Remote Assessment of the Cardiovascular Function Using Camera-Based Photoplethysmography

Camera-based photoplethysmography (cbPPG) is a novel measurement technique that allows the continuous monitoring of vital signs by using common video cameras. In the last decade, the technology has attracted a lot of attention as it is easy to set up, operates remotely, and offers new diagnostic opportunities. Despite the growing interest, cbPPG is not completely established yet and is still primarily the object of research. There are a variety of reasons for this lack of development including that reliable and autonomous hardware setups are missing, that robust processing algorithms are needed, that application fields are still limited, and that it is not completely understood which physiological factors impact the captured signal. In this thesis, these issues will be addressed. A new and innovative measuring system for cbPPG was developed. In the course of three large studies conducted in clinical and non-clinical environments, the system’s great flexibility, autonomy, user-friendliness, and integrability could be successfully proven. Furthermore, it was investigated what value optical polarization filtration adds to cbPPG. The results show that a perpendicular filter setting can significantly enhance the signal quality. In addition, the performed analyses were used to draw conclusions about the origin of cbPPG signals: Blood volume changes are most likely the defining element for the signal's modulation. Besides the hardware-related topics, the software topic was addressed. A new method for the selection of regions of interest (ROIs) in cbPPG videos was developed. Choosing valid ROIs is one of the most important steps in the processing chain of cbPPG software. The new method has the advantage of being fully automated, more independent, and universally applicable. Moreover, it suppresses ballistocardiographic artifacts by utilizing a level-set-based approach. The suitability of the ROI selection method was demonstrated on a large and challenging data set. In the last part of the work, a potentially new application field for cbPPG was explored. It was investigated how cbPPG can be used to assess autonomic reactions of the nervous system at the cutaneous vasculature. The results show that changes in the vasomotor tone, i.e. vasodilation and vasoconstriction, reflect in the pulsation strength of cbPPG signals. These characteristics also shed more light on the origin problem. Similar to the polarization analyses, they support the classic blood volume theory. In conclusion, this thesis tackles relevant issues regarding the application of cbPPG. The proposed solutions pave the way for cbPPG to become an established and widely accepted technology

Analysis of Venous Blood Flow and Deformation in the Calf under External Compression

Deep vein thrombosis (DVT) is a common post-operative complication, and a serious threat to the patient’s general recovery. In recent years, there has been increasing awareness of the risk of DVT in healthy individuals after prolonged immobility, such as people taking long-period flights or sitting at a computer. Mechanical methods of DVT prophylaxis, such as compression stockings, have gained widespread acceptance, but the haemodynamic mechanism of their action is still not well understood. In this study, computational modelling approaches based on magnetic resonance (MR) images are used to (i) predict the deformation of calf and deep veins under external compression, (ii) determine blood flow and wall shear stress in the deep veins of the calf, and (iii) quantify the effect of external compression on flow and wall shear stress in the deep veins. As a first step, MR images of the calf obtained with and without external compression were analysed, which indicated different levels of compressibility for different calf muscle compartments. A 2D finite element model (FEM) with specifically tailored boundary conditions for different muscle components was developed to simulate the deformation of the calf under compression. The calf tissues were described by a linear elastic model. The simulation results showed a good qualitative agreement with the measurements in terms of deep vein deformation, but the area reduction predicted by the FEM was much larger than that obtained from the MR images. In an attempt to improve the 2D FEM, a hyperelastic material model was employed and a finite element based non-rigid registration algorithm was developed to calculate the bulk modulus of the calf tissues. Using subject-specific bulk modulus derived with this method together with a hyperelastic material model, the numerical results showed better quantitative agreement with MR measured deformations of deep veins and calf tissues. In order to understand the effect of external compression on flow in the deep veins, MR imaging and real-time flow mapping were performed on 10 healthy volunteers before and after compression. Computational fluid dynamics was then employed to calculate the haemodynamic wall shear stress (WSS), based on the measured changes in vessel geometry and flow waveforms. The overall results indicated that application of the compression stocking led to a reduction in both blood flow rate and cross sectional area of the peroneal veins in the calf, which resulted in an increase in WSS, but the individual effects were highly variable. Finally, a 3D fluid-structure interactions (FSI) model was developed for a segment of the calf with realistic geometry for the calf muscle and bones but idealised geometry for the deep vein. The hyperelastic material properties evaluated previously were employed to describe the solid behaviours. Some predictive ability of the FSI model was demonstrated, but further improvement and validation are still needed

