Structure and Function of Asthma Evaluated Using Pulmonary Imaging

Asthma has been understood to affect the airways in a spatially heterogeneous manner for over six decades. Computational models of the asthmatic lung have suggested that airway abnormalities are diffusely and randomly distributed throughout the lung, however these mechanisms have been challenging to measure in vivo using current clinical tools. Pulmonary structure and function are still clinically characterized by the forced expiratory volume in one-second (FEV1) – a global measurement of airflow obstruction that is unable to capture the underlying regional heterogeneity that may be responsible for symptoms and disease worsening. In contrast, pulmonary magnetic resonance imaging (MRI) provides a way to visualize and quantify regional heterogeneity in vivo, and preliminary MRI studies in patients suggest that airway abnormalities in asthma are spatially persistent and not random. Despite these disruptive results, imaging has played a limited clinical role because the etiology of ventilation heterogeneity in asthma and its long-term pattern remain poorly understood. Accordingly, the objective of this thesis was to develop a deeper understanding of the pulmonary structure and function of asthma using functional MRI in conjunction with structural computed tomography (CT) and oscillometry, to provide a foundation for imaging to guide disease phenotyping, personalized treatment and prediction of disease worsening. We first evaluated the biomechanics of ventilation heterogeneity and showed that MRI and oscillometry explained biomechanical differences between asthma and other forms of airways disease. We then evaluated the long-term spatial and temporal nature of airway and ventilation abnormalities in patients with asthma. In nonidentical twins, we observed a spatially-matched CT airway and MRI ventilation abnormality that persisted for seven-years; we estimated the probability of an identical defect occurring in time and space to be 1 in 130,000. In unrelated asthmatics, ventilation defects were spatially-persistent over 6.5-years and uniquely predicted longitudinal bronchodilator reversibility. Finally, we investigated the entire CT airway tree and showed that airways were truncated in severe asthma related to thickened airway walls and worse MRI ventilation heterogeneity. Together, these results advance our understanding of asthma as a non-random disease and support the use of MRI ventilation to guide clinical phenotyping and treatment decisions

Acoustic sensing as a novel wearable approach for cardiac monitoring at the wrist

This paper introduces the concept of using acoustic sensing over the radial artery to extract cardiac parameters for continuous vital sign monitoring. It proposes a novel measurement principle that allows detection of the heart sounds together with the pulse wave, an attribute not possible with existing photoplethysmography (PPG)-based methods for monitoring at wrist. The validity of the proposed principle is demonstrated using a new miniature, battery-operated wearable device to sense the acoustic signals and a novel algorithm to extract the heart rate from these signals. The algorithm utilizes the power spectral analysis of the acoustic pulse signal to detect the S1 sounds and additionally, the K-means method to remove motion artifacts for an accurate heartbeat detection. It has been validated on a dataset consisting of 12 subjects with a data length of 6 hours. The results demonstrate an accuracy of 98.78\%, mean absolute error of 0.28 bpm, limits of agreement between -1.68 and 1.69 bpm, and a correlation coefficient of 0.998 with reference to a state-of-the-art PPG-based commercial device. The results in this proof of concept study demonstrate the potential of this new sensing modality to be used as an alternative, or to complement existing methods, for continuous monitoring of heart rate at wrist

Assessment of trends in the cardiovascular system from time interval measurements using physiological signals obtained at the limbs

