Dynamic relationship between cardiac imaging and physiological measurements

PhD ThesisImpedance cardiography (ICG) is a non-invasive technique to measure the dynamic changes in electrical impedance of the thorax. Photoplethymgraphy (PPG) is an optical- based non-invasive physiological measurement technique used to detect the blood volume pulses in the microvascular bed of tissue. These two physiological measurements have potential clinical importance to enable simple and cost-efficient ways to examine cardiovascular function and provide surrogate or additional clinical information to the measures from cardiac imaging. However, because the origins of the characteristic waveforms of the impedance and pulse are still not well understood, the clinical applications of these two techniques are limited. There were two main aims in this study: 1) to obtain a better understanding of the origins of the pulsatile impedance changes and peripheral pulse by linking their characteristic features beat-by-beat to those from simultaneous echocardiograms; 2) to validate the clinical indices from ICG and PPG with those well-established echocardiographic indices. Physiological signals, including ECGs, impedance, the first derivative impedance and finger and ear pulses, were simultaneously recorded with echocardiograms from 30 male healthy subjects at rest. The timing sequence of cardiovascular events in a single cardiac cycle was reconstructed with the feature times obtained from the physiological measurements and images. The relations of the time features from the impedance with corresponding features from images and pulses were investigated. The relations of the time features from peripheral pulses with corresponding features from images were also investigated. Furthermore, clinical time indices measured from the impedance and pulse were validated with the reference to the echocardiograms. Finally, the effects of age, heart rate and blood pressure on the image and physiological measurements were examined. According to the reconstructed timing sequence, it was evident that the systolic waves of the thoracic impedance and peripheral pulse occurred following left ventricular ejection. The impedance started to fall 26 ms and the pulse arrived at the fingertip 162 ms after the aortic valve opened. A diastolic wave was observed during the ventricular passive filling phase on the impedance and pulse. The impedance started to recover during the late ventricular ejection phase when the peripheral pulse was rising up. While the pulsatile impedance changes were mainly correlated with valve movement, the derivative impedance (velocity of impedance change) was more correlated with aortic flow (velocity of blood 2 flow). The foot of the finger pulse was significantly correlated with aortic valve open (R = 0.361, P < 0.05), while its systolic peak was strongly correlated with the aortic valve 2 closing (R = 0.579, P < 0.001). Although the pulse had similar waveform shapes to the inverted impedance waveform, the associations between the time features of these two signals were weak. During the validation of potential clinical indices from ICG, significant correlation was found between the overall duration of the derivative impedance systolic wave (359 ms) and the left ventricular ejection time (LVET) measured by aortic valve open duration from M- 2 mode images (329 ms) (R = 0.324, P < 0.001). The overall duration from the finger pulse foot to notch (348 ms) was also significantly correlated with the LVET from M-mode 2 images (R = 0.461, P < 0.001). Therefore, both ICG and PPG had the potential to provide surrogates to the LVET measurement. Age influenced the cardiovascular diastolic function more than systolic function on normal subjects. With age increasing, the reduction of the left ventricular passive filling was compensated by active filling. The ratio of the passive filling duration to the active 2 filling duration decreased with age (R = 0.143, P < 0.05). The influence of age on the diastolic wave of the impedance signals was striking. The impedance diastolic wave disappeared gradually with age. The effects of age on the peripheral pulse were mainly on the shortened pulse foot transit time (PPT) and prolonged pulse rise time. The large artery f stiffness index (SI) increased with age. Most time intervals were prolonged with heart rate slowing down. The effects of systolic blood pressure were evident on pulse transit time and pulse diastolic rising time. Driven by higher systolic blood pressure, both PPT and rising f time decreased significantly (P < 0.001). In conclusion, from the analysis based on simultaneous physiological measurements and echocardiograms, both the pulsatile impedance changes and peripheral volume pulse were initiated by left ventricular ejection. The thoracic impedance changes reflected volume changes in the central great vessels, while the first derivative impedance was associated with the velocity of blood flow. Both ICG and PPG had the potential to provide surrogates for the measures of cardiac mechanical functions from images. The PPG technique also enabled the assessment of changes in vascular function caused by age.Institute of Cellular Medicine Newcastle Universit