Characterization and processing of novel neck photoplethysmography signals for cardiorespiratory monitoring

Epilepsy is a neurological disorder causing serious brain seizures that severely affect the patients' quality of life. Sudden unexpected death in epilepsy (SUDEP), for which no evident decease reason is found after post-mortem examination, is a common cause of mortality. The mechanisms leading to SUDEP are uncertain, but, centrally mediated apneic respiratory dysfunction, inducing dangerous hypoxemia, plays a key role. Continuous physiological monitoring appears as the only reliable solution for SUDEP prevention. However, current seizure-detection systems do not show enough sensitivity and present a high number of intolerable false alarms. A wearable system capable of measuring several physiological signals from the same body location, could efficiently overcome these limitations. In this framework, a neck wearable apnea detection device (WADD), sensing airflow through tracheal sounds, was designed. Despite the promising performance, it is still necessary to integrate an oximeter sensor into the system, to measure oxygen saturation in blood (SpO2) from neck photoplethysmography (PPG) signals, and hence, support the apnea detection decision. The neck is a novel PPG measurement site that has not yet been thoroughly explored, due to numerous challenges. This research work aims to characterize neck PPG signals, in order to fully exploit this alternative pulse oximetry location, for precise cardiorespiratory biomarkers monitoring. In this thesis, neck PPG signals were recorded, for the first time in literature, in a series of experiments under different artifacts and respiratory conditions. Morphological and spectral characteristics were analyzed in order to identify potential singularities of the signals. The most common neck PPG artifacts critically corrupting the signal quality, and other breathing states of interest, were thoroughly characterized in terms of the most discriminative features. An algorithm was further developed to differentiate artifacts from clean PPG signals. Both, the proposed characterization and classification model can be useful tools for researchers to denoise neck PPG signals and exploit them in a variety of clinical contexts. In addition to that, it was demonstrated that the neck also offered the possibility, unlike other body parts, to extract the Jugular Venous Pulse (JVP) non-invasively. Overall, the thesis showed how the neck could be an optimum location for multi-modal monitoring in the context of diseases affecting respiration, since it not only allows the sensing of airflow related signals, but also, the breathing frequency component of the PPG appeared more prominent than in the standard finger location. In this context, this property enabled the extraction of relevant features to develop a promising algorithm for apnea detection in near-real time. These findings could be of great importance for SUDEP prevention, facilitating the investigation of the mechanisms and risk factors associated to it, and ultimately reduce epilepsy mortality.Open Acces

Cutaneous vascular haemodynamics in diabetes mellitus.