Cardiovascular diseases are an increasing source of concern in modern societies due to their increasing prevalence and high impact on the lives of many people. Monitoring cardiovascular parameters in ambulatory scenarios is an emerging approach that can provide better medical access to patients while decreasing the costs associated to the treatment of these diseases. This work analyzes systems and methods to measure time intervals between the electrocardiogram (ECG), impedance plethysmogram (IPG), and the ballistocardiogram (BCG), which can be obtained at the limbs in ambulatory scenarios using simple and cost-effective systems, to assess cardiovascular intervals of interest, such as the pulse arrival time (PAT), pulse transit time (PTT), or the pre-ejection period (PEP). The first section of this thesis analyzes the impact of the signal acquisition system on the uncertainty in timing measurements in order to establish the design specifications for systems intended for that purpose. The minimal requirements found are not very demanding yet some common signal acquisition systems do not fulfill all of them while other capabilities typically found in signal acquisition systems could be downgraded without worsening the timing uncertainty. This section is also devoted to the design of systems intended for timing measurements in ambulatory scenarios according to the specifications previously established. The systems presented have evolved from the current state-of-the-art and are designed for adequate performance in timing measurements with a minimal number of active components. The second section is focused on the measurement of time intervals from the IPG measured from limb to limb, which is a signal that until now has only been used to monitor heart rate. A model to estimate the contributions to the time events in the measured waveform of the different body segments along the current path from geometrical properties of the large arteries is proposed, and the simulation under blood pressure changes suggests that the signal is sensitive to changes in proximal sites of the current path rather than in distal sites. Experimental results show that the PAT to the hand-to-hand IPG, which is obtained from a novel four-electrode handheld system, is correlated to changes in the PEP whereas the PAT to the foot-to-foot IPG shows good performance in assessing changes in the femoral PAT. Therefore, limb-to-limb IPG measurements significantly increase the number of time intervals of interest that can be measured at the limbs since the signals deliver information from proximal sites complementary to that of other measurements typically performed at distal sites. The next section is devoted to the measurement of time intervals that involve different waves of the BCG obtained in a standing platform and whose origin is still under discussion. From the relative timing of other physiological signals, it is hypothesized that the IJ interval of the BCG is sensitive to variations in the PTT. Experimental results show that the BCG I wave is a better surrogate of the cardiac ejection time than the widely-used J wave, which is also supported by the good correlation found between the IJ interval and the aortic PTT. Finally, the novel time interval from the BCG I wave to the foot of the IPG measured between feet, which can be obtained from the same bathroom scale than the BCG, shows good performance in assessing the aortic PAT. The results presented reinforce the role of the BCG as a tool for ambulatory monitoring since the main time intervals targeted in this thesis can be obtained from the timing of its waves. Even though the methods described were tested in a small group of subjects, the results presented in this work show the feasibility and potential of several time interval measurements between the proposed signals that can be performed in ambulatory scenarios, provided the systems intended for that purpose fulfill some minimal design requirements.Les malalties cardiovasculars són una tema de preocupació creixent en societats modernes, degut a l’augment de la seva prevalença i l'elevat impacte en les vides dels pacients que les sofreixen. La mesura i monitoratge de paràmetres cardiovasculars en entorns ambulatoris és una pràctica emergent que facilita l’accés als serveis mèdics i permet reduir dràsticament els costos associats al tractament d'aquestes malalties. En aquest treball s’analitzen sistemes i mètodes per la mesura d’intervals temporals entre l’electrocardiograma (ECG), el pletismograma d’impedància (IPG) i el balistocardiograma (BCG), que es poden obtenir de les extremitats i en entorns ambulatoris a partir de sistemes de baix cost, per tal d’avaluar intervals cardiovasculars d’interès com el pulse arrival time (PAT), pulse transit time (PTT) o el pre-ejection period (PEP). En la primera secció d'aquesta tesi s’analitza l’impacte del sistema d’adquisició del senyal en la incertesa de mesures temporals, per tal d’establir els requeriments mínims que s’han de complir en entorns ambulatoris. Tot i que els valors obtinguts de l’anàlisi no són especialment exigents, alguns no són assolits en diversos sistemes habitualment utilitzats mentre que altres solen estar sobredimensionats i es podrien degradar sense augmentar la incertesa en mesures temporals. Aquesta secció també inclou el disseny i proposta de sistemes per la mesura d’intervals en entorns ambulatoris d’acord amb les especificacions anteriorment establertes, a partir de l’estat de l’art i amb l’objectiu de garantir un correcte funcionament en entorns ambulatoris amb un nombre mínim d’elements actius per reduir el cost i el consum. La segona secció es centra en la mesura d’intervals temporals a partir de l’IPG mesurat entre extremitats, que fins al moment només s’ha fet servir per mesurar el ritme cardíac. Es proposa un model per estimar la contribució de cada segment arterial per on circula el corrent a la forma d’ona obtinguda a partir de la geometria i propietats físiques de les artèries, i les simulacions suggereixen que la senyal entre extremitats és més sensible a canvis en arteries proximals que en distals. Els resultats experimentals mostren que el PAT al hand-to-hand IPG, obtingut a partir d’un innovador sistema handheld de quatre elèctrodes, està fortament correlacionat amb els canvis de PEP, mentre que el PAT al foot-to-foot IPG està correlat amb els canvis en PAT femoral. Conseqüentment, l’ILG entre extremitats augmenta de manera significativa els intervals d’interès que es poden obtenir en extremitats degut a que proporciona informació complementària a les mesures que habitualment s’hi realitzen. La tercera secció està dedicada a la mesura d’intervals que inclouen les ones del BCG vertical obtingut en plataformes, de les que encara se’n discuteix l’origen. A partir de la posició temporal relativa respecte altres ones fisiològiques, s’hipostatitza que l’interval IJ del BCG es sensible a variacions del PTT. Els resultats experimentals mostren que la ona I del BCG és un millor indicador de l’ejecció cardíaca que el pic J, tot i que aquest és el més utilitzat habitualment, degut a la bona correlació entre l’interval IJ i el PTT aòrtic. Finalment, es presenta un mètode alternatiu per la mesura del PTT aòrtic a partir de l’interval entre el pic I del BCG i el peu del foot-to-foot IPG, que es pot obtenir de la mateixa plataforma que el BCG i incrementa la robustesa de la mesura. Els resultats presentats reforcen el paper del BCG com a en mesures en entorns ambulatoris, ja que els principals intervals objectiu d’aquesta tesi es poden obtenir a partir de les seves ones. Tot i que els mètodes descrits han estat provats en grups petits de subjectes saludables, els resultats mostren la viabilitat i el potencial de diversos intervals temporals entre les senyals proposades que poden ésser realitzats en entorns ambulatoris, sempre que els sistemes emprats compleixin els requisits mínims de disseny.Postprint (published version