Imaging fascicular organisation in mammalian vagus nerve for selective VNS

Nerves contain a large number of nerve fibres, or axons, organised into bundles known as fascicles. Despite the somatic nervous system being well understood, the organisation of the fascicles within the nerves of the autonomic nervous system remains almost completely unknown. The new field of bioelectronics medicine, Electroceuticals, involves the electrical stimulation of nerves to treat diseases instead of administering drugs or performing complex surgical procedures. Of particular interest is the vagus nerve, a prime target for intervention due to its afferent and efferent innervation to the heart, lungs and majority of the visceral organs. Vagus nerve stimulation (VNS) is a promising therapy for treatment of various conditions resistant to standard therapeutics. However, due to the unknown anatomy, the whole nerve is stimulated which leads to unwanted off-target effects. Electrical Impedance Tomography (EIT) is a non-invasive medical imaging technique in which the impedance of a part of the body is inferred from electrode measurements and used to form a tomographic image of that part. Micro-computed tomography (microCT) is an ex vivo method that has the potential to allow for imaging and tracing of fascicles within experimental models and facilitate the development of a fascicular map. Additionally, it could validate the in vivo technique of EIT. The aim of this thesis was to develop and optimise the microCT imaging method for imaging the fascicles within the nerve and to determine the fascicular organisation of the vagus nerve, ultimately allowing for selective VNS. Understanding and imaging the fascicular anatomy of nerves will not only allow for selective VNS and the improvement of its therapeutic efficacy but could also be integrated into the study on all peripheral nerves for peripheral nerve repair, microsurgery and improving the implementation of nerve guidance conduits. Chapter 1 provides an introduction to vagus nerve anatomy and the principles of microCT, neuronal tracing and EIT. Chapter 2 describes the optimisation of microCT for imaging the fascicular anatomy of peripheral nerves in the experimental rat sciatic and pig vagus nerve models, including the development of pre-processing methods and scanning parameters. Cross-validation of this optimised microCT method, neuronal tracing and EIT in the rat sciatic nerve was detailed in Chapter 3. Chapter 4 describes the study with microCT with tracing, EIT and selective stimulation in pigs, a model for human nerves. The microCT tracing approach was then extended into the subdiaphragmatic branches of the vagus nerves, detailed in Chapter 5. The ultimate goal of human vagus nerve tracing was preliminarily performed and described in Chapter 6. Chapter 7 concludes the work and describes future work. Lastly, Appendix 1 (Chapter 8) is a mini review on the application of selective vagus nerve stimulation to treat acute respiratory distress syndrome and Appendix 2 is morphological data corresponding to Chapter 4

Biosensors for Diagnosis and Monitoring

Biosensor technologies have received a great amount of interest in recent decades, and this has especially been the case in recent years due to the health alert caused by the COVID-19 pandemic. The sensor platform market has grown in recent decades, and the COVID-19 outbreak has led to an increase in the demand for home diagnostics and point-of-care systems. With the evolution of biosensor technology towards portable platforms with a lower cost on-site analysis and a rapid selective and sensitive response, a larger market has opened up for this technology. The evolution of biosensor systems has the opportunity to change classic analysis towards real-time and in situ detection systems, with platforms such as point-of-care and wearables as well as implantable sensors to decentralize chemical and biological analysis, thus reducing industrial and medical costs. This book is dedicated to all the research related to biosensor technologies. Reviews, perspective articles, and research articles in different biosensing areas such as wearable sensors, point-of-care platforms, and pathogen detection for biomedical applications as well as environmental monitoring will introduce the reader to these relevant topics. This book is aimed at scientists and professionals working in the field of biosensors and also provides essential knowledge for students who want to enter the field