In this thesis the laser Doppler flowmeter and other microvascular methods were used to investigate the skin microcirculation in non-diabetic and diabetic subjects in order to gain a greater understanding of the normal microcirculation and to define abnormalities relevant to the diabetic state. The principle findings were- 1. The normal skin microvascular response to thermal and mechanical injury is a substantial increase in blood flow. In diabetic subjects with and without complications this hyperaemic response was reduced and degree of impairment was found to be greatest in those with the severest complications. 2. In diabetic patients, the diameter of foot skin capillaries was reduced and the basement membrane width was found to increase progressively with increasing severity of complications. These structural changes may partly explain the reduced hyperaemic responses and their relationship with severity of complications. These structural and functional abnormalities may be implicated in the pathogenesis and impaired healing of diabetic foot lesions. 3. In normal subjects, blood flow in the toe pulp fell by 80% when the foot was lowered 50 cm below the heart. Toe blood flow in neuropathic diabetic subjects was three fold higher than in normal subjects, and on lowering the foot this difference was even greater; dependent flow was seven fold higher and the fall in blood flow was only 50%. These findings are compatible with reduced central sympathetic tone and/or peripheral sympathetic nerve failure. 4. In young non-neuropathic diabetic subjects, the more severe stress of sitting still for 50 minutes with the foot 1 meter below heart level, also revealed an increase in toe pulp blood flow. This was associated with elevated capillary pressure, failure in the expected rise in plasma osmotic pressure, and increased foot swelling. These results provide evidence of capillary hypertension and impairment of oedema preventing mechanisms in the dependent foot of diabetic subjects. These abnormalities may be important in initiating structural and functional damage to the skin microcirculation

Optimising outcomes in the treatment of superficial venous insufficiency

The traditional “gold-standard” treatment for symptomatic SVI affecting the GSV is conventional open surgery and stripping under general anaesthesia. Despite improved QoL and cost-effectiveness when compared to conservative management, conventional surgery is not without drawbacks. Endovenous ablative treatments have been developed, which seek to address some of these limitations. Randomised clinical trial (RCT) data has demonstrated the superiority of endovenous laser ablation (EVLA) over surgery in the short term. Attention is now focused on evaluating its mid- and long-term outcomes, and to further evolve the technique to improve patient outcomes.In this thesis, five studies were conceived to address two main objectives. Firstly, two-year follow-up of the HELP-1 RCT of EVLA versus conventional surgery was performed to assess clinical, QoL and duplex ultrasound (DUS) outcomes and identify potential for EVLA technique evolution. Four further studies were performed, aimed at improvement of patient outcomes by modification of the EVLA technique via i) pH buffering of tumescent anaesthesia, ii) concomitant treatment of varicosities, and iii) endovenous energy delivery via longer wavelength laser.Two-year outcomes from the HELP-1 RCT demonstrated continued superiority of EVLA over conventional surgery in terms of lower clinical recurrence rates, with maintained improvements in clinical and QoL outcomes. DUS outcomes identified patterns of clinical recurrence that can be addressed by simple modifications of the EVLA technique.Buffering of tumescent anaesthesia resulted in significantly reduced patient-reported periprocedural pain. Concomitant treatment of varicosities with ambulatory phlebectomy under tumescent anaesthesia demonstrated significant benefits in clinical severity and disease-specific QoL over foam sclerotherapy. Use of longer laser wavelength (1470nm) resulted in significantly reduced postprocedural pain in comparison to shorter (810nm) wavelength.EVLA is demonstrated to have significant short- and medium-term benefits over conventional surgery. Further evolution of the technique, including the modifications described, should provide additional benefit in terms of patient outcomes