Understanding Vibration Transmitted to the Human Finger

Prolonged exposure of the hand to tool-induced vibrations is associated with the occurrence of debilitating conditions such as vibration white finger. The primary aim of this work is to gain a better understanding of the effects of different aspects of exposure to finger transmitted vibration (FTV) related to operators using hand-held vibrating tools. To achieve this, firstly, a new method for measuring finger transmitted vibration was developed and assessed, including a tool vibration test rig and measurement protocol. The effect on FTV measurement of using a small accelerometer attached to the back of the finger was investigated using 2D finite element modelling. Comparisons were also made using a laser vibrometer. Analysis showed that the new test rig is capable of measuring FTV at frequencies ranging from 10 to 400 Hz, under different grip force levels, and that adding a small accelerometer mass (0.3 grams) did not significantly affect measurements. A human participant study then carried out using the new rig. Various characteristic measurements were collected in tandem, including anthropometry, skin characterisation and behaviour under loading to investigate the effect of different factors on FTV. The results showed that FTV varied among individuals and the key finding was that exposure to vibration has a significant effect on finger temperature even for a short period of testing. Anti-vibration (AV) glove materials were investigated using dynamic mechanical analysis (DMA) and tested using human participants. The results showed that the mechanical properties of AV materials change under real world industrial conditions such as excitation frequencies and temperature. Finally, a new artificial test-bed was developed to replicate the transmitted vibration of the index finger. Studies were conducted on a range of 5 test-beds, to allow comparison with the human measurements, including indentation, vibration transmissibility and FE modelling. FE modelling showed that the distribution of dynamic strain was found to be highest in the vasculature region of the finger, indicating that this could be one of the contributing factors of VWF. One of the finger test-bed was selected as best replicating the mechanical properties of the real finger. The artificial test-bed provided better consistency than human participants, for testing parameters, such as grip force, and can be used in future for testing AV gloves with no need for human subjects.ii Further investigations are suggested to be made to enhance the limitations of this project, including material analysis, testing protocol and finite element modelling. Keywords:, hand-arm vibration syndromes, vibration white finger, FTV, transmissibility, resonance frequency, grip force, AV glove, finger mechanical properties, artificial finger, finite element modellin