A portable EIT system for emergency medical care

Electrical Impedance Tomography (EIT) is a medical imaging technique in which images of tissue conductivity within a body can be inferred from surface electrode measurements. The main goal of this study is to develop a portable EIT system incorporating an optimized electrode layout to detect intracranial haematomas for use in emergency care. A growing haematoma can cause severe and even permanent damage to the delicate tissue of the brain, morbidity, and eventual death of the patient. No capability is at present available for the diagnosis of haematomas pre-hospitalisation or by first-responders. The lack of this crucial information can lead to bad decisions on patient management, and in particular, where to send the patient. Blood has a high electrical conductivity contrast relative to other cranial tissue and can be detected and monitored using electrical impedance methods. EIT is a non-invasive, low-cost monitoring alternative to other imaging modalities, and has the potential to detect bleeding and to localize the approximate bleeding site. A device of this nature would reduce treatment delays, save on costs and waste, and most significantly, positively impact patient outcomes. The first step was a numerical simulation study on FE models. The full array and the hemi-array electrode layouts were modelled and the anomalies were simulated in different positions with different sizes. The results were obtained using TSVD and WMNM reconstruction methods by COMSOL linked with MATLAB. The simulated anomalies were detected for all the positions using both layouts; however those from the full array were in general superior to the hemi-array. In order to perform realistic experiments, a prototype EIT system was constructed in the laboratory. The constructed EIT has 16 channels and operates in the frequency range of 10 kHz to 100 kHz with a temporal resolution of 100 frames per second and high level of accuracy of 93.5 %. The minimum number of 8 electrodes was chosen in this study for emergency care. Minimizing the number of electrodes speeds up the electrode setup process and avoids the need to move the patient s head in emergency care. In the second part of this study, phantom experiments were performed to find an optimised electrode layout for emergency care. The full array and the hemi-array were investigated using phantom experiments. As expected, the full array layout had the best performance in general; however, the performance of the hemi-array layout was very poor. Thus a novel optimised electrode layout (semi-array) for emergency care was proposed and evaluated in phantom experiments. For the hemi-array and the semi-array layouts, measurement sensitivity depends strongly on the anomaly location since the electrodes are not placed all over the head. The HA layout performed very badly, with the best radial localization error of 0.8100 mm, compared to the SA layout with the worst error of 0.2486 mm. Some reconstructed anomalies located far from the electrodes in the posterior region were almost invisible or erroneous for the hemi-array layout; however, it is enhanced by using the semi-array layout. Finally, in vitro experiments were conducted on ovine models. In most of the experiments carried out by other researchers, since the location of the simulated anomalies was not known and the simulated blood was normally injected into the body or the head, localization of the anomalies was not considered and the quantity of the injected blood was investigated solely. In our new method of experiment, the position of the anomalies was known a priori and thus could be compared accurately to the EIT results. The full array and the semi-array layouts were compared in terms of detection, localisation and size estimation of haematomas. As expected, the full array layout was found to be more robust than the semi-array layout with the best mean value of the localization error of 0.0564 mm and the worst QI error of around 30%. Using a minimum number of electrodes in an optimised layout is always desirable in clinical applications. The semi-array 8-electrode layout prevents unnecessary movements and the electrode connections to the head would be very quick in emergency care. Although the semi-array 8-electrode layout reduced the sensitivity of the measurements, the findings from the experiments indicated its potential to detect and monitor haematomas and probably extend its application for emergency applications where the required accuracy is not critical

A novel approach to bioelectrical impedance plethysmography for the assessment of arterial and venous circulatory problems in the forearm

Peripheral vascular disease (PVD) and/or peripheral arterial disease (PAD) are sicknesses known to inadequate delivery of either arterial or venous blood towards the extremities. Such sickness may trigger complications owing to the lack of transport of oxygen and nutrients, thus causing hypoxic events that may eventually prompt to ischaemic tissue or even the loss of the compromised limb. One of the most prominent indicators of prosperous health is blood volume and flow. The basic information within these health parameters may show cardiovascular problems or the advance of further complications related to other diseases like diabetes. In clinical setting, there effective methods to measure these parameters like Doppler ultrasound, photoplethysmography or venous occlusion plethysmography. These methods take measurements from either single vessels and/or small volume of tissue. However, it is difficult to establish a relation between the obstruction of arterial and/or venous circulation and the amount of blood received by the tissue. Bioelectrical impedance plethysmography (iPG) measures blood changes by driving a small amount of AC current into the body and after measuring the potential created by fluids flowing through tissue. This technique apart from taking measures within defined volumes of tissue, it is easy to use as only needs four electrodes on the skin. Hence, a bespoken bioelectrical impedance device including hardware and software was built ready to measure changes in blood volume/flow in the upper limbs. The system was assessed in an in-vivo controlled environment with 8 participants. The blood flow towards their left arms was altered by constricting the upper arm with a cuff at three levels: 1) below venous pressure 2) amongst venous and arterial pressure and 3) during total occlusion. Simultaneously, measurements from various instruments like ECG, Doppler ultrasound, laser Doppler flowmetry and PPG were taken and compared to the measurements obtained from the iPG instrument and defining its correlation with the impedimetric signal. The results from the experiments showed that the bioelectrical impedance signal changed in basal and arterial pulses showing specific characteristics for each kind of occlusion. The data indicated that it is possible to differentiate between a venous and arterial occlusion by examining both components of the impedance signal. The impedance during venous occlusion dropped in average 0.658±0.230% from the baseline. On the other hand, during arterial occlusion the base impedance dropped in a higher rate approximately 1.13±04.82%, indicating a differentiator during both type of blood flow disruption. Furthermore, the impedance plethysmography waveform morphology also reshaped during these occlusive periods. The whole waveform during artificial venous obstruction increased in magnitude, the systolic peak rose 31.80%, the dicrotic notch 47.73% and the diastolic point 31.92%, where the value of the latter was higher than the dicrotic notch point. In contrast, in the time of partial arterial occlusion the waveform also increased in size at all these points, but its shape was altered. The impedance magnitude at the diastolic point went below the ones at the dicrotic notch. These fluctuations provided additional further information that it might be possible to differentiate amongst venous and arterial occlusions. By consolidating the data obtained by the iPG device, it is possible to produce an index ratio between the basal impedance and these three reference points which may help to identify early circulatory problems in the arterial and/or venous systems

Movement artefact rejection in impedance pneumography.