Mechanochemical ablation in the treatment of superficial venous incompetence

BackgroundThe routine management of venous incompetence has undergone considerable changes in the last two decades led by the introduction of minimally invasive endovenous techniques. At the heart of these changes has been a drive to offer patients effective symptomatic relief whilst minimising disruption to patient quality of life and periprocedural pain. Endovenous thermal ablation (EVTA) has been the main mode of treatment in this minimally invasive era, however, non-thermal methods are challenging this established order and include mechanochemical ablation (MOCA) which is an exciting new technique that combines liquid sclerotherapy with mechanical damage to vessel intima.AimsThe studies contained within this thesis aim to assess the evidence supporting the use of MOCA for the treatment of venous incompetence, to independently validate these results, to optimise a strategy of performing MOCA, and to test the efficacy and clinical effectiveness of MOCA against EVTA.MethodsStudy 1 is a systematic review of the current literature of MOCA, focusing on objective assessment of clinical success including duplex ultrasound (DUS) measurements and health related patient reported outcomes (PROMS). Study 2 is a cohort study of symptomatic patients with superficial venous incompetence (SVI), treated with MOCA and 1.5% Sodium tetradecyl sulphate (STS). Outcomes included clinical examination, DUS, health related PROMS at baseline and weeks 1,6,26 and 52. Study 3 compares the approach of treating varicose tributaries with phlebectomy at the time of performing MOCA (MOCAP) against sequential treatment of tributary varicosities at a later date (MOCAS). A similar outcomes assessment and follow up strategy to study 2 was adopted. Study 4 takes forward the results of the previous studies and compares endovenous laser ablation (EVLA) to MOCA in a randomised controlled study comparing the clinical and technical outcomes of each intervention at baseline and weeks 1,6,26 and 52.ResultsStudy 1: MOCA is a safe and effective method of treating SVI in the short-term, however, the evidence for the longevity of its results beyond 6 months is poor. Moreover, the data on anatomical occlusion rates is questionable and may not match those of EVTA.Study 2: Thirty-two patients were recruited to the study. Complete target vein occlusion at one year was achieved in 21 (75%) patients. Six patients (21.4%) required secondary procedures, of which three had axial EVLA and three required ambulatory phlebectomy with perforator ligation. There was a significant improvement in the median (interquartile range) Venous Clinical Severity Score (VCSS) from baseline 6 (5–8) to a score of 1 (0–2) at one year (p<0.001). There was also a significant improvement in health-related quality of life (HRQoL), both generic (p<0.001) and disease specific (p<0.001). One patient (3.1%) had a post-procedural non-fatal pulmonary embolus.Study 3: Fifty patients underwent MOCAP and 33 patients MOCAS. The two groups were comparable at baseline. MOCAP was associated with lower (better) AVVQ scores at six weeks (3.4 (0.5–6.0) vs. 6.1 (1.8–12.1); p=0.009) and at six months (1.6 (0.0–4.5) vs. 3.34 (1.8–8.4); p=0.009) but by one year the difference was no longer statistically significant (1.81 (0.0–4.5) vs. 3.81 (0.2–5.3); p=0.099). MOCAP was associated with longer procedural duration (45 min (36–56) vs. 30 min (25–37); p<0.001) and higher maximal periprocedural pain (31 (21–59) vs. 18 (7–25); p<0.001). VCSS at all time points was lower in MOCAP group compared to MOCAS (0 (0–1) vs. 1 (0–3); p<0.001). MOCAP was associated with fewer episodes of clinically significant thrombophlebitis (6 of 50 (12%) vs. 10 of 33 (30%); p=0.039) and lower numbers of secondary procedures (2 (4%) vs. 6 (18%); p=0.032)Study 4: One hundred and fifty patients were randomised equally between MOCA and EVLA. Both groups reported low intraprocedural pain scores; on a 100 mm visual analogue scale, pain during axial EVLA was 22 (9-44) compared to 15 (9-29) during MOCA; p=0.210. At 1 year, duplex derived anatomical occlusion rates after EVLA were 63/69 (91%) compared to 53/69 (77%) in the MOCA group; p=0.020. Both groups experienced significant improvement in VCSS and AVVQ after treatment, without a significant difference between groups. Median VCSS improved from 6 (5-8) to 0 (0-1) at one year; p<0.001. Median AVVQ improved from 13.8 (10.0-17.7) to 2.0 (0.0-4.9); p<0.001. One patient in the MOCA group experienced DVT.ConclusionMOCA with 1.5% STS is safe, effective and leads to significant improvement in patient health related quality of life (HRQoL) outcomes up to 1 year follow up. However, the anatomical occlusion rates achieved with MOCA are lower than has been previously reported in the literature and do not match EVLA results. Patient HRQoL gains are better when MOCA is combined with concomitant phlebectomy of varicose tributaries and using this approach HRQoL gains following MOCA are equivalent to those achieved by EVLA. Long-term follow up is needed however to ascertain the effect of the increased recanalisation following MOCA on disease recurrence and progression