Understanding Vibration Transmitted to the Human Finger

Prolonged exposure of the hand to tool-induced vibrations is associated with the occurrence of debilitating conditions such as vibration white finger. The primary aim of this work is to gain a better understanding of the effects of different aspects of exposure to finger transmitted vibration (FTV) related to operators using hand-held vibrating tools. To achieve this, firstly, a new method for measuring finger transmitted vibration was developed and assessed, including a tool vibration test rig and measurement protocol. The effect on FTV measurement of using a small accelerometer attached to the back of the finger was investigated using 2D finite element modelling. Comparisons were also made using a laser vibrometer. Analysis showed that the new test rig is capable of measuring FTV at frequencies ranging from 10 to 400 Hz, under different grip force levels, and that adding a small accelerometer mass (0.3 grams) did not significantly affect measurements. A human participant study then carried out using the new rig. Various characteristic measurements were collected in tandem, including anthropometry, skin characterisation and behaviour under loading to investigate the effect of different factors on FTV. The results showed that FTV varied among individuals and the key finding was that exposure to vibration has a significant effect on finger temperature even for a short period of testing. Anti-vibration (AV) glove materials were investigated using dynamic mechanical analysis (DMA) and tested using human participants. The results showed that the mechanical properties of AV materials change under real world industrial conditions such as excitation frequencies and temperature. Finally, a new artificial test-bed was developed to replicate the transmitted vibration of the index finger. Studies were conducted on a range of 5 test-beds, to allow comparison with the human measurements, including indentation, vibration transmissibility and FE modelling. FE modelling showed that the distribution of dynamic strain was found to be highest in the vasculature region of the finger, indicating that this could be one of the contributing factors of VWF. One of the finger test-bed was selected as best replicating the mechanical properties of the real finger. The artificial test-bed provided better consistency than human participants, for testing parameters, such as grip force, and can be used in future for testing AV gloves with no need for human subjects.ii Further investigations are suggested to be made to enhance the limitations of this project, including material analysis, testing protocol and finite element modelling. Keywords:, hand-arm vibration syndromes, vibration white finger, FTV, transmissibility, resonance frequency, grip force, AV glove, finger mechanical properties, artificial finger, finite element modellin

The design and evaluation of discrete wearable medical devices for vital signs monitoring

The observation, recording and appraisal of an individual’s vital signs, namely temperature, heart rate, blood pressure, respiratory rate and blood oxygen saturation (SpO2), are key components in the assessment of their health and wellbeing. Measurements provide valuable diagnostic data, facilitating clinical diagnosis, management and monitoring. Respiratory rate sensing is perhaps the most under-utilised of all the vital signs, being routinely assessed by observation or estimated algorithmically from respiratory-induced beat-to-beat variation in heart rate. Moreover there is an unmet need for wearable devices that can measure all or most of the vital signs. This project therefore aims to a) develop a device that can measure respiratory rate and b) develop a wearable device that can measure all or most of the vital signs. An accelerometer-based clavicular respiratory motion sensor was developed and compared with a similar thoracic motion sensor and reference using exhalatory flow. Pilot study results established that the clavicle sensor accurately tracked the reference in monitoring respiratory rate and outperformed the thoracic device. An Ear-worn Patient Monitoring System (EPMS) was also developed, providing a discrete telemonitoring device capable of rapidly measuring tympanic temperature, heart rate, SpO2 and activity level. The results of a comparative pilot study against reference instruments revealed that heart rate matched the reference for accuracy, while temperature under read (< 1°C) and SpO2 was inconsistent with poor correlation. In conclusion, both of the prototype devices require further development. The respiratory sensor would benefit from product engineering and larger scale testing to fully exploit the technology, but could find use in both hospital and community-based The design and evaluation of discrete wearable medical devices for vital signs monitoring DG Pitts ii Cranfield University monitoring. The EPMS has potential for clinical and community use, having demonstrated its capability of rapidly capturing and wirelessly transmitting vital signs readings. Further development is nevertheless required to improve the thermometer probe and resolve outstanding issues with SpO2 readings

