instrumentación necesarias para el correcto acondicionamiento de las señales ECG y BCG, de las cuales se obtiene la PTT. En particular, el procedimiento de diseño propuesto busca minimizar el impacto de los retrasos espurios entre las señales fisiológicas, que eventualmente degradan la computación de la PTT. Además, dicho procedimiento podría ser aprovechado por otros desarrolladores del método sin importar las definiciones de PTT que éstos usen. La limitación de banda con bajo retardo es necesario para esta aplicación biomédica, y el hardware de acondicionamiento propuesto proporciona menos de 2 ms de retraso en las se~nales (ECG y BCG) mientras consigue limitar sus bandas a decenas de Hz, lo que muestra la efectividad de la metodología propuesta. Adicionalmente, con el fin de proporcionar a la metodología de una mayor autonomía e integración, se propone una implementación altamente miniaturizada de la sección de filtrado con bajo retraso. Se incluye el diseño de nuevas topologías propuestas en tecnología CMOS para implementar el particular filtro de bajo retraso con reducido ancho de banda, y con características de ultra bajo consumo de potencia. El diseño integrado consigue obtener resultados similares al obtenido anteriormente (con componentes discretos) alcanzando un retraso de menos de 2 ms para el complejo QRS del ECG, pero con un consumo de IDD = 2:1 nA a un VDD = 1:2 V . Tal desarrollo significó otra contribución de este trabajo en el área de circuitos altamente autónomos para instrumentación biomédica. La primera etapa de validaciones en la estimación vestible de la CABP se basó en experimentaciones con un voluntario, mostrando que, la estimación vestible podría alcanzar los mismos resultados que los alcanzados utilizando equipos de investigación, permitiendo así avanzar en la validación del método propuesto utilizando el equipamiento vestible diseñado. Además de esto, se encontró que la estimación de CABP a partir del dispositivo vestible podría ser factible utilizando varios tiempos característicos (FT) extraídos de las señales vestibles ECG y BCG (intervalos RI, RJ e IJ) junto con un popular PTTBM. La primera validación del método también arrojó que la metodología propuesta podría estimar con precisión la CABP cuando el tiempo entre calibraciones es del orden de un día. La segunda etapa de validación implicó un estudio con un grupo de voluntarios, nuevas alternativas se exploraron esta vez (veintisiete: nueve PTTBM con tres FT) para la estimación de CABP. Descubrimos que CABP podría estimarse con precisión (dentro de los requisitos de AAMI) a través de la metodología presentada mediante el uso de cuatro de las alternativas exploradas, mientras que el intervalo RI, siendo un FT que a priori no tiene ninguna vinculación con un PTT, surge como el mejor estimador de la CABP. Se concluye entonces, que un principio diferente del método tradicional basado en PTT podría ser más ventajoso para la estimación de CABP a la luz de la evidencia encontrada en esta validación y, adicionalmente, a nuestro entender, esta es la primera vez que CABP se estima con éxito a partir de un dispositivo vestible. La contribución final de esta tesis significó el último eslabón de la cadena en el proceso de lograr un método completamente original para estimar CABP de punta a punta. Se propone un nuevo PTTBM para estimar CABP, éste es basado en una red Windkesel de dos elementos bajo una excitación de flujo. Estos elementos del PTTBM son construidos a partir de cantidades extraídas a través de procesamiento de las señales vestibles ECG y BCG. Cuando se aplican los PTTBM clásicos, el ajuste de sus parámetros (en calibración) a menudo conducen a valores sin base fisiológica, mostrando a su vez, una dispersión en sus valores a lo largo de distintas calibraciones que podrían ser inaceptables en la práctica. En contraposición, los parámetros del PTTBM propuesto convergen a cantidades con significado fisiologico claro y estable a lo largo de las calibraciones. En conclusión, esta tesis presenta un dispositivo novedoso que explota un método alternativo e indirecto para la estimación de CABP. El método propuesto es basado en la metodología de PTT, que si bien ha sido previamente explotado para estimar PBP, no se ha dirigido éste hacia el monitoreo vestible de la PA aórtica central. En este marco se desarrolla un dispositivo vestible, causando baja molestia en el usuario durante las mediciones, lo que permitiría un monitoreo continuo y ambulatorio real de la presión aórtica central. El sistema vestible desarrollado, validado en una serie de voluntarios, ha mostrado resultados prometedores hacia el monitoreo continuo de CABP

Enabling Wearable Hemodynamic Monitoring Using Multimodal Cardiomechanical Sensing Systems

Hemodynamic parameters such as blood pressure and stroke volume are instrumental to understanding the pathogenesis of cardiovascular disease. Unfortunately, the monitoring of these hemodynamic parameters is still limited to in-clinic measurements and cumbersome hardware precludes convenient, ubiquitous use. To address this burden, in this work, we explore seismocardiogram-based wearable multimodal sensing techniques to estimate blood pressure and stroke volume. First, the performance of a multimodal, wrist-worn device capable of obtaining noninvasive pulse transit time measurements is used to estimate blood pressure in an unsupervised, at-home setting. Second, the feasibility of this wrist-worn device is comprehensively evaluated in a diverse and medically underserved population over the course of several perturbations used to modulate blood pressure through different pathways. Finally, the ability of wearable signals—acquired from a custom chest-worn biosensor—to noninvasively quantify stroke volume in patients with congenital heart disease is examined in a hospital setting. Collectively, this work demonstrates the advancements necessary towards enabling noninvasive, longitudinal, and accurate measurements of these hemodynamic parameters in remote settings, which offers to improve health equity and disease monitoring in low-resource settings.Ph.D

Acute changes in carotid-femoral pulse-wave velocity are tracked by heart-femoral-pulse-wave velocity

Background: Carotid-femoral pulse-wave velocity (cfPWV) is the reference standard measure of central arterial stiffness. However, it requires assessment of the carotid artery, which is technically challenging, and subject-level factors, including carotid artery plaque, may confound measurements. A promising alternative that overcomes these limitations is heart-femoral PWV (hfPWV), but it is not known to what extent changes in cfPWV and hfPWV are associated. Objectives: To determine, (1) the strength of the association between hfPWV and cfPWV; and (2) whether change in hfPWV is associated with change in cfPWV when central arterial stiffness is perturbed. Methods: Twenty young, healthy adults (24.0 [SD: 3.1] years, 45% female) were recruited. hfPWV and cfPWV were determined using Doppler ultrasound at baseline and following a mechanical perturbation in arterial stiffness (120mmHg thigh occlusion). Agreement between the two measurements was determined using mixed-effects regression models and Bland-Altman analysis. Results: There was, (1) strong (ICC >0.7) agreement between hfPWV and cfPWV (ICC= 0.82, 95%CI: 0.69,0.90), and, (2) very strong (ICC >0.9) agreement between change in hfPWV and cfPWV (ICC = 0.92, 95%CI: 0.86,0.96). cfPWV was significantly greater than hfPWV at baseline and during thigh occlusion (both P <0.001). Inspection of the Bland-Altman plot, comparing cfPWV and corrected hfPWV, revealed no measurement magnitude bias. Discussion: The current findings indicate that hfPWV and cfPWV are strongly associated, and that change in cfPWV is very strongly associated with change in hfPWV. hfPWV may be a simple alternative to cfPWV in the identification of cardiovascular risk in clinical and epidemiological settings