Systems Radiology and Personalized Medicine

Medicine has evolved into a high level of specialization using the very detailed imaging of organs. This has impressively solved a multitude of acute health-related problems linked to single-organ diseases. Many diseases and pathophysiological processes, however, involve more than one organ. An organ-based approach is challenging when considering disease prevention and caring for elderly patients, or those with systemic chronic diseases or multiple co-morbidities. In addition, medical imaging provides more than a pretty picture. Much of the data are now revealed by quantitating algorithms with or without artificial intelligence. This Special Issue on “Systems Radiology and Personalized Medicine” includes reviews and original studies that show the strengths and weaknesses of structural and functional whole-body imaging for personalized medicine

Special Topics in Cardiac Surgery

This book considers mainly the current perioperative care, as well as progresses in new cardiac surgery technologies. Perioperative strategies and new technologies in the field of cardiac surgery will continue to contribute to improvements in postoperative outcomes and enable the cardiac surgical society to optimize surgical procedures. This book should prove to be a useful reference for trainees, senior surgeons and nurses in cardiac surgery, as well as anesthesiologists, perfusionists, and all the related health care workers who are involved in taking care of patients with heart disease which require surgical therapy. I hope these internationally cumulative and diligent efforts will provide patients undergoing cardiac surgery with meticulous perioperative care methods

Non-invasive Multimodal Monitoring in Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability, often resulting in increased intracranial pressure (ICP) and cerebral ischemia. Current ICP measurement methods involve invasive, non-therapeutic procedures. This research aims to develop a non-invasive, continuous optical system for monitoring ICP and cerebral oxygenation. Using backscattered brain optical signals, it leverages cerebral pulsatile photoplethysmograms (PPGs) and non-pulsatile near-infrared spectroscopy (NIRS) signals to assess ICP and oxygenation. The innovation lies in using cerebral NIRS-PPGs to measure ICP, based on the hypothesis that changes in ICP affect cerebral PPG signal morphology. These changes in morphological features, with the support of advanced algorithms including Machine Learning (ML) models, could be utilised in translating the changes in the pulsatile signals in absolute measurements of ICP. The research firstly implemented Monte Carlo simulations to fully understand the effect of multi-source detector separations on brain light tissue interaction. Secondly, a novel reflectance, custom-made TBI multiwavelength and multisource-detector optical sensor and instrumentation, including advanced signal processing algorithms, was designed to acquire, pre-process, and analyse raw PPG signals (AC + DC) from the brain. Thirdly, a novel head phantom and an in vitro brain haemodynamic system were developed for evaluating the sensor. The phantom was the ideal tool for simulating different clinical scenarios that cannot be implemented in real in vivo studies. Fourthly, this research carried out three in vitro studies to investigate the sensor's capability to non-invasively monitor intracranial pressure and oxygenation. The first study evaluated the quality of the optical signals acquired from the developed probe at different source-detector (S-D) separations and multiple wavelengths. It was concluded that the optimal S-D separation to reach the cerebral tissue, and acquire good quality PPG signals, was within 3 cm and 4 cm. The second study assessed the central hypothesis of this research by recording PPG signals from the phantom’s brain at different intracranial pressure levels and implementing ML models utilising pertinent features from the PPG. Results from the second study showed a correlation coefficient of 0.86, mean absolute error of 3.7 mmHg, and limits of agreement of ±4 mmHg, which suggest that NIRS-PPG signals could estimate ICP non invasively. Finally, a third study demonstrated the sensor’s response to in vitro changes in blood oxygenation levels, with less than 33.8% error in half the measurements compared to the reference. This final implementation of spatially resolved spectroscopy algorithms actualize the proposed non-invasive multimodal monitoring sensor for traumatic brain injury. The novel technological developments and the new knowledge acquired from this research paves the way for the development of a transformative non-invasive optical sensor technology for the continuous monitoring of ICP and cerebral oxygenation in TBI patients and beyond