Hemodynamic monitor for rapid, cost-effective assessment of peripheral vascular function

Worldwide, at least 200 million people are affected by peripheral vascular diseases (PVDs), including peripheral arterial disease (PAD), chronic venous insufficiency (CVI) and deep vein thrombosis (DVT). These diseases have considerable socioeconomic impacts due to their high prevalence, cost of investigation, treatment and their effects on quality of life. PVDs are often undiagnosed with up to 60% of patients with PVD remaining asymptomatic. Early diagnosis is essential for effective treatment and reducing socioeconomic costs, particularly in patients with diabetes where early endovascular treatment can prevent lower extremity amputation. However, available diagnostic methods simply do not meet the needs of clinicians. For example, duplex ultrasound or plethysmography are time-consuming methods, costly and require access to highly trained clinicians. Due to the cost and time requirements of such methods, they are often reserved for symptomatic patients. On the other hand, the Ankle Brachial Index (ABI) test is cheap but has poor sensitivity for those patients with diabetes and the elderly, both growing high-risk populations. There is an urgent need for new diagnostic tools to enable earlier intervention. Researchers at the MARCS Institute have developed a novel hemodynamic monitor platform named HeMo, specifically for the assessment of peripheral blood flow in the leg. This development aimed to provide a fast and low-cost diagnosis of both peripheral arterial disease and chronic venous insufficiency. This work first provides a comprehensive literature review of the existing non-invasive diagnostic devices developed since 1677 to highlight the need of development of a new blood monitoring tool. Second, it presents the simplified circuit of the HeMo device and provides series of pilot experiments with HeMo demonstrating its potential for diagnosis of both peripheral arterial disease and chronic venous insufficiency. Third, it presents a quantitative characterisation of the electrical behaviour of the electro-resistive band sensors with the development of an expansion/contraction simulator rig and using spectral analysis. The characterisation of the electro-resistive band was essential to understand the nonlinear electrical behaviour of such sensors and would be of interest for other users and uses of the electro-resistive band sensors. However, in another perspective this sinusoidal linear stretching movement and the presented method shows an example for the application of the presented rig, highlighting that the same technique could be used for characterisation of similar stretchable sensors. Fourth, it shows data from a healthy population, assessing the performance of HeMo compared to light reflection rheography (LRR sensor-VasoScreen 5000) for the assessment of venous function. Fifth, it presents human study data where the performance of HeMo is compared to photoplethysmography (PPG sensor-VasoScreen 5000) for the evaluation of the arterial function. Overall, the presented work here, steps toward development of the final version of a novel hemodynamic monitoring device, and its validation

Aerospace Medicine and Biology: A continuing bibliography with indexes, (supplement 154), May 1976

This bibliography lists 253 reports, articles, and other documents introduced into the NASA scientific and technical information system in April 1976

Multidimensional embedded MEMS motion detectors for wearable mechanocardiography and 4D medical imaging