Impedance pneumography is a non-invasive and a very convenient technique for monitoring breathing. However, a major drawback of this technique is that it is impossible to monitor breathing due to large artefacts introduced by the body movements. The aim of this project was to develop a technique for reducing these 'movement artefacts'. In the first stage of the project, experimental and theoretical studies were carried out to identify an 'optimum' electrode placement that would maximise the 'sensitivity' of measured thoracic impedance to lung resistivity changes. This maximum sensitivity was obtained when the drive and the receive electrode pairs were placed in two different horizontal planes. This sensitivity was also found to increase with increase in electrode spacing. In the second stage, the optimum electrode placement was used to record thoracic impedance during movements. Movement artefacts occurred only when the electrodes moved from their initial location along with the skin, during movements. Taking into consideration these observations, a strategy was decided for placing 4 electrodes in one plane so that movement artefacts could be reduced by combining the two independent measurements. Further studies showed that movement artefacts could be reduced using a strategic 6- electrode placement in three dimensions. It was also possible to detect obstructive apnoea, as the amplitude of the breathing signal was higher than that due to obstructive apnoea and this difference was statistically significant. In these studies, the main cause of movement artefacts was identified as the movement of electrodes with the skin. A significant reduction in movement artefacts was obtained using the 6-electrode placement. This advantage of the 6-electrode placement proposed in this project, can be of great use in clinical applications such as apnoea monitoring in neonates. Further studies can be carried out to determine an optimum frequency of injected current to achieve reduction in residual movement artefacts

Evaluating Electrode-Tissue Contact Force Using the Moving Pattern of the Catheter Tip and the Electrogram Characteristics

As an important reference for the physician during catheter ablation, the electrode-tissue contact force (CF), is one of the key points for the success of the catheter ablation. With the guide of CF sensing, the ablation procedure can be safer and more effective. Techniques and apparatus have been refined since catheter ablation was invented to treat cardiac arrhythmia. In the review part, different techniques for evaluating the electrode-tissue CF are discussed, including both direct and indirect measurement. Sensor-based direct measurement is broadly applied but restricted by the high cost. Surrogate markers of catheter-tissue contact such as impedance, electrogram (EGM) quality, catheter tip temperature and so on, are taken as reference evaluating CF as well, but each of them has their own drawbacks. In this dissertation, our approach estimating the CF is based on the moving pattern of the catheter tip in the heart chamber. The factors determining the catheter tip motion, include the cardiac and respiratory cycles, blood flow, and so on. If the position of the catheter tip can be recorded, then the motion of the catheter tip can be tracked and analyzed. Based on our collected data, the moving pattern of the catheter tip is different when the electrode-tissue CF level varies. Features extracted from catheter tip motion are significant for CF evaluation. There are different features selected to describe the moving pattern of the catheter tip, which are identified to best represent the movement by checking the corresponding CF as reference. In summary, if the feature has a strong correlation with the CF, then it can be taken as a good feature. Using the features as input, the CF evaluating mechanism is based on a multi-class classification decision tree to make an optimum and comprehensive estimation

Models and image: reconstruction in electrical impedance tomography of human brain function

Electrical Impedance Tomography (EIT) of brain function has the potential to provide a rapid portable bedside neuroimaging device. Recently, our group published the first ever EIT images of evoked activity recorded with scalp electrodes. While the raw data showed encouraging, reproducible changes of a few per cent, the images were noisy. The poor image quality was due, in part, to the use of a simplified reconstruction algorithm which modelled the head as a homogeneous sphere. The purpose of this work has been to develop new algorithms in which the model incorporates extracerebral layers and realistic geometry, and to assess their effect on image quality. An algorithm was suggested which allowed fair comparison between reconstructions assuming analytical and numerical (Finite Element Method - FEM) models of the head as a homogeneous sphere and as concentric spheres representing the brain, CSF, skull and scalp. Comparison was also made between these and numerical models of the head as a homogeneous, head-shaped volume and as a head-shaped volume with internal compartments of contrasting resistivity. The models were tested on computer simulations, on spherical and head-shaped, saline-filled tanks and on data collected during human evoked response studies. EIT also has the potential to image resistance changes which occur during neuronal depolarization in the cortex and last tens of milliseconds. Also presented in this thesis is an estimate of their magnitude made using a mathematical model, based on cable theory, of resistance changes at DC during depolarization in the cerebral cortex. Published values were used for the electrical properties and geometry of cell processes (Rail, 1975). The study was performed in order to estimate the resultant scalp signal that might be obtained and to assess the ability of EIT to produce images of neuronal depolarization