Background: Cardiovascular diseases are the number one cause of death. Of these deaths, almost 80% are due to coronary artery disease (CAD) and cerebrovascular disease. Multidimensional microelectromechanical systems (MEMS) sensors allow measuring the mechanical movement of the heart muscle offering an entirely new and innovative solution to evaluate cardiac rhythm and function. Recent advances in miniaturized motion sensors present an exciting opportunity to study novel device-driven and functional motion detection systems in the areas of both cardiac monitoring and biomedical imaging, for example, in computed tomography (CT) and positron emission tomography (PET). Methods: This Ph.D. work describes a new cardiac motion detection paradigm and measurement technology based on multimodal measuring tools — by tracking the heart’s kinetic activity using micro-sized MEMS sensors — and novel computational approaches — by deploying signal processing and machine learning techniques—for detecting cardiac pathological disorders. In particular, this study focuses on the capability of joint gyrocardiography (GCG) and seismocardiography (SCG) techniques that constitute the mechanocardiography (MCG) concept representing the mechanical characteristics of the cardiac precordial surface vibrations. Results: Experimental analyses showed that integrating multisource sensory data resulted in precise estimation of heart rate with an accuracy of 99% (healthy, n=29), detection of heart arrhythmia (n=435) with an accuracy of 95-97%, ischemic disease indication with approximately 75% accuracy (n=22), as well as significantly improved quality of four-dimensional (4D) cardiac PET images by eliminating motion related inaccuracies using MEMS dual gating approach. Tissue Doppler imaging (TDI) analysis of GCG (healthy, n=9) showed promising results for measuring the cardiac timing intervals and myocardial deformation changes. Conclusion: The findings of this study demonstrate clinical potential of MEMS motion sensors in cardiology that may facilitate in time diagnosis of cardiac abnormalities. Multidimensional MCG can effectively contribute to detecting atrial fibrillation (AFib), myocardial infarction (MI), and CAD. Additionally, MEMS motion sensing improves the reliability and quality of cardiac PET imaging.Moniulotteisten sulautettujen MEMS-liiketunnistimien käyttö sydänkardiografiassa sekä lääketieteellisessä 4D-kuvantamisessa Tausta: Sydän- ja verisuonitaudit ovat yleisin kuolinsyy. Näistä kuolemantapauksista lähes 80% johtuu sepelvaltimotaudista (CAD) ja aivoverenkierron häiriöistä. Moniulotteiset mikroelektromekaaniset järjestelmät (MEMS) mahdollistavat sydänlihaksen mekaanisen liikkeen mittaamisen, mikä puolestaan tarjoaa täysin uudenlaisen ja innovatiivisen ratkaisun sydämen rytmin ja toiminnan arvioimiseksi. Viimeaikaiset teknologiset edistysaskeleet mahdollistavat uusien pienikokoisten liiketunnistusjärjestelmien käyttämisen sydämen toiminnan tutkimuksessa sekä lääketieteellisen kuvantamisen, kuten esimerkiksi tietokonetomografian (CT) ja positroniemissiotomografian (PET), tarkkuuden parantamisessa. Menetelmät: Tämä väitöskirjatyö esittelee uuden sydämen kineettisen toiminnan mittaustekniikan, joka pohjautuu MEMS-anturien käyttöön. Uudet laskennalliset lähestymistavat, jotka perustuvat signaalinkäsittelyyn ja koneoppimiseen, mahdollistavat sydämen patologisten häiriöiden havaitsemisen MEMS-antureista saatavista signaaleista. Tässä tutkimuksessa keskitytään erityisesti mekanokardiografiaan (MCG), joihin kuuluvat gyrokardiografia (GCG) ja seismokardiografia (SCG). Näiden tekniikoiden avulla voidaan mitata kardiorespiratorisen järjestelmän mekaanisia ominaisuuksia. Tulokset: Kokeelliset analyysit osoittivat, että integroimalla usean sensorin dataa voidaan mitata syketiheyttä 99% (terveillä n=29) tarkkuudella, havaita sydämen rytmihäiriöt (n=435) 95-97%, tarkkuudella, sekä havaita iskeeminen sairaus noin 75% tarkkuudella (n=22). Lisäksi MEMS-kaksoistahdistuksen avulla voidaan parantaa sydämen 4D PET-kuvan laatua, kun liikeepätarkkuudet voidaan eliminoida paremmin. Doppler-kuvantamisessa (TDI, Tissue Doppler Imaging) GCG-analyysi (terveillä, n=9) osoitti lupaavia tuloksia sydänsykkeen ajoituksen ja intervallien sekä sydänlihasmuutosten mittaamisessa. Päätelmä: Tämän tutkimuksen tulokset osoittavat, että kardiologisilla MEMS-liikeantureilla on kliinistä potentiaalia sydämen toiminnallisten poikkeavuuksien diagnostisoinnissa. Moniuloitteinen MCG voi edistää eteisvärinän (AFib), sydäninfarktin (MI) ja CAD:n havaitsemista. Lisäksi MEMS-liiketunnistus parantaa sydämen PET-kuvantamisen luotettavuutta ja